Verhaar, J.A.N.

Unfocused extracorporeal shock waves induce anabolic effects in osteoporotic rats (Article)

2013-05-01T00:00:00Z

Unfocused extracorporeal shock waves (UESW) have been shown to have an anabolic effect on bone mass. Therefore we investigated the effects of UESW on bone in osteoporotic rats with and without anti-resorptive treatment. Twenty-week-old rats were ovariectomized (n = 27). One group was treated with saline and another group with Alendronate (ALN) 2.4 μg/kg, 3×/week. UESW were applied 2 weeks after ovariectomy. Thousand UESW were applied to one hind leg, the contra-lateral hind leg was not treated and served as control. With the use of in vivo micro-CT scanning it was shown that in saline treated rats trabecular bone volume fraction (BV/TV) was higher at 2 weeks follow-up in UESW treated legs compared to control legs. However, at 4 and 10 weeks no difference was found. In ALN treated animals UESW led to a pronounced anabolic response resulting in an increase in BV/TV at all time-points. Furthermore, UESW resulted in increased cortical volume (CtV), higher trabecular connectivity and, more plate-like and thicker trabeculae. Biomechanical testing showed that UESW lead to a higher maximum force before failure and higher stiffness in all treatment groups. With histology abundant areas of intramembranous bone formation along the periosteal cortex and within the bone marrow were observed. In conclusion this study shows promising results for the use of UESW in the treatment of osteoporosis, especially when this treatment is combined with an anti-resorptive treatment. Copyright

Selective laser melting-produced porous titanium scaffolds regenerate bone in critical size cortical bone defects (Article)

2013-05-01T00:00:00Z

Porous titanium scaffolds have good mechanical properties that make them an interesting bone substitute material for large bone defects. These scaffolds can be produced with selective laser melting, which has the advantage of tailoring the structure's architecture. Reducing the strut size reduces the stiffness of the structure and may have a positive effect on bone formation. Two scaffolds with struts of 120-μm (titanium-120) or 230-μm (titanium-230) were studied in a load-bearing critical femoral bone defect in rats. The defect was stabilized with an internal plate and treated with titanium-120, titanium-230, or left empty. In vivo micro-CT scans at 4, 8, and 12 weeks showed more bone in the defects treated with scaffolds. Finally, 18.4 ± 7.1 mm3(titanium-120, p = 0.015) and 18.7 ± 8.0 mm3(titanium-230, p = 0.012) of bone was formed in those defects, significantly more than in the empty defects (5.8 ± 5.1 mm3). Bending tests on the excised femurs after 12 weeks showed that the fusion strength reached 62% (titanium-120) and 45% (titanium-230) of the intact contralateral femurs, but there was no significant difference between the two scaffolds. This study showed that in addition to adequate mechanical support, porous titanium scaffolds facilitate bone formation, which results in high mechanical integrity of the treated large bone defects. Copyright

Relationship between neovascularization and clinical severity in Achilles tendinopathy in 556 paired measurements (Article)

2013-04-30T00:00:00Z

Neovascularization is frequently observed in tendinopathy. Previous studies have focused on the role of neovascularization in Achilles tendinopathy, but have been conducted in small series. It is still unclear whether the degree of neovascularization is related to severity of symptoms. The purpose was to study the relationship between ultrasonographic neovascularization and clinical severity in patients with Achilles tendinopathy. In this prospective cohort study, data on 127 patients (141 tendons) were assembled from databases of three clinical trials. All patients followed an eccentric exercise program. The Öhberg neovascularization score (0-4+) and Victorian Institute of Sports Assessment-Achilles (VISA-A) score (split into domains: pain, function and activity) were collected during baseline and follow-up. The relationship between neovascularization and VISA-A score was calculated. At baseline, 107 tendons (76%) showed some degree of neovascularization. In 556 coupled measurements, neovascularization was weakly related to the VISA-A score [Exp (B) 1.017, 95% confidence interval (CI), 1.007-1.026]. No significant relationship was found between neovascularization and the pain domain (P=0.277) and the activity domain (P=0.283), but there was between neovascularization and the function domain of the VISA-A score [Exp (B)=1.067, 95% CI 1.018-1.119]. In conclusion, neovascularization in Achilles tendinopathy is weakly related to clinical severity, mainly based on the function domain of the VISA-A score.

Epidemiology and health-care utilisation of wrist fractures in older adults in The Netherlands, 1997-2009 (Article)

2013-04-01T00:00:00Z

Introduction: Wrist fractures are common in older adults and are expected to increase because of ageing populations worldwide. The introduction of plate and screw fixation has changed the management of this trauma in many patients. For policymaking it is essential to gain insight into trends in epidemiology and healthcare utilisation. The purpose of this study was to determine trends in incidence, hospitalisation and operative treatment of wrist fractures. Methods: A population-based study of patients aged 50 years and older using the Dutch National Injury Surveillance System and the National Hospital Discharge Registry. Data on emergency department visits, hospitalisations and operative treatment for wrist fractures within the period 1997-2009 were analysed. Results: In women, the age-standardised incidence rate of wrist fractures decreased from 497.2 per 100,000 persons (95% confidence interval, 472.3-522.1) in 1997 to 445.1 (422.8-467.4) in 2009 (P for trend <0.001). In men, no significant trends were observed in the same time period. Hospitalisation rates increased from 30.1 (28.3-31.9) in 1997 to 78.9 (75.1-82.8) in 2009 in women (P < 0.001), and from 6.4 (6.0-6.8) to 18.4 (17.3-19.5) in men (P < 0.001). There was a strong increase in operative treatment of distal radius fractures, especially due to plate fixation techniques in all age groups. Conclusion: Incidence rates of wrist fractures decreased in women and remained stable in men, but hospitalisation rates strongly increased due to a steep rise in operative treatments. The use of plate and screw fixation techniques for distal radius fractures increased in all age groups.

Total hip replacement but not clinical osteoarthritis can be predicted by the shape of the hip: A prospective cohort study (CHECK) (Article)

2013-04-01T00:00:00Z

Objective: To investigate the association between baseline hip shape and both clinical hip osteoarthritis (OA) and total hip replacement (THR) at 5-year follow-up. Design: Individuals from the Cohort Hip and Cohort Knee (CHECK) study, with early symptomatic OA, having standardized anteroposterior pelvic radiographs at baseline and 5-year follow-up (n = 723) were included. Hip shape on the radiographs was assessed using statistical shape modeling (SSM). Hips fulfilling the American College of Rheumatology (ACR) criteria at follow-up were classified as clinical OA. The association between each mode of shape variation and both outcome measures was calculated by Generalized Estimating Equations (GEE). Results: The included individuals comprised 575 females and 148 males (mean age 55.9 ± 5.2 years). At baseline, 8% fulfilled the ACR criteria, 76% had no radiographic hip OA [Kellgren & Lawrence (K&L) = 0] and 24% had doubtful OA (K&L = 1). At follow-up, 147 hips (10.4%) fulfilled the ACR criteria and 35 hips (2.5%) had received THR. Five shape variants (modes) at baseline associated significantly with THR within 5 years. When combined in one GEE model, these shape variants resulted in a predictive power indicated by an area under the curve of 0.81. No shape variants associated with the presence of clinical OA at follow-up. Conclusion: The shape of the hip as quantified by an SSM has a good predictive value for THR, whereas variation in shape cannot predict clinical OA. Minor shape variants may be used as a radiographic biomarker to predict the future risk of THR.

Knee injury and osteoarthritis outcome score or international knee documentation committee subjective knee form: Which questionnaire is most useful to monitor patients with an anterior cruciate ligament rupture in the short term? (Article)

2013-04-01T00:00:00Z

Purpose: To evaluate which questionnaire, the Knee Injury and Osteoarthritis Outcome Score (KOOS) or the International Knee Documentation Committee Subjective Knee Form (IKDC subjective), is most useful to evaluate patients with recent anterior cruciate ligament (ACL) ruptures or those within 1 year of an ACL reconstruction. Methods: Patients with recent (0-6 months) ACL ruptures or those with indications for ACL reconstruction were included. All patients completed the questionnaires shortly after trauma or preoperatively and again 1 year later. The KOOS has 5 subscales, each scored separately. The IKDC subjective consists of one total score. The following measurement properties of the KOOS and IKDC subjective were assessed: content validity (n = 45), construct validity (n = 100), test-retest reliability (n = 50), and responsiveness (n = 50). Results: Regarding content validity, 2 KOOS subscales (Pain and Activities of Daily Living) were scored as nonrelevant. Two of the 18 questions on the IKDC subjective were assessed as nonrelevant. Only the KOOS subscale Sport and Recreation Function had acceptable construct validity (79% confirmation of the predefined hypotheses). None of the KOOS subscales had a sufficient score for responsiveness (<75% confirmation of the predefined hypotheses). The IKDC subjective scored acceptable for construct validity (84% confirmation of the predefined hypotheses) and responsiveness (86% confirmation of the predefined hypotheses). All KOOS subscales and the IKDC subjective had a reliability (intraclass correlation coefficient [ICC]) of 0.81 or higher. Conclusions: The IKDC subjective is more useful than the KOOS questionnaire to evaluate both patients with recent ACL ruptures and those in the first year after ACL reconstruction. Level of Evidence: Level III, prognostic validation study.

Re-displacement of stable distal both-bone forearm fractures in children: A randomised controlled multicentre trial (Article)

2012-12-04T00:00:00Z

Introduction: Displaced metaphyseal both-bone fractures of the distal forearm are generally reduced and stabilised by an above-elbow cast (AEC) with or without additional pinning. The purpose of this study was to find out if re-displacement of a reduced stable metaphyseal both-bone fracture of the distal forearm in a child could be prevented by stabilisation with Kirschner wires. Methods: Consecutive children aged <16 years with a displaced metaphyseal both-bone fracture of the distal forearm (n = 128) that was stable after reduction were randomised to AEC with or without percutaneous fixation with Kirschner wires. The primary outcome was re-displacement of the fracture. Results: A total of 67 children were allocated to fracture reduction and AEC and 61 to reduction of the fracture, fixation with Kirschner wires and AEC. The follow-up rate was 96% with a mean follow-up of 7.1 months. Fractures treated with additional pinning showed less re-displacement (8% vs. 45%), less limitation of pronation and supination (mean limitation 6.9 (±9.4)° vs. 14.3 (±13.6)°) but more complications (14 vs. 1). Conclusions: Pinning of apparent stable both-bone fractures of the distal forearm in children might reduce fracture re-displacement. The frequently seen complications of pinning might be reduced by a proper surgical technique.

Effect of arthritic synovial fluids on the expression of immunomodulatory factors by mesenchymal stem cells: An explorative in vitro study (Article)

2012-12-01T00:00:00Z

Background:In diseased joints, the catabolic environment results in progressive joint damage. Mesenchymal stem cells (MSCs) can have immunomodulatory effects by secreting anti-inflammatory factors. To exert these effects, MSCs need to be triggered by proinflammatory cytokines. To explore the potential of MSCs as a treatment for diseased joints, we studied the effect of synovial fluid (SF) from donors with different joint diseases and donors without joint pathology on the immunomodulatory capacities of human MSCs in vitro. We hypothesized that SF of diseased joints influences the immunomodulatory effects of MSCs. Materials and Methods: MSCs were cultured in medium with SF of six osteoarthritis (OA) or six rheumatoid arthritis (RA) donors and three donors without joint pathology were used as control. Gene expressions of IL-6, HGF, TNFa, TGFb1, and indoleamine 2,3-dioxygenase (IDO) were analyzed. L-kynurenine concentration in conditioned medium (CM) by MSCs with SF was determined as a measure of IDO activity by MSCs. Furthermore, the effect of CM with SF on proliferation of activated lymphocytes was analyzed. Results: Addition of SF significantly up-regulated the mRNA expression of IL-6 and IDO in MSCs. SF(OA) induced significantly higher expression of IDO than SF(control), although no difference in IDO activity of the MSCs could be shown with a L-kynurenine assay. Medium conditioned by MSCs with SF(OA or RA) suppressed activated lymphocyte proliferation in vitro more than medium conditioned by MSCs without SF or with SF(control). Discussion: SF can influence the expression of genes involved in immunomodulation by MSCs and the effect on lymphocyte proliferation. We found indications for disease-specific differences between SFs but the variation between donors, even within one disease group was high. These data warrant further research to examine the potential application of MSC therapy in arthritic joints.

A guideline to medical photography: A perspective on digital photography in an orthopaedic setting (Article)

2012-12-01T00:00:00Z

Purpose: Quality photographs are essential for clinical documentation, research, and publication in scientific journals and teaching. Oftentimes, non-ideal lighting and a sterile environment restrict the medical photographer, resulting in lower-quality photographs. This article aims to provide a clear and comprehensible guideline for medical photography in an orthopaedic setting. Methods: This article is based on extensive photographic involvement in operating and laboratory settings, in close collaboration with medical professionals from the Steadman Clinic (Vail, Colorado, USA), Gothenburg University (Göteborg, Sweden) and Erasmus MC (Rotterdam, the Netherlands). Background literature was searched through Google Scholar and PubMed. Results: Three relevant journal articles, and one book on medical photography, were used to write this paper. Seventeen Internet articles were used for background information. Conclusion: A relevant, up-to-date and comprehensive guideline to medical photography for medical professionals, with or without photographic experience, is provided. Level of evidence: Expert opinion, Level V.

Mesenchymal stem cells secrete factors that inhibit inflammatory processes in short-term osteoarthritic synovium and cartilage explant culture (Article)

2012-10-01T00:00:00Z

Objective: Mesenchymal stem cells (MSCs) are promising candidates for osteoarthritis (OA) therapies, although their mechanism of action remains unclear. MSCs have recently been discovered to secrete anti-inflammatory cytokines and growth factors. We studied the paracrine effects of MSCs on OA cartilage and synovial explants in vitro. Design: MSC-conditioned medium was prepared by stimulating primary human MSCs with tumour necrosis factor alpha (TNFα) and (50. ng/ml each). Human synovium and cartilage explants were cultured in MSC-conditioned medium or in control medium, containing the same amount of added TNFα and IFNγ but not incubated with MSCs. Explants were analyzed for gene expression and the production of nitric oxide (NO). The presence of the inhibitor of nuclear factor kappa B alpha (IκBa) was assessed by Western blot analysis. Results: Synovial explants exposed to MSC-conditioned medium showed decreased gene expression of interleukin-1 beta (IL-1β), matrix metalloproteinase (MMP). 1 and MMP13, while suppressor of cytokine signaling (SOCS). 1 was upregulated. In cartilage, expression of IL-1 receptor antagonist (IL-1RA) was upregulated, whereas a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS). 5 and collagen type II alpha 1 (COL2A1) were downregulated. MSC-conditioned medium reduced NO production in cartilage explants and the presence of IκBa was increased in synoviocytes and chondrocytes treated with MSC-conditioned medium. Conclusions: In an inflammatory environment, MSCs secrete factors which cause multiple anti-inflammatory effects and influence matrix turnover in synovium and cartilage explants. Thereby, the presented data encourage further study of MSCs as a treatment for joint diseases.

TGFβ inhibition during expansion phase increases the chondrogenic re-differentiation capacity of human articular chondrocytes (Article)

2012-10-01T00:00:00Z

Objective: Autologous chondrocyte implantation is a cell-based treatment to repair articular cartilage defects, relying on the availability of expanded (de-differentiated) chondrocytes. Unfortunately, the expansion process causes several phenotypical changes, requiring re-establishment of the native chondrogenic phenotype to sustain proper repair. Among other proteins, transforming growth factor-β (TGFβ) is known to influence the chondrogenic re-differentiation of human articular chondrocytes (HACs) and their matrix deposition. Thus we investigated the effects of TGFβ-depletion during the expansion phase. Design: HACs were isolated from articular cartilage and expanded in the canonical serum-supplemented medium [fetal calf serum (FCS)] or in a chemically-defined (CD) medium, with or without anti-TGFβ antibody administration. The re-differentiation potential of the cells was assessed by pellet cultures, gene expression analysis and histology. Results: Cell proliferation proceeded more rapidly in CD-medium than in FCS-medium; it was not affected by the use of anti-TGFβ antibody but was further increased by addition of exogenous TGFβ1, via increased p-Smad1/5/8. Conversely, in FCS-medium, addition of anti-TGFβ antibody decreased both proliferation and p-Smad1/5/8 level. Challenging either FCS- or CD-medium with anti-TGFβ antibody during expansion enhanced chondrogenesis in the subsequent pellet cultures. Moreover, TGFβ-depletion during expansion in CD-medium inhibited mRNA expression of hypertrophic markers, collagen type-X (COL10) and matrix metalloproteinase-13 (MMP-13). Interestingly, the TGFβ1 level detected by enzyme-linked immunosorbent sandwich assay (ELISA) during cell expansion was correlated with COL10 mRNA expression after re-differentiation. Conclusion: TGFβ-depletion during expansion improves the re-differentiation capacity of chondrocytes and inhibits hypertrophy. These results indicate the importance of the expansion medium composition to improve chondrogenic re-differentiation and to inhibit hypertrophy.

De harde les van metaal-op-metaalheupprothesen (Article)

2012-10-01T00:00:00Z

Een toename van de concentratie van kobalt in het bloed blijkt niet ongevaarlijk. In dit nummer van het Tijdschrift schrijven Dijkman et al. dat een toxische concentratie kan leiden tot hypothyreoïdie, polyneuropathie, aantasting van oog- en gehoorzenuwen en cardiomyopathie.1 Daarnaast is er nog de onzekerheid over de langetermijngevolgen van een verhoogde, maar niet-toxische kobaltconcentratie in het bloed. Geen wonder dat er wereldwijd veel aandacht is voor deze mogelijke gevolgen van plaatsing van metaal-op-metaalheupprothesen (MoM-prothese) met grote kop, de heupprothese van de laatste generatie.2 Deze prothesen zijn in opzet bedoeld voor jonge patiënten. De kop en kom zijn beide van metaal in tegenstelling tot de traditionele heupprothese, waarbij de kom van plastic (polyethyleen) is.

Computer-assisted surgery is not more accurate or precise than conventional arthroscopic ACL reconstruction: A prospective randomized clinical trial (Article)

2012-09-05T00:00:00Z

Background: Accurate and precise tunnel placement is critical to the success of anterior cruciate ligament (ACL) reconstruction. A new development, computer-assisted surgery, aids in placement of the ACL bone tunnels during surgery. Our hypothesis was that computer-assisted ACL reconstruction would allow more accurate and precise tunnel placement compared with conventional surgery. Methods: In a prospective, double-blind, randomized clinical study, 100 patients eligible for ACL reconstruction with a transtibial technique were stratified by surgeon and randomized to either conventional or computer-assisted surgery. Measurement of femoral and tibial tunnel placement with use of three-dimensional computed tomography (CT) was used as the primary outcome to compare conventional ACL surgery with computer-assisted surgery. Results: The placement of the femoral tunnel did not differ between groups (mean, 39.7% of the proximal-distal distance on the intracondylar axis [Blumensaat line] in the conventional group compared with 39.0% in the computer-assisted surgery group; p = 0.70). The anterior-posterior positioning of the tibial tunnel on the tibial plateau also did not differ significantly (38.9% in the conventional group compared with 38.2% in the computer-assisted surgery group; p = 0.58). There was no significant difference in the precision of either the femoral or the tibial tunnel placement between the two groups. Conclusions: There was no significant difference in either the accuracy or the precision of tunnel placement between conventional and computer-assisted ACL reconstruction. Level of Evidence: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence. Copyright

Re-sprains during the first 3 months after initial ankle sprain are related to incomplete recovery: An observational study (Article)

2012-09-01T00:00:00Z

Question: What are prognostic factors for incomplete recovery, instability, re-sprains and pain intensity 12 months after patients consult primary care practitioners for acute ankle sprains? Design: Observational study. Participants: One hundred and two patients who consulted their general practitioner or an emergency department for an acute ankle sprain were included in the study. Outcome measures: Possible prognostic factors were assessed at baseline and at 3 months follow-up. Outcome measures assessed at 12 months follow-up were self-reported recovery, instability, re-sprains and pain intensity. Results: At 3 months follow-up, 65% of the participants reported instability and 24% reported one or more re-sprains. At 12 months follow-up, 55% still reported instability and more than 50% regarded themselves not completely recovered. None of the factors measured at baseline could predict the outcome at 12 months follow-up. Additionally, prognostic factors from the physical examination of the non-recovered participants at 3 months could not be identified. However, among the non-recovered participants at 3 months follow-up, re-sprains and self-reported pain at rest at 3 months were related to incomplete recovery at 12 months. Conclusion: A physical examination at 3 months follow-up for the non-recovered ankle sprain patient seems to have no additional value for predicting outcome at 12 months. However, for the non-recovered patients at 3 months follow-up, self-reported pain at rest and re-sprains during the first 3 months of follow-up seem to have a prognostic value for recovery at 12 months.

Reproducibility of 3D delayed gadolinium enhanced MRI of cartilage (dGEMRIC) of the knee at 3.0 T in patients with early stage osteoarthritis (Article)

2012-08-13T00:00:00Z

Objectives: To assess the reproducibility of 3D delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) at 3 T in early stage knee osteoarthritis (OA) patients. Methods: In 20 patients, 3D dGEMRIC at 3 T was acquired twice within 7 days. To correct for patient motion during acquisition, all images were rigidly registered in 3D. Eight anatomical cartilage ROIs were analysed on both images of each patient. Capability of dGEMRIC to yield T1 maps that reproducibly distinguish spatial differences in cartilage quality was assessed in two ROIs within a single slice in each patient. Reproducibility was assessed using ICCs and Bland-Altman plots. Results: ICCs ranged from 0.87 to 0.95, indicating good reproducibility. T1 maps revealed reproducible spatial differences in cartilage quality (ICC 0.79). Based on the Bland-Altman plots, we defined a threshold of 95 ms to determine if a change in dGEMRIC outcome in longitudinal research was statistically significant. Conclusions: 3D knee dGEMRIC at 3 T combined with 3D image registration is a highly reproducible measure of cartilage quality in early stage OA. Therefore, dGEMRIC may be a valuable tool in the non-invasive evaluation of cartilage quality changes in longitudinal research in patients with early stage OA and focal cartilage defects. Key Points: • Delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) can assess osteoarthritis • dGEMRIC yields highly reproducible T1 values in early stage osteoarthritic patients • A threshold was established to determine significant changes in dGEMRIC outcomes • dGEMRIC can be used to evaluate cartilage quality in longitudinal research

Predictors of persistent complaints after a knee injury in primary care (Article)

2012-08-01T00:00:00Z

Background: Prognosis of persistent complaints after knee injury is based on secondary care populations. In a primary care setting, however, no studies have addressed this issue. Aim: To identify possible predictors of persistent complaints 1 year after a knee injury. These predictors are important for guiding the GP's therapeutic management, and giving advice to patients about work and/or sports-related activities. Design and setting: Primary care prospective cohort study with a 1- year follow-up period in five municipalities in the southwest region of the Netherlands. Method: Patients who were eligible were recruited to the study by a GP research network with around 84 000 patients and 40 participating GPs. A total of 134 patients (aged 18-65 years) who consulted their GP within 5 weeks after a knee injury entered the study. Follow-up after 1 year was conducted in 122 patients. The main outcome was persistent complaints 1 year after injury; possible predictors for these complaints were obtained with a questionnaire, a physical examination, and magnetic resonance imaging (MRI), according to a standardised protocol. Results: After 1 year, of the 122 available patients, 21 (17%) reported persistent complaints and 101 (83%) reported full recovery ormajor improvement. In this study being aged >40 years had a significant association (P<0.05) with persistent complaints (odds ratio 8.0, 95% confidence interval 2.1 to 30.5). Physical examination and MRI findings revealed no predictors that were associated with these complaints. Conclusion: Being aged >40 years was the only determinant with a significant association with persistent complaints. As physical examination and MRI had no predictive value, they are not recommended for prognosis of persistent complaints.

Below-elbow cast for metaphyseal both-bone fractures of the distal forearm in children: A randomised multicentre study (Article)

2012-07-01T00:00:00Z

Introduction: Minimally displaced metaphyseal both-bone fractures of the distal forearm in children are often treated with an above-elbow cast (AEC). Treatment with a below-elbow cast (BEC) could give more comfort, but might lead to fracture displacement reducing pronation and supination. Because this has not been systematically investigated, we set up a randomised multicentre study. The purpose of this study was to find out whether BEC causes equal limitation of pronation and supination but with higher comfort level, compared with AEC. Patients and methods: In four hospitals, consecutive children aged < 16 (mean 7.1) years with a minimally displaced metaphyseal both-bone fracture of the distal forearm were randomised to 4 weeks BEC (n = 35) or 4 weeks AEC (n = 31). Primary outcome was limitation of pronation and supination 6 months after initial trauma. The secondary outcomes were cast comfort, limitation of flexion/extension of wrist/elbow, complications, cosmetics, complaints, and radiological assessment. Results: A group of 35 children received BEC and 31 children received AEC. All children attended for the final examination at a mean follow-up of 7.0 months (range 5.0-11.6 months). Limitation of pronation and supination 6 months after initial trauma showed no significant difference between the two groups [4.4°(±5.8) for BEC and 5.8°(±9.8) for AEC]. Children treated with BEC had significantly higher cast comfort on a visual analogue scale [5.6 (±2.7) vs. 8.4 (±1.4)] and needed significantly less help with dressing (8.2 days vs. 15.1 days). Six complications occurred in the BEC group and 14 in the AEC group. Other secondary outcomes were similar between the two groups. Conclusions: Children with minimally displaced metaphyseal both-bone fractures of the distal forearm should be treated with a below-elbow cast.

Systemic treatment with pulsed electromagnetic fields do not affect bone microarchitecture in osteoporotic rats (Article)

2012-07-01T00:00:00Z

Purpose: Pulsed electromagnetic fields (PEMF) are currently used in the treatment of spinal fusions and non-unions. There are indications that PEMF might also be effective in the treatment of osteoporosis. In this study we examined whether whole-body PEMF treatment affects the bone microarchitecture in an osteoporotic rat model. Methods: Twenty-week-old female rats were ovariectomised (n020). Four different PEMF treatment protocols based on previous experimental studies and based on clinically used PEMF signals were examined (2 h/day, 5 days/week). A control group did not receive PEMF. At zero, three and six weeks cancellous and cortical bone architectural changes at the proximal tibia were evaluated using in vivo microCT scanning. Results: PEMF treatment did not induce any changes in cancellous or cortical bone compared to untreated controls. Conclusions: Although previous studies have shown strong effects of PEMF in osteoporosis we were unable to demonstrate this in any of the treatment protocols. Using in vivo microCT scanning we were able to identify small bone changes in time. Subtle differences in the experimental setup might explain the differences in study outcomes in the literature. Since PEMF treatment is safe, future experimental studies on the effect of PEMF on bone can better be performed directly on humans, eliminating the potential translation issues between animals and humans. In this study we found no support for the use of PEMF in the treatment of osteoporosis.

CT arthrography of the human knee to measure cartilage quality with low radiation dose (Article)

2012-07-01T00:00:00Z

Objective: Recently, CT arthrography (CTa) was introduced as a non-destructive technique to quantitatively measure cartilage quality in human knees. This study investigated whether this is also possible using lower radiation dose CT protocols. Furthermore, we studied the ability of (lower radiation) CTa to distinguish between local sulphated glycosaminoglycan (sGAG) content differences. Design: Of ten human cadaveric knee joints, six CT scans using different radiation doses (81.33-8.13 mGy) were acquired after intra-articular ioxaglate injection. The capability of CTa to measure overall cartilage quality was determined in seven anatomical regions of interest (ROIs), using equilibrium partitioning of an ionic contrast agent using (EPIC)-microCT (μCT) as reference standard for sGAG content. To test the capability of CTa to spatially distinguish between local differences in sGAG content, we calculated the percentage of pixels incorrectly predicted as having high or low sGAG content by the different CTa protocols. Results: Low radiation dose CTa correlated well with EPIC-μCT in large ROIs (R = 0.78; R2= 0.61; P < 0.0001). CTa can also distinguish between high and low sGAG content within a single slice. However, the percentage of incorrectly predicted quality pixels increases (from 35% to 41%) when less radiation is used. This makes is hard or even impossible to differentiate between spatial differences in sGAG content in the lowest radiation scans. Conclusions: CTa acquired using low radiation exposure, comparable to a regular knee CT, is able to measure overall cartilage quality. Spatial sGAG distribution can also be determined using CTa, however for this purpose a higher radiation dose is necessary. Nevertheless, radiation dose reduction makes CTa suitable for quantitative analysis of cartilage in clinical research.

Productivity costs and medical costs among working patients with knee osteoarthritis (Article)

2012-06-01T00:00:00Z

Objective: Although the knee joint is one of the joints most affected by osteoarthritis (OA), research on the economic implications of joint disease has generally focused only on OA. The goal of this study was to identify and quantify knee-related productivity and medical costs in knee OA patients with paid employment. Furthermore, we evaluated associations between productivity loss and relevant patient, health, and work characteristics. Methods: Consecutive knee OA patients with mild to moderate knee OA who were 18-65 years of age, had conservative treatment for ≥6 months, and had paid employment were included. Productivity loss and health care consumption were measured by questionnaires. The associations between productivity loss and patient, health, and work characteristics were explored with regression analyses. Results: In total, 117 knee OA patients with a mean age of 53.2 years and a mean body mass index of 28.8 kg/m2 were included. Total knee-related productivity costs and medical costs were €871 (median €411, interquartile range [IQR] €107-1,200) per patient per month, with total productivity costs of €722 (median €217, IQR €0-1,041) and total medical costs of €149 (median €137, IQR €72-198). More pain during activity and performing physically intensive work were significantly associated with productivity loss. Conclusion: The total knee-related productivity costs and medical costs of conservatively treated symptomatic knee OA patients with paid employment in The Netherlands are €871 per patient per month, with productivity costs accounting for 83% and medical costs for 17%. Productivity loss is associated with having more pain during activity and performing physically intensive work. Developing adequate treatment strategies for knee OA may be cost beneficial.

Cytokine production by infrapatellar fat pad can be stimulated by interleukin 1β and inhibited by peroxisome proliferator activated receptor α agonist (Article)

2012-06-01T00:00:00Z

Background: Infrapatellar fat pad (IPFP) might be involved in osteoarthritis (OA) by production of cytokines. It was hypothesised that production of cytokines is sensitive to environmental conditions. Objectives: To evaluate cytokine production by IPFP in response to interleukin (IL)1β and investigate the ability to modulate this response with an agonist for peroxisome proliferator activated receptor α (PPARα), which is also activated by lipid-lowering drugs such as fi brates. Methods: Cytokine secretion of IPFP was analysed in the medium of explant cultures of 29 osteoarthritic patients. IPFP (fi ve donors) and synovium (six donors) were cultured with IL-1β and PPARα agonist Wy14643. Gene expression of IL-1β, monocyte chemoattractant protein (MCP1), (IL-6, tumour necrosis factor (TNF)α, leptin, vascular endothelial growth factor (VEGF), IL-10, prostaglandin-endoperoxide synthase (PTGS)2 and release of TNFα, MCP1 and prostaglandin E2were compared with unstimulated IPFP and synovium explants. Results: IPFP released large amounts of infl ammatory cytokines, adipokines and growth factors. IL-1β increased gene expression of PTGS2, TNFα, IL-1β, IL-6 and VEGF and increased TNFα release in IPFP. MCP1, leptin, IL-10 gene expression and MCP1, leptin and PGE2release did not increase signifi cantly. Synovium responded to IL-1βsimilarly to IPFP, except for VEGF gene expression. Wy14643 decreased gene expression of PTGS2, IL-1β, TNFα, MCP1, VEGF and leptin in IPFP explants and IL-1β, TNFα, IL-6, IL-10 and VEGF in synovium that responded to IL-1β. Conclusion: IPFP is an active tissue within the joint. IPFP cytokine production is increased by IL-1β and decreased by a PPARα agonist. The effects were similar to effects seen in synovium. Fibrates may represent a potential disease-modifying drug for OA by modulating infl ammatory properties of IPFP and synovium.

Inhibiting calcineurin activity under physiologic tonicity elevates anabolic but suppresses catabolic chondrocyte markers (Article)

2012-06-01T00:00:00Z

Objective The physiologic interstitial tonicity of healthy articular cartilage (350-480 mOsm) is lowered to 280-350 mOsm in osteoarthritis (OA). This results in loss of tissue prestress, altered compressive behavior, and, thus, inferior tissue properties. This study was undertaken to determine whether physiologic tonicity in combination with the inhibition of calcineurin (Cn) activity by FK-506 has synergistic effects on human articular chondrocytes and explants in vitro. Methods OA chondrocytes and explants and non-OA chondrocytes were cultured in cytokine-free medium of 280 mOsm or 380 mOsm with or without Cn inhibition by FK-506. Chondrogenic, hypertrophic, and catabolic marker expression was evaluated at the messenger RNA (mRNA), protein, and activity levels. Results Compared to OA chondrocytes cultured at 280 mOsm, those cultured at 380 mOsm had increased expression of mRNA for chondrogenic markers (e.g., ∼13 fold for COL2; P < 0.001), and decreased COL1 expression (∼0.5 fold, P < 0.01). Inhibiting Cn activity under physiologic tonicity further enhanced the expression of anabolic markers at the mRNA level (∼50 fold for COL2; P < 0.001, ∼2 fold for AGC1; P < 0.001, and ∼3.5 fold for SOX9; P < 0.001) and at the protein level (∼6 fold for type II collagen; P < 0.001). Cn inhibition suppressed relevant collagenases as well as hypertropic and mineralization markers at the mRNA and activity levels. Expression of aggrecanase 1 and aggrecanase 2 was not influenced by tonicity or FK-506 alone, but the combination suppressed both, by ∼50% (P < 0.05) and ∼40% (P < 0.001), respectively. Generally, similar anabolic and antihypertrophic effects were observed in ex vivo cartilage explant cultures and non-OA chondrocytes. Conclusion Our findings indicate that Cn at physiologic tonicity exerts a superior effect compared to physiologic tonicity or FK-506 alone, increasing anabolic markers while suppressing hypertrophic and catabolic markers. Our data may aid in the development of improved cell-based chondral repair and OA treatment strategies. Copyright

Statin use is associated with reduced incidence and progression of knee osteoarthritis in the Rotterdam study (Article)

2012-05-01T00:00:00Z

Background: Osteoarthritis is the most frequent chronic joint disease causing pain and disability. Besides biomechanical mechanisms, the pathogenesis of osteoarthritis may involve inflammation, vascular alterations and dysregulation of lipid metabolism. As statins are able to modulate many of these processes, this study examines whether statin use is associated with a decreased incidence and/or progression of osteoarthritis. Methods: Participants in a prospective population-based cohort study aged 55 years and older (n=2921) were included. x-Rays of the knee/hip were obtained at baseline and after on average 6.5 years, and scored using the Kellgren and Lawrence score for osteoarthritis. Any increase in score was defined as overall progression (incidence and progression). Data on covariables were collected at baseline. Information on statin use during follow-up was obtained from computerised pharmacy databases. The overall progression of osteoarthritis was compared between users and non-users of statins. Using a multivariate logistic regression model with generalised estimating equation, OR and 95% CI were calculated after adjusting for confounding variables. Results: Overall progression of knee and hip osteoarthritis occurred in 6.9% and 4.7% of cases, respectively. The adjusted OR for overall progression of knee osteoarthritis in statin users was 0.43 (95% CI 0.25 to 0.77, p=0.01). The use of statins was not associated with overall progression of hip osteoarthritis. Conclusions: Statin use is associated with more than a 50% reduction in overall progression of osteoarthritis of the knee, but not of the hip.

The development of cam-type deformity in adolescent and young male soccer players (Article)

2012-05-01T00:00:00Z

Background: Cam impingement is a well-recognized cause of hip pain and might cause osteoarthritis of the hip. Clinically, cam impingement is mostly observed in young, active male patients, but only a few studies have focused on the manifestation of cam-type deformities during skeletal development.Purpose: To determine the age of onset and prevalence of cam-type deformities in young male soccer players versus controls.Study Design: Cross-sectional study; Level of evidence, 3.Methods: In this study, 89 elite preprofessional soccer players and 92 controls aged 12 to 19 years were included. In the soccer players, range of motion and impingement tests were performed. Both an anteroposterior (AP) pelvic radiograph and a frog-leg lateral radiograph of the hip were obtained according to a standardized protocol. Controls with both an AP pelvic and a frog-leg lateral radiograph and no hip disorders were obtained from radiology databases. The α angle was automatically determined in all radiographs, using a threshold value of 60°to define a cam-type deformity. Further, all radiographs were scored using a 3-point scoring system. The anterosuperior head-neck junction was classified as (1) normal, (2) flattened, or (3) having a prominence. Differences in prevalence were tested using logistic regression. Differences in range of motion were calculated using generalized estimating equations.Results: An α angle >60°was already found at the age of 12 years in some soccer players and controls. A cam-type deformity defined by α angle tended to be more prevalent in soccer players (26%) than in controls (17%; P =.31). In 13% of soccer players, a prominence was visible on radiographs and was first seen at the age of 13 years. The anterosuperior flattening (56% vs 18%, P =.0001) and prominence (13% vs 0%, P <.03) were more prevalent in soccer players than in controls.Conclusion: Cam-type deformities were recognizable and present from the age of 13 years and were more prevalent in soccer players than in their nonathletic peers. Cam-type deformity develops during adolescence and is likely to be influenced by high-impact sports practice.

Femoral revision surgery with impaction bone grafting (Article)

2012-05-01T00:00:00Z

The purpose of this prospective study was to evaluate the long-term clinical and radiological outcomes of revision of the femoral component of a total hip replacement using impaction bone grafting. Femoral revision with an impacted allograft was performed on 29 patients (31 hips). In all, 21 hips (68%) had grade III or IV femoral defects according to the Endo-Klinik classification. A total of 11 patients (12 hips) died before the ten-year follow-up period. Of the remaining patients, 18 patients (19 hips) were followed for 10 to 15 years; three further patients died during this time. None of the 31 stems underwent further revision of their stem. However, four stems showed extensive subsidence (> 15 mm). One of these patients had a femoral fracture that required fixation. Three other patients had a femoral fracture, two of which required fixation and the other was treated conservatively. Patients with a femoral fracture and/or severe subsidence had significantly more grade IV defects (six of seven hips; p = 0.004). One patient needed a closed reduction for dislocation. Impaction allografting in revision hip surgery gives good long-term results for femora with grades I, II and III Endo-Klinik-classified defects. Extensive subsidence and femoral fractures were seen mainly in patients with grade IV damaged femora.

Effectiveness of audio feedback for partial weight-bearing in and outside the hospital: A randomized controlled trial (Article)

2012-04-01T00:00:00Z

Effectiveness of audio feedback for partial weight-bearing in and outside the hospital: a randomized controlled trial. Objective: To determine the effectiveness of partial weight-bearing (PWB) training with audio feedback in patients after total hip arthroplasty (THA). Design: Randomized controlled trial. Setting: Orthopedic clinic and patients' homes. Participants: Patients (N=38) after THA with trochanteric osteotomy. Intervention: Patients were trained with (n=18) or without (n=20) audio feedback to perform PWB at a 10% body weight (BW) target load. PWB training started on day 2 or 3 postoperatively and was given once per day during the entire hospital stay. Main Outcome Measures: Mean peak load (%BW), and the percentage of steps below, equal to, and above the target load. Weight-bearing was measured using an insole pressure system on postoperative day 7 in the hospital during PWB training (condition 1 [C1]) and when patients walked unsupervised (condition 2 [C2]), and on postoperative day 21 at home (condition 3 [C3]). Results: PWB training with audio feedback resulted in better PWB (11.1% BW vs control, 21.9% BW; P=.006) at C1. The audio feedback group had more steps below the target load (21.4% vs control, 7.8%; P=.020) and fewer steps above the target load (15.6% vs control, 45.0%; P=.015). For C2 and C3, no significant differences were found between the patients receiving PWB training with and without audio feedback, for all outcome measures. Conclusions: Patients with THA who received audio feedback were able to accurately perform PWB at the prescribed target load during PWB training, but were unable to replicate the prescribed target load when they walked unsupervised in the hospital or at home.

A 5-year follow-up study of Alfredson's heel-drop exercise programme in chronic midportion Achilles tendinopathy (Article)

2012-03-01T00:00:00Z

Background: Eccentric exercises have the most evidence in conservative treatment of midportion Achilles tendinopathy. Although short-term studies show significant improvement, little is known of the long-term (>3 years) results. Aim: To evaluate the 5-year outcome of patients with chronic midportion Achilles tendinopathy treated with the classical Alfredson's heel-drop exercise programme. Study design: Part of a 5-year follow-up of a previously conducted randomised controlled trial. Methods: 58 patients (70 tendons) were approached 5 years after the start of the heel-drop exercise programme according to Alfredson. At baseline and at 5-year follow-up, the validated Victorian Institute of Sports Assessment-Achilles (VISA-A) questionnaire score, pain status, alternative treatments received and ultrasonographic neovascularisation score were recorded. Results: In 46 patients (58 tendons), the VISA-A score significantly increased from 49.2 at baseline to 83.6 after 5 years (p<0.001) and from the 1-year to 5-year follow-up from 75.0 to 83.4 (p<0.01). 39.7% of the patients were completely pain-free at follow-up and 48.3% had received one or more alternative treatments. The sagittal tendon thickness decreased from 8.05 mm (SD 2.1) at baseline to 7.50 mm (SD 1.6) at the 5-year follow-up (p=0.051). Conclusion: At 5-year follow-up, a significant increase of VISA-A score can be expected. After the 3-month Alfredson's heel-drop exercise programme, almost half of the patients had received other therapies. Although improvement of symptoms can be expected at long term, mild pain may remain.

Psychological factors affecting the outcome of total hip and knee arthroplasty: A systematic review (Article)

2012-02-01T00:00:00Z

Objectives: Recently, numerous studies have reported that psychological factors can influence the outcome of total knee arthroplasty (TKA) and total hip arthroplasty (THA). However, a systematic overview is missing. The objective of this study was to examine which psychological factors influence the outcome of TKA and THA and to what extent. Methods: Data were obtained from the MEDLINE and EMBASE databases from inception to January 2011. Search terms included TKA and THA, outcome measures, and psychological aspects. Two reviewers independently selected the studies. Studies with a prospective before-after design with a minimum follow-up time of 6 weeks were included. One reviewer extracted the results and 2 reviewers independently conducted quality assessment. We distinguished between follow-up shorter and equal or longer than 1 year. Results: Thirty-five of 1837 studies met the inclusion criteria and were included in this systematic review. In follow-ups shorter than 1 year, and for knee patients only, strong evidence was found that patients with pain catastrophizing reported more pain postoperatively. Furthermore, strong evidence was found that preoperative depression had no influence on postoperative functioning. In long-term follow-up, 1 year after TKA, strong evidence was found that lower preoperative mental health (measures with the SF-12 or SF-36) was associated with lower scores on function and pain. For THA, only limited, conflicting, or no evidence was found. Conclusions: Low preoperative mental health and pain catastrophizing have an influence on outcome after TKA. With regard to the influence of other psychological factors and for hip patients, only limited, conflicting, or no evidence was found.

Infrapatellar fat pad of patients with end-stage osteoarthritis inhibits catabolic mediators in cartilage (Article)

2012-02-01T00:00:00Z

Objective: Adipose tissue is known to release inflammatory cytokines and growth factors. In this exploratory study, the authors examined whether the infrapatellar fat pad (IPFP) closely located to cartilage in the knee joint can affect cartilage metabolism. In addition, the authors analysed whether the macrophage types present in IPFP could explain the effect on cartilage. Methods: IPFP explants obtained during total knee replacement of 29 patients with osteoarthritis (OA) were used to make fat-conditioned medium (FCM). Explants of bovine cartilage were cultured with or without FCM. Nitric oxide (NO) and glycosaminoglycan release and gene expression of matrix-degrading enzymes in cartilage were analysed. To stimulate catabolic processes in the cartilage, the authors added interleukin 1β, and the effect of six FCMs was evaluated. The presence of different types of macrophages (CD68+, CD86+ and CD206+) in OA IPFPs was compared with subcutaneous adipose tissue samples and IPFP samples from patients with an anterior cruciate ligament rupture. Results: FCM alone reduced NO and glycosaminoglycan release and matrix metalloproteinase (MMP)1 gene expression by the cartilage. Moreover, when catabolic conditions were enhanced with interleukin 1β, FCM inhibited NO production as well as MMP1 and MMP3 gene expression and increased collagen type II gene expression. Significantly more CD206+ cells were present in OA IPFP samples than in subcutaneous fat or anterior cruciate ligament IPFP samples. Conclusion: In contrast to the authors' expectations, medium conditioned by end-stage OA IPFP inhibited catabolic processes in cartilage. CD206+ cells present in the IPFPs used for making the FCM might have contributed to the inhibition of catabolic processes in the cartilage.

Therapeutic interventions for acute hamstring injuries: A systematic review (Article)

2012-02-01T00:00:00Z

Background Despite the high rate of hamstring injuries, there is no consensus on their management, with a large number of different interventions being used. Recently several new injection therapies have been introduced. Objective To systematically review the literature on the effectiveness of therapeutic interventions for acute hamstring injuries. Data sources The databases of PubMed, EMBASE, Web of Science, Cochrane Library, CINAHL and SPORTDiscus were searched in May 2011. Study eligibility criteria Prospective studies comparing the effect of an intervention with another intervention or a control group without intervention in subjects with acute hamstring injuries were included. Data analysis Two authors independently screened the search results and assessed risk of bias. Quality assessment of the included studies was performed using the Physiotherapy Evidence Database score. A best evidence synthesis was used to identify the level of evidence. Main results Six studies were included in this systematic review. There is limited evidence for a positive effect of stretching, agility and trunk stability exercises, intramuscular actovegin injections or slump stretching in the management of acute hamstring injuries. Limited evidence was found that there is no effect of non-steroidal anti-inflammatory drugs or manipulation of the sacroiliac joint. Conclusions There is a lack of high quality studies on the treatment of acute hamstring injuries. Only limited evidence was found to support the use of stretching, agility and trunk stability exercises, intramuscular actovegin injections or slump stretching. Further research is needed using an appropriate control group, randomisation and blinding.

An osteochondral culture model to study mechanisms involved in articular cartilage repair (Article)

2012-01-01T00:00:00Z

Although several treatments for cartilage repair have been developed and used in clinical practice the last 20 years, little is known about the mechanisms that are involved in the formation of repair tissue after these treatments. Often, these treatments result in the formation of fibrocartilaginous tissue rather than normal articular cartilage. Because the repair tissue is inferior to articular cartilage in terms of mechanical properties and zonal organization of the extracellular matrix, complaints of the patient may return. The biological and functional outcome of these treatments should thus be improved. For this purpose, an in vitro model allowing investigation of the involved repair mechanisms can be of great value. We present the development of such a model. We used bovine osteochondral biopsies and created a system in which cartilage defects of different depths can be studied. First, our biopsy model was characterized extensively: we studied the viability by means of lactate dehydrogenase (LDH) excretion over time and we investigated expression of cartilage-related genes in osteochondral biopsies and compared it with conventional cartilage-only explants. After 28 days of culture, LDH was detected at low levels and mRNA could be retrieved. The expression of cartilage-related genes decreased over time. This was more evident in cartilage-only explants, indicating that the biopsy model provided a more stable environment. We also characterized the subchondral bone: osteoclasts and osteoblasts were active after 28 days of culture, which was indicated by tartrate acid phosphatase staining and alkaline phosphatase measurements, respectively, and matrix deposition during culture was visualized using calcein labeling. Second, the applicability of the model was further studied by testing two distinct settings: (1) implantation of chondrocytes in defects of different depths; (2) two different seeding strategies of chondrocytes. Differences were observed in terms of volume and integration of newly formed tissue in both settings, suggesting that our model can be used to model distinct conditions or even to mimic clinical treatments. After extensive characterization and testing of our model, we present a representative and reproducible in vitro model that can be used to evaluate new cartilage repair treatments and study mechanisms in a controlled and standardized environment.

Low-magnitude whole body vibration does not affect bone mass but does affect weight in ovariectomized rats (Article)

2012-01-01T00:00:00Z

Mechanical loading has stimulating effects on bone architecture, which can potentially be used as a therapy for osteoporosis. We investigated the skeletal changes in the tibia of ovariectomized rats during treatment with whole body vibration (WBV). Different low-magnitude WBV treatment protocols were tested in a pilot experiment using ovariectomized rats with loading schemes of 2 x 8 min/day, 5 days/ week (n = 2 rats per protocol). Bone volume and architecture were evaluated during a 10 week follow-up using in-vivo microcomputed tomography scanning. The loading protocol in which a 45 Hz sine wave was applied at 2 Hz with an acceleration of 0.5g showed an anabolic effect on bone and was therefore further analyzed in two groups of animals (n = 6 each group) with WBV starting directly after or 3 weeks after ovariectomy and compared to a control (non- WBV) group at 0, 3, 6 and 10 weeks' follow-up. In the follow-up experiment the WBV stimulus did not significantly affect trabecular volume fraction or cortical bone volume in any of the treatment groups during the 10 week follow-up. WBV did reduce weight gain that was induced as a consequence of ovariectomy. We could not demonstrate any significant effects of WBV on bone loss as a consequence of ovariectomy in rats; however, the weight gain that normally results after ovariectomy was partly prevented. Treatment with WBV was not able to prevent bone loss during induced osteoporosis.

An osteochondral culture model to study mechanisms involved in articular cartilage repair (Article)

2012-01-01T00:00:00Z

Effectiveness of intramuscular corticosteroid injection versus placebo injection in patients with hip osteoarthritis: Design of a randomized double-blinded controlled trial (Article)

2011-12-13T00:00:00Z

Background: Recent international guidelines recommend intra-articular corticosteroid injections for patients with hip osteoarthritis who have moderate to severe pain and do not respond satisfactorily to oral analgesic/anti- inflammatory agents. Of the five available randomized controlled trials, four showed positive effects with respect to pain reduction. However, intra-articular injection in the hip is complex because the joint is adjacent to important neurovascular structures and cannot be palpated. Therefore fluoroscopic or ultrasound guidance is needed. The systemic effect of corticosteroids has been studied in patients with impingement shoulder pain. Gluteal corticosteroid injection was almost as effective as ultrasound-guided subacromial corticosteroid injection. Such a clinically relevant effect of a systemic corticosteroid injection offers a less complex alternative for treatment of patients with hip osteoarthritis not responsive to oral pain medication. Methods/Design. This is a double-blinded, randomized controlled trial. A total of 135 patients (aged > 40 years) with hip osteoarthritis and persistent pain despite oral analgesics visiting a general practitioner or orthopaedic surgeon will be included. They will be randomized to a gluteal intramuscular corticosteroid injection or a gluteal intramuscular placebo (saline) injection. The randomization will be stratified for setting (general practitioner and outpatient clinics of department of orthopaedics). Treatment effect will be evaluated by questionnaires at 2, 4, 6, and 12 weeks follow-up and a physical examination at 12 weeks. Primary outcome is severity of hip pain reported by the patients at 2-week follow-up. Statistical analyses will be based on the intention-to-treat principle. Discussion. This study will evaluate the effectiveness of an intramuscular corticosteroid injection on pain in patients with hip osteoarthritis. Patient recruitment has started. Trial Registration. This trial is registered in the Dutch Trial Registry: number NTR2966.

Visualization of postoperative anterior cruciate ligament reconstruction bone tunnels: Reliability of standard radiographs, CT scans, and 3D virtual reality images (Article)

2011-12-01T00:00:00Z

Background and purpose: Non-anatomic bone tunnel placement is the most common cause of a failed ACL reconstruction. Accurate and reproducible methods to visualize and document bone tunnel placement are therefore important. We evaluated the reliability of standard radiographs, CT scans, and a 3-dimensional (3D) virtual reality (VR) approach in visualizing and measuring ACL reconstruction bone tunnel placement. Methods: 50 consecutive patients who underwent single-bundle ACL reconstructions were evaluated postoperatively by standard radiographs, CT scans, and 3D VR images. Tibial and femoral tunnel positions were measured by 2 observers using the traditional methods of Amis, Aglietti, Hoser, Stubli, and the method of Benereau for the VR approach. Results: The tunnel was visualized in 50-82% of the standard radiographs and in 100% of the CT scans and 3D VR images. Using the intraclass correlation coefficient (ICC), the inter- and intraobserver agreement was between 0.39 and 0.83 for the standard femoral and tibial radiographs. CT scans showed an ICC range of 0.49-0.76 for the inter- and intraobserver agreement. The agreement in 3D VR was almost perfect, with an ICC of 0.83 for the femur and 0.95 for the tibia. Interpretation: CT scans and 3D VR images are more reliable in assessing postoperative bone tunnel placement following ACL reconstruction than standard radiographs. Copyright:

Platelet-rich plasma releasate inhibits inflammatory processes in osteoarthritic chondrocytes (Article)

2011-11-01T00:00:00Z

Background: Platelet-rich plasma (PRP) has recently been postulated as a treatment for osteoarthritis (OA). Although anabolic effects of PRP on chondrocytes are well documented, no reports are known addressing effects on cartilage degeneration. Since OA is characterized by a catabolic and inflammatory joint environment, the authors investigated whether PRP was able to counteract the effects of such an environment on human osteoarthritic chondrocytes.Hypothesis: Platelet-rich plasma inhibits inflammatory effects of interleukin-1 (IL-1) beta on human osteoarthritic chondrocytes.Study Design: Controlled laboratory study.Methods: Human osteoarthritic chondrocytes were cultured in the presence of IL-1 beta to mimic an osteoarthritic environment. Medium was supplemented with 0%, 1%, or 10% PRP releasate (PRPr, the active releasate of PRP). After 48 hours, gene expression of collagen type II alpha 1 (COL2A1), aggrecan (ACAN), a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)4, ADAMTS5, matrix metalloproteinase (MMP)13, and prostaglandin-endoperoxide synthase (PTGS)2 was analyzed. Additionally, glycosaminoglycan (GAG) content, nitric oxide (NO) production, and nuclear factor kappa B (NFB) activation were studied.Results: Platelet-rich plasma releasate diminished IL-1 beta-induced inhibition of COL2A1 and ACAN gene expression. The PRPr also reduced IL-1 beta-induced increase of ADAMTS4 and PTGS2 gene expression. ADAMTS5 gene expression and GAG content were not influenced by IL-1 beta or additional PRPr. Matrix metalloproteinase 13 gene expression and NO production were upregulated by IL-1 beta but not affected by added PRPr. Finally, PRPr reduced IL-1 beta-induced NFB activation to control levels containing no IL-1 beta.Conclusion: Platelet-rich plasma releasate diminished multiple inflammatory IL-1 beta-mediated effects on human osteoarthritic chondrocytes, including inhibition of NFB activation.Clinical Relevance: Platelet-rich plasma releasate counteracts effects of an inflammatory environment on genes regulating matrix degradation and formation in human chondrocytes. Platelet-rich plasma releasate decreases NFB activation, a major pathway involved in the pathogenesis of OA. These results encourage further study of PRP as a treatment for OA.

Quantifying osteoarthritic cartilage changes accurately using in vivo microCT arthrography in three etiologically distinct rat models (Article)

2011-11-01T00:00:00Z

In vivo microCT arthrography (μCTa) can be used to measure both quantity (volumetric) and quality (glycosaminoglycan content) of cartilage. This study investigated the accuracy of four segmentation techniques to isolate cartilage from μCTa datasets and then used the most accurate one to investigate if the μCTa method could show osteoarthritic changes in rat models during longitudinal follow-up. Volumetric measurements and glycosaminoglycan contents of patellar cartilage from in vivo μCTa-scans were compared with an ex vivo gold standard μCT-scan. Cartilage was segmented with three global thresholds and one local threshold algorithm. Comparisons were made for healthy and osteoarthritic cartilage. Next, three rat models were investigated for 24 weeks using μCTa. Osteoarthritis was induced by injection with a chemical (mono-iodoacetate), a surgical intervention (grooves applied in articular cartilage), and via exercise (strenuous running). After euthanasia, all knee joints were isolated for histology. Local thresholds accurately segmented cartilage from in vivo μCTa scans and best measured cartilage quantity and glycosaminoglycan content. Each of the three osteoarthritic rat models showed a specific pattern of osteoarthritis progression. All μCTa results were comparable to histology. In vivo μCTa is a sensitive technique for imaging cartilage degradation. Local thresholds enhanced the sensitivity of this method and will probably more accurately detect disease-modulating effects from interventional strategies. The data from rat models may serve as a reference for the time sequence of cartilage degeneration during in vivo testing of new strategies in osteoarthritis treatment. Copyright

Tendon structure's lack of relation to clinical outcome after eccentric exercises in chronic midportion Achilles tendinopathy (Article)

2011-11-01T00:00:00Z

CONTEXT: Chronic midportion Achilles tendinopathy is a common and hard-to-treat disorder characterized by degenerative changes of the tendon matrix. Ultrasonographic tissue characterization (UTC) was successfully used to quantify structural human Achilles tendon changes. This novel and reliable technique could be used in follow-up studies to relate tendon structure to symptoms. OBJECTIVE: To quantify structural tendon changes and assess clinical change in patients with tendinopathy. DESIGN: Prospective observational study. SETTING: Orthopedic department in a university medical center. PATIENTS: 23 patients with chronic midportion Achilles tendinopathy. INTERVENTION: The patients performed a 16-wk home-based eccentric exercise program. An experienced researcher performed the ultrasonographic data collection with the UTC procedure. These data were assessed by a blinded observer. The severity of symptoms was established with the validated Victorian Institute of Sport Assessment-Achilles (VISA-A) questionnaire. MAIN OUTCOME MEASURES: UTC was performed to quantify tendon structure through measuring the proportion of 4 echo types. Echo types I and II represent more or less organized tendon bundles, and echo types III and IV represent disintegrated tendon structure. On the VISA-A, the total possible score is divided by 100 for a percentage score, with a perfect score of 100. Follow-up was at 2, 8, 16, and 24 wk. RESULTS: The mean percentage of echo types I and II changed by 0.3% after 24 wk (P = .92, 95% CI -5.8 to 5.3). The mean VISA-A score increased slightly but significantly by 11.3 points after 24 wk (P = .01, 95% CI 2.6-20.0). An increased VISA-A score was not correlated with an increased percentage of echo types I and II (P = .94, r = -.02), and the baseline percentage of echo types I and II did not correlate with an increased VISA-A score (P = .74, r = .07). CONCLUSIONS: There is no short-term increase in organized tendon structure after eccentric exercises. Tendon structure is not related to symptom severity and cannot be used as a predictor of clinical outcome.

Cost-effectiveness of exercise therapy versus general practitioner care for osteoarthritis of the hip: Design of a randomised clinical trial (Article)

2011-10-13T00:00:00Z

Background: Osteoarthritis (OA) is the most common joint disease, causing pain and functional impairments. According to international guidelines, exercise therapy has a short-term effect in reducing pain/functional impairments in knee OA and is therefore also generally recommended for hip OA. Because of its high prevalence and clinical implications, OA is associated with considerable (healthcare) costs. However, studies evaluating cost-effectiveness of common exercise therapy in hip OA are lacking. Therefore, this randomised controlled trial is designed to investigate the cost-effectiveness of exercise therapy in conjunction with the general practitioner's (GP) care, compared to GP care alone, for patients with hip OA. Methods/Design. Patients aged 45 years with OA of the hip, who consulted the GP during the past year for hip complaints and who comply with the American College of Rheumatology criteria, are included. Patients are randomly assigned to either exercise therapy in addition to GP care, or to GP care alone. Exercise therapy consists of (maximally) 12 treatment sessions with a physiotherapist, and home exercises. These are followed by three additional treatment sessions in the 5th, 7th and 9th month after the first treatment session. GP care consists of usual care for hip OA, such as general advice or prescribing pain medication. Primary outcomes are hip pain and hip-related activity limitations (measured with the Hip disability Osteoarthritis Outcome Score [HOOS]), direct costs, and productivity costs (measured with the PROductivity and DISease Questionnaire). These parameters are measured at baseline, at 6 weeks, and at 3, 6, 9 and 12 months follow-up. To detect a 25% clinical difference in the HOOS pain score, with a power of 80% and an alpha 5%, 210 patients are required. Data are analysed according to the intention-to-treat principle. Effectiveness is evaluated using linear regression models with repeated measurements. An incremental cost-effectiveness analysis and an incremental cost-utility analysis will also be performed. Discussion. The results of this trial will provide insight into the cost-effectiveness of adding exercise therapy to GPs' care in the treatment of OA of the hip. This trial is registered in the Dutch trial registry http://www.trialregister.nl: trial number NTR1462.

Unraveling the human bone microenvironment beyond the classical extracellular matrix proteins: A human bone protein library (Article)

2011-10-07T00:00:00Z

A characteristic feature of bone, differentiating it from other connective tissues, is the mineralized extracellular matrix (ECM). Mineral accounts for the majority of the bone tissue volume, being the remainder organic material mostly derived from collagen. This, and the fact that only a limited number of noncollagenous ECM proteins are described, provides a limited view of the bone tissue composition and bone metabolism, the more so considering the increasing understanding of ECM significance for cellular form and function. For this reason, we set out to analyze and extensively characterize the human bone proteome using large-scale mass spectrometry-based methods. Bone samples of four individuals were analyzed identifying 3038 unique proteins. A total of 1213 of these were present in at least 3 out of 4 bone samples. For quantification purposes, we were limited to noncollagenous proteins (NCPs) and we could quantify 1051 NCPs. Most classical bone matrix proteins mentioned in literature were detected but were not among the highly abundant ones. Gene ontology analyses identified high-abundance groups of proteins with a functional link to mineralization and mineral metabolism such as transporters, pyrophosphatase activity, and Ca2+-dependent phospholipid binding proteins. ECM proteins were as well overrepresented together with nucleosome and antioxidant activity proteins, which have not been extensively characterized as being important for bone. In conclusion, our data clearly demonstrates that human bone tissue is a reservoir of a wide variety of proteins. In addition to the classical osteoblast-derived ECM, we have identified many proteins from different sources and of unknown function in bone. Thus, this study represents an informative library of bone proteins forming a source for novel bone formation modulators as well as biomarkers for bone diseases such as osteoporosis.

Incidence of midportion Achilles tendinopathy in the general population (Article)

2011-10-01T00:00:00Z

Background Achilles tendon disorders, like Achilles tendinopathy, are very common among athletes. In the general population, however, knowledge about the incidence of Achilles tendinopathy is lacking. Design Cross-sectional study. Methods In a cohort of 57.725 persons registered in primary care, the number of patients visiting the general practitioner (GP) with diagnosis of mid-portion Achilles tendon problems was counted using computerized registration networks of GPs in 2009. Subsequently, the authors assessed associations of these rates with demographic characteristics. Results The incidence rate of Achilles tendinopathy is 1.85 per 1,000 Dutch GP registered patients. In the adult population (21-60 years), the incidence rate is 2.35 per 1,000. In 35% of the cases, a relationship with sports activity was recorded. Conclusion This is the fi rst report on incidence rates of mid-portion Achilles tendinopathy in general practice. With an incidence of 1.85 per 1,000 registered persons, Achilles tendinopathy is frequently seen by GPs. The actual incidence might even be higher due to study limitations. More research on the frequency of this injury is required.

The Most Accurate Approach for Intra-Articular Needle Placement in the Knee Joint: A Systematic Review (Article)

2011-10-01T00:00:00Z

Introduction: Intra-articular needle placement in the knee joint, such as injection or aspirations, are commonly used for therapeutic, diagnostic, and research purposes. Although several approaches can be used to establish an intra-articular injection or aspiration of the knee joint, the accuracy differs per approach. Objective: To summarize the evidence concerning the accuracy of different approaches for intra-articular needle placements in the knee. Additionally, to assess whether the accuracy of different approaches is related to factors such as underlying disease, severity of underlying disease, approach-related factors, and/or the rate of local reactions. Methods: The literature was systemically reviewed until July 2010. Risk of bias of the included studies was assessed by the QUADAS tool. Study characteristics were extracted; accuracy results were pooled per approach. Results: Nine studies were included. The superolateral approach with the leg in extension was studied most (230 injections) and resulted in the highest pooled accuracy of 91% (95% CI 84-99%). The lateral midpatellar approach, the anterolateral approach, and the anteromedial approach resulted in the lowest pooled accuracy rates, 85% (95% CI 68-100%), 67% (95% CI 43-91%) and 72% (95% CI 65-78%), respectively. Conclusions: The superolateral approach was investigated most and resulted in the highest pooled accuracy rate of 91% (95% CI 84-99%). Nevertheless, this approach still results in a substantial amount of extra-articular needle placements. Guidance of intra-articular needle placements by imaging techniques may enhance the accuracy. The costs and extra time associated with these techniques should be taken into consideration.

Clinically applied CT arthrography to measure the sulphated glycosaminoglycan content of cartilage (Article)

2011-10-01T00:00:00Z

Objective: Similar to delayed gadolinium enhanced MRI of cartilage, it might be possible to image cartilage quality using CT arthrography (CTa). This study assessed the potential of CTa as a clinically applicable tool to evaluate cartilage quality in terms of sulphated glycosaminoglycan content (sGAG) and structural composition of the extra-cellular matrix (ECM). Methods: Eleven human cadaveric knee joints were scanned on a clinical CT scanner. Of each knee joint, a regular non-contrast CT (ncCT) and an ioxaglate injected CTa scan were performed. Mean X-ray attenuation of both scans was compared to identify contrast influx in seven anatomical regions of interest (ROIs). All ROIs were rescanned with contrast-enhanced μCT, which served as the reference standard for sGAG content. Mean X-ray attenuation from both ncCT and CTa were correlated with μCT results and analyzed with linear regression. Additionally, residual values from the linear fit between ncCT and μCT were used as a covariate measure to identify the influence of structural composition of cartilage ECM on contrast diffusion into cartilage in CTa scans. Results: CTa resulted in higher X-ray attenuation in cartilage compared to ncCT scans for all anatomical regions. Furthermore, CTa correlated excellent with reference μCT values (sGAG) (R=0.86; R2=0.73; P<0.0001). When corrected for structural composition of cartilage ECM, this correlation improved substantially (R=0.95; R2=0.90; P<0.0001). Conclusions: Contrast diffusion into articular cartilage detected with CTa correlates with sGAG content and to a lesser extent with structural composition of cartilage ECM. CTa may be clinically applicable to quantitatively measure the quality of articular cartilage.

Complications after hip arthroplasty and the association with hospital procedure volume: A nationwide retrospective cohort study on 50,080 total hip replacements with a follow-up of 3 months after surgery (Article)

2011-10-01T00:00:00Z

Background and purpose: It has been suggested that a higher procedure volume is associated with less complications after hip arthroplasty. In order to investigate the incidence of serious negative outcomes and a possible association with procedure volume, we performed a retrospective nationwide cohort study on total hip replacements in all Dutch hospitals. Methods: All total hip replacements (n = 50,080) that were identified as primary intervention in all general and university medical centers between January 1, 2002 and October 1, 2004 were included. Primary endpoints of follow-up were mortality and complications during admission, and re-admission within 3 months due to complications. Variables that were assessed as potential risk factor were age, sex, duration of (preoperative) admission, specific diagnosis, acute/non-planned admission, co-morbidity, and hospital procedure volume. Results: Age, sex, and comorbidity were associated with complications and mortality. Additionally, acute admission was a risk factor for mortality but not for complications. There was no linear trend indicating that decreasing volume led to an increasing number of complications, and no statistically sginificant effect for mortality was found. Interpretation: After adjustment for several risk factors, we found that the hospitals performing most hip procedures every year had fewer complications during index admission, but that they did not have a lower mortality than groups performing fewer procedures. The lack of a linear trend may be explained by the fact that almost all Dutch hospitals perform a high number of hip arthroplasties each year.

Six-year course and prognosis of nontraumatic knee symptoms in adults in general practice: A prospective cohort study (Article)

2011-09-01T00:00:00Z

Objective To examine the 6-year course of nontraumatic knee symptoms in adults in general practice, to identify prognostic factors for unfavorable outcome, and to develop a clinical prediction rule. Methods Adults (ages >35 years) with incident nontraumatic knee symptoms (n = 549) were followed for 6 years. Multivariable logistic regression analysis was used to identify prognostic factors associated with an unfavorable outcome, the area under the receiver operating curve (AUC) was calculated to determine discriminative ability, and a clinical prediction rule was developed. Unfavorable outcome is defined as persistent knee symptoms at 6-year followup or having undergone knee replacement surgery during followup. Results At 6-year followup, 42.1% of patients had an unfavorable outcome. Having persistent knee symptoms (odds ratio [OR] 5.31, 95% confidence interval [95% CI] 3.27-8.61) and fulfilling the clinical American College of Rheumatology (ACR) criteria for osteoarthritis (OA; OR 2.65, 95% CI 1.48-4.73) at 1-year followup were significantly associated with unfavorable outcome, while fulfilling the clinical ACR criteria for OA at baseline was not. Baseline factors independently associated with an unfavorable outcome were low/middle education level, comorbidity of the skeletal system, duration of knee symptoms of >3 months, bilateral knee symptoms, self-reported warm knee, history of nontraumatic knee symptoms, valgus alignment, pain at passive knee flexion/extension, and bony enlargement of the knee joint (AUC 0.80). Conclusion Nontraumatic knee symptoms in adults in general practice appear to become a chronic disorder in nearly half of the patients. The developed clinical prediction rule with 10 baseline prognostic factors can be used to select high-risk patients for an unfavorable outcome at long-term followup. Copyright

Walking and chair rising performed in the daily life situation before and after total hip arthroplasty (Article)

2011-09-01T00:00:00Z

Objective: An earlier study showed that 6 months after total hip arthroplasty (THA) patients' overall daily activity level had not increased, despite significant improvement in their perceived physical functioning. This discrepancy might be because postoperative recovery is not expressed by a more overall active lifestyle, but by the fact that patients could perform the individual activities of daily living (ADL) faster and/or for a longer period of time. The aim of this study was to assess whether patients perform ADL faster and/or for a longer period of time 6 months post-THA compared to baseline. Also examined was whether patients perform activities on the level of healthy matched controls. Method: Thirty patients were measured at home with an accelerometry-based Activity Monitor, pre-operatively and 6 months post-THA. Patients were matched with healthy controls on gender and age (±2 years). Results: Compared with baseline, 6 months post-THA the stride frequency and body motility during walking of patients had increased [56.1 (54.3, 57.8). strides/min vs 52.1 (50.3, 54.1). strides/min; P-value < 0.0001, and 0.265 (0.245, 0.286). g vs 0.219 (0.197, 0.240). g; P-value < 0.0001], and they rose faster from a chair [2.6 (2.5, 2.8). s vs 3.0 (2.8, 3.2). s; P-value < 0.0001]. Compared with controls, preoperative all patients had lower values for these parameters. Six months post-THA the stride frequency and body motility during walking were similar to that of controls, but patients rose slower from a chair than controls. Conclusion: Six months post-THA patients walked faster and rose from a chair faster compared to baseline. Patients walked as fast as healthy controls but took longer rising from a chair.

One-year follow-up of platelet-rich plasma treatment in chronic achilles tendinopathy: A double-blind randomized placebo-controlled trial (Article)

2011-08-01T00:00:00Z

Background: Achilles tendinopathy is a common disease among both athletes and in the general population in which the use of platelet-rich plasma has recently been increasing. Good evidence for the use of this autologous product in tendinopathy is limited, and data on longer-term results are lacking. Purpose: To study the effects of a platelet-rich plasma injection in patients with chronic midportion Achilles tendinopathy at 1-year follow-up. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: Fifty-four patients, aged 18 to 70 years, with chronic tendinopathy 2 to 7 cm proximal to the Achilles tendon insertion were randomized to receive either a blinded injection containing platelet-rich plasma or saline (placebo group) in addition to an eccentric training program. The main outcome was the validated Victorian Institute of Sports Assessment-Achilles score. Patient satisfaction was recorded and ultrasound examination performed at baseline and follow-up. Results: The mean Victorian Institute of Sports Assessment-Achilles score improved in both the platelet-rich plasma group and the placebo group after 1 year. There was no significant difference in increase between both groups (adjusted between-group difference, 5.5; 95% confidence interval,-4.9 to 15.8, P = .292). In both groups, 59% of the patients were satisfied with the received treatment. Ultrasonographic tendon structure improved significantly in both groups but was not significantly different between groups (adjusted between-group difference, 1.2%; 95% confidence interval,-4.1 to 6.6, P = .647). Conclusion: This randomized controlled trial showed no clinical and ultrasonographic superiority of platelet-rich plasma injection over a placebo injection in chronic Achilles tendinopathy at 1 year combined with an eccentric training program.

Peroxisome proliferator activated receptor alpha activation decreases inflammatory and destructive responses in osteoarthritic cartilage (Article)

2011-07-01T00:00:00Z

Objective: Peroxisome proliferator activated receptor α (PPARα) agonists are used in clinical practice as lipid-lowering drugs and are also known to exert anti-inflammatory effects on various tissues. We hypothesized that PPARα activation leads to anti-inflammatory and anti-destructive effects in human OA cartilage. Methods: Cartilage explants obtained from six OA patients were cultured for 48h with 10ng/ml interleukin (IL)1β as a pro-inflammatory stimulus. 100μM Wy-14643, a potent and selective PPARα agonist, was added to the cultures and gene expression of matrix metalloproteinase (MMP)1, MMP3, MMP13, collagen type II (COL2A1), aggrecan and PPARα in cartilage explants and the release of glycosaminoglycans (GAGs), nitric oxide (NO) and prostaglandin E2(PGE2) in the culture media were analyzed and compared to the control without Wy-14643. Results: Addition of Wy-14643 decreased mRNA expression of MMP1, MMP3 and MMP13 in cartilage explants that responded to IL1β, whereas Wy-14643 did not affect gene expression of COL2A1 and aggrecan. Wy-14643 also decreased secretion of inflammatory marker NO in the culture medium of cartilage explants responding to IL1β. Wy-14643 inhibited the release of GAGs by cartilage explants in culture media. Conclusion: PPARα agonist Wy-14643 inhibited the inflammatory and destructive responses in human OA cartilage explants and did not have an effect on COL2A1 or aggrecan mRNA expression. These effects of PPARα agonists on osteoarthritic cartilage warrant further investigation of these drugs as a potential therapeutic strategy for osteoarthritis (OA).

Trochanteric osteotomy versus posterolateral approach: Function the first year post surgery. A pilot study (Article)

2011-06-26T00:00:00Z

Background: Although no prospective studies have compared functional results of trochanteric osteotomy and a non-trochanteric approach, most surgeons feel that trochanteric osteotomy is outdated in simple hip arthroplasty. Reasons not to perform an osteotomy include the fear of longer rehabilitation and worse (final) functional outcome. METHOD: This prospective study examines differences in rehabilitation between posterolateral and trochanteric approach one year post-surgery using questionnaires (WOMAC, SF-36, HHS) and functional tests (walking, climbing stairs, rising from sitting, and strength tests). Of the 109 patients 24 had a trochanteric osteotomy: the selected approach was based on the surgeon's preference. The trochanteric osteotomy group included more patients with developmental dysplasia of the hip. Before the start of the study no power analysis was performed. Results: Data from the questionnaires showed no significant differences between the two groups at 3, 6 and 12-months follow-up. At 3-months follow-up patients in the trochanteric osteotomy group scored lower on the functional tests. This difference had disappeared at 6 and 12-months follow-up, except for abduction force which remained lower in the trochanteric osteotomy group in patients with a non union of the TO. Conclusion: For simple hip arthroplasty an approach without osteotomy seems a logical choice. Although the power of this study is low, in experienced hands trochanteric osteotomy seems to give good functional results at 6-12 months post surgery if trochanteric union is obtained. Therefore, one should not hesitate to perform an osteotomy in difficult cases.

Current evidence for effectiveness of interventions to treat rotator cuff tears (Article)

2011-06-01T00:00:00Z

Abstract: In this systematic review we assessed effectiveness of non-surgical and (post)surgical interventions for symptomatic rotator cuff tears (RotCuffTear). The Cochrane Library, PubMed, Embase, Cinahl, and Pedro were searched for relevant systematic reviews and randomized controlled trials (RCTs). Two reviewers independently selected relevant studies, extracted data and assessed the methodological quality. Three Cochrane reviews (7 RCTs) and 14 RCTs were included (3 non-surgery, 10 surgery, 8 post-surgery). For small or medium RotCufftears, moderate evidence was found in favour of surgery versus physiotherapy in mid- and long-term. In surgery, tendon-to-bone fixation with one metal suture anchor loaded with double sutures (TB) was more effective (moderate evidence) than a side-to-side repair with permanent sutures (SS) in the mid- and long-term; limited evidence for effectiveness was found in favour of debridement versus anchor replacement and suture repair of the type II SLAP tear in the long-term. Further, no evidence was found in favour of any non-surgical, surgical or post-surgical intervention. In conclusion, although surgery seems to give better results compared to non-surgery and TB is more effective than SS in rotator cuff repair (RCR), it remains hard to draw firm evidence-based conclusions for effectiveness of non-surgical or (post)surgical interventions to treat RotCuffTears. More research is clearly needed.

Corticosteroid injections for greater trochanteric pain syndrome: a randomized controlled trial in primary care (Article)

2011-05-01T00:00:00Z

Abstract. PURPOSE: We undertook a study to evaluate the effectiveness of corticosteroid injections in primary care patients with greater trochanteric pain syndrome (GTPS). METHODS: We evaluated the effect of corticosteroid injections compared with expectant treatment (usual care) in a pragmatic, multicenter, open-label, randomized clinical trial in the Netherlands. Patients (aged 18 to 80 years) with GTPS visiting 81 participating primary care physicians were randomly allocated to receive either local corticosteroid injections (n = 60) or usual care (n = 60). Primary outcomes of pain severity (numerical rating scale 0 to 10) and recovery (yes or no total or major recovery) were evaluated at 3-month and 12-month follow-up visits. Adverse events were collected at 6 weeks. RESULTS: At the 3-month follow-up visit, 34% of the patients in the usual care group had recovered compared with 55% in the injection group (adjusted OR = 2.38; 95% CI, 1.14-5.00, number needed to treat = 5). Pain severity at rest and on activity decreased in both groups, but the decrease was greater in the injection group, for an adjusted difference in pain at rest of 1.18 (95% CI, 0.31-2.05) and in pain with activity of 1.30 (95% CI, 0.32-2.29). At the 12-month follow-up, 60% of the patients in the usual care group had recovered compared with 61% in the injection group (OR = 1.05; 95% CI, 0.50-2.27). Pain severity at rest and on activity decreased in both groups and the 12-month follow-up showed no significant differences, with adjusted differences of 0.14 (95% CI, -0.75 to 1.04) for pain at rest and 0.45 (95% CI, -0.55 to 1.46) for pain with activity. Aside from a short period with superficial pain at the site of the injection, no differences in adverse events were found. CONCLUSION: In this first randomized controlled trial assessing the effectiveness of corticosteroid injections vs usual care in GTPS, a clinically relevant effect was shown at a 3-month follow-up visit for recovery and for pain at rest and with activity. At a 12-month follow-up visit, the differences in outcome were no longer present.

Recovery of Physical Functioning After Total Hip Arthroplasty: Systematic Review and Meta-Analysis of the Literature (Article)

2011-05-01T00:00:00Z

Abstract. BACKGROUND: After total hip arthroplasty (THA), patients today (who tend to be younger and more active than those who previously underwent this surgical procedure) have high expectations regarding functional outcome. Therefore, patients need to be well informed about recovery of physical functioning after THA. PURPOSE: The purpose of this study was to review publications on recovery of physical functioning after THA and examine the degree of recovery with regard to 3 aspects of functioning (ie, perceived physical functioning, functional capacity to perform activities, and actual daily activity in the home situation). DATA SOURCES: Data were obtained from the MEDLINE and EMBASE databases from inception to July 2009, and references in identified articles were tracked. STUDY SELECTION: Prospective studies with a before-after design were included. Patients included in the analysis had to have primary THA for osteoarthritis. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently checked the inclusion criteria, conducted the risk of bias assessment, and extracted the results. Data were pooled in a meta-analysis using a random-effects model. RESULTS: A total of 31 studies were included. For perceived physical functioning, patients recovered from less than 50% preoperatively to about 80% of that of controls (individuals who were healthy) 6 to 8 months postsurgery. On functional capacity, patients recovered from 70% preoperatively to about 80% of that of controls 6 to 8 months postsurgery. For actual daily activity, patients recovered from 80% preoperatively to 84% of that of controls at 6 months postsurgery. LIMITATIONS: Only a few studies were retrieved that investigated the recovery of physical functioning longer than 8 months after surgery. CONCLUSIONS: Compared with the preoperative situation, the 3 aspects of physical functioning showed varying degrees of recovery after surgery. At 6 to 8 months postoperatively, physical functioning had generally recovered to about 80% of that of controls.

No effects of PRP on ultrasonographic tendon structure and neovascularisation in chronic midportion Achilles tendinopathy (Article)

2011-04-01T00:00:00Z

Abstract. OBJECTIVE: To assess whether a platelet-rich plasma (PRP) injection leads to an enhanced tendon structure and neovascularisation, measured with ultrasonographic techniques, in chronic midportion Achilles tendinopathy. DESIGN: Double-blind, randomised, placebo-controlled clinical trial. SETTING: Sports medical department of The Hague medical centre. PATIENTS: 54 patients with chronic midportion Achilles tendinopathy were included. INTERVENTIONS: Patients were randomised to eccentric exercise therapy with either a PRP injection (PRP group) or a saline injection (placebo group). MAIN OUTCOME MEASUREMENTS: Tendon structure was evaluated by ultrasonographic tissue characterisation, a novel technique which quantifies tendon structure into four echo-types: echo-types I+II represent organised tendon bundles, whereas echo-types III+IV represent a disorganised tendon structure. Colour Doppler ultrasonography was used to measure the degree of neovascularisation. Follow-up was at 6, 12 and 24 weeks. RESULTS: A significant improvement in echo-types I+II was found after 24 weeks within both the PRP group (n=27) and the placebo group (n=27), but there was no significant between-group difference (95% CI -1.6 to 7.8, p=0.169). After 6 weeks, the neovascularisation score increased within the PRP group (p=0.001) and the placebo group (p=0.002), but there was no significant between-group difference in change in neovascularisation score at any point in time. CONCLUSION: Injecting PRP for the treatment of chronic midportion Achilles tendinopathy does not contribute to an increased tendon structure or alter the degree of neovascularisation, compared with placebo.

Clinically Translatable Cell Tracking and Quantification by MRI in Cartilage Repair Using Superparamagnetic Iron Oxides (Article)

2011-03-02T00:00:00Z

Abstract BACKGROUND: Articular cartilage has very limited intrinsic regenerative capacity, making cell-based therapy a tempting approach for cartilage repair. Cell tracking can be a major step towards unraveling and improving the repair process of these therapies. We studied superparamagnetic iron oxides (SPIO) for labeling human bone marrow-derived mesenchymal stem cells (hBMSCs) regarding effectivity, cell viability, long term metabolic cell activity, chondrogenic differentiation and hBMSC secretion profile. We additionally examined the capacity of synovial cells to endocytose SPIO from dead, labeled cells, together with the use of magnetic resonance imaging (MRI) for intra-articular visualization and quantification of SPIO labeled cells. METHODOLOGY/PRINICIPAL FINDINGS: Efficacy and various safety aspects of SPIO cell labeling were determined using appropriate assays. Synovial SPIO re-uptake was investigated in vitro by co-labeling cells with SPIO and green fluorescent protein (GFP). MRI experiments were performed on a clinical 3.0T MRI scanner. Two cell-based cartilage repair techniques were mimicked for evaluating MRI traceability of labeled cells: intra-articular cell injection and cell implantation in cartilage defects. Cells were applied ex vivo or in vitro in an intra-articular environment and immediately scanned. SPIO labeling was effective and did not impair any of the studied safety aspects, including hBMSC secretion profile. SPIO from dead, labeled cells could be taken up by synovial cells. Both injected and implanted SPIO-labeled cells could accurately be visualized by MRI in a clinically relevant sized joint model using clinically applied cell doses. Finally, we quantified the amount of labeled cells seeded in cartilage defects using MR-based relaxometry. CONCLUSIONS: SPIO labeling appears to be safe without influencing cell behavior. SPIO labeled cells can be visualized in an intra-articular environment and quantified when seeded in cartilage defects.

In-vivo generation of bone via endochondral ossification by in-vitro chondrogenic priming of adult human and rat mesenchymal stem cells (Article)

2011-02-02T00:00:00Z

Abstract Background: Bone grafts are required to repair large bone defects after tumour resection or large trauma. The availability of patients’ own bone tissue that can be used for these procedures is limited. Thus far bone tissue engineering has not lead to an implant which could be used as alternative in bone replacement surgery. This is mainly due to problems of vascularisation of the implanted tissues leading to core necrosis and implant failure. Recently it was discovered that embryonic stem cells can form bone via the endochondral pathway, thereby turning in-vitro created cartilage into bone in-vivo. In this study we investigated the potential of human adult mesenchymal stem cells to form bone via the endochondral pathway. Methods: MSCs were cultured for 28 days in chondrogenic, osteogenic or control medium prior to implantation. To further optimise this process we induced mineralisation in the chondrogenic constructs before implantation by changing to osteogenic medium during the last 7 days of culture. Results: After 8 weeks of subcutaneous implantation in mice, bone and bone marrow formation was observed in 8 of 9 constructs cultured in chondrogenic medium. No bone was observed in any samples cultured in osteogenic medium. Switch to osteogenic medium for 7 days prevented formation of bone in-vivo. Addition of b-glycerophosphate to chondrogenic medium during the last 7 days in culture induced mineralisation of the matrix and still enabled formation of bone and marrow in both human and rat MSC cultures. To determine whether bone was formed by the host or by the implanted tissue we used an immunocompetent transgenic rat model. Thereby we found that osteoblasts in the bone were almost entirely of host origin but the osteocytes are of both host and donor origin. Conclusions: The preliminary data presented in this manuscript demonstrates that chondrogenic priming of MSCs leads to bone formation in vivo using both human and rat cells. Furthermore, addition of b-glycerophosphate to the chondrogenic medium did not hamper this process. Using transgenic animals we also demonstrated that both host and donor cells played a role in bone formation. In conclusion these data indicate that in-vitro chondrogenic differentiation of human MSCs could lead to an alternative and superior approach for bone tissue engineering.

Unfocused Extracorporeal Shock Waves Induce Anabolic Effects in Rat Bone (Article)

2011-01-05T00:00:00Z

Abstract. BACKGROUND: Extracorporeal shock waves are known to stimulate the differentiation of mesenchymal stem cells toward osteoprogenitors and induce the expression of osteogenic-related growth hormones. The aim of this study was to investigate if and how extracorporeal shock waves affected new bone formation, bone microarchitecture, and the mechanical properties of bone in a healthy rat model, in order to evaluate whether extracorporeal shock wave therapy might be a potential treatment for osteoporosis. METHODS: Thirteen rats received 1000 electrohydraulically generated unfocused extracorporeal shock waves to the right tibia. The contralateral, left tibia was not treated and served as a control. At two, seven, twenty-one, and forty-nine days after administration of the shock waves, in vivo single-photon-emission computed tomography (SPECT) scanning was performed to measure new bone formation on the basis of uptake of technetium-labeled methylene diphosphonate ((99m)Tc-MDP) (n = 6). Prior to and forty-nine days after the extracorporeal shock wave therapy, micro-computed tomography (micro-CT) scans were made to examine the architectural bone changes. In addition, mechanical testing, microcrack, and histological analyses were performed. RESULTS: Extracorporeal shock waves induced a strong increase in (99m)Tc-MDP uptake in the treated tibia compared with the uptake in the untreated, control tibia. Micro-CT analysis showed that extracorporeal shock waves stimulated increases in both trabecular and cortical volume, which resulted in higher bone stiffness compared with that of the control tibiae. Histological analysis showed intramedullary soft-tissue damage and de novo bone with active osteoblasts and osteoid in the bone marrow of the legs treated with extracorporeal shock waves. Microcrack analysis showed no differences between the treated and control legs. CONCLUSIONS: This study shows that a single treatment with extracorporeal shock waves induces anabolic effects in both cancellous and cortical bone, leading to improved biomechanical properties. Furthermore, treatment with extracorporeal shock waves results in transient damage to the bone marrow, which might be related to the anabolic effects. After further examination and optimization, unfocused extracorporeal shock waves might enable local treatment of skeletal sites susceptible to fracture.

Adverse effects of extra-articular corticosteroid injections: A systematic review (Article)

2010-09-16T00:00:00Z

Background. To estimate the occurrence and type of adverse effects after application of an extra-articular (soft tissue) corticosteroid injection. Methods. A systematic review of the literature was made based on a PubMed and Embase search covering the period 1956 to January 2010. Case reports were included, as were prospective and retrospective studies that reported adverse events of corticosteroid injection. All clinical trials which used extra-articular corticosteroid injections were examined. We divided the reported adverse events into major (defined as those needing intervention or not disappearing) and minor ones (transient, not requiring intervention). Results. The search yielded 87 relevant studies:44 case reports, 37 prospective studies and 6 retrospective studies. The major adverse events included osteomyelitis and protothecosis; one fatal necrotizing fasciitis; cellulitis and ecchymosis; tendon ruptures; atrophy of the plantar fat was described after injecting a neuroma; and local skin effects appeared as atrophy, hypopigmentation or as skin defect. The minor adverse events effects ranged from skin rash to flushing and disturbed menstrual pattern. Increased pain or steroid flare after injection was reported in 19 studies. After extra-articular injection, the incidence of major adverse events ranged from 0-5.8% and that of minor adverse events from 0-81%. It was not feasible to pool the risk for adverse effects due to heterogeneity of study populations and difference in interventions and variance in reporting. Conclusion. In this literature review it was difficult to accurately quantify the incidence of adverse effects after extra-articular corticosteroid injection. The reported adverse events were relatively mild, although one fatal reaction was reported.

Stiffer Fixation of the Tibial Double-Tunnel Anterior Cruciate Ligament Complex Versus the Single Tunnel: A Biomechanical Study (Article)

2010-09-01T00:00:00Z

Purpose: The primary objective of this study was to evaluate the difference in graft pullout forces, stiffness, and failure mode of double-bundle anterior cruciate ligament (ACL) reconstruction of the tibial insertion by use of a single tunnel compared with a double-tunnel technique with interference screw fixation. Methods: ACL reconstruction on the tibial side was performed on 40 fresh-frozen porcine knees (mean bone mineral density of 0.64 g/cm2 measured by dual-energy x-ray absorptiometry scan), randomly assigned to the single- or double-tunnel group. Interference screw fixation of the soft-tissue graft was used for both types of tibial reconstruction. Maximum failure load, stiffness, and failure mode were recorded. Results: There was no significant difference in maximum failure load between the single-tunnel group (400 ± 26 N) and double-tunnel group (440 ± 20 N). Stiffness of the tibial tunnel complex was significantly higher in the double-tunnel group (76 ± 3 N/mm) than in the single-tunnel group (62 ± 4 N/mm) (P = .013). All but 2 grafts (38 of 40) failed by slippage of the tendon past the interference screw. Conclusions: There was significantly stiffer fixation of the tibial double-tunnel ACL complex when compared with the single tunnel. Our study did not show a different failure mode for the double-tunnel reconstruction compared with the single-tunnel reconstruction. Clinical Relevance: This study shows a biomechanical advantage with no potential deleterious side effects for fixation of the ACL with a double-tunnel technique on the tibial side.

Diagnostic accuracy of history taking and physical examination for assessing anterior cruciate ligament lesions of the knee in primary care (Article)

2010-09-01T00:00:00Z

Abstract OBJECTIVE: To assess the diagnostic accuracy of history taking and physical examination for assessing anterior cruciate ligament (ACL) lesions in primary care. DESIGN: Cross-sectional diagnostic study. SETTING: Primary care. PARTICIPANTS: Patients (N=134; age, 18-65y) who consulted their general practitioner (GP) within 5 weeks after injury. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Index tests were obtained with a questionnaire and physical examination. Magnetic resonance imaging (MRI) was used as the reference test. Logistic regression analysis was used to determine associations with ACL lesions. Diagnostic accuracy was determined by calculating sensitivity (Se), specificity (Sp), predictive values, and likelihood ratio (LR). RESULTS: MRI showed an ACL lesion in 28 of 134 included patients. "Effusion," "popping sensation," "giving way," and "anterior drawer test (ADT)" showed associations with an ACL lesion (P<.05). Popping sensation showed Se, Sp, positive predictive value (PPV), and positive LR (LR(+)) of .63, .73, .39, and 2.3, respectively. Combining determinants from history taking (2 of 3 positive results regarding effusion, popping sensation, and giving way) improved diagnostic accuracy (Se, .71; Sp, .71; PPV, .42; and LR(+), 2.5). The ADT added diagnostic accuracy to these combinations (Se, .63; Sp, .85; PPV, .52; and LR(+), 4.2). CONCLUSIONS: ACL lesions are seen frequently. Based on history taking (effusion, popping sensation, and/or giving way) and physical examination (ADT), GPs can screen for ACL lesions in primary care.

Stimulation of osteogenic differentiation in human osteoprogenitor cells by pulsed electromagnetic fields: An in vitro study (Article)

2010-08-26T00:00:00Z

Background: Although pulsed electromagnetic field (PEMF) stimulation may be clinically beneficial during fracture healing and for a wide range of bone disorders, there is still debate on its working mechanism. Mesenchymal stem cells are likely mediators facilitating the observed clinical effects of PEMF. Here, we performed in vitro experiments to investigate the effect of PEMF stimulation on human bone marrow-derived stromal cell (BMSC) metabolism and, specifically, whether PEMF can stimulate their osteogenic differentiation. Methods: BMSCs derived from four different donors were cultured in osteogenic medium, with the PEMF treated group being continuously exposed to a 15 Hz, 1 Gauss EM field, consisting of 5-millisecond bursts with 5-microsecond pulses. On culture day 1, 5, 9, and 14, cells were collected for biochemical analysis (DNA amount, alkaline phosphatase activity, calcium deposition), expression of various osteoblast-relevant genes and activation of extracellular signal-regulated kinase (ERK) signaling. Differences between treated and control groups were analyzed using the Wilcoxon signed rank test, and considered significant when p < 0.05. Results: Biochemical analysis revealed significant, differentiation stage-dependent, PEMF-induced differences: PEMF increased mineralization at day 9 and 14, without altering alkaline phosphatase activity. Cell proliferation, as measured by DNA amounts, was not affected by PEMF until day 14. Here, DNA content stagnated in PEMF treated group, resulting in less DNA compared to control. Quantitative RT-PCR revealed that during early culture, up to day 9, PEMF treatment increased mRNA levels of bone morphogenetic protein 2, transforming growth factor-beta 1, osteoprotegerin, matrix metalloproteinase-1 and-3, osteocalcin, and bone sialoprotein. In contrast, receptor activator of NF-B ligand expression was primarily stimulated on day 14. ERK1/2 phosphorylation was not affected by PEMF stimulation. Conclusions: PEMF exposure of differentiating human BMSCs enhanced mineralization and seemed to induce differentiation at the expense of proliferation. The osteogenic stimulus of PEMF was confirmed by the up-regulation of several osteogenic marker genes in the PEMF treated group, which preceded the deposition of mineral itself. These findings indicate that PEMF can directly stimulate osteoprogenitor cells towards osteogenic differentiation. This supports the theory that PEMF treatment may recruit these cells to facilitate an osteogenic response in vivo. © 2010 Jansen et al; licensee BioMed Central Ltd.

The infrapatellar fat pad should be considered as an active osteoarthritic joint tissue: A narrative review (Article)

2010-07-01T00:00:00Z

Introduction: Osteoarthritis (OA) of the knee joint is caused by genetic and hormonal factors and by inflammation, in combination with biomechanical alterations. It is characterized by loss of articular cartilage, synovial inflammation and subchondral bone sclerosis. Considerable evidence indicates that the menisci, ligaments, periarticular muscles and the joint capsule are also involved in the OA process. This paper will outline the theoretical framework for investigating the infrapatellar fat pad (IPFP) as an additional joint tissue involved in the development and progression of knee-OA. Methods: A literature search was performed in Pubmed from 1948 until October 2009 with keywords InFrapatellar fat pad, Hoffa fat pad, intraarticular adipose tissue, knee, cartilage, bone, cytokine, adipokine, inflammation, growth factor, arthritis, and OA. Results: The IPFP is situated intracapsularly and extrasynovially in the knee joint. Besides adipocytes, the IPFP from patients with knee-OA contains macrophages, lymphocytes and granulocytes, which are able to contribute to the disease process of knee-OA. Furthermore, the IPFP contains nociceptive nerve fibers that could in part be responsible for anterior pain in knee-OA. These nerve fibers secrete substance P, which is able to induce inflammatory responses and cause vasodilation, which may lead to IPFP edema and extravasation of the immune cells.The IPFP secretes cytokines, interleukins, growth factors and adipokines that influence cartilage by upregulating the production of matrix metalloproteinases (MMPs), stimulating the expression of pro-inflammatory cytokines and inhibiting the production of cartilage matrix proteins. They may also stimulate the production of pro-inflammatory mediators, growth factors and MMPs in synovium. Conclusion: These data are consistent with the hypothesis that the IPFP is an osteoarthritic joint tissue capable of modulating inflammatory and destructive responses in knee-OA.

Medial knee osteoarthritis treated by insoles or braces: a randomized trial. (Article)

2010-07-01T00:00:00Z

BACKGROUND: There is controversial evidence regarding whether foot orthoses or knee braces improve pain and function or correct malalignment in selected patients with osteoarthritis (OA) of the medial knee compartment. However, insoles are safe and less costly than knee bracing if they relieve pain or improve function. QUESTIONS/PURPOSES: We therefore asked whether laterally wedged insoles or valgus braces would reduce pain, enhance functional scores, and correct varus malalignment comparable to knee braces. PATIENTS AND METHODS: We prospectively enrolled 91 patients with symptomatic medial compartmental knee OA and randomized to treatment with either a 10-mm laterally wedged insole (index group, n = 45) or a valgus brace (control group, n = 46). All patients were assessed at 6 months. The primary outcome measure was pain severity as measured on a visual analog scale. Secondary outcome measures were knee function score using WOMAC and correction of varus alignment on AP whole-leg radiographs taken with the patient in the standing position. Additionally, we compared the percentage of responders according to the OMERACT-OARSI criteria for both groups. RESULTS: We observed no differences in pain or WOMAC scores between the two groups. Neither device achieved correction of knee varus malalignment in the frontal plane. According to the OMERACT-OARSI criteria, 17% of our patients responded to the allocated intervention. Patients in the insole group complied better with their intervention. Although subgroup analysis results should be translated into practice cautiously, we observed a slightly higher percentage of responders for the insole compared with bracing for patients with mild medial OA. CONCLUSIONS: Our data suggest a laterally wedged insole may be an alternative to valgus bracing for noninvasively treating symptoms of medial knee OA. LEVEL OF EVIDENCE: Level I, therapeutic study. See the Guidelines for Authors for a complete description of level of evidence.

One-year follow-up of a randomised controlled trial on added splinting to eccentric exercises in chronic midportion Achilles tendinopathy (Article)

2010-07-01T00:00:00Z

OBJECTIVE: The study examined whether the addition of a night splint to eccentric exercises is beneficial for functional outcome in chronic mid-portion Achilles tendinopathy. DESIGN: One-year follow-up of a randomised controlled single blinded clinical trial. SETTING: Sports medicine department in a general hospital. PATIENTS: 58 patients (70 tendons) were included. INTERVENTIONS: All patients completed a 12-week heavy load eccentric training programme. One group received a night splint in addition to eccentric exercises. Main outcome measurements: Outcome scores were: Victorian Institute of Sport Assessment - Achilles (VISA-A) score, subjective patient satisfaction and neovascularisation score measured with Power Doppler Ultrasonography. RESULTS: For both groups the VISA-A score increased significantly (from 50 to 76 (P < 0.01) in the eccentric group and from 49 to 78 (P < 0.01) in the night splint group). No significant differences in VISA-A score were found between the groups from baseline to one year (P = 0.32). Presence of neovessels at baseline did not predict change in VISA-A score after one year in the whole group (P = 0.71). CONCLUSION: Eccentric exercises with or without a night splint improved functional outcome at one-year follow-up. At follow-up there was no significant difference in clinical outcome when a night splint was used in addition to an eccentric exercise program. Between three months and one year follow-up, a continuing increase in VISA-A score was found. Assessment of the neovascularisation score with PDU at baseline has no prognostic value on long-term clinical outcome.

Elevated levels of cartilage oligomeric matrix protein during in vitro cartilage matrix generation decrease collagen fibril diameter (Article)

2010-07-01T00:00:00Z

Cartilage oligomeric matrix protein (COMP) is a protein present in the cartilage matrix and is expressed more abundantly in osteoarthritis cartilage than in healthy cartilage. The present study was designed to investigate the effect of transforming growth factor β (TGFβ) on COMP deposition and the influence of COMP on collagen biochemistry in a long-term 3-dimensional culture. Bovine chondrocytes in alginate beads were cultured with or without 25 ng/mL TGFβ2 for 21 or 35 days. COMP was overexpressed in bovine chondrocytes using lentiviral transfection. COMP gene expression, COMP protein production, collagen and proteoglycan deposition, and collagen fibril thickness were determined. Addition of TGFβ2 resulted in more COMP mRNA and protein than the control condition without growth factors. Lentiviral transduction with COMP resulted in elevated gene expression of COMP and increased COMP levels in the alginate bead and culture medium compared to untransfected cells. Overexpression of COMP did not affect the deposition of collagen, collagen cross-linking, proteoglycan deposition, or the mechanical properties. Stimulating COMP production by either TGFβ2 or lentivirus resulted in collagen fibrils with a smaller diameter. Taken together, COMP deposition can be modulated in cartilage matrix production by the addition of growth factors or by overexpression of COMP. Inducing COMP protein expression resulted in collagen fibrils with a smaller diameter. Because it has been demonstrated that the collagen fibril diameter is associated with mechanical functioning of the matrix, modulating COMP levels should be taken into account in cartilage regeneration strategies.

Functional capacity and actual daily activity do not contribute to patient satisfaction after total knee arthroplasty (Article)

2010-06-18T00:00:00Z

Abstract Background: After total knee arthroplasty (TKA) only 75-89% of patients are satisfied. Because patient satisfaction is a prime goal of all orthopaedic procedures, optimization of patient satisfaction is of major importance. Factors related to patient satisfaction after TKA have been explored, but no studies have included two potentially relevant factors, i.e. the functional capacity of daily activities and actual daily activity. This present prospective study examines whether functional capacity and actual daily activity (in addition to an extensive set of potential factors) contribute to patient satisfaction six months after TKA. Methods: A total of 44 patients were extensively examined preoperatively and six months post surgery. Functional capacity was measured with three capacity tests, focusing on walking, stair climbing, and chair rising. Actual daily activity was measured in the patient's home situation by means of a 48-hour measurement with an Activity Monitor. To establish which factors were related to patient satisfaction six months post surgery, logistic regression analyses were used to calculate odds ratios. Results: Preoperative and postoperative functional capacity and actual daily activity had no relation with patient satisfaction. Preoperatively, only self-reported mental functioning was positively related to patient satisfaction. Postoperatively, based on multivariate analysis, only fulfilled expectations regarding pain and experienced pain six months post surgery were related to patient satisfaction. Conclusions: Functional capacity and actual daily activity do not contribute to patient satisfaction after TKA. Patients with a better preoperative self-reported mental functioning, and patients who experienced less pain and had fulfilled expectations regarding pain postoperatively, were more often satisfied.

A statistical model of shape and density of the proximal femur in relation to radiological and clinical OA of the hip (Article)

2010-06-01T00:00:00Z

Objective: Common radiological measures of osteoarthritis (OA) relate poorly to symptoms as experienced by patients. We created a statistical model of shape and density to see if Dual Energy X-ray (DXA) images of the hip contain symptom-related information that is not captured by common radiological measures. Methods: DXA images of the hip were made in a prospective study of patients that met the American College of Rheumatology (ACR) criteria for hip OA. From the DXA scans, we constructed a statistical model of the appearance (shape combined with density) of the proximal femur of left and right side. The model yields a number of independent descriptors of the appearance (modes) which we related to various measures of radiological and clinical OA. These outcome measures were defined using Joint Space Width (JSW), Kellgren and Lawrence (KeL) scores, Visual Analogue Scale (VAS) and Western Ontario MacMaster Universities (WOMAC) pain scores and a self-reported global assessment score. Results: Various modes showed significant relations with measures of OA. Interestingly, the modes that related well with radiological OA did not relate to clinical OA and vice-versa. Moreover, the modes were predictors of status and progression of clinical OA, independent from JSW and KeL. Conclusion: Statistical modeling of the appearance captures the patterns of variation in projected femoral morphology as visible on DXA images. We showed that these descriptors of subtle aspects of shape and density of the hip contain information about clinical status which common radiological measures do not. The presented results warrant further careful study of the method as a monitoring tool in clinical trials.

Pronation and supination after forearm fractures in children: Reliability of visual estimation and conventional goniometry measurement (Article)

2010-06-01T00:00:00Z

Abstract BACKGROUND: Forearm fractures are common amongst children and often result in limited rotational function. In daily practice, pronation and supination of the arm are often visually estimated or measured using a conventional goniometer. The aim of this study was to compare the reliability of these two methods in paediatric patients who had previously sustained a forearm fracture. METHODS: Intra- and interrater reliability of visual estimation and conventional goniometry were determined in 47 children who had previously sustained a forearm fracture. RESULTS: Intra- and interrater reliability of visual estimation and conventional goniometry was fair to excellent, with intraclass correlation coefficients (ICCs) ranging between 0.75 and 0.94. In addition, the overall goniometer data consistently showed lower smallest detectable differences (SDDs) compared to the visual estimation data, also indicating better reliability for the goniometer method. CONCLUSIONS: A conventional goniometer is an easy, fast and reliable method to determine the pronation and supination in a child who had sustained a forearm fracture. If an uncooperative child hinders the measurement, visual estimation is a good second choice. Measurements are more reliable when repeated by the same professional.

Tendinopathy platelet-rich plasma for treatment of Achilles: Reply (Article)

2010-05-05T00:00:00Z

The posterior bone block procedure in posterior shoulder instability: A long-term follow-up study (Article)

2010-05-01T00:00:00Z

We present the long-term outcome, at a median of 18 years (12.8 to 23.5) of open posterior bone block stabilisation for recurrent posterior instability of the shoulder in a heterogenous group of 11 patients previously reported on in 2001 at a median follow-up of six years. We found that five (45%) would not have chosen the operation again, and that four (36%) had further posterior dislocation. Clinical outcome was significantly worse after 18 years than after six years of follow-up (median Rowe score of 60 versus 90 (p = 0.027)). The median Western Ontario Shoulder Index was 60% (37% to 100%) at 18 years' follow-up, which is a moderate score. At the time of surgery four (36%) had glenohumeral radiological osteoarthritis, which was present in all after 18 years. This study showed poor long-term results of the posterior bone block procedure for posterior instability and a high rate of glenohumeral osteoarthritis although three patients with post-traumatic instability were pleased with the result of their operations.

Physiological tonicity improves human chondrogenic marker expression through nuclear factor of activated T-cells 5 in vitro (Article)

2010-05-01T00:00:00Z

Abstract Introduction: Chondrocytes experience a hypertonic environment compared to plasma (280 mOsm) due to the high fixed negative charge density of cartilage. Standard isolation of chondrocytes removes their hypertonic matrix, exposing them to non-physiological conditions. During in-vitro expansion, chondrocytes quickly lose their specialized phenotype, making them inappropriate for cell-based regenerative strategies. We aimed to elucidate the effects of tonicity during isolation and in-vitro expansion on chondrocyte phenotype. Methods: Human articular chondrocytes were isolated and subsequently expanded at control tonicity (280 mOsm) or at moderately elevated, physiological, tonicity (380 mOsm). The effects of physiological tonicity on chondrocyte proliferation and chondrogenic marker expression were evaluated. The role of Tonicity-responsive Enhancer Binding Protein (TonEBP/NFAT5) in response to physiological tonicity was investigated using nuclear factor of activated T-cells 5 (NFAT5) RNA interference. Results: Moderately elevated, physiological, tonicity (380 mOsm) did not affect chondrocyte proliferation, while higher tonicities inhibited proliferation and diminished cell viability. Physiological tonicity improved expression of chondrogenic markers and NFAT5 and its target genes, while suppressing dedifferentiation marker collagen type I and improving type II/type I expression ratios >100-fold. Effects of physiological tonicity were similar in osteoarthritic and ‘normal’ (non-osteoarthritic) chondrocytes, indicating a disease-independent mechanism. NFAT5 RNA interference abolished tonicity-mediated effects and revealed that NFAT5 positively regulates collagen type II expression, while suppressing type I. Conclusions: Physiological tonicity provides a simple, yet effective, means to improve phenotypical characteristics during cytokine-free isolation and in-vitro expansion of human articular chondrocytes. Our findings will lead to the development of improved cell-based repair strategies for chondral lesions and provides important insights into mechanisms underlying osteoarthritic progression.

Stretch-Induced Inhibition of Wnt/b-Catenin Signaling in Mineralizing Osteoblasts (Article)

2010-03-01T00:00:00Z

Wnt signaling is important for bone formation and osteoblastic differentiation. Recent findings indicate a stimulating role of Wnt signaling in bone mechanotransduction. However, negative effects of Wnt signaling on osteoblast differentiation and mineralization have been described as well. We conducted in vitro stretch experiments using human pre-osteoblasts to study short- and long-term effects of mechanical loading on Wnt/beta-catenin signaling. As the extracellular regulated kinase (ERK) pathway is known to be involved in mechanotransduction in osteoblasts, we also evaluated its role in Wnt/beta-catenin signaling. Stretch experiments up to 21 days (using stretch episodes of 15 min, alternated with 90 min rest) resulted in higher mineralization compared to static control cultures. We found that 15 min of stretch initially increased nuclear beta-catenin, but ultimately resulted in significant decrease at 12 and 40 h after stretch. Downregulation of Wnt-responsive element activity 16 h after stretch, using a luciferase construct, further supported these findings. The presence of the ERK inhibitor U0126 did not alter the stretch-induced decrease of beta-catenin levels. Our data indicate a biphasic effect of mechanical loading on beta-catenin in mineralizing human differentiating osteoblasts, which is independent of the ERK pathway. The osteogenic potential of our loading regime was confirmed by an increase in osteogenic differentiation markers such as alkaline phosphatase activity and calcium deposition after 3 weeks of culture. We conjecture that the biphasic aspect of Wnt/beta-catenin signaling with a strong decrease up to 40 h after the stretch induction, is important for the anabolic effects of mechanical stretch on bone.

Platelet-rich plasma injection for chronic Achilles tendinopathy: A randomized controlled trial (Article)

2010-01-13T00:00:00Z

Context: Tendon disorders comprise 30% to 50% of all activity-related injuries; chronic degenerative tendon disorders (tendinopathy) occur frequently and are difficult to treat. Tendon regeneration might be improved by injecting platelet-rich plasma (PRP), an increasingly used treatment for releasing growth factors into the degenerative tendon. Objective: To examine whether a PRP injection would improve outcome in chronic midportion Achilles tendinopathy. Design, Setting, and Patients: A stratified, block-randomized, double-blind, placebo-controlled trial at a single center (The Hague Medical Center, Leidschendam, the Netherlands) of 54 randomized patients aged 18 to 70 years with chronic tendinopathy 2 to 7 cm above the Achilles tendon insertion. The trial was conducted between August 28, 2008, and January 29, 2009, with follow-up until July 16, 2009. Intervention: Eccentric exercises (usual care) with either a PRP injection (PRP group) or saline injection (placebo group). Randomization was stratified by activity level. Main Outcome Measures: The validated Victorian Institute of Sports Assessment-Achilles (VISA-A) questionnaire, which evaluated pain score and activity level, was completed at baseline and 6, 12, and 24 weeks. The VISA-A score ranged from 0 to 100, with higher scores corresponding with less pain and increased activity. Treatment group effects were evaluated using general linear models on the basis of intention-to-treat. Results: After randomization into the PRP group (n=27) or placebo group (n=27), there was complete follow-up of all patients. The mean VISA-A score improved significantly after 24 weeks in the PRP group by 21.7 points (95% confidence interval [CI], 13.0-30.5) and in the placebo group by 20.5 points (95% CI, 11.6-29.4). The increase was not significantly different between both groups (adjusted betweengroup difference from baseline to 24 weeks, -0.9; 95% CI, -12.4 to 10.6). This CI did not include the predefined relevant difference of 12 points in favor of PRP treatment. Conclusion: Among patients with chronic Achilles tendinopathy who were treated with eccentric exercises, a PRP injection compared with a saline injection did not result in greater improvement in pain and activity. Trial Registration: clinicaltrials.gov Identifier: NCT00761423.

Predictors of partial weight-bearing performance after total hip arthroplasty (Article)

2010-01-01T00:00:00Z

Abstract OBJECTIVE: To determine which patient characteristics, postoperative characteristics, and walking features influence patients' partial weight-bearing performance after total hip arthroplasty. DESIGN: A descriptive prospective study. PATIENTS: Fifty patients with total hip arthroplasty were included; partial weight-bearing was performed at a 10% body weight target load (n=33) and at a 50% body weight target load (n=17). METHODS: Patient (age, gender, body weight, upper arm muscle strength) and postoperative (pain, fatigue, anxiety) characteristics, and walking features (step frequency, total walking time, total number of steps, walking aid) were measured postoperatively on day 7 (with and without a physical therapist) and on day 21 (at home). Multilevel regression analyses were conducted to identify determinants that influence partial weight-bearing. RESULTS: Gender (female) (regression coefficient B=8.18, p=0.03) and total walking time (B=0.58, p<0.001) were positively, and pain during walking was negatively (B=-2.43, p=0.02), associated with the mean peak load. For partial weight-bearing at 10% body weight, postoperative overall anxiety (B=6.40, p=0.002) and total steps (B=0.05, p=0.02) were positively associated with the percentage of steps above the target load. For partial weight-bearing at home, postoperative overall anxiety was negatively associated with the percentage of steps above the target load (B=-5.32, p=0.001). Conclusion: Gender, pain during walking, walking time, postoperative anxiety and total number of steps influence the patient's partial weight-bearing performance.

Calcineurin inhibitors promote chondrogenic marker expression of dedifferentiated human adult chondrocytes via stimulation of endogenous TGFβ1 production (Article)

2010-01-01T00:00:00Z

In vitro chondrocyte expansion is required for several cell-based approaches for the repair of chondral lesions. During expansion, loss of chondrogenic phenotype takes place (dedifferentiation). The objective of this study was to investigate calcineurin (Cn) as a potential target to improve chondrocyte phenotype for cartilage repair purposes. Cn activity in human articular chondrocytes was significantly increased during dedifferentiation and decreased during redifferentiation in vitro. Inhibition of Cn activity by FK506 increased the expression of chondrogenic markers collagen type 2, aggrecan, and SOX9 in culture-expanded cells. Addition of FK506 increased endogenous transforming growth factor 2(TGF) β1 expression on both mRNA and protein level. The effect of FK506 on chondrogenic markers was abolished by addition of anti-TGFβ1 antibody, indicating that the endogenous TGFβ1 was necessary to increase chondrogenic marker expression. We also showed that chondrocyte redifferentiation by TGFβ requires calcium influx and does not depend on changes in Cn activity. In conclusion, inhibition of Cn activity by FK506 increases the expression of chondrogenic markers via endogenous TGFβ1 production in human articular chondrocytes. Cn inhibitors might be an alternative for the application of (recombinant) TGFβ, to promote chondrocyte phenotype for cell-based cartilage repair procedures.

No positive effect of autologous platelet gel after total knee arthroplasty: A double-blind randomized controlled trial: 102 patients with a 3-month follow-up (Article)

2009-11-27T00:00:00Z

Background and purpose Activated platelets release a cocktail of growth factors, some of which are thought to stimulate repair. We investigated whether the use of autologous platelet gel (PG) in total knee arthroplasty (TKA) would improve wound healing and knee function, and reduce blood loss and the use of analgesics. Patients and methods 102 patients undergoing TKA were randomly assigned to a PG group (n 50) or to a control (C) group (n 52). The primary analysis was based on 73 participants (PG: 32; C: 41) with comparison of postoperative wound scores, VAS, WOMAC, knee function, use of analgesics, and the pre- and postoperative hemoglobin values after a follow-up of 3 months. 29 participants were excluded due to insufficient data. Results The characteristics of the protocol-compliant patients were similar to those of the patients who were excluded. Analysis was per protocol and focused on the remaining 73 patients. At baseline and after 3 months of follow-up, there were no statistically significant differences between both groups regarding age, height, weight, sex, side of operation, platelet count, hemoglobin values, severity of complaints (WOMAC), and level of pain. Interpretation In our patients undergoing TKA, application of PG to the wound site did not promote wound healing. Also, we found that PG had no effect on pain, knee function, or hemoglobin values.

Supervised exercise therapy versus usual care for patellofemoral pain syndrome: an open label randomised controlled trial. (Article)

2009-11-24T00:00:00Z

OBJECTIVE: To assess the effectiveness of supervised exercise therapy compared with usual care with respect to recovery, pain, and function in patients with patellofemoral pain syndrome. DESIGN: Open label randomised controlled trial. SETTING: General practice and sport physician practice. PARTICIPANTS: Patients with a new episode of patellofemoral pain syndrome recruited by their general practitioner or sport physician. INTERVENTIONS: The intervention group received a standardised exercise programme for 6 weeks tailored to individual performance and supervised by a physical therapist, and were instructed to practise the tailored exercises at home for 3 months. The control group were assigned usual care, which comprised a "wait and see" approach of rest during periods of pain and refraining from pain provoking activities. Both the intervention group and the control group received written information about patellofemoral pain syndrome and general instructions for home exercises. MAIN OUTCOME MEASURES: The primary outcomes were self reported recovery (7 point Likert scale), pain at rest and pain on activity (0-10 point numerical rating scale), and function (0-100 point Kujala patellofemoral score) at 3 months and 12 months follow-up. RESULTS: A total of 131 participants were included in the study: 65 in the intervention group and 66 in the control group. After 3 months, the intervention group showed better outcomes than the control group with regard to pain at rest (adjusted difference -1.07, 95% confidence interval -1.92 to -0.22; effect size 0.47), pain on activity (-1.00, -1.91 to -0.08; 0.45), and function (4.92, 0.14 to 9.72; 0.34). At 12 months, the intervention group continued to show better outcomes than the control group with regard to pain (adjusted difference in pain at rest -1.29, -2.16 to -0.42; effect size 0.56; pain on activity -1.19, -2.22 to -0.16; effect size 0.54), but not function (4.52, -0.73 to 9.76). A higher proportion of patients in the exercise group than in the control group reported recovery (41.9% v 35.0% at 3 months and 62.1% v 50.8% at 12 months), although the differences in self reported recovery between the two groups were not statistically significant. Predefined subgroup analyses revealed that patients recruited by sport physicians (n=30) did not benefit from the intervention, whereas those recruited by general practitioners (n=101) showed significant and clinically relevant differences in pain and function in favour of the intervention group. CONCLUSION: Supervised exercise therapy resulted in less pain and better function at short term and long term follow-up compared with usual care in patients with patellofemoral pain syndrome in general practice. Exercise therapy did not produce a significant difference in the rate of self reported recovery. TRIAL REGISTRATION: ISRCTN83938749.

Unfocused Extracorporeal Shock Wave Therapy as Potential Treatment for Osteoporosis (Article)

2009-11-01T00:00:00Z

Extracorporeal shock wave therapy (ESWT) influences the differentiation of bone marrow stroma cells towards osteoprogenitors and increases the expression of several growth factors. To assess whether unfocused ESWT might serve as a treatment for osteoporosis, we examined the bone architecture dynamics of ESWT-treated and untreated rat tibiae using in vivo micro-computed tomography (CT) scanning. In addition, the effects of ESWT on fracture healing, using a bilateral fibula osteotomy, were examined. Unilateral unfocused ESWT with 2,000 pulses and an energy flux density of 0.16 mJ/mm(2) was applied to the hind leg of ovariectomized and sham-ovariectomized rats. A single treatment with unfocused ESWT resulted in a higher trabecular bone volume fraction (BV/TV) in the proximal tibia of the sham-ovariectomized animals. Three weeks after ESWT, BV/TV was 110% of baseline BV/TV in treated legs versus 101% in untreated contralateral control legs (p = 0.001) and 105% of baseline BV/TV versus 95% at 7 weeks after ESWT (p = 0.0004). In ovariectomized rats, shock wave treatment resulted in a diminished bone loss. At 7 weeks, the BV/TV of the treated legs was 50% of baseline BV/TV, whereas in untreated control legs this was 35% (p = 0.0004). ESWT did not influence acute fracture healing. This study shows that bone microarchitecture can be affected by unfocused shock waves, and indicates that unfocused ESWT might be useful for the treatment of osteopenia and osteoporosis.

Computer assisted surgery for knee ligament reconstruction (Article)

2009-09-18T00:00:00Z

Imaging of activated macrophages in experimental osteoarthritis using folate targeted animal SPECT/CT (Article)

2009-09-09T00:00:00Z

Objective. Evaluation of macrophage activation may provide essential information about aetiology and progression rate of osteoarthritis. Activated macrophages abundantly express the folate-receptor-beta (FR-β), which can be targeted using radioactive labelled folic acid. The purpose of this study was to investigate if macrophage activation can be monitored in small animal OA models using a folate radiotracer and to test if macrophage activation differs in different models of OA and subsequent different OA progression. Methods. Two rat models of OA were used: the monoiodoacetate (MIA) model, which is a fast progressing biochemical induced model and the anterior cruciate ligament transaction (ACLT) model that induces OA at a slower pace. Images were obtained using high resolution small animal SPECT/CT. Specificity of the technique was tested by eradicating macrophages using clodronate laden liposomes and blockade of the FR-β by cold folic acid. Results. The MIA model had a high initial activation with a peak after two weeks which disappeared after eight weeks. The ACLT model showed less activation but was still active 12 weeks after induction. The technique allowed monitoring of the disease process over time, in which late stage disease showed less macrophage activation than early onset stages especially in the fast progressing MIA model for OA. Conclusion. Macrophage activation in experimental OA could clearly be demonstrated and monitored by the folate radiotracer. The high resolution, high sensitivity and high specificity of the used technique allowed clear localisation of macrophage activity in a disease model, which is not known for abundant macrophage involvement.

Management decisions in nontraumatic complaints of arm, neck, and shoulder in general practice (Article)

2009-09-01T00:00:00Z

OBJECTIVE: We wanted to evaluate associations between diagnosis and characteristics of the patient, complaint, and general practitioner (GP), as well as 6 common management decisions, in patients with nontraumatic arm, neck, and shoulder complaints at the time of the first consultation with their physician. METHODS: We undertook an observational cohort study set in 21 Dutch general practices, including 682 patients with nontraumatic complaints of arm, neck, and shoulder. The outcome measure was application (yes/no) of a specific management option: watchful waiting, additional diagnostic tests, prescription of medication, corticosteroid injection, referral for physiotherapy, and referral for medical specialist care. RESULTS: Separate multilevel analyses showed that overall, the diagnostic category, having long duration of complaints, and reporting many functional limitations were most frequently associated with the choice of a management option. For watchful waiting, only complaint variables played a role (long duration of complaints, high complaint severity, many functional limitations, recurrent complaint). All these variables were negatively associated with watchful waiting. When opting for 1 of the 5 other management options, several physician characteristics played a role as well. Less clinical experience was associated with additional diagnostic tests and referral to a medical specialist. GPs working in a solo practice more frequently referred to a medical specialist. GPs working in a rural area more frequently referred for physiotherapy. Female GPs prescribed medication less frequently. Physicians with special interest in musculoskeletal complaints gave corticosteroid injections more frequently. CONCLUSIONS: Diagnostic category, long duration of complaints, and high functional limitations were key variables in management decisions with these complaints. In addition, several physician characteristics played a role as well.

Total knee arthroplasty after high tibial osteotomy. A systematic review (Article)

2009-08-24T00:00:00Z

Background: Previous osteotomy may compromise subsequent knee replacement, but no guidelines considering knee arthroplasty after prior osteotomy have been developed. We describe a systematic review of non-randomized studies to analyze the effect of high tibial osteotomy on total knee arthroplasty. Methods: A computerized search for relevant studies published up to September 2007 was performed in Medline and Embase using a search strategy that is highly sensitive to find nonrandomized studies. Included were observational studies in which patients had total knee arthroplasty performed after prior high tibial osteotomy. Studies that fulfilled these criteria, were assessed for methodologic quality by two independent reviewers using the critical appraisal of observational studies developed by Deeks and the MINORS instrument. The study characteristics and data on the intervention, follow-up, and outcome measures, were extracted using a pre-tested standardized form. Primary outcomes were: knee range of motion, knee clinical score, and revision surgery. The grade of evidence was determined using the guidelines of the GRADE working group. Results: Of the 458 articles identified using our search strategy, 17 met the inclusion criteria. Fifteen studies were cohort study with a concurrent control group, one was a historical cohort study and one a case-control study. Nine studies scored 50% or more on both methodological quality assessments. Pooling of the results was not possible due to the heterogeneity of the studies, and our analysis could not raise the overall low quality of evidence. No significant differences between primary total knee arthroplasty and total knee arthroplasty after osteotomy were found for knee range of motion in four out of six studies, knee clinical scores in eight out of nine studies, and revision surgery in eight out of eight studies after a median follow-up of 5 years. Conclusion: Our analysis suggests that osteotomy does not compromise subsequent knee replacement. However, the low quality of evidence precludes solid clinical conclusions.

Tendon degeneration is not mediated by regulation of Toll-like receptors 2 and 4 in human tenocytes (Article)

2009-08-01T00:00:00Z

We hypothesized that expression of Toll-like receptors (TLRs) 2 and 4 by tenocytes is involved in the catabolic processes of tendon degeneration. We investigated TLR2 and TLR4 expression by tenocytes in healthy and tendinotic Achilles tendons. We also investigated whether TLR2 and TLR4 could be upregulated in tendon explants using proinflammatory cytokines interleukin (IL)-1beta and tumor necrosis factor alphpa (TNFalpha). Peroperatively harvested healthy (n = 5) and tendinotic (n = 13) Achilles tendon samples were examined by real-time RT-PCR and immunohistochemical staining for TLR2 and TLR4. In addition, the catabolic process in tendinopathy was analyzed by real-time RT-PCR for matrix metalloproteinases MMP1, MMP3, MMP9, and MMP13. Furthermore, healthy tendon explants were cultured in the presence of 20 ng/ml IL-1beta (n = 10) or 10 ng/mL TNFalpha (n = 8) for 4, 24, 48, and 72 h before analysis of TLR and MMP expression levels. Although mRNA levels for both TLR2 and TLR4 were detected in healthy and tendinotic Achilles tendons, we could not confirm expression of these receptors by immunohistochemical staining in either healthy or tendinotic tendon samples. Both receptors did not show significant transcriptional regulation in tendinopathy, although MMP3 was downregulated and MMP9 was upregulated in tendinopathy. In tendon explant cultures TLR2 mRNA was upregulated by TNFalpha (p < 0.05) and IL-1beta (not significant). TLR4 gene expression was not altered by addition of IL-1beta or TNFalpha. Tendon tissue can be stimulated to increase TLR2 gene expression by addition of catabolic factors TNFalpha or IL-1beta. However, the catabolic processes in Achilles tendinopathy cannot be attributed to regulation of TLR2 and TLR4 by tenocytes.

Vitamin D Status, Bone Mineral Density, and the Development of Radiographic Osteoarthritis of the Knee (Article)

2009-08-01T00:00:00Z

OBJECTIVE: To study the association between baseline vitamin D status, bone mineral density (BMD), and the development of radiographic osteoarthritis (ROA) of the knee in a large population-based cohort of men and women. METHODS: A sample of 1248 subjects (728 women and 520 men) was drawn from the Rotterdam Study, a prospective population-based cohort study of the elderly. At baseline, vitamin D dietary intake was determined, and BMD and 25-hydroxy vitamin D (25(OH)D) serum levels were measured. After a mean follow-up time of 6.5 years incidence and progression of knee ROA of was assessed. RESULTS: The mean vitamin D intake in our study population was 64 IU/d and the mean 25(OH)D level 66 nmol/L. Vitamin D levels were associated with baseline BMD, particularly in subjects with baseline knee ROA. Progressive ROA occurred in 5.1% of the participants in the highest tertile of vitamin D intake against 12.6% in the lowest tertile, resulting in an adjusted odds ratio of 7.7 (95% CI: 1.3-43.5). Both intake and levels of 25(OH)D were not significantly related to incident ROA. However, we found a significant interaction between vitamin D intake and BMD in the association with incident knee ROA (P = 0.03): in subjects with low lumbar spine BMD at baseline we observe an increasing incidence of knee ROA with decreasing vitamin D intake and serum levels. CONCLUSIONS: Low dietary vitamin D intake increases the risk of progression of knee ROA. Particularly in subjects with low baseline BMD, vitamin D status seems to influence the incidence and progression of knee ROA. Thus, improving the vitamin D status in the elderly could protect against the development and worsening of knee OA, especially in those with low BMD.

Ultrasonographic tissue characterisation of human Achilles tendons: quantification of tendon structure through a novel non-invasive approach (Article)

2009-08-01T00:00:00Z

OBJECTIVE: To asses if three-dimensional imaging of the Achilles tendon by Ultrasonographic Tissue Characterisation (UTC) can differentiate between symptomatic and asymptomatic tendons. DESIGN: Case-control study. SETTING: Sports medical department of The Hague medical centre. PATIENTS: Twenty-six tendons from patients with chronic midportion Achilles tendinopathy were included. The "matched" control group consisted of 26 asymptomatic tendons. INTERVENTIONS: Symptomatic and asymptomatic tendons were scanned using the UTC-procedure. One researcher performed the ultrasonographic data-collection. These blinded data were randomised and outcome measures were determined by two independent observers. Main outcome measurements: The raw ultrasonographic images were analysed with a custom-designed algorithm that quantifies the three-dimensional stability of echopatterns, qua intensity and distribution over contiguous transverse images. This three-dimensional stability was related to tendon structure in previous studies. UTC categorizes four different echo-types that represent: I) highly stable; II) medium stable; III) highly variable and IV) constantly low intensity and variable distribution. The percentages of echo-types were calculated and the maximum tendon-thickness was measured. Finally, the inter-observer reliability of UTC was determined. RESULTS: Symptomatic tendons showed less pixels in echo-types I and II than asymptomatic tendons (51.5% versus 76.6%, p<0.001), thus less three-dimensional stability of the echopattern. The mean maximum tendon thickness was 9.2 mm in the symptomatic group and 6.8 mm in the asymptomatic group (p<0.001). The Intra-class Correlation Coefficient (ICC) for the inter-observer reliability of determining the echo-types I+II was 0.95. The ICC for tendon thickness was 0.84. CONCLUSION: UTC can quantitatively evaluate tendon structure and thereby discriminate symptomatic and asymptomatic tendons. As such UTC might be useful to monitor treatment protocols.

In vitro model to study chondrogenic differentiation in tendinopathy (Article)

2009-06-01T00:00:00Z

BACKGROUND: Treatment of midportion Achilles tendinopathy is hampered by limited knowledge of the pathophysiology. HYPOTHESIS: Chondrogenic differentiation of tendon cells might take place in midportion Achilles tendinopathy and could be used as a target for drug treatment. An in vitro model for chondrogenic differentiation would be useful to evaluate existing and future treatment opportunities. Study: A controlled laboratory study. METHODS: Perioperatively harvested tissue from human midportion Achilles tendinotic lesions and healthy Achilles tendons was analyzed by microscopy and real-time reverse transcription polymerase chain reaction. In vitro chondrogenic differentiation of tendon explants was induced using transforming-growth-factor beta. This model was modulated by removing the chondrogenic stimulus or adding triamcinolone or platelet-rich plasma. RESULTS: Midportion Achilles tendinotic lesions had increased glycosaminoglycan staining and more rounded cell nuclei. Chondrogenic markers (sex-determining region Y)-box9, aggrecan, collagen 2, and RUNT-related transcription factor 2 were upregulated, but collagen 10 was not. Nondegenerative tendon explants cultured on chondrogenic medium had higher expression of aggrecan, collagen 2, and collagen 10 but not (sex-determining region Y)-box9 and RUNT-related transcription factor 2. Removing the chondrogenic stimulus decreased expression of aggrecan, collagen 2, and collagen 10. Both triamcinolone and platelet-rich plasma influenced the chondrogenic gene expression pattern in the in vitro model. CONCLUSION: Chondrogenic differentiation is present in midportion Achilles tendinopathy. An in vitro model to study this chondrogenic differentiation was developed. CLINICAL RELEVANCE: This model can be used to investigate chondrogenic differentiation as a possible target for drug treatment, contributing to the development of more successful mechanism-based treatment opportunities.

Chondrogenic priming of human bone marrow stromal cells: A better route to bone repair? (Article)

2009-06-01T00:00:00Z

The use of bioengineered cell constructs for the treatment of bone defects has received much attention of late. Often, bone marrow stromal cells (BMSCs) are used that are in vitro stimulated toward the osteogenic lineage, aiming at intramembranous bone formation. The success of this approach has been disappointing. A major concern with these constructs is core degradation and necrosis caused by lack of vascularization. We hypothesized that stimulation of cells toward the endochondral ossification process would be more successful. In this study, we tested how in vitro priming of human BMSCs (hBMSCs) along osteogenic and chondrogenic lineages influences survival and osteogenesis in vivo. Scaffolds that were pre-cultured on chondrogenic culture medium showed collagen type II and collagen type X production. Moreover, vessel ingrowth was observed. Priming along the osteogenic lineage led to a mineralized matrix of poor quality, with few surviving cells and no vascularization. We further characterized this process in vitro using pellet cultures. In vitro, pellets cultured in chondrogenic medium showed progressive production of collagen type II and collagen type X. In the culture medium of these chondrogenic cultured pellets, vascular endothelial growth factor (VEGF) release was observed at days 14, 21, and 35. When pellets were switched to culture medium containing β-glycerophosphate, independent of the presence or absence of transforming growth factor beta (TGF-β), mineralization was observed with a concomitant reduction in VEGF and matrix metalloproteinase (MMP) release. By showing that VEGF and MMPs are produced in chondrogenically differentiated hBMSCs in vitro, we demonstrated that these cells produce factors that are known to be important for the induction of vascularization of the matrix. Inducing mineralization in this endochondral process does, however, severely diminish these capacities. Taken together, these data suggest that optimizing chondrogenic priming of hBMSCs may further improve vessel invasion in bioengineered constructs, thus leading to an alternative and superior approach to bone repair.

Ten year follow-up study comparing conservative versus operative treatment of anterior cruciate ligament ruptures. A matched-pair analysis of high level athletes (Article)

2009-05-01T00:00:00Z

OBJECTIVE: To compare long term outcome of highly active patients with anterior cruciate ligament ruptures treated operatively versus non-operatively. DESIGN: We reviewed high level athletes with an anterior cruciate ligament rupture on either MRI or arthroscopic evaluation more than 10 years previously, who were treated conservatively. They were pair-matched with patients who had had an anterior cruciate ligament reconstruction with bone-patella-tendon-bone, with respect to age, gender and Tegner activity score before injury. PARTICIPANTS: In total 50 patients were pair-matched. RESULTS: We found no statistical difference between the patients treated conservatively or operatively with respect to osteoarthritis or meniscal lesions of the knee, as well as activity level, objective and subjective functional outcome. The patients who were treated operatively had a significantly better stability of the knee at examination. CONCLUSION: We conclude that the instability repair using a bone-patella-tendon-bone anterior cruciate ligament reconstruction is a good knee stabilising operation. Both treatment options however show similar patient outcome at 10 year follow up.

Varus inclination of the proximal tibia or the distal femur does not influence high tibial osteotomy outcome (Article)

2009-04-01T00:00:00Z

We have analysed retrospectively the influence of different sources of knee deformity on failure of closing wedge high tibial valgus osteotomy (HTO). Preoperative frontal plane varus deformities of the lower extremity, distal femur and proximal tibia, and medial convergence of the knee joint line were assessed on a standard whole leg radiograph in 76 patients. Using the logistic regression model, the probability of survival for HTO was 77% (SD 4%) at 10-years follow-up. Varus deformity of the lower extremity (< 175 degrees ), and medial convergence of the knee joint line (> 3 degrees ) were identified as preoperative risk factors for conversion to arthroplasty (P = 0.03 and P = 0.006). We found no evidence that varus inclination of the proximal tibia or distal femur influences long-term survival of HTO.

Effect of glucosamine sulphate on joint space narrowing, pain and function in patients with hip osteoarthritis; subgroup analyses of a randomized controlled trial (Article)

2009-04-01T00:00:00Z

Objective: Recently we reported that glucosamine sulphate (GS) did not have an effect on the symptoms and progression of primary care patients with hip osteoarthritis (OA). The aim of this present study was to investigate whether there are subgroups of patients with hip OA for whom GS might be an effective therapy. Method: We randomized 222 patients with hip OA that met one of the American College of Rheumatology criteria to either 1500 mg of oral GS or placebo once daily for 2 years. Subgroup analyses were predefined for radiographic severity (Kellgren & Lawrence (KL) = 1 vs ≥2) and for type of OA (localised vs generalised). Additional exploratory subgroup analyses focused on groups based on pain level, pain medication use, baseline joint space width (JSW), and concomitant knee OA at baseline. Primary outcome measures were Western Ontario MacMaster Universities (WOMAC) pain and function scores over 24 months, and joint space narrowing (JSN) after 24 months. Results: In the predefined subgroups based on radiographic severity and type of OA, the outcomes WOMAC pain, function and JSN were similar for the GS and placebo group. Conclusion: GS was not significantly better than placebo in reducing symptoms and progression of hip OA in subgroups of patients.

Inhibition of glycosaminoglycan incorporation influences collagen network formation during cartilage matrix production (Article)

2009-02-06T00:00:00Z

To understand cartilage degenerative diseases and improve repair procedures, we investigate the influence of glycosaminoglycans (GAGs) on cartilage matrix biochemistry and functionality. Bovine articular chondrocytes were cultured in alginate beads with(out) para-nitrophenyl-beta-d-xyloside (PNPX) to inhibit GAG incorporation into newly formed proteoglycans. As expected, GAG deposition in alginate beads decreased with increasing PNPX concentration. Next to GAGs, collagen deposition and cross-linking also decreased. In the presence of PNPX, GAGs and collagen were deposited further away from the chondrocyte than in the control and increased amounts were found in the culture medium. These changes resulted in decreased functional properties of the construct. We conclude that in our culture system, intact proteoglycans play a role in deposition of collagen and thus the formation of a functional matrix. The effect of less proteoglycans on the collagen network could explain why cartilage repair is ineffective in osteoarthritis and help us with development of new therapies.

Failure load of patellar tendon grafts at the femoral side: 10- versus 20-mm-bone blocks (Article)

2009-02-01T00:00:00Z

The aim of the study was to investigate whether use of short bone blocks is safe in anterior cruciate ligament (ACL) reconstruction. Our hypothesis was that the smaller 10-mm-length bone blocks will fail at lower loads than 20-mm-bone blocks. Ten paired human cadaver knees were randomly assigned to the 10- or 20-mm group (group 1 and 2) and underwent bone-patellar tendon-bone femoral fixation with interference screw. Tensile tests were performed using a tensile testing machine (Instron). Stiffness, failure load and failure mode were recorded. Median stiffness was 72 N/mm (16-103) for 10-mm-bone blocks and 91 N/mm (40-130) for 20-mm-bone blocks. Median failure loads were 402 N (87-546) for 10-mm-long bone block and 456 N (163-636) for 20-mm-bone blocks. There was no statistically significant difference between groups (P = 0.35). All bone-patellar tendon-bone grafts were pulled out of the femoral tunnel with interference screw, due to slippage. We concluded that a 10-mm-long bone block was not significantly weaker than a 20-mm-long bone block. Failure loads of a 10-mm-bone block exceeded loading values at passive and active extension of the knee under normal conditions. Ten millimetre bone blocks offered sufficient fixation strength in ACL reconstruction.

Costs and effectiveness of a brief MRI examination of patients with acute knee injury (Article)

2009-02-01T00:00:00Z

The aim of this study was to assess the costs and effectiveness of selective short magnetic resonance imaging (MRI) in patients with acute knee injury. A model was developed to evaluate the selective use of MRI in patients with acute knee injury and no fracture on radiography based on the results of a trial in which 208 patients were randomized between radiography only and radiography plus MRI. We analyzed medical (diagnostic and therapeutic) costs, quality of life, duration of diagnostic workup, number of additional diagnostic examinations, time absent from work, and time to convalescence during a 6-month follow-up period. Quality of life was lowest (EuroQol at 6 weeks 0.61 (95% CI 0.54–0.67)); duration of diagnostic workup, absence from work, and time to convalescence were longest; and the number of diagnostic examinations was largest with radiography only. These outcomes were more favorable for both MRI strategies (EuroQol at 6 weeks 0.72 (95% CI 0.67–0.77) for both). Mean total costs were 2,593 euros (95% CI 1,815–3,372) with radiography only, 2,116 euros (95% CI 1,488–2,743) with radiography plus MRI, and 1,973 euros (95% CI 1,401–2,543) with selective MRI. The results suggest that selective use of a short MRI examination saves costs and potentially increases effectiveness in patients with acute knee injury without a fracture on radiography.

Proteoglycan production is required in initial stages of new cartilage matrix formation but inhibits integrative cartilage repair (Article)

2009-02-01T00:00:00Z

The optimal stimulus to repair or regenerate cartilage is not known. We therefore modulated collagen deposition, collagen crosslinking and GAG deposition simultaneously during cartilage matrix production and integrative repair, creating more insight into their role in cartilage repair processes. Insulin-like growth factor 1 (IGF-1; increases proteoglycan and collagen synthesis), beta-aminopropionitrile (BAPN; a reversible inhibitor of collagen crosslinking) and para-nitrophenyl-beta-D-xyloside (PNPX; interferes with proteoglycan production) were used. Bovine articular chondrocytes were cultured in alginate beads for 3 weeks with or without IGF-1, BAPN or PNPX alone and in all possible combinations, followed by 3 weeks in control medium. DNA content, GAG and collagen deposition and collagen crosslinks were determined. Cartilage constructs were cultured under the same conditions and histologically analysed for integration of two opposing cartilage matrices. In alginate cultures, inhibition of collagen crosslinking with BAPN, in combination with promotion of matrix synthesis using IGF1, was most beneficial for matrix deposition. Addition of PNPX was always detrimental for matrix deposition. For integration of opposing cartilage constructs, the combination of BAPN, IGF1 and temporary prevention of proteoglycan formation with PNPX was most beneficial. When a new matrix is produced, proteoglycans are important to retain collagen in the matrix. When two already formed cartilage matrices have to integrate, a temporary absence of proteoglycans and temporary inhibition of collagen crosslinking might be more beneficial in combination with stimulation of collagen production, e.g. by IGF1. Therefore, the choice of soluble factors to promote cartilage regeneration depends on the type of therapy that will be used.

Is the disability of arm, shoulder, and hand questionnaire (DASH) also valid and responsive in patients with neck complaints (Article)

2009-02-01T00:00:00Z

STUDY DESIGN: Prospective cohort study. OBJECTIVE: To evaluate whether the DASH is not only a valid and responsive instrument to measure patients with shoulder, arm, and hand complaints, but also to evaluate patients with neck complaints. SUMMARY OF BACKGROUND DATA: The DASH has shown to be a valid and responsive questionnaire to evaluate disability in patients with shoulder, arm, and hand complaints. However, patients with shoulder, arm, or hand complaints frequently report neck complaints as well. Therefore, a valid and responsive questionnaire designed for the whole upper extremity, including the neck, would be very useful and practical in upper-extremity research. METHODS: Six hundred seventy-nine patients visiting their general practitioner with a new episode of nontraumatic complaints of the neck and upper extremity were evaluated by use of questionnaires at baseline and at 6-months follow-up. Six (sub)groups were formulated according to the location of complaints, including a subgroup with complaints in the shoulder-arm-hand region only and a group with complaints of the neck only. Disability (DASH), general health [SF-12 (physical and mental component)], severity, and persistence of complaints were assessed. Construct validity, floor and ceiling effects, and responsiveness were studied. RESULTS.: Correlations between the DASH and the other measures within the 6 (sub)groups at baseline (construct validity), for the change scores at 6-months follow-up (responsiveness), and the responsiveness ratios were classified as acceptable. No floor and ceiling effects were found. CONCLUSION: The DASH performed well with regard to the a priori hypotheses. This study has shown acceptable validity and responsiveness of the DASH for use in patients with nontraumatic neck complaints in addition to shoulder, arm, and hand complaints. We would caution against using the DASH in patients with neck complaints only, since fewer of the hypotheses could be confirmed in this subgroup.

Validation of the Dutch version of the Hip disability and Osteoarthritis Outcome Score (Letter To Editor)

2009-01-01T00:00:00Z

Calcineurin inhibitors promote chondrogenic marker expression of dedifferentiated human adult chondrocytes via stimulation of TGFss1 production (Article)

2009-01-01T00:00:00Z

In-vitro chondrocyte expansion is required for several cell-based approaches for the repair of chondral lesions. During expansion, loss of chondrogenic phenotype takes place (dedifferentiation). The objective of this study was to investigate calcineurin as a potential target to improve chondrocyte phenotype for cartilage repair purposes. Calcineurin activity in human articular chondrocytes was significantly increased during dedifferentiation and decreased during redifferentiation in vitro. Inhibition of calcineurin activity by FK506 increased the expression of chondrogenic markers collagen type 2, aggrecan and SOX9 in culture expanded cells. Addition of FK506 increased endogenous Transforming Growth Factor (TGF) beta1 expression on both mRNA and protein level. The effect of FK506 on chondrogenic markers was abolished by addition of anti-TGFbeta1 antibody, indicating that the endogenous TGFbeta1 was necessary to increase chondrogenic marker expression. We also showed that chondrocyte redifferentiation by TGFbeta requires calcium influx and does not depend on changes in calcineurin activity. In conclusion, inhibition of calcineurin activity by FK506 increases the expression of chondrogenic markers via endogenous TGFbeta1 production in human articular chondrocytes. Calcineurin inhibitors might be an alternative for the application of (recombinant) TGFbeta, to promote chondrocyte phenotype for cell-based cartilage repair procedures.

Calcineurin inhibitors promote chondrogenic marker expression of dedifferentiated human adult chondrocytes via stimulation of TGFss1 production (Article)

2009-01-01T00:00:00Z

Chondrogenic Priming of Human Bone Marrow Stromal Cells: A Better Route to Bone Repair? (Article)

2008-12-01T00:00:00Z

The use of bioengineered cell constructs for the treatment of bone defects has received much attention of late. Often, bone marrow stromal cells (BMSCs) are used that are in vitro-stimulated toward the osteogenic lineage, aiming at intramembranous bone formation. The success of this approach has been disappointing. A major concern with these constructs is core degradation and necrosis caused by lack of vascularization. We hypothesized that stimulation of cells toward the endochondral ossification process would be more successful. In this study, we tested how in vitro priming of human BMSCs (hBMSCs) along osteogenic and chondrogenic lineages influences survival and osteogenesis in vivo. Scaffolds that were pre-cultured on chondrogenic culture medium showed collagen type II and collagen type X production. Moreover, vessel ingrowth was observed. Priming along the osteogenic lineage led to a mineralized matrix of poor quality, with few surviving cells and no vascularization. We further characterized this process in vitro using pellet cultures. In vitro, pellets cultured in chondrogenic medium showed progressive production of collagen type II and collagen type X. In the culture medium of these chondrogenic cultured pellets, vascular endothelial growth factor (VEGF) release was observed at days 14, 21, and 35. When pellets were switched to culture medium containing beta-glycerophosphate, independent of the presence or absence of transforming growth factor beta (TGF-beta), mineralization was observed with a concomitant reduction in VEGF and matrix metalloproteinase (MMP) release. By showing that VEGF and MMPs are produced in chondrogenically differentiated hBMSCs in vitro, we demonstrated that these cells produce factors that are known to be important for the induction of vascularization of the matrix. Inducing mineralization in this endochondral process does, however, severely diminish these capacities. Taken together, these data suggest that optimizing chondrogenic priming of hBMSCs may further improve vessel invasion in bioengineered constructs, thus leading to an alternative and superior approach to bone repair.

Assessing Medial Collateral Ligament Knee Lesions in General Practice (Article)

2008-11-01T00:00:00Z

Purpose: To assess the diagnostic value of history-taking and physical examination of medial collateral ligament lesions after a knee injury presenting in general practice. Methods: Patients aged 18 to 65 years with a traumatic knee injury who consulted their general practitioner within 5 weeks after trauma filled out a questionnaire, underwent a standardized physical examination, and underwent a magnetic resonance imaging scan. Logistic regression analysis was used to test possible associations between determinants from history-taking/physical examination and medial collateral ligament lesions. The diagnostic value of history-taking and physical examination was determined for those variables indicating an association (P <.15) with medial collateral ligament lesions and was assessed by sensitivity, specificity, predictive value, and likelihood ratios. Results: Of the 134 patients included in this study, 35 had a medial collateral ligament lesion seen on magnetic resonance imaging scan. From history-taking, the determinants "trauma by external force to leg" and "rotational trauma" showed an association with medial collateral ligament lesion after multivariate analysis (P <.15). From physical examination, "pain valgus stress 30°" and "laxity valgus stress 30°" showed an association (P <.15). Isolated determinants from history-taking and physical examination showed some diagnostic value; the likelihood ratio positive was 2.0 for "trauma by external force to leg" and 2.3 for "pain valgus stress 30°." Adding "pain valgus stress 30°" and "laxity valgus stress 30°" from physical examination to history-taking improved the diagnostic value to a likelihood ratio positive of 6.4. Conclusion: Medial collateral ligament lesions are frequently seen in patients with traumatic knee injury. History-taking has a diagnostic value, while adding physical examination increases the diagnostic value. © 2008 Elsevier Inc. All rights reserved.

Surgeon equipoise as an inclusion criterion for the evaluation of nonoperative versus operative treatment of thoracolumbar spinal injuries (Article)

2008-11-01T00:00:00Z

BACKGROUND CONTEXT: Prospective studies have failed to demonstrate the superiority of either operative or nonoperative treatment of thoracolumbar fractures. Similar to other surgical fields, research has been limited by the variability in surgical interventions, difficult recruitment, infrequent pathology, and the urgency of interventions. PURPOSE: To outline factors precluding randomized controlled trials in spinal fractures research, and describe a novel methodology that seeks to improve on the design of observational studies. STUDY DESIGN/SETTING: A preliminary report describing an observational study design with clinical equipoise as an inclusion criterion. The proposed methodology is a cohort study with head-to-head comparison of operative and nonoperative treatment regimens in an expertise-based trial fashion. Patients are selected retrospectively by an expert panel and clinical outcomes are assessed to compare competing treatment regimens. Surgeon equipoise served as an inclusion criterion. PATIENT SAMPLE: Patients with closed or open thoracolumbar spinal fracture with or without neurological impairment, presenting to one of two different trauma centers between 1991 and 2005 (N = 760). OUTCOME MEASURES: Homogeneity of baseline clinical and demographic data and distribution of prognostic risk factors between the operative and the nonoperative cohort. METHODS: Patients treated for spine fractures at two University hospitals practicing opposing methods of fracture intervention were identified by medical diagnosis code searches (n = 760). A panel of spine treatment experts, blinded to the treatment received clinically has assessed each case retrospectively. Patients were included in the study when there was disagreement on the preferred treatment, that is, operative or nonoperative treatment of the injury. Baseline and initial data of a study evaluating nonoperative versus operative spinal fracture treatment are presented. RESULTS: One hundred and ninety patients were included in the study accounting for a panel discordance rate of 29%. The distribution of baseline characteristics and demographics of the study populations were equal across the parallel cohorts enrolled in the study, that is, no differences in prognostic factors were observed. CONCLUSIONS: The use of clinical equipoise as an inclusion criterion in comparative studies may be used to avoid selection bias. Using multivariate analysis of retrospectively assembled parallel cohorts, a valid comparison of operative and nonoperative spine fracture treatment strategies and their outcomes is possible.

Glucosamine increases hyaluronic acid production in human osteoarthritic synovium explants (Article)

2008-10-08T00:00:00Z

Background. Glucosamine (GlcN) used by patients with osteoarthritis was demonstrated to reduce pain, but the working mechanism is still not clear. Viscosupplementation with hyaluronic acid (HA) is also described to reduce pain in osteoarthritis. The synthesis of HA requires GlcN as one of its main building blocks. We therefore hypothesized that addition of GlcN might increase HA production by synovium tissue. Methods. Human osteoarthritic synovium explants were obtained at total knee surgery and pre-cultured for 1 day. The experimental conditions consisted of a 2 days continuation of the culture with addition of N-Acetyl-glucosamine (GlcN-Ac; 5 mM), glucosamine-hydrochloride (GlcN-HCl; 0.5 and 5 mM), glucose (Gluc; 0.5 and 5 mM). Hereafter HA production was measured in culture medium supernatant using an enzyme-linked binding protein assay. Real time RT-PCR was performed for hyaluronic acid synthase (HAS) 1, 2 and 3 on RNA isolated from the explants. Results. 0.5 mM and 5 mM GlcN-HCl significantly increased HA production compared to control (approximately 2 - 4-fold), whereas GlcN-Ac had no significant effect. Addition of 5 mM Gluc also increased HA production (approximately 2-fold), but 0.5 mM Gluc did not. Gene expression of the HA forming enzymes HAS 1, 2 and 3 was not altered by the addition of GlcN or Gluc. Conclusion. Our data suggest that exogenous GlcN can increase HA production by synovium tissue and is more effective at lower concentrations than Gluc. This might indicate that GlcN exerts its potential analgesic properties through stimulation of synovial HA production.

One-year follow-up of a randomised controlled trial on added splinting to eccentric exercises in chronic midportion Achilles tendinopathy (Article)

2008-10-01T00:00:00Z

Incidence of non-traumatic complaints of arm, neck and shoulder in general practice (Article)

2008-10-01T00:00:00Z

Incidence densities in primary care are often based on disease or region-specific code registration (e.g. 'epicondylitis', 'shoulder symptom') according to the International Classification of Primary Care (ICPC). Few estimates are available on arm, neck and shoulder complaints. Unknown, is the proportion missed due to registration with a non-region-specific code (e.g. 'muscle pain'). Therefore, we estimated the incidence in non-traumatic arm, neck and shoulder complaints in the age-group 18-64 years, and determined the contribution of non-specific codes to the total figure. In this prospective registration study, 21 general practitioners (GPs) from 13 Dutch general practices classified and registered patient's symptoms and diagnoses according to ICPC at each consultation during 12 consecutive months. Incidence densities were calculated. The incidence density was 97.4/1000 person-years (95% CI: 91.2-103.7). This results in 147 (95% CI: 138-157) incident cases/year for an average-sized GP-practice (2350 patients). Main contributors were: shoulder (L92, L08) and neck complaints (L01, L83). Of all incident consultations, 23% were registered with non-region-specific codes, mainly 'other musculoskeletal disease' (L99). Non-traumatic complaints of arm, neck and shoulder are frequently consulted for in Dutch primary care. When estimating morbidity in primary care, based on diagnostic codes, one should be aware of possible underestimation of morbidity and corresponding workload, when excluding codes not specific for that region or disease.

Het effect van glucosaminesulfaat op de progressie van heupartrose (Article)

2008-10-01T00:00:00Z

Introduction: Het effect van glucosaminesulfaat bij de behandeling van artrose is omstreden. Een systematische review uit 2005 met twintig onderzoeken kon geen definitieve conclusie trekken.1 Van de vijftien onderzoeken die glucosamine vergeleken met een placebo was het algehele effect op pijn gemiddeld weliswaar in het voordeel van glucosamine, maar meer dan de helft van deze onderzoeken vond geen verschil tussen glucosamine en een placebo. Ook recente onderzoeken gaven geen duidelijkheid.2-4 Uit eerdere onderzoeken kon men concluderen dat patiënten met milde radiologische artrose meer baat zouden hebben bij glucosamine dan patiënten met een ernstiger ziektebeeld.5,6 We vonden slechts twee onderzoeken over het effect van glucosaminesulfaat op radiologische progressie,10,11 waarbij bovendien discussie ontstond over het radiologisch protocol.12-14 Daarom is verder onderzoek nodig. Tot nu toe is vooral het effect van glucosamine op knieartrose onderzocht, slechts drie onderzoeken includeerden ook patiënten met andere aangedane gewrichten.7-9 Wij vonden geen onderzoeken bij patiënten met heupartrose. En hoewel knieartrose meer voorkomt, komt heupartrose voldoende voor om het effect van glucosamine bij deze groep te testen. Al met al genoeg aanleiding voor een tweejarig, geblindeerd, gerandomiseerd, placebo-gecontroleerd onderzoek naar het effect van glucosaminesulfaat op de symptomatische en radiologische progressie van eerstelijns patiënten met heupartrose.

Imaging of experimental osteoarthritis in small animal models (Article)

2008-09-30T00:00:00Z

Normally, tissue alterations in small animal models for osteoarthritis (OA) are assessed by time-consuming and destructive histology or biochemical assays. Some high resolution imaging modalities are used for longitudinal monitoring of the OA disease process in vivo. μCT is one of these imaging modalities, which is known for superb high-resolution imaging of bone architecture alterations. A major drawback of μCT is that it has low soft-tissue contrast, which makes direct imaging of cartilage impossible. The use of μCT in combination with negatively charged radiopaque contrast agents enables imaging of cartilage degeneration. We demonstrate the possibility of μCT to image cartilage degeneration as a consequence of experimental OA, by the use contrast enhanced μCT in vivo in a rat model for OA. Furthermore, for the assessment of alterations in molecular processes involved in OA we used the recently developed technique of multi pinhole SPECT. This enables us to assess molecular processes involved in experimental OA in a rat at sub-millimeter level. Here we show quantification of subchondral bone turnover in an OA rat knee. These new techniques demonstrate the possibilities of quantitative experimental OA assessment in small animal models such as mice and rats and might enable substitution of the conventional destructive methods.

Management in non-traumatic arm, neck and shoulder complaints: differences between diagnostic groups (Article)

2008-09-01T00:00:00Z

Arm, neck and/or shoulder complaints are common in western societies. In the Netherlands, general practice guidelines are issued on shoulder pain and epicondylitis only. Little is known about actual management of the total range of diagnoses. The objectives of the study are: to determine management in patients consulting the GP with a new episode of non-traumatic arm neck and shoulder complaints up to 6 months after the first consultation. To evaluate differences in management between patients with specific diagnoses versus non-specific diagnoses and between specific diagnostic groups. In a prospective cohort study in general practice. We recruited 682 eligible patients. Data on diagnosis, management, patient- and complaint-characteristics were collected. Co-occurrence of treatment options was presented in scaled rectangles. After 6 months, additional diagnostic tests had been performed in 18% of the patients, mainly radiographic examination (14%). Further, 49% had been referred for physiotherapy and 12% to the medical specialist. Patients with specific diagnoses were more frequently referred for specialist treatment, and patients with non-specific diagnoses for physiotherapy. Corticosteroid injections (17%) were mainly applied specific diagnoses (e.g. impingement syndrome, frozen shoulder, carpal tunnel and M. Quervain). Frequencies of prescribed medication (51%) did not differ between specific and non-specific diagnoses. In 19% of the patients no referral, prescribed analgesics or injection was applied. Braces (4%) were mainly prescribed in epicondylitis. Overall, management most frequently consisted of prescribed analgesics and referral for physiotherapy. Specific and non-specific diagnostic subgroups differed in the frequency corticosteroid injections were applied, and referrals to physiotherapy and to a medical specialist.

In vivo imaging of cartilage degeneration using microCT-arthrography (Article)

2008-09-01T00:00:00Z

OBJECTIVE: In vivo imaging of cartilage degeneration in small animal models is nowadays practically impossible. In the present study, we investigated the use of micro-computed tomography (microCT) in combination with a negatively charged ionic iodine dimer (ioxaglate) for in vivo assessment of cartilage degeneration in a small animal model. METHODS: Cartilage degeneration was induced in the right knee of rats by injection of mono-iodoacetate (MIA). We imaged the rat knees with ioxaglate enhanced microCT-arthrography at 4, 16 and 44 days after MIA injection. Subsequently, microCT-arthrographic findings were evaluated and compared with quantitative histology of the patellar cartilage. RESULTS: In vivo microCT-arthrography clearly detected cartilage degeneration in the rat knee-joints, in which the ioxaglate diffused into the degenerated cartilage layer. Higher microCT-attenuation values and smaller total volumes of the cartilage layer were detected at longer time periods after MIA injection, which is quantitatively confirmed by histology. CONCLUSION: In vivo microCT-arthrography is a valuable tool for detection of minor cartilage alterations and distinguishes different stages of cartilage degeneration in a small animal model. Since microCT, at the same time, also visualizes osteophyte formation and changes in the underlying subchondral bone structures, the technique will be very useful for longitudinal overall assessment of the development of (osteo)arthritis and to study interventions in small animal models.

Small increase of actual physical activity 6 months after total hip or knee arthroplasty (Article)

2008-09-01T00:00:00Z

Limitation in daily physical activity is one of the reasons for total hip arthroplasty (THA) or total knee arthroplasty (TKA). However, studies of the effects of THA or TKA generally do not determine actual daily activity as part of physical functioning. We determined the effect of THA or TKA on patients' actual physical activity and body function (pain, stiffness), capacity to perform tasks, and self-reported physical functioning. We also assessed whether there are differences in the effect of the surgery between patients undergoing THA or TKA and whether the improvements vary between these different outcome measures. We recruited patients with long-standing end-stage osteoarthritis of the hip or knee awaiting THA or TKA. Measurements were performed before surgery and 3 and 6 months after surgery. Actual physical activity improved by 0.7%. Patients' body function, capacity, and self-reported physical functioning also improved. The effects of the surgery on these aspects of physical functioning were similar for THA and TKA. The effect on actual physical activity (8%) was smaller than on body function (80%-167%), capacity (19%-36%), and self-reported physical functioning (87%-112%). Therefore, in contrast to the large effect on pain and stiffness, patients' capacity, and their self-reported physical functioning, the improvement in actual physical activity of our patients was less than expected 6 months after surgery. Level of Evidence: Level I, prospective study. See the Guidelines for Authors for a complete description of levels of evidence.

Anterior cruciate ligament injury in professional dancers (Article)

2008-08-01T00:00:00Z

BACKGROUND: Anterior cruciate ligament injury (ACL) is a common sport injury; however, there are no data concerning dance and ACL injury. We report the incidence, injury mechanism, and clinical follow-up of ACL injury in professional dancers. PATIENTS AND METHODS: In a retrospective cohort study involving the three major dance companies in the Netherlands, by interviewing all 253 dancers who had had a full-time contract during 1991-2002, dancers with symptomatic ACL injury or past ACL reconstruction were identified and examined. RESULTS: 6 dancers (2 of whom were women) had had a symptomatic ACL rupture and reconstruction. Interestingly, all had been on the left side and had had a similar trauma mechanism: while dancing a classical variation they landed, after a jump, on their left leg, in the turned out position with a valgus force on their knee. There was a higher risk of ACL injury in the classical company than in the two contemporary companies. The risk of dancers having a rupture of the left ACL during a 10-year career in this classical company was 7%. INTERPRETATION: ACL injuries are not an infrequently seen type of injury in professional classical dancers, with a very specific mechanism of injury--a landing on the left leg in exorotation. More attention and prophylactic measures should be given to this specific injury mechanism.

Opposite cortical fracture in high tibial osteotomy: lateral closing compared to the medial opening-wedge technique (Article)

2008-08-01T00:00:00Z

BACKGROUND AND PURPOSE: The aim with high tibial valgus osteotomy (HTO) is to correct the mechanical axis in medial compartmental osteoarthritis of the knee. Loss of operative correction may threaten the long-term outcome. In both a lateral closing-wedge procedure and a medial opening-wedge procedure, the opposite cortex of the tibia is usually not osteotomized, leaving 1 cm of bone intact as fulcrum. A fracture of this cortex may, however, lead to loss of correction; this was examined in the present study. PATIENTS AND METHODS: We used a prospective cohort of 92 consecutive patients previously reported by Brouwer et al. (2006). The goal in that randomized controlled trial, was to achieve a correction of 4 degrees in excess of physiological valgus. In retrospect, we evaluated the 1-year radiographic effect of opposite cortical fracture. Opposite cortical fracture was identified on the postero-anterior radiographs in supine position on the first day after surgery. RESULTS: 44 patients with a closing-wedge HTO (staples and cast fixation) and 43 patients with an opening-wedge HTO (non-angular-stable plate fixation) were used for analysis. 36 patients (four-fifths) in the closing-wedge group and 15 patients (one-third) in the opening-wedge group had an opposite cortical fracture (p < 0.001). At 1 year, the closing-wedge group with opposite cortical fracture had a valgus position with a mean HKA angle of 3.2 (SD 3.5) degrees of valgus. However, the opening-wedge group with disruption of the opposite cortex achieved varus malalignment with a mean HKA angle of 0.9 (SD 6.6) degrees of varus. INTERPRETATION: Fracture of the opposite cortex is more common for the lateral closing wedge technique. Medial cortex disruption has no major consequences, however, and does not generally lead to malalignment. Lateral cortex fracture in the medial opening-wedge technique, with the use of a non-angular stable plate, leads more often to varus malalignment.

Can platelet-rich plasma enhance tendon repair? A cell culture study (Article)

2008-06-01T00:00:00Z

BACKGROUND: Autologous platelet-rich plasma (PRP) application appears to improve tendon healing in traumatic tendon injuries, but basic knowledge of how PRP promotes tendon repair is needed. HYPOTHESIS: Platelet-rich plasma has a positive effect on cell proliferation and collagen production and induces the production of matrix-degrading enzymes and endogenous growth factors by human tenocytes. STUDY DESIGN: Controlled laboratory study. METHODS: Human tenocytes were cultured 14 days in 2% fetal calf serum medium complemented with 0%, 10%, or 20% vol/vol platelet-rich clot releasate ([PRCR] the active releasate of PRP) or platelet-poor clot releasate (PPCR). At day 4, 7, and 14, cell amount, total collagen, and gene expression of collagen I alpha 1 (COL1) and III alpha 1 (COL3), matrix metalloproteinases ([MMPs] MMP1, MMP3, and MMP13), vascular endothelial-derived growth factor (VEGF)-A, and transforming growth factor (TGF)-beta1 were analyzed. RESULTS: Platelet numbers in PRP increased to 2.55 times baseline. Growth-factor concentrations of VEGF and platelet-derived growth factor (PDGF)-BB were higher in PRCR than PPCR. Both PRCR and PPCR increased cell number and total collagen, whereas they decreased gene expression of COL1 and COL3 without affecting the COL3/COL1 ratio. PRCR, but not PPCR, showed upregulation of MMP1 and MMP3 expression. Matrix metalloproteinase 13 expression was not altered by either treatment. PRCR increased VEGF-A expression at all time points and TGF-beta1 expression at day 4. CONCLUSION: In human tenocyte cultures, PRCR, but also PPCR, stimulates cell proliferation and total collagen production. PRCR, but not PPCR, slightly increases the expression of matrix-degrading enzymes and endogenous growth factors. CLINICAL RELEVANCE: In vivo use of PRP, but also of PPP to a certain extent, in tendon injuries might accelerate the catabolic demarcation of traumatically injured tendon matrices and promote angiogenesis and formation of a fibrovascular callus. Whether this will also be beneficial for degenerative tendinopathies remains to be elucidated.

TGFbeta affects collagen cross-linking independent of chondrocyte phenotype but strongly depending on physical environment (Article)

2008-06-01T00:00:00Z

Transforming growth factor beta (TGFbeta) is often used in cartilage tissue engineering to increase matrix formation by cells with various phenotypes. However, adverse effects of TGFbeta, such as extensive crosslinking in cultured fibroblasts, have also been reported. Our goal was to study effects of TGFbeta on collagen cross-linking and evaluating the role of cellular phenotype and physical environment. We therefore used four different cell populations in two very different physical environments: primary and expanded chondrocytes and fibroblasts embedded in alginate gel and attached to tissue culture plastic. Matrix production, collagen cross-linking, and alpha-smooth muscle actin (alphaSMA) were analyzed during 4 weeks with or without 2.5 ng/ mL TGFbeta2. TGFbeta2 did not affect collagen deposition by primary cells. In expanded cells, TGFbeta2 increased collagen deposition. Chondrocytes and fibroblasts in monolayer produced more collagen cross-links with TGFbeta2. In alginate, primary and expanded cells displayed an unexpected decrease in collagen cross-linking with TGFbeta2. alphaSMA was not present in alginate cultures and barely upregulated by TGFbeta2. Organized alphaSMA fibers were present in all monolayer cultures and became more pronounced with TGFbeta2. This study demonstrates that the physical environment determined by the substrate used co-determines the response of cells to TGFbeta. The presence of mechanical stress, determined with alphaSMA-staining, is probably responsible for the increase in collagen cross-linking upon addition of TGFbeta.

Oefentherapie bij volwassenen met een acuut lateraal enkeltrauma (Article)

2008-06-01T00:00:00Z

Enkeldistorsies zijn een van de meest voorkomende blessures aan het bewegingsapparaat. Men schat dat in Nederland jaarlijks ongeveer 600.000 mensen een enkeldistorsie oplopen. In de Nederlandse huisartsenpraktijk ligt de incidentie op 12,8 enkelblessures per 1000 patiënten per jaar.1 Experimentele onderzoeken naar ligamentherstel laten zien dat progressieve oefeningen en oefeningen met functionele belasting het herstel stimuleren en de ligamenten versterken.2-4 Hoewel letsel aan de ligamenten tot een afname van de mechanische stabiliteit van de enkel leidt, is het aannemelijk dat er ook neuromusculaire gebreken ontstaan aan het musculotendineuze weefsel.5-7 Dit kan resulteren in een onstabiele enkel en eventueel leiden tot een recidief en een gevoel van instabiliteit. Diverse auteurs stellen dat balanstraining als onderdeel van de revalidatie na een enkeldistorsie de functionele instabiliteit kan beperken en de controle over de houding kan verbeteren.8-10 Verschillende systematische reviews wijzen erop dat de standaardzorg moet bestaan uit vroegtijdige mobilisatie, met mobilisatie- instructies en vroegtijdige belasting gecombineerd met of zonder externe ondersteuning.11-16 Van Os et al. concluderen in een recente systematische review dat er beperkt bewijs is dat de standaardzorg gecombineerd met oefentherapie bij acuut letsel aan het laterale ligamentencomplex beter is dan alleen standaardzorg. 17 Het is dus niet duidelijk of de standaardbehandeling moet worden aangevuld met oefentherapie om op de lange termijn het gevoel van instabiliteit en, belangrijker nog, het aantal recidieven te verminderen. Verschillende systematische reviews adviseren om in dit kader een gerandomiseerde, gecontroleerde trial op te zetten.12,15,17 In dit prospectieve gerandomiseerde onderzoek vergelijken wij de korte- en langetermijneffecten van de standaardbehandeling van een acuut lateraal enkeltrauma bij volwassen patiënten met die van de standaardbehandeling gecombineerd met oefentherapie onder begeleiding van een fysiotherapeut.

Effects of iron oxide incorporation for long term cell tracking on MSC differentiation in vitro and in vivo (Article)

2008-05-01T00:00:00Z

Successful cell therapy will depend on the ability to monitor transplanted cells. With cell labeling, it is important to demonstrate efficient long term labeling without deleterious effects on cell phenotype and differentiation capacity. We demonstrate long term (7 weeks) retention of superparamagnetic iron oxide particles (SPIO) by mesenchymal stem cells (MSCs) in vivo, detectable by MRI. In vitro, multilineage differentiation (osteogenic, chondrogenic and adipogenic) was demonstrated by histological evaluation and molecular analysis in SPIO labeled and unlabeled cells. Gene expression levels were comaparable to unlabeled controls in adipogenic and chondrogenic conditions however not in the osteogenic condition. MSCs seeded into a scaffold for 21 days and implanted subcutaneously into nude mice for 4 weeks, showed profoundly altered phenotypes in SPIO labeled samples compared to implanted unlabeled control scaffolds, indicating chondrogenic differentiation. This study demonstrates long term MSC traceability using SPIO and MRI, uninhibited multilineage MSC differentiation following SPIO labeling, though with subtle but significant phenotypical alterations.

Survival of closing-wedge high tibial osteotomy: good outcome in men with low-grade osteoarthritis after 10-16 years (Article)

2008-04-01T00:00:00Z

BACKGROUND AND PURPOSE: High tibial valgus osteotomy (HTO) is a well-accepted treatment for medial unicompartmental osteoarthritis of the knee with varus alignment in relatively young and active patients. Controversies about the factors affecting survival of HTO still exist. We assessed preoperative risk factors for failure of closing-wedge HTO at long-term follow-up. PATIENTS AND METHODS: A cohort of 100 patients with a mean age of 49 (24-67) years, who had closing-wedge HTO performed between January 1991 and December 1996, were analyzed retrospectively. A survival analysis was carried out according to the Kaplan-Meier method. Logistic regression analysis was used to assess the association between failure of the osteotomy and known potential preoperative risk factors. RESULTS: The probability of survival for HTO was 75% (SD 4%) at 10 years with knee replacement as the endpoint. Female sex and osteoarthritis of grade > or = 2 were identified as preoperative risk factors for conversion to arthroplasty 10 years after HTO. INTERPRETATION: Our findings suggest that ideal candidates for corrective osteotomy are men with symptomatic medial compartmental osteoarthritis of Ahlback grade 1, who, 10 years after surgery, have an almost tenfold lower probability of failure of HTO than women with more advanced osteoarthritis.

Long-term results after a triple arthrodesis of the hindfoot: function and satisfaction in 36 patients (Article)

2008-04-01T00:00:00Z

The long-term functional results of a triple arthrodesis of the hindfoot are not well known. In this retrospective cohort study we therefore investigated pain, function and alignment of the tibiotalar joint, patient satisfaction with the procedure and the prevalence of osteoarthritis (OA) of the tibiotalar joint after a median follow-up of six years. We also aimed to investigate whether there are patient and surgical characteristics associated with the outcome. Patients who underwent a triple arthrodesis for OA between January 1992 and July 2002 were invited to participate. A clinical examination was performed, the Ankle-Hindfoot Scale was completed, and radiographs were taken. Patient characteristics (e.g., age, gender and the indication for operation) and surgical characteristics (e.g., fixation material and use of bone graft) were collected. Sixty-one percent (22 patients) of the patients had a good total score on the Ankle-Hindfoot Scale. Nineteen patients (53%) were satisfied with the result of the operation and 47% of the patients had radiographic OA of the tibiotalar joint. In a univariate regression analysis, male gender and the score on the Ankle-Hindfoot Scale were significantly associated with radiographic OA. Patient satisfaction was significantly associated with a higher score on the Ankle-Hindfoot Scale and better dorsi-flexion of the ankle. Our study shows that 61% of the procedures in 36 patients with a triple arthrodesis for OA had a good score on the Ankle-Hindfoot Scale. Radiographic OA of the ankle was present in 47% of the cases and was not related to patient satisfaction. No patient characteristics or surgical characteristics were associated with the score on the Ankle-Hindfoot Scale.

Cartilage damage pattern in relation to subchondral plate thickness in a collagenase-induced model of osteoarthritis (Article)

2008-04-01T00:00:00Z

OBJECTIVE: To see how initial differences in subchondral bone phenotype influence the development of cartilage damage and changes in subchondral bone architecture in an osteoarthritis (OA)-induced mouse model. METHOD: Intra-articular collagenase injections (right knee joint) and saline controls (left knee joint) were applied in the knees of two mouse strains known to have either a low or a high bone mass phenotype: the low bone mass C57Bl/6 mice with a thin subchondral bone plate and high bone mass C3H/HeJ mice with a thick subchondral bone plate. The ages of the mice were 16 and 30 weeks, with n=8 per group. The collagenase injection induced an osteoarthritic phenotype that was evaluated 4 weeks later in the tibia using histological analyses and micro-computed tomography (micro-CT). RESULTS: Both strains developed cartilage damage in the collagenase-injected right knee joints to a comparable extent, however, the spatial distribution of cartilage damage differed significantly: C57Bl/6 mice had most damage at the postero-lateral side, whereas in C3H/HeJ mice the postero-medial region was the most affected. Spontaneous cartilage damage was found in the saline-injected left control knees of C57Bl/6 mice, but in C3H/HeJ mice spontaneous cartilage damage was virtually absent. In both strains the subchondral bone plate of collagenase-injected joints became thinner, independent of the site of cartilage damage. TRAP-positive osteoclasts were observed underneath the subchondral bone plate, in line with the observed decreased thickness. No link was found between subchondral bone plate thickness and cartilage damage in the collagenase-injected joints. The subchondral trabecular architecture only changed in the high bone mass C3H/HeJ mice, with thinning of trabeculae and increased trabecular spacing. CONCLUSION: Thinning of the subchondral bone plate was found as a common observation 4 weeks after OA had been induced in two strains of mice having either a high or low bone phenotype, but no relation was found with the amount of cartilage damage. In addition, this study shows that different strains of mice can react differently to instability-induced OA with respect to the spatial arrangement of cartilage damage and changes in subchondral trabecular structure.

Prevalence and characteristics of complaints of the arm, neck, and/or shoulder (CANS) in the open population (Article)

2008-04-01T00:00:00Z

OBJECTIVE: To study the prevalence of upper extremity disorders (UEDs) and neck as a total and complaints of the arm, neck and/or shoulder (CANS) not caused by acute trauma or any systemic disease as defined in the CANS model in the open population and to assess sociodemographic and health characteristics of chronic symptoms. METHODS: Data were obtained from the DMC3-study, a Dutch questionnaire survey on musculoskeletal conditions (>25 y, n=3664). Data on four anatomic sites were assessed: neck, shoulder, elbow, and wrist. Various health characteristics were measured including the Short Form-36. Rectangle diagrams were used to illustrate cooccurrence of pain in the four anatomic sites. RESULTS: The 12-month prevalence of CANS was 36.8%, the point prevalence was 26.4%, and 19.0% patients reported chronic CANS. Women, aged 45 to 64 years, with the lowest education level and working were the most affected. Within those with UEDs, around 25% of cases were caused by an acute trauma or by some systemic disease. Of those with chronic CANS, 58% reported use of healthcare. Healthcare users scored worse on general health, limitations in daily living, pain, and sickness absence than nonhealthcare users; >43% reported symptoms in more than 1 anatomic site. DISCUSSION: UEDs and CANS frequently occur in the open population. Excluding acute traumas and systemic diseases reduced the prevalence of CANS and resulted in a relatively healthier population. A compound definition of CANS seems indicated because of the large overlap of affected anatomic sites.

Actual everyday physical activity in patients with end-stage hip or knee osteoarthritis compared with healthy controls (Article)

2008-04-01T00:00:00Z

OBJECTIVE: Few data are available on the level of actual physical activity in patients with osteoarthritis (OA) of the hip and knee. The aim of this study was to measure the level of actual physical activity of patients with end-stage OA of the hip and the knee, to compare this with that of matched healthy controls, and to analyze the data in order to ascertain the factors of influence. METHOD: The actual physical activity was measured with an activity monitor (AM) in 40 hip and 44 knee OA patients, and compared with measurements obtained from healthy controls. Data were also collected on pain and psychological aspects as anxiety, depression and mental functioning. The primary outcome parameter of the actual physical activity was the percentage of movement-related activity. RESULTS: The percentage of movement-related activity did not differ between the two OA groups. It was 8.8 (4.2)% for the hip and 8.1 (3.8)% for the knee OA patients. The matched controls were significantly higher movement-related active than OA patients (about 11.0 (2.9)%). Increasing age and body mass index were negatively associated with the percentage of movement-related activity (beta=-0.29 and beta=-0.25, respectively), whereas mental functioning was positively related (beta=0.30). CONCLUSION: The impact of end-stage OA on the level of actual physical activity is equal for hip and knee OA patients. The actual physical activity for both of the OA groups was significantly and clinically relevantly lower compared to controls. However, this difference was smaller than expected and less dominant than patients' perception of limitations in daily life. Clinicians must be aware that the patients' perception of physical functioning in daily life does not always correspond to the actual physical activity.

Traumatic thoracic and lumbar spinal fractures: operative or nonoperative treatment: comparison of two treatment strategies by means of surgeon equipoise (Article)

2008-04-01T00:00:00Z

STUDY DESIGN: A center parallel cohort study with blinded inclusion based on clinical equipoise. OBJECTIVE: To compare outcomes of nonoperative and operative treatment strategies in terms of quality of life and neurologic and functional status. SUMMARY OF BACKGROUND DATA: Despite a considerable body of literature, sound evidence regarding the optimal treatment for traumatic thoracic and lumbar spine fractures is lacking. METHODS: Medical records of patients hospitalized for traumatic spinal fractures between 1991 and 2002 were identified in 2 trauma centers in the same country with established and different treatment strategies. Eligibility was retrospectively assessed for each case by a panel of orthopaedic surgeons who were representative of the 2 medical centers, and who were blinded to the treatment actually administered. Patients were included in the study when there was disagreement on the suggested treatment method. Thus, 2 comparable groups were identified undergoing nonoperative or operative treatment. Outcome assessment and comparison across groups focused on quality of life, residual pain, neurologic recovery, and employment in the middle-long-term follow-up. RESULTS: Discordance in regards to choice of treatment was identified in 190 (95 treated nonoperative, 95 operative) of 636 potentially eligible patients. Patients were comparable regarding baseline characteristics, except for a somewhat higher proportion of males and neurologic impairment in the operative group. Seventeen percent of the nonoperative and 21% of the operative group developed complications and 3 patients displayed neurologic deterioration for which a treatment change was considered necessary. Follow-up was complete in 79%; mean follow-up time was 6.2 years with a minimum of 2 years. Pain scores, disability indexes, and general health outcome were comparable at follow-up. Compared with matched population norms, outcomes were poorer regardless of treatment method. Neurologic recovery was better in the operative group, but this difference did not reach statistical significance. Multivariate regression analyses revealed that female gender and neurologic impairment were independent predictors of poor functional outcome. Eighty-eight and 83% of the nonoperatively and operatively treated patients were employed at some point after a rehabilitation period. CONCLUSION: Overall outcome of nonoperative and operative treatment in middle-long-term follow up is comparable, although there seems to be a difference in neurologic recovery patterns. Studies on the cost-effectiveness of treatment options and the patterns of recovery within 2 years after injury would assist in guideline development and stimulate interest for future research.

In vitro expansion affects the response of chondrocytes to mechanical stimulation (Article)

2008-03-01T00:00:00Z

OBJECTIVE: Expansion of autologous chondrocytes is a common step in procedures for cartilage defect repair. Subsequent dedifferentiation can alter cellular response to mechanical loading, having major consequences for the cell's behavior in vivo after reimplantation. Therefore, we examined the response of primary and expanded human articular chondrocytes to mechanical loading. METHOD: Primary and expanded chondrocytes were stretched at either 0.5% or 3.0% at 0.5Hz, 2h per day, for 3 days. Gene expression levels of matrix components (aggrecan (AGC1), lubricin (PRG4), collagen type I (COL1), type II (COL2) and type X (COL10)) as well as matrix enzymes (matrix metalloproteinase 1 (MMP1), MMP3, MMP13) and SOX9 were compared to unstretched controls. To evaluate the effect of a chondrogenic environment on cellular response to stretch, redifferentiation medium was used on expanded cells. RESULTS: In primary chondrocytes, stretch led to mild decreases in AGC1, COL1 and COL10 gene expression (maximum of 3.8-fold) and an up-regulation of PRG4 (2.0-fold). In expanded chondrocytes, expression was down-regulated for AGC1 (up to 21-fold), PRG4 (up to 5.0-fold), COL1 (10-fold) and COL2 (2.9-fold). Also, expression was up-regulated for MMP1 (20-fold) and MMP3 (up to 4-fold), while MMP13 was down-regulated (2.8-fold). A chondrogenic environment appeared to temper effects of stretch. DISCUSSION: Our results show that expansion alters the response of human chondrocytes to stretch. Expanded chondrocytes greatly decrease gene expression of matrix constituents and increase expression of MMPs, whereas primary chondrocytes hardly respond. Our data could be a reference for optimization of cell sources or expansion protocols for reimplanted chondrocytes.

Contribution of collagen network features to functional properties of engineered cartilage (Article)

2008-03-01T00:00:00Z

BACKGROUND: Damage to articular cartilage is one of the features of osteoarthritis (OA). Cartilage damage is characterised by a net loss of collagen and proteoglycans. The collagen network is considered highly important for cartilage function but little is known about processes that control composition and function of the cartilage collagen network in cartilage tissue engineering. Therefore, our aim was to study the contribution of collagen amount and number of crosslinks on the functionality of newly formed matrix during cartilage repair. METHODS: Bovine articular chondrocytes were cultured in alginate beads. Collagen network formation was modulated using the crosslink inhibitor beta-aminopropionitrile (BAPN; 0.25mM). Constructs were cultured for 10 weeks with/without BAPN or for 5 weeks with BAPN followed by 5 weeks without. Collagen deposition, number of crosslinks and susceptibility to degradation by matrix metalloproteinase-1 (MMP-1) were examined. Mechanical properties of the constructs were determined by unconfined compression. RESULTS: BAPN for 5 weeks increased collagen deposition accompanied by increased construct stiffness, despite the absence of crosslinks. BAPN for 10 weeks further increased collagen amounts. Absence of collagen crosslinks did not affect stiffness but ability to hold water was lower and susceptibility to MMP-mediated degradation was increased. Removal of BAPN after 5 weeks increased collagen amounts, allowed crosslink formation and increased stiffness. DISCUSSION: This study demonstrates that both collagen amounts and its proper crosslinking are important for a functional cartilage matrix. Even in conditions with elevated collagen deposition, crosslinks are needed to provide matrix stiffness. Crosslinks also contribute to the ability to hold water and to the resistance against degradation by MMP-1

The Dutch version of the Knee Injury and Osteoarthritis Outcome Score: a validation study (Article)

2008-02-26T00:00:00Z

BACKGROUND: The Knee Injury and Osteoarthritis Outcome Score (KOOS) was constructed in Sweden. This questionnaire has proved to be valid for several orthopedic interventions of the knee. It has been formally translated and validated in several languages, but not yet in Dutch. The purpose of the present study was to evaluate the clinimetric properties of the Dutch version of the KOOS questionnaire in knee patients with various stages of osteoarthritis (OA). METHODS: The Swedish version of the KOOS questionnaire was first translated into Dutch according to a standardized procedure and second tested for clinimetric quality. The study population consisted of patients with different stages of OA (mild, moderate and severe) and of patients after primary TKA, and after a revision of the TKA. All patients filled in the Dutch KOOS questionnaire, as well as the SF-36 and a Visual Analogue Scale for pain. The following analyses were performed to evaluate the clinimetric quality of the KOOS: Cronbach's alpha (internal consistency), principal component analyses (factor analysis), intraclass correlation coefficients (reliability), spearman's correlation coefficient (construct validity), and floor and ceiling effects. RESULTS: For all patients groups Cronbach's alpha was for all subscales above 0.70. The ICCs, assessed for the patient groups with mild and moderate OA and after revision of the TKA patients, were above 0.70 for all subscales. Of the predefined hypotheses 60% or more could be confirmed for the patients with mild and moderate OA and for the TKA patients. For the other patient groups less than 45% could be confirmed. Ceiling effects were present in the mild OA group for the subscales Pain, Symptoms and ADL and for the subscale Sport/Recreation in the severe OA group. Floor effects were found for the subscales Sport/Recreation and Qol in the severe OA and revision TKA groups. CONCLUSION: Based on these different clinimetric properties within the present study we conclude that the KOOS questionnaire seems to be suitable for patients with mild and moderate OA and for patients with a primary TKA. The Dutch version of the KOOS had a lower construct validity for patients with severe OA on a waiting list for TKA and patients after revision of a TKA. Further validation studies on the Dutch version of the KOOS should also include a knee specific questionnaire for assessing the construct validity.

Cellular origin of neocartilage formed at wound edges of articular cartilage in a tissue culture experiment (Article)

2008-02-01T00:00:00Z

OBJECTIVE: The regeneration capacity of cartilage in general is limited. Complete repair of partial thickness articular cartilage has only been reported in a fetal sheep model. However, in long-term culture studies of articular cartilage explants we have observed outgrowth of chondrocytes and neocartilage formation at wound edges. This illustrates that under optimal circumstances articular cartilage is capable to regenerate hyaline cartilage. Recent studies suggest the presence of mesenchymal stem cells in articular cartilage. In the present study we investigated the origin of chondrocyte outgrowth and neocartilage formation at wound edges from immature and mature articular bovine cartilage explants in vitro, in order to understand which cells are responsible for repair. DESIGN: Full-thickness explants from immature and mature animals were cultured for 4 weeks and superficial and deep zone cartilage explants of immature animals were separately cultured. RESULTS: Significant more outgrowth was observed from immature explants as compared to mature explants. At wound edges of immature explants, this outgrowth showed high cell-densities, rounded cells, the extracellular matrix contained proteoglycans and collagen types I and II. We found proliferation activity both in the superficial zone and deep zone chondrocytes in immature explants, using the Ki67 proliferation marker. In the experiment culturing immature superficial and deep zone cartilage explants separately, there was abundant new tissue formation originating from deep cartilage and almost no outgrowth from the superficial cartilage. This indicates that neocartilage originates from chondrocytes in the deep zone cartilage and not from chondrocytes in the superficial zone cartilage. CONCLUSIONS: Present data can help to understand wound healing in partial-thickness and full-thickness defects of immature and mature cartilage and can be of help in finding methods to stimulate the regeneration of articular cartilage.

Conventional knee films hamper accurate knee alignment determination in patients with varus osteoarthritis of the knee (Article)

2008-01-01T00:00:00Z

Surgical therapeutic procedures such as knee osteotomy and knee replacement depend on proper knee alignment assessment. The aim of this study was to evaluate if femorotibial (FT) measurement on short knee films may be used in clinical settings. The study population comprised 68 patients with symptomatic medial compartmental knee osteoarthritis. We measured the FT angle with the use of mid-diaphyseal lines (FTa), and the knee joint centre (FTb) to determine anatomical knee alignment on a short knee image. Then, the accuracy of alignment was compared to the gold standard Hip-Knee-Ankle (HKA) angle on a full-limb view. FTa angle assessment correlated well (r = 0.65) with the HKA angle. However, this method showed poor inter-observer agreement (ICC = 0.37). 3% of patients were incorrectly classified as having valgus alignment. Good intra- and inter-observer agreements were observed for FTb angle measurement (ICC = 0.89 and 0.79; respectively). But correlation between HKA and FTb angles was low (r = 0.34). 15% of patients were incorrectly classified as having valgus alignment. Short knee images cannot substitute whole leg views when accurate assessment of knee alignment is essential.

Diagnostic value of history-taking and physical examination for assessing meniscal tears of the knee in general practice (Article)

2008-01-01T00:00:00Z

OBJECTIVE: To assess the diagnostic value of history-taking and physical examination of meniscal tears in general practice. DESIGN: An observational study determining diagnostic values (sensitivity, specificity, predictive value, and likelihood ratios). SETTING: General practice. PATIENTS: Consecutive patients aged 18 to 65 years with a traumatic knee injury who consulted their general practitioner within 5 weeks after trauma. ASSESSMENT: Participating patients filled out a questionnaire (history-taking) followed by a standardized physical examination. MAIN OUTCOME: Assessment of meniscal tears was determined by means of magnetic resonance imaging (MRI) and was performed blinded for the results of physical examination and history-taking. RESULTS: Of the 134 patients included in this study, 47 had a meniscal tear. From history-taking, the determinants "age over 40 years," "continuation of activity impossible," and "weight-bearing during trauma" indicated an association with a meniscal tear after multivariate logistic regression analysis, whereas from physical examination only "pain at passive flexion" indicated an association. These associated determinants from history-taking showed some diagnostic value; the positive likelihood ratio (LR+) reached up to 2.0 for age over 40 years, whereas the isolated test pain at passive flexion from physical examination has less diagnostic value, with an LR+ of 1.3. Combining determinants from history-taking and physical examination improved the diagnostic value with a maximum LR+ of 5.8; however, this combination only applied to a limited number of patients. CONCLUSION: History-taking has some diagnostic value, whereas physical examination did not add any diagnostic value for detecting meniscal tears in general practice.

Interventions for treating the radial tunnel syndrome: a systematic review of observational studies (Article)

2008-01-01T00:00:00Z

PURPOSE: For some disorders, such as radial tunnel syndrome (RTS), no randomized controlled trials and controlled clinical trials are available. To gain insight into the effectiveness of conservative and surgical interventions for treating RTS, we systematically reviewed all available observational studies on treatment of RTS. Although the validity of case series is inferior to that of controlled trials, the case series might provide valuable data about the efficacy of treatment options. METHODS: A literature search and additional reference checking resulted in 21 eligible case series for this review. Based on previous checklists, we constructed a new quality assessment and rating system to analyze the included case series. The methodological quality was assessed, and data extraction was performed. Studies with less than 50% of the maximum points on the methodological quality assessment were considered inadequate and were excluded from the analysis. To summarize the results according to the rating system for the strength of the scientific evidence for these case series, we introduced 4 levels: (1) tendency, (2) slight tendency, (3) conflicting tendency, and (4) no tendency. RESULTS: After the methodological quality assessment, 6 articles were included in the final analysis. They all reported on surgical treatment. CONCLUSIONS: There is a tendency that surgical decompression of the radial tunnel might be effective in patients with RTS. The effectiveness of conservative treatments for RTS is unknown because, for most treatments, no studies were available. Additional high-quality controlled studies are needed to assess the level of conclusive evidence for surgical treatment and also to evaluate conservative treatments for RTS. For this, we recommend a multicenter, randomized clinical trial. Due to the lack of a clear protocol for diagnosing RTS, a reliable and valid diagnostic tool should be developed. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Prognosis of hip pain in general practice: a prospective followup study (Article)

2007-12-01T00:00:00Z

OBJECTIVE: Hip pain in the elderly is the main feature of osteoarthritis of the hip. In this prospective followup study, we wanted to determine which patients with hip pain show disease progression, and what the incidence of total hip replacement (THR) is in this group of patients after 3 and 6 years of followup. METHODS: Within general practices in the area of Rotterdam (The Netherlands), persons age > or = 50 years with incident hip pain were included. After 3 and 6 years, progression of hip pain was assessed. RESULTS: A total of 224 patients were included. After 3 years disease progressed in 29 (15%) patients and 23 (12%) received a THR. After 6 years disease progressed in 45 (28%) patients and 36 (22%) received a THR. The prognostic variables for a THR after 3 and 6 years related to history taking were age > or = 60 years, morning stiffness, and pain in the groin/medial thigh; variables related to physical examination were decreased extension/adduction, painful internal rotation, and a body mass index < or = 30 kg/m(2); and the variable related to radiologic findings was a Kellgren/Lawrence grade of 2 or higher. CONCLUSION: In this study population, approximately 12% of patients presenting with hip pain to their general practitioner will undergo a THR within 3 years, and approximately 22% after 6 years. Using the variables obtained from history taking, physical examination, and radiologic findings enables better identification of persons at high risk for a THR.

Effect of corticosteroid injection for trochanter pain syndrome: Design of a randomised clinical trial in general practice (Article)

2007-11-08T00:00:00Z

Background. Regional pain in the hip in adults is a common cause of a general practitioner visit. A considerable part of patients suffer from (greater) trochanteric pain syndrome or trochanteric bursitis. Local corticosteroid injections is one of the treatment options. Although clear evidence is lacking, small observational studies suggest that this treatment is effective in the short-term follow-up. So far, there are no randomised controlled trials available evaluating the efficacy of injection therapy. This study will investigate the efficacy of local corticosteroid injections in the trochanter syndrome in the general practice, using a randomised controlled trial design. The cost effectiveness of the corticosteroid injection therapy will also be assessed. Secondly, the role of co-morbidity in relation to the efficacy of local corticosteroid injections will be investigated. Methods/Design. This study is a pragmatic, open label randomised trial. A total of 150 patients (age 18-80 years) visiting the general practitioner with complaints suggestive of trochanteric pain syndrome will be allocated to receive local corticosteroid injections or to receive usual care. Usual care consists of analgesics as needed. The randomisation is stratified for yes or no co-morbidity of low back pain, osteoarthritis of the hip, or both. The treatment will be evaluated by means of questionnaires at several time points within one year, with the 3 month and 1 year evaluation of pain and recovery as primary outcome. Analyses of primary and secondary outcomes will be made according to the intention-to-treat principle. Direct and indirect costs will be assessed by questionnaires. The cost effectiveness will be estimated using the following ratio: CE ratio = (cost of injection therapy minus cost of usual care)/(effect of injection therapy minus effect of usual care). Discussion. This study design is appropriate to estimate effectiveness and cost-effectiveness of the injection therapy. We choose to use a pragmatic study design and are thus not able to study specific effects of the injection with corticosteroids. A distinction between placebo effect of the injection and specific effects of the corticosteroids is therefore not possible. Trial Registration. The trial is listed in the Dutch Trial Registry with the number ISRCTN16994576.

Glucosamine reduces anabolic as well as catabolic processes in bovine chondrocytes cultured in alginate (Article)

2007-11-01T00:00:00Z

OBJECTIVE: To investigate the working mechanism of glucosamine (GlcN) by studying the effect of different GlcN derivatives on bovine chondrocytes in alginate beads under anabolic and catabolic culture conditions. METHODS: Bovine chondrocytes seeded in alginate beads were treated with different concentrations of glucosamine-sulfate (GlcN-S), glucosamine-hydrochloride (GlcN-HCl) or N-acetyl-glucosamine (GlcN-Ac). Culture conditions were anabolic, 3 day pre-culture followed by 14 days' treatment; catabolic, extracellular matrix (ECM) breakdown induced by 10ng/ml interleukin-1beta (IL-1beta); or a situation with balance between ECM breakdown and synthesis, 24 days' pre-culture followed by 14 days' treatment. The outcome measurements were total glycosaminoglycan (GAG) and DNA content per bead. RESULTS: In the situation with balance between ECM breakdown and synthesis, GlcN-Ac had a small stimulatory effect on total GAG content. GlcN-S and GlcN-HCl had no effect. Under anabolic condition 5mM GlcN-S and GlcN-HCl significantly reduced total GAG content. GlcN-Ac did not show this effect. IL-1beta induced catabolic effects were prevented by adding 5mM GlcN-HCl. Interference of GlcN with glucose (Gluc) was demonstrated by adding extra Gluc to the medium in the anabolic culture conditions. Increasing extracellular Gluc concentrations diminished the effect of GlcN. CONCLUSION: GlcN-S and GlcN-HCl, but not GlcN-Ac, reduce anabolic and catabolic processes. For anabolic processes this was demonstrated by decreased ECM synthesis, for catabolic processes by protection against IL-1beta mediated ECM breakdown. This might be due to interference of GlcN with Gluc utilization. We suggest that the claimed structure modifying effects of GlcN are more likely based on protection against ECM degradation than new ECM production.

Kinesiophobia in patients with non-traumatic arm, neck and shoulder complaints: a prospective cohort study in general practice (Article)

2007-11-01T00:00:00Z

BACKGROUND: Complaints of arm, neck and shoulder are common in Western societies. Of those consulting a general practitioner (GP) with non-traumatic arm, neck or shoulder complaints, about 50% do not recover within 6 months.Kinesiophobia (also known as fear of movement/(re)injury) may also play a role in these complaints, as it may lead to avoidance behaviour resulting in hypervigilance to bodily sensations, followed by disability, disuse and depression. However, in relation to arm, neck and shoulder complaints little is known about kinesiophobia and its associated variables.Therefore this study aimed to: describe the degree of kinesiophobia in patients with non-traumatic complaints of arm, neck and shoulder in general practice; to determine whether mean scores of kinesiophobia change over time in non-recovered patients; and to evaluate variables associated with kinesiophobia at baseline. METHODS: In this prospective cohort study set in general practice, consulters with a first or new episode of non-traumatic arm, neck or shoulder complaints (aged 18-64 years) entered the cohort. Baseline data were collected on kinesiophobia using the Tampa Scale for Kinesiophobia, the 13-item adjusted version: TSK-AV, and on patient-, complaint-, and psychosocial variables using self-administered questionnaires. The mean TSK-AV score was calculated. In non-recovered patients the follow-up TSK-AV scores at 6 and 12 months were analyzed with the general linear mixed model. Variables associated with kinesiophobia at baseline were evaluated using multivariate linear regression analyses. RESULTS: The mean TSK-AV score at baseline was 24.8 [SD: 6.2]. Among non-recovered patients the mean TSK-AV score at baseline was 26.1 [SD: 6.6], which remained unchanged over 12- months follow-up period. The strongest associations with kinesiophobia were catastrophizing, disability, and comorbidity of musculoskeletal complaints. Additionally, having a shoulder complaint, low social support, high somatization and high distress contributed to the kinesiophobia score. CONCLUSION: The mean TSK-AV score in our population seems comparable to those in other populations in primary care.In patients who did not recover during the 12- month follow-up, the degree of kinesiophobia remained unchanged during this time period.The variables associated with kinesiophobia at baseline appear to be in line with the fear-avoidance model.

Supervised exercises for adults with acute lateral ankle sprain: a randomised controlled trial (Article)

2007-10-01T00:00:00Z

BACKGROUND: During the recovery period after acute ankle sprain, it is unclear whether conventional treatment should be supported by supervised exercise. AIM: To evaluate the short- and long-term effectiveness of conventional treatment combined with supervised exercises compared with conventional treatment alone in patients with an acute ankle sprain. DESIGN: Randomised controlled clinical trial. SETTING: A total of 32 Dutch general practices and the hospital emergency department. METHOD: Adults with an acute lateral ankle sprain consulting general practices or the hospital emergency department were allocated to either conventional treatment combined with supervised exercises or conventional treatment alone. Primary outcomes were subjective recovery (0-10 point scale) and the occurrence of a resprain. Measurements were carried out at intake, 4 weeks, 8 weeks, 3 months, and 1 year after injury. Data were analysed using intention-to-treat analyses. RESULTS: A total of 102 patients were enrolled and randomised to either conventional treatment alone or conventional treatment combined with supervised exercise. There was no significant difference between treatment groups concerning subjective recovery or occurrence of resprains after 3 months and 1-year of follow-up. CONCLUSION: Conventional treatment combined with supervised exercises compared to conventional treatment alone during the first year after an acute lateral ankle sprain does not lead to differences in the occurrence of resprains or in subjective recovery.

Achilles tendinosis: changes in biochemical composition and collagen turnover rate (Article)

2007-09-01T00:00:00Z

BACKGROUND: Understanding biochemical and structural changes of the extracellular matrix in Achilles tendinosis might be important for developing mechanism-based therapies. HYPOTHESIS: In Achilles tendinosis, changes occur in biochemical composition and collagen turnover rate. STUDY DESIGN: Descriptive laboratory study. METHODS: From 10 patients undergoing surgery for Achilles tendinopathy, 1 tendinosis biopsy specimen and 1 biopsy specimen of macroscopically healthy tendon tissue adjacent to the lesion were collected. Furthermore, biopsy samples were collected from 3 donors with asymptomatic Achilles tendons. Water content, collagen content, percentage of denatured collagen, amount of lysine hydroxylation, number of enzymatic and nonenzymatic crosslinks, matrix metalloproteinase activity, and matrix metalloproteinase and collagen gene-expression levels were analyzed. RESULTS: In tendinotic lesions, the water content was highest, and collagen content was subnormal with higher amounts of denatured/damaged collagen. Low pentosidine levels in tendinotic tissue indicated the presence of relatively young collagenous matrix. More hydroxylated lysine residues were present in tendinotic samples, but enzymatic crosslinks revealed no differences between tendinotic, adjacent, and healthy samples. In tendinotic specimens, matrix metalloproteinase activity was higher, matrix metalloproteinase gene-expression profile was altered, and collagen type I and III gene expression were upregulated. CONCLUSION: In Achilles tendinosis, the collagen turnover rate is increased, and the natural biochemical composition of the collagenous matrix is compromised. CLINICAL RELEVANCE: Although tendon tissue directly adjacent to an Achilles tendinosis lesion looks macroscopically healthy, histological and biochemical degenerative changes in adjacent tissue are evident, which may have implications for surgical interventions.

Vacuum-assisted wound closure of deep infections after instrumented spinal fusion in six children with neuromuscular scoliosis (Article)

2007-09-01T00:00:00Z

BACKGROUND CONTEXT: The rate of infection after spinal fusion in neuromuscular scoliosis is reported to range from 4% to 20%. Infection persists in about 50% after traditional treatment including debridement and closure. Instrumentation removal is necessary in up to 28%. PURPOSE: To analyze the outcome of vacuum-assisted wound closure (VAC) in combination with antibiotics for the treatment of deep wound infection after instrumented spinal fusion in pediatric neuromuscular scoliosis. STUDY DESIGN: Six prospective consecutive neuromuscular patients with scoliosis. PATIENT SAMPLE: Between 2001 and 2005, six consecutive pediatric patients (average age, 12.6 years) with neuromuscular scoliosis with a postoperative deep wound infection after instrumented spinal fusion were included in the study. OUTCOME MEASURES: Measurement of the duration of wound closure and infection parameters during treatment. METHODS: The patients were treated with a VAC system in combination with antibiotics. RESULTS: Wound closure averaged 3 months. Infection parameters were normalized within 6 weeks. Removal of the instrumentation was not necessary in any patient, and there were no signs of infection at follow-up ranging from 9 to 42 months. CONCLUSION: The VAC system, in combination with antibiotic therapy, seems to be a useful method for treatment of deep wound infections after spinal fusion in pediatric neuromuscular scoliosis. It may prevent removal of the instrumentation and multiple surgery for irrigation and closure of the wound.

De levensduur van totaleheupprothesen: het belang van een implantaatregister (Article)

2007-09-01T00:00:00Z

The survival of total hip arthroplasty is mainly determined by the loosening of implants. Wear particles generated at the articular contact of head and cup are engulfed by macrophages. These activated macrophages induce the production of RANKL, leading to proliferation and activation of osteoclasts resulting in osteolysis around the hip implant. Higher activity leads to increased particles production, which explains the lower survival rate of total hip arthroplasties in young patients compared to older patients. Implant fixation with bone cement still is an excellent technique, but uncemented techniques also give good results. Randomised controlled studies are necessary to give the final answer but are expensive. National hip registers are a good alternative and are an essential element for quality control.

Heupfracturen zo snel mogelijk opereren (Article)

2007-09-01T00:00:00Z

A recent retrospective study in the Netherlands found no significant association between delayed hip fracture surgery and the occurrence of complications. This argues against the use of the Dutch hospital quality indicator measuring the percentage of patients with hip fracture operated within 24 to 48 hours. However, much larger international prospective studies have shown that delaying surgery results in prolonged duration of pain and hospitalisation and increased rate of complications. There is no evidence that delaying surgery is beneficial for the patient. Therefore, the current Dutch hospital quality indicator for timely initiation of treatment for hip fractures should remain unchanged in the interest of this fragile patient group.

Klinische uitkomsten van totale heupprothese na eerdere artrodese van de heup (Article)

2007-09-01T00:00:00Z

OBJECTIVE: To describe the clinical results of conversion of an arthrodesis of the hip to a total hip arthroplasty (THA) at the Erasmus MC, Rotterdam, the Netherlands. DESIGN: Retrospective study. METHOD: Data were collected from the case notes of patients who had undergone conversion ofarthrodesis of the hip to a total hip prosthesis between 1 January 1985 and 31December 2003. This was a total of 13 patients, 1 of whom had died and 2 of whom were excluded because of dementia and severe psychiatric disorder respectively. The remaining 10 patients (5 men and 5 women) were sent the Short form-36 quality-of-life questionnaire and asked, if, in hindsight, they would undergo the operation again. Their hip function was assessed using the Harris Hip Score (HHS) and the weakness of the gluteus muscles using Trendelenburg's test. The preoperative and most recent postoperative X-rays of the pelvis were evaluated. RESULTS: Median age at the time ofTHA was 45 years (range: 21-62). THA was done median 15 years (range: 2-50) after arthrodesis. Follow-up was done median 5 years (range: 0-18) after THA. The main reasons for conversion were ipsilateral knee pain and low back pain, which both improved after conversion. The median HHS was 75.0 (range: 44.7-99.4) and the Trendelenburg test was positive in 5 patients. 6 patients had heterotopic ossification without limitation in joint range. 9 patients confirmed they would undergo the operation again. CONCLUSION: Arthrodesis ofthe hip was a reasonable treatment option for young patients with monoarticular hip disease.

The effect of high tibial osteotomy on the results of total knee arthroplasty: a matched case control study (Article)

2007-08-03T00:00:00Z

BACKGROUND: We performed a matched case control study to assess the effect of prior high tibia valgus producing osteotomy on results and complications of total knee arthroplasty (TKA). METHODS: From 1996 until 2003 356 patients underwent all cemented primary total knee replacement in our institution. Twelve patients with a history of 14 HTO were identified and matched to a control group of 12 patients with 14 primary TKA without previous HTO. The match was made for gender, age, date of surgery, body mass index, aetiology and type of prosthesis. Clinical and radiographic outcome were evaluated after a median duration of follow-up of 3.7 years (minimum, 2.3 years). The SPSS program was used for statistical analyses. RESULTS: The index group had more perioperative blood loss and exposure difficulties with one tibial tuberosity osteotomy and three patients with lateral retinacular releases. No such procedures were needed in the control group. Mid-term HSS, KSS and WOMAC scores were less favourable for the index group, but these differences were not significant. The tibial slope of patients with prior HTO was significantly decreased after this procedure. The tibial posterior inclination angle was corrected during knee replacement but posterior inclination was significantly less compared to the control group. No deep infection or knee component loosening were seen in the group with prior HTO. CONCLUSION: We conclude that TKA after HTO seems to be technically more demanding than a primary knee arthroplasty, but clinical outcome was almost identical to a matched group that had no HTO previously.

Multidisciplinary consensus on the terminology and classification of complaints of the arm, neck and/or shoulder (Article)

2007-05-01T00:00:00Z

BACKGROUND: There is no universally accepted way of labelling or defining upper-extremity musculoskeletal disorders. A variety of names are used and many different classification systems have been introduced. OBJECTIVE: To agree on an "unambiguous language" concerning the terminology and classification that can be used by all relevant medical and paramedical disciplines in the Netherlands. METHODS: A Delphi consensus strategy was initiated. The outcomes of a multidisciplinary conference were used as a starting point. In total, 47 experts in the field of upper-extremity musculoskeletal disorders were delegated by 11 medical and paramedical professional associations to form the expert panel for the Delphi consensus strategy. Each Delphi round consisted of a questionnaire, an analysis and a feedback report. RESULTS: After three Delphi rounds, consensus was achieved. The experts reported the consensus in a model. This so-called CANS model describes the term, definition and classification of complaints of arm, neck and/or shoulder (CANS) and helps professionals to classify patients unambiguously. CANS is defined as "musculoskeletal complaints of arm, neck and/or shoulder not caused by acute trauma or by any systemic disease". The experts classified 23 disorders as specific CANS, because they were judged as diagnosable disorders. All other complaints were called non-specific CANS. In addition, the experts defined "alert symptoms" on the top of the model. CONCLUSIONS: The use of the CANS model can increase accurate and meaningful communication among healthcare workers, and may also have a positive influence on the quality of scientific research, by enabling comparison of data of different studies.

Intrinsic differentiation potential of adolescent human tendon tissue: an in-vitro cell differentiation study (Article)

2007-02-23T00:00:00Z

Tendinosis lesions show an increase of glycosaminoglycan amount, calcifications, and lipid accumulation. Therefore, altered cellular differentiation might play a role in the etiology of tendinosis. This study investigates whether adolescent human tendon tissue contains a population of cells with intrinsic differentiation potential. METHODS: Cells derived from adolescent non-degenerative hamstring tendons were characterized by immunohistochemistry and FACS-analysis. Cells were cultured for 21 days in osteogenic, adipogenic, and chondrogenic medium and phenotypical evaluation was carried out by immunohistochemical and qPCR analysis. The results were compared with the results of similar experiments on adult bone marrow-derived stromal cells (BMSCs). RESULTS: Tendon-derived cells stained D7-FIB (fibroblast-marker) positive, but alpha-SMA (marker for smooth muscle cells and pericytes) negative. Tendon-derived cells were 99% negative for CD34 (endothelial cell marker), and 73% positive for CD105 (mesenchymal progenitor-cell marker). In adipogenic medium, intracellular lipid vacuoles were visible and tendon-derived fibroblasts showed upregulation of adipogenic markers FABP4 (fatty-acid binding protein 4) and PPARG (peroxisome proliferative activated receptor gamma). In chondrogenic medium, some cells stained positive for collagen 2 and tendon-derived fibroblasts showed upregulation of collagen 2 and collagen 10. In osteogenic medium Von Kossa staining showed calcium deposition although osteogenic markers remained unaltered. Tendon-derived cells and BMCSs behaved largely comparable, although some distinct differences were present between the two cell populations. CONCLUSION: This study suggests that our population of explanted human tendon cells has an intrinsic differentiation potential. These results support the hypothesis that there might be a role for altered tendon-cell differentiation in the pathophysiology of tendinosis.

The difference between actual and prescribed weight bearing of total hip patients with a trochanteric osteotomy: long-term vertical force measurements inside and outside the hospital (Article)

2007-02-01T00:00:00Z

OBJECTIVE: To determine whether patients load the operated leg at a prescribed weight-bearing target load during postoperative recovery. DESIGN: A descriptive prospective study. SETTING: Orthopedic clinic and patients' homes. PARTICIPANTS: Fifty patients who had undergone total hip arthroplasty (THA) with trochanteric osteotomy. INTERVENTION: Patients were verbally instructed by a physical therapist to perform partial weight bearing at a 10% body weight (BW) target load (n=33) or at a 50% BW target load (n=17). MAIN OUTCOME MEASURES: Mean peak load (%BW) and percentage of patients and mean percentage of steps below, equal to, and above the target load. Weight bearing was measured when patients walked with (condition 1) and without (condition 2) a physical therapist in the hospital and walked at home (condition 3). RESULTS: The mean peak load was significantly higher than the target in the 10% BW group for all 3 conditions (condition 1, 19.2% BW; condition 2, 20.0% BW; condition 3, 26.8% BW). In the 50% BW group, the mean peak load was significantly lower than the target in conditions 1 (28.1% BW) and 2 (32.5% BW). No significant difference in weight bearing was found when walking with or without a physical therapist (change in 10% BW, -0.1% BW; change in 50% BW, -3.17% BW). At home, the mean peak load was significantly larger compared with walking without a physical therapist in the hospital (change in 10% BW, -7.0% BW; change in 50% BW, -11.5% BW). CONCLUSIONS: Partial weight bearing at a specific target load was not achieved by patients with a THA when given verbal instructions. Especially when using a low target load and when walking at home with no supervision of a physical therapist, patients loaded the operated leg higher and more frequently above the target load. Other training methods (eg, biofeedback) have to be evaluated to use as training tools for partial weight bearing at specific target loads.

Prognostic indicators for non-recovery of non-traumatic complaints at arm, neck and shoulder in general practice--6 months follow-up (Article)

2007-01-01T00:00:00Z

OBJECTIVES: To identify predictors of non-recovery in non-traumatic complaints at the arm, neck and shoulder in general practice 6 months after the first consultation. METHODS: A prospective cohort study was set in 21 Dutch general practices. Consulters with a first or new episode of non-traumatic arm, neck or shoulder complaints and age 18 through 64 yrs entered the cohort. Complaint, patient, physical, psychosocial and work characteristics were investigated as possible predictors of non-recovery at 6 months using multiple logistic regression analyses (backward Wald). RESULTS: At 6 months, 46% of the total population (n = 612) and 42% of the working subpopulation (n = 473) still reported complaints. Complaint characteristics (long duration of the complaint before consultation, recurrent complaint, musculoskeletal comorbidity and complaint mainly located at wrist or hand) were most predictive of non-recovery followed by psychosocial characteristics (more somatization and experiencing less social support). Having a specific diagnosis was associated with recovery. In the working subpopulation, the same variables were predictors of non-recovery. Additionally, low supervisory support was associated with non-recovery. The models correctly classified 72-75% of the patients (explained variance 0.27-0.28). CONCLUSIONS: Besides questions on complaint characteristics, information on somatization and support can help a general practitioner to recognize patients at risk of persistent complaints.

Validation of the Dutch version of the Hip disability and Osteoarthritis Outcome Score (Article)

2007-01-01T00:00:00Z

INTRODUCTION: The Hip disability and Osteoarthritis Outcome Score (HOOS) was constructed in Sweden; this questionnaire has proved to be valid for persons with hip disability with or without hip osteoarthritis (OA) and with high demands of physical function. OBJECTIVE: The objective of this study was to evaluate the internal consistency, reliability, construct validity, and floor and ceiling effects of the Dutch version of the HOOS questionnaire. PATIENTS AND METHODS: After translation with a forward/backward protocol, 74 hip arthroplasty patients and 88 hip OA patients filled in the Dutch HOOS, as well as a Short Form-36 (SF-36), an Oxford Hip Score (OHS) and a VAS-pain questionnaire. RESULTS: The Dutch version of the HOOS questionnaire achieved excellent scores in all of the clinimetric properties. CONCLUSION: The Dutch HOOS questionnaire has a good internal consistency and reliability. Moreover, the construct validity is good and no floor and ceiling effects were found. The HOOS is a good instrument for patients with different stadia of hip OA.

Validity of the Pedar Mobile system for vertical force measurement during a seven-hour period (Article)

2006-12-01T00:00:00Z

Objective measurement of weight bearing during a long-term period can give insight into the postoperative loading of the lower extremity of orthopedic patients to avoid complications. This study investigated the validity of vertical ground reaction force measurements during a long-term period using the Pedar Mobile insole pressure system, by comparing it with a Kistler force platform. In addition, the validity of a new sensor drift correction algorithm to correct for offset drift in the Pedar signal was evaluated. Ground reaction force data were collected during dynamic and static conditions from five healthy subjects every hour for 7 h. A mean offset drift of 14.6% was found after 7 h. After applying the drift correction algorithm the Pedar system showed a high accuracy for the second peak in the ground reaction force-time curve (1.1 to 3.4% difference, p>0.05) and step duration (-2.0 to 4.4% difference, p>0.05). Less accuracy was found for the first peak in the ground reaction force-time curve (5.2 to 12.0% difference; p<0.05 for the first 3 h, p>0.05 for the last 4 h) and, consequently, in the vertical force impulse (5.5 to 11.0% difference, p>0.05). The Pedar Mobile system appeared to be a valid instrument to measure the vertical force during a long-term period when using the drift correction program described in this study.

Qualitative evaluation of a form for standardized information exchange between orthopedic surgeons and occupational physicians (Article)

2006-11-02T00:00:00Z

BACKGROUND: Both occupational physicians and orthopedic surgeons can be involved in the management of work relevant musculoskeletal disorders. These physicians hardly communicate with each other and this might lead to different advice to the patient. Therefore, we evaluated a standardized information exchange form for the exchange of relevant information between the orthopedic surgeon and the occupational physician. The main goals of this qualitative study are to evaluate whether the form improved information exchange, whether the form gave relevant information, and to generate ideas to further improve this information exchange. METHODS: The information exchange form was developed in two consensus meetings with five orthopedic surgeons and five occupational physicians. To evaluate the information exchange form, a qualitative evaluation was set up. Structured telephone interviews were undertaken with the patients, interviews with the physicians were face-to-face and semi-structured, based on a topic list. These interviews were recorded and literally transcribed. Each interview was analyzed separately in Atlas-Ti. RESULTS: The form was used for 8 patients, 7 patients agreed to participate in the qualitative evaluation. All three orthopedic surgeons involved and three of the six involved occupational physicians agreed to be interviewed. The form was transferred to 4 occupational physicians, the other 3 patients recovered before they visited the occupational physician. The information on the form was regarded to be useful. All orthopedic surgeons agreed that the occupational physician should take the initiative. Most physicians felt that the form should not be filled out for each patient visiting an orthopedic surgeon, but only for those patients who do not recover as expected. Orthopedic surgeons suggested that a copy of the medical information provided to the general practitioner could also be provided to occupational physicians. CONCLUSION: The information exchange form was regarded to be useful and could be used in practice. The occupational physician should take the initiative for using this form and most physicians felt the information should only be exchanged for patients who do not recover as expected. That means that the advantage of giving information early in the treatment is lost.

Biochemical and functional modulation of the cartilage collagen network by IGF1, TGFbeta2 and FGF2 (Article)

2006-11-01T00:00:00Z

OBJECTIVE: Examine effects of insulin-like growth factor 1 (IGF1), transforming growth factor beta2 (TGFbeta2) and fibroblast growth factor 2 (FGF2) on proteoglycan and collagen network and biomechanical properties of the newly formed cartilage matrix. METHODS: Bovine articular chondrocytes were cultured in alginate beads for 3 weeks with or without FGF2, TGFbeta2 or IGF1 in the presence of 10% FCS. Proteoglycan content, collagen content, hydroxylysylpyridinoline cross-links and overall matrix metalloproteinase (MMP) activity in the culture medium were measured. Alginate disks cultured for 5 weeks were used to evaluate the effect of growth factors on mechanical properties of the construct by determining the equilibrium aggregate modulus and secant modulus. RESULTS: IGF1 increased collagen and proteoglycan deposition. FGF2 mainly decreased collagen deposition and TGFbeta2 proteoglycan deposition. A decrease in cross-links was observed in matrix produced by chondrocytes cultured in the presence of TGFbeta2. IGF1 and FGF2 had no influence on the number of cross-links per collagen molecule. Overall MMP activity was significantly higher in culture medium of cells cultured with FGF2. TGFbeta2 and IGF1 had no effect on MMP activity. After 35 days of culture, the matrix produced under influence of IGF1 had a lower permeability and a trend to increase stiffness. FGF2 showed a trend to lower both properties. TGFbeta2 had no effect on these parameters. CONCLUSION: IGF1, TGFbeta2 and FGF2 had differential effects on collagen network formation. Of the three growth factors tested, IGF1 seems to be best in promoting the formation of a functional collagen network since it increased proteoglycan and collagen deposition and improved the mechanical properties.

Osteotomy for medial compartment arthritis of the knee using a closing wedge or an opening wedge controlled by a Puddu plate. A one-year randomised, controlled study (Article)

2006-11-01T00:00:00Z

A prospective, randomised, controlled trial compared two different techniques of high tibial osteotomy with a lateral closing wedge or a medial opening wedge, stabilised by a Puddu plate. The clinical outcome and radiological results were examined at one year. The primary outcome measure was the achievement of an overcorrection of valgus of 4 degrees . Secondary outcome measures were the severity of pain (visual analogue scale), knee function (Hospital for Special Surgery score), and walking distance. Between January 2001 and April 2004, 92 patients were randomised to one or other of the techniques. At follow-up at one year the post-operative hip-knee-ankle angle was 3.4 degrees (+/- 3.6 degrees SD) valgus after a closing wedge and 1.3 degrees (+/- 4.7 degrees SD) of valgus after an opening wedge. The adjusted mean difference of 2.1 degrees was significant (p = 0.02). The deviation from 4 degrees of valgus alignment was 2.7 degrees (+/- 2.4 degrees SD) in the closing wedge and 4.0 degrees (+/- 3.6 degrees sd) in the opening-wedge groups. The adjusted mean difference of 1.67 degrees was also significant (p = 0.01). The severity of pain, knee score and walking ability improved in both groups, but the difference was not significant. Because of pain, the staples required removal in 11 (23%) patients in the closing-wedge group and a Puddu plate was removed in 27 (60%) patients in the opening-wedge group. This difference was significant (p < 0.001). We conclude that closing-wedge osteotomy achieves a more accurate correction with less morbidity, although both techniques had improved the function of the knee at one year after the procedure.

Brace treatment for osteoarthritis of the knee: a prospective randomized multi-centre trial (Article)

2006-08-01T00:00:00Z

OBJECTIVE: To evaluate the effect of a brace intended to reduce load in patients with medial or lateral compartmental osteoarthritis (OA) and concurrent varus or valgus alignment, respectively. DESIGN: This multi-centre randomized controlled trial (performed 2001-2003) studies the additive effect of a brace intended to reduce load in conservative treatment of unicompartmental OA of the knee. Setting: Orthopedic department of a university medical centre and of one general hospital. The follow-up was 12 months. Patients: 117 patients with unicompartmental OA of the knee. Intervention group (n=60) comprising conservative treatment with additional brace treatment and a control group (n=57) comprising conservative treatment alone. Primary outcome measures: Pain severity and knee function score. Secondary outcome measures: Walking distance and quality of life. Analysis: Multiple linear regression models according to the intention-to-treat-principle were used to assess outcome differences for the entire group of patients. In addition, we performed explorative subgroup analyses on primary overall outcomes stratified for alignment, degree of OA, origin of OA, and age. RESULTS: Although the primary outcome measures were improved in the intervention group in comparison with the controls at each assessment point, the differences reached only borderline significance. The reported walking distances at 3 months, 12 months and overall were significantly longer in the brace group (P=0.03, P=0.04 and P=0.02, respectively). Subgroup analysis showed a better effect in the varus group, in patients with severe OA, in patients with secondary OA and in patients younger then 60 years. In total 25 patients in the brace group and 14 in the control group changed their initial treatment, mostly (74%) because of a lack of beneficial effect. CONCLUSIONS: The results indicate that a brace intended to reduce load shows small effects in patients with unicompartmental OA. However, many patients do not adhere in the long run to this kind of conservative treatment.

Stretch-induced modulation of matrix metalloproteinases in mineralizing osteoblasts via extracellular signal-regulated kinase-1/2 (Article)

2006-07-01T00:00:00Z

Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) produced by osteoblasts play an essential role in bone remodeling. Hence, these proteins could provide an interesting means by which mechanical loading leads to adaptation of bone. Here, we examined the effect of stretch on MMP-1, -2, -3, -8, -9, -13, and -14, as well as TIMP-1 and -2 gene expression in differentiating, mineralizing, and nonmineralizing human SV-40 immortalized preosteoblast cells. In the mineralizing osteoblast culture, but not in the nonmineralizing cultures, cyclic stretch for only 15 min resulted in an increase of MMP-1 (fourfold) and -3 (depending on differentiation stage up to 25-fold) transcript abundance. No clear effect was observed for other MMPs, TIMP-1 or -2. The increase of MMP-1 and -3 was confirmed on the protein level. Stretching experiments performed in the presence of a specific inhibitor of extracellular signal-regulated kinase (ERK) showed a strong suppression of the stretch-induced increase in MMP-1 and -3. In conclusion, we show that MMP-1 and MMP-3 are mechanosensitive genes in mineralizing the human osteoblast, and that the mechano-induction of these genes is mediated via the ERK pathway. Our findings implicate that these MMPs are important factors in the mechanoregulation of bone turnover. With the ability to generate MMPs at highly stretched sites, osteoblasts can potantially direct osteoclasts to specific bone surface areas prepared for resorption.

Prediction of torsional failure in 22 cadaver femora with and without simulated subtrochanteric metastatic defects: a CT scan-based finite element analysis (Article)

2006-07-01T00:00:00Z

BACKGROUND: In metastatic bone disease, prophylactic fixation of impending long bone fracture is preferred over surgical treatment of a manifest fracture. There are no reliable guidelines for prediction of pathological fracture risk, however. We aimed to determine whether finite element (FE) models constructed from quantitative CT scans could be used for predicting pathological fracture load and location in a cadaver model of metastatic bone disease. MATERIAL AND METHODS: Subject-specific FE models were constructed from quantitative CT scans of 11 pairs of human femora. To simulate a metastatic defect, a transcortical hole was made in the subtrochanteric region in one femur of each pair. All femora were experimentally loaded in torsion until fracture. FE simulations of the experimental set-up were performed and torsional stiffness and strain energy density (SED) distribution were determined. RESULTS: In 15 of the 22 cases, locations of maximal SED fitted with the actual fracture locations. The calculated torsional stiffness of the entire femur combined with a criterion based on the local SED distribution in the FE model predicted 82% of the variance of the experimental torsional failure load. INTERPRETATION: In the future, CT scan-based FE analysis may provide a useful tool for identification of impending pathological fractures requiring prophylactic stabilization.

Interventions for treating the posterior interosseus nerve syndrome: a systematic review of observational studies (Article)

2006-06-01T00:00:00Z

For the posterior interosseus nerve syndrome (PINS), no randomised controlled trials or controlled clinical trials about the effectiveness of interventions are available; only case series can be found. Although the validity of case series is inferior to controlled trials, they may provide valuable data about the efficacy of treatment options. Therefore, we systematically reviewed all available observational studies on treatment of PINS. A literature search and additional reference checking was done. On the basis of previous checklists, we constructed a quality assessment and rating system to analyse the included case series. Studies with less than 50% of the maximum points on the methodological quality assessment were excluded from the analysis. The results are summarised according to a rating system for the strength of the scientific evidence. Six eligible case series for this review were found. After the data extraction and methodological quality assessment, two higher quality studies that evaluated the effectiveness of surgical decompression of the PIN were included in the final analysis. There is a tendency for the effectiveness of surgical decompression of the PIN in patients with PINS. The effectiveness of a conservative treatment for PINS is unknown because no higher quality studies are available. Additional high-quality controlled studies are needed to assess the level of 'conclusive evidence' for surgical treatment. There is also a need for high-quality controlled trials into the effectiveness of conservative treatments for PINS.

Bone loss dynamics result in trabecular alignment in aging and ovariectomized rats (Article)

2006-05-01T00:00:00Z

Because of the destructive nature of techniques used to measure bone morphometry, studies of architectural changes and bone loss have utilized cross-sectional study designs, with all its inherent limitations in nuances. Here, the results of a longitudinal study using in vivo micro-CT are presented elucidating the dynamics of bone loss and architectural adaptation in rat models of aging and postmenopausal bone loss. Using 3-D methodology, we observed the changes in bone architecture in the proximal tibia of normally aging and ovariectomized rats for 54 weeks. Spatial patterns in bone resorption were observed that were similar for both groups. Remaining trabeculae increased in thickness or were remodeled into new trabecular structures, especially in the ovariectomized animals. The combination of bone loss and bone formation resulted in alignment of trabeculae across the growth plate. Cortical modeling that was associated with growth continued after cessation of longitudinal growth in the ovariectomized animals, resulting in shape changes of the proximal tibia. The organized nature of the changes in bone architecture that occurred after ovariectomy and the high similarity with the changes observed in the normally aging animals, suggest that estrogen depletion resulted in an acceleration of a normal bone adaptation process. The observed aligning of trabeculae suggests regulation through mechanical loading.

The PEX study - Exercise therapy for patellofemoral pain syndrome: design of a randomized clinical trial in general practice and sports medicine [ISRCTN83938749]. (Article)

2006-03-17T00:00:00Z

BACKGROUND: Patellofemoral complaints are frequently seen in younger and active patients. Clinical strategy is usually based on decreasing provoking activities as sports and demanding knee activities during work and leisure and reassuring the patient on the presumed good outcome.Exercise therapy is also often prescribed although evidence on effectiveness is lacking.The objective of this article is to present the design of a randomized clinical trial that examines the outcome of exercise therapy supervised by a physical therapist versus a clinically accepted "wait and see" approach (information and advice about the complaints only).The research will address to both effectiveness and cost effectiveness of supervised exercise therapy in patients with patellofemoral pain syndrome (PFPS). METHODS/DESIGN: 136 patients (adolescents and young adults) with patellofemoral pain syndrome are recruited in general practices and sport medicine centers. They will be randomly allocated receiving either 3 months of exercise therapy (or usual care.The primary outcome measures are pain, knee function and perception of recovery after 3 months and 12 months of follow up and will be measured by self reporting.Measurements will take place at baseline, 6 weeks, and 3 monthly until 1 year after inclusion in the study.Secondary outcome measurements include an economic evaluation.A cost-utility analysis will be performed that expresses health improvements in Quality Adjusted Life Years (QALYs) and incorporates direct medical costs and productivity costs DISCUSSION: This study has been designed after reviewing the literature on exercise therapy for patellofemoral pain syndrome. It was concluded that to merit the effect of exercise therapy a trial based on correct methodological concept needed to be executed.The PEX study is a randomized clinical trial where exercise therapy is compared to usual care. This trial started in April 2005 and will finish in June 2007. The first results will be available around December 2007.

Glucosamine decreases expression of anabolic and catabolic genes in human osteoarthritic cartilage explants (Article)

2006-03-01T00:00:00Z

OBJECTIVE: To investigate the effect of glucosamine (GlcN) in a human osteoarthritic explant model on expression of genes involved in anabolic and catabolic activities of chondrocytes. METHODS: Human osteoarthritic explants, obtained during knee arthroplasty surgery, were pre-cultured (3 days) and treated with glucosamine-hydrochloride (GlcN-HCl) or glucosamine-3-sulphate (GlcN-S) at 0.5mM and 5mM (4 days). RNA was isolated from the explants and real time RT-PCR was performed. Additionally, total matrix metalloproteinase (MMP) activity was measured in culture medium. RESULTS: Addition of 5mM GlcN led to significant down-regulation of aggrecan (2.65-7.73-fold) and collagen type II (7.75-22.17-fold) gene expression, indicating inhibited anabolic activity. Considering catabolic activities, 5mM GlcN significantly down-regulated aggrecanase-1 and MMP3 and 5mM GlcN-S additionally down-regulated aggrecanase-2 and tissue inhibitor of MMP gene expression significantly. Gene expression was not significantly altered by 0.5mM GlcN. Total MMP activity in culture medium was only significantly reduced after addition of 5mM GlcN-HCl. CONCLUSION: The effects of GlcN on gene expression in a human osteoarthritic explant model suggest that enzymatic breakdown of the extra-cellular matrix might be reduced by the addition of 5mM GlcN. Additionally, restoration of already damaged cartilage is not to be expected, because gene expression of anabolic genes is also down-regulated. We suggest that chondroprotective properties of GlcN in vivo may be based on inhibiting further degradation due to catabolic activities, rather than on the ability to rebuild cartilage.

Treatment of impingement syndrome: a systematic review of the effects on functional limitations and return to work (Article)

2006-03-01T00:00:00Z

The goal of this systematic review is to evaluate the effectiveness of different treatments for impingement syndrome and rotator cuff tear on the improvement in functional limitations and concomitant duration of sick leave. A systematic search for clinical trials or controlled studies was conducted with the following text words: should*, rotator cuff, impingement, work, sick leave, disabilit*, function*. Nineteen articles were included in this review. For functional limitations, there is strong evidence that extracorporeal shock-wave therapy is not effective, moderate evidence that exercise combined with manual therapy is more effective than exercise alone, that ultrasound is not effective, and that open and arthroscopic acromioplasty are equally effective on the long term. For all other interventions there is only limited evidence. We found many studies using range of motion and pain as outcome measures but functional limitations were less often used as an outcome measure in this type of research. Duration of sick leave was seldom included as an outcome measure.

Incidence and prevalence of upper-extremity musculoskeletal disorders. A systematic appraisal of the literature. (Article)

2006-01-31T00:00:00Z

BACKGROUND: A systematic appraisal of the worldwide incidence and prevalence rates of UEDs available in scientific literature was executed to gauge the range of these estimates in various countries and to determine whether the rates are increasing in time. METHODS: Studies that recruited at least 500 people, collected data by using questionnaires, interviews and/or physical examinations, and reported incidence or prevalence rates of the whole upper-extremity including neck, were included. RESULTS: No studies were found with regard to the incidence of UEDs and 13 studies that reported prevalence rates of UEDs were included. The point prevalence ranged from 1.6-53%; the 12-months prevalence ranged from 2.3-41%. One study reported on the lifetime prevalence (29%). We did not find evidence of a clear increasing or decreasing pattern over time. The case definitions for UEDs used in the studies, differed enormously. Therefore, it was not possible to pool the data. CONCLUSION: There are substantial differences in reported prevalence rates on UEDs. Main reason for this is the absence of a universally accepted way of labelling or defining UEDs. If we want to make progress in this field, the first requirement is to agree on unambiguous terminology and classification of EUDs.

Quantification of subchondral bone changes in a murine osteoarthritis model using micro-CT (Article)

2006-01-01T00:00:00Z

In the past few years there has been a considerable interest in the role of bone in osteoarthritis. Despite the increasing evidence of the involvement of bone in osteoarthritis, it remains very difficult to attribute the cause or effect of changes in subchondral bone to the process of osteoarthritis. Although osteoarthritis in mice provides a useful model to study changes in the subchondral bone, detailed quantification of these changes is lacking. Therefore, the goal of this study was to quantify subchondral bone changes in a murine osteoarthritis model by use of micro-computed tomography (micro-CT). We induced osteoarthritis-like characteristics in the knee joints of mice using collagenase injections, and after four weeks we calculated various 3D morphometric parameters in the epiphysis of the proximal tibia. The collagenase injections caused cartilage damage, visible in histological sections, particularly on the medial tibial plateau. Micro-CT analysis revealed that the thickness of the subchondral bone plate was decreased both at the lateral and the medial side. The trabecular compartment demonstrated a small but significant reduction in bone volume fraction compared to the contralateral control joints. Trabeculae in the collagenase-injected joints were thinner but their shape remained rod-like. Furthermore, the connectivity between trabeculae was reduced and the trabecular spacing was increased. In conclusion, four weeks after induction of osteoarthritis in the murine knee subtle but significant changes in subchondral bone architecture could be detected and quantified in 3D with micro-CT analysis.

Accuracy and repeatability of the Pedar Mobile system in long-term vertical force measurements (Article)

2006-01-01T00:00:00Z

Portable insole pressure systems can be used to measure the vertical force during long-term (hours) measurements to determine the patient's amount of weight bearing during daily activities in the hospital and at home. Especially for long-term measurements, the amount and duration of loading pressure insoles can have a large influence on the accuracy, as previous studies found a time-dependent behavior after a relatively short period (minutes) of constant loading. Therefore, this study assessed the accuracy and repeatability of a portable capacitive insole system (Pedar, Novel(GmbH)) to measure vertical force during long-term loading. Static loading experiments were performed during which the Pedar insoles were loaded with 5 and 10 N/cm2 for 7 h. Dynamic loading experiments were performed with one Pedar insole which was cyclically loaded with 300, 500 and 1000 N during two sessions of 1200 load cycles. The static and dynamic experiments were repeated 3 days later. Accuracy, due to offset drift, decreased in time during the start of the static experiments (percent error: -1.9% to 0.3% at hour 0; 26.3% to 34% at hour 7). The percent error for the dynamic experiments ranged from -16% to -19%, from -3% to -7% and from -8% to approximately 0% when the insole was loaded with 300, 500 and 1000 N, respectively. The amount of drift ranged from 12 to 62 N for the 500 and 1000 N loads, respectively. The mean day-to-day percentage difference for the static and dynamic experiments ranged from -2.3% to 0.5%, and from -2.9% to 3.0%, respectively. The results indicate that drift correction is necessary for accurate assessment of vertical force by the Pedar Mobile system to determine the amount of weight bearing during long-term measurements.

Bone mineral density and vertebral fracture history are associated with incident and progressive radiographic knee osteoarthritis in elderly men and women: the Rotterdam Study (Article)

2005-10-01T00:00:00Z

OBJECTIVE: To study the association between baseline femoral neck and lumbar spine bone mineral density (BMD), prevalent fractures and incident and progressive radiographic osteoarthritis (ROA) of the knee in men and women. METHODS: A sample of 1403 subjects (829 women and 574 men) was drawn from the Rotterdam Study, a prospective population-based cohort study of the elderly. Incidence and progression of ROA in quartiles of femoral neck (FN) and lumbar spine (LS) BMD were determined using the Kellgren score, and separate analyses were made for men and women. Furthermore, incidence and progression of ROA were compared in subjects with and without a prevalent vertebral or non-vertebral fracture at baseline. RESULTS: The incidence of knee ROA of subject in the highest FN BMD (10.5%) and LS BMD (14.3%) was significantly higher than of those in the lowest quartiles (3.4% and 3.3% respectively), with corresponding adjusted odds ratios (95% confidence interval) of 2.8 (1.2-6.8) and 4.7 (2.1-10.7). The same trend was seen in the association between LS BMD and the progression of knee ROA, but no association was found between FN BMD and progression of ROA. Separate analyses for men and women both showed significant increased risks in the presence of high baseline BMD, with higher odds ratios in men than in women but larger confidence limits due to lower number of cases in men. Combined incidence and progression of knee ROA in subjects with a prevalent vertebral but not with a prevalent non-vertebral fracture at baseline was 8 times lower than subject without a fracture, independent of baseline BMD. CONCLUSIONS: High systemic BMD at baseline is associated with increased incidence and progression of knee ROA in both men and women, while a prevalent vertebral fracture has a protective effect.

Acute peripheral joint injury: cost and effectiveness of low-field- strength MR imaging--results of randomized controlled trial. (Article)

2005-09-01T00:00:00Z

PURPOSE: To assess prospectively if a short imaging examination performed with low-field-strength dedicated magnetic resonance (MR) imaging in addition to radiography is effective and cost saving compared with the current diagnostic imaging strategy (radiography alone) in patients with recent acute traumatic injury of the wrist, knee, or ankle. MATERIALS AND METHODS: Institutional review board approval and informed consent were obtained. Patients with recent trauma of the wrist, knee, or ankle were randomized across two diagnostic strategies: radiography alone (reference group) or radiography followed by a short MR imaging examination (intervention group). Measures of effectiveness included the number of additional diagnostic procedures, time to last diagnostic procedure, and number of days absent from work. Measures of effectiveness were analyzed by using an exact Wilcoxon-Mann-Whitney test. Time to convalescence and quality of life were analyzed by using a t test. Cost analysis was performed from a societal perspective and analyzed by using a t test. RESULTS: Five hundred patients (207 women, 293 men; mean age, 34.8 years) with acute injury of the wrist, knee, or ankle were randomized. In the intervention group, quality of life for patients with knee injuries was significantly higher during the first 6 weeks, and time to completion of diagnostic work-up was significantly shorter (mean, 3.5 days for intervention group vs 17.3 days for reference group). The number of additional diagnostic procedures was significantly lower in the intervention group versus the reference group (nine vs 35, respectively) for patients with knee injuries. Patients with knee injuries showed the largest difference in costs (intervention group, 1820 [$1966]; reference group, 2231 [$2409]) owing to a reduction in productivity loss. Costs were higher in patients with wrist injuries and almost equal in patients with ankle injuries. All cost differences, however, were not significant. CONCLUSION: Compared with radiography, MR imaging in patients with acute wrist or ankle injuries is neither cost saving nor effective in expediting diagnostic work-up or improving quality of life. In patients with knee injuries, a short MR imaging examination shortens the time to completion of diagnostic work-up, reduces the number of additional diagnostic procedures, improves quality of life in the first 6 weeks, and may reduce costs associated with lost productivity.

Patellar height and the inclination of the tibial plateau after high tibial osteotomy. The open versus the closed-wedge technique (Article)

2005-09-01T00:00:00Z

Our aim was to compare the degree of patellar descent and alteration in angle of the inclination of the tibial plateau in lateral closing-wedge and medial opening-wedge high tibial osteotomy (HTO) in 51 consecutive patients with osteoarthritis of the medial compartment and varus malalignment. Patellar height was measured by the Insall-Salvati (IS) and the Blackburne-Peel (BP) ratios. The tibial inclination was determined by the Moore-Harvey (MH) method. Multivariate linear regression analysis was used to determine the influence of the type of HTO (closing vs opening wedge) on the post-operative patellar height or tibial inclination. The intra- and interobserver variability of these methods was determined before operation and at follow-up at one year. After an opening-wedge HTO the patellar height was significantly more decreased (mean post-operative difference: IS = 0.15; 95% confidence interval (CI) 0.06 to 0.23; BP = 0.11; 95% CI 0.05 to 0.18) compared with a closing-wedge HTO. The angle of tibial inclination differed significantly (mean post-operative difference MH = -6.40 degrees; 95% CI -8.74 to -4.02) between the two HTO techniques, increasing after opening-wedge HTO and decreasing after closing-wedge HTO. There was no clinically-relevant difference in the intra- and interobserver variability of measurements of patellar height either before or after HTO.

The effect of glucosamine sulphate on osteoarthritis: design of a long- term randomised clinical trial [ISRCTN54513166]. (Article)

2005-04-26T00:00:00Z

BACKGROUND: Pharmacological treatment for osteoarthritis (OA) can be divided into two groups: symptom-modifying drugs and disease-modifying drugs. Symptom-modifying drugs are currently the prescription of choice for patients with OA, as disease-modifying drugs are not yet available in usual care. However, there has recently been a lot of debate about glucosamine sulphate (GS), a biological agent that is thought to have both symptom-modifying and disease-modifying properties. This assumption has yet to be proved. The objective of this article is to present the design of a blind randomised clinical trial that examines the long-term symptom-modifying and disease-modifying effectiveness of GS in patients with hip OA. This trial is ongoing and will finish in March 2006. METHODS/DESIGN: Patients with hip OA meeting the ACR-criteria are randomly allocated to either 1500 mg of oral GS or placebo for the duration of two years. The primary outcome measures, which are joint space narrowing (JSN), and change in the pain and function score of the Western Ontario McMaster Universities Osteoarthritis index (WOMAC), are determined at baseline and after two years of follow-up during the final assessment. Intermediate measures at three-month intervals throughout the trial are used to study secondary outcome measures. Secondary outcome measures are changes in WOMAC stiffness score, quality of life, medical consumption, side effects and differences in biomarker CTX-II.

High incidence and recurrence of shoulder and neck pain in nursing home employees was demonstrated during a 2-year follow-up (Article)

2005-04-01T00:00:00Z

OBJECTIVE: This study describes the course of shoulder and neck complaints in a working population over time. STUDY DESIGN AND SETTING: Questionnaires were administered on neck and shoulder complaints over 3 consecutive years. RESULTS: We observed 12-month incidence rates for neck and shoulder complaints of 16% to 18%, 12-month prevalence rates roughly twice as high, and 12-month recurrence rates approximately twice the prevalence rates. Each year, medical care was sought by 21% to 38% of the subjects with neck or shoulder pain, and 13% to 21% were absent from work. Although at the population level the occurrence of neck and shoulder complaints remained constant, the course of complaints within individuals demonstrated a strong episodic nature of neck and shoulder pain. Results from this study suggest that neck and shoulder complaints for most subjects run a recurrent course characterized by a strong variation in occurrence and a self-limiting course. CONCLUSION: These findings suggest that clinical trials should have a sufficiently long follow-up period to demonstrate sustainability of the therapeutic results.

Prognosis of trochanteric pain in primary care (Article)

2005-01-01T00:00:00Z

BACKGROUND: Trochanteric pain is the second most important diagnosis of hip problems presenting in primary care, but its incidence and prognosis in this context is largely unknown. AIM: To determine the 1- and 5-year prognoses of trochanteric pain and the predictive variables for consistent complaints. DESIGN OF THE STUDY: Retrospective cohort study. SETTING: One hundred and sixty-four patients (mean age = 55 years, 80% female) with incidental trochanteric pain in the years 1996 or 2000 were asked in 2001 for past and present symptoms of trochanteric pain. Therapeutic interventions, demographic factors and comorbidity were also investigated. METHOD: The databases of 39 GPs were screened in order to identify all incident cases with a suspicion of trochanteric pain in the years 1996 or 2000. These cases were sent a questionnaire. RESULTS: The incidence of trochanteric pain in primary care is 1.8 patients per 1000 per year. After 1 year at least 36% still suffered from trochanteric pain, and after 5 years this was 29%. Patients with osteoarthritis (OA) in the lower limbs had a 4.8-fold risk of persistent symptoms after 1 year, as compared to patients without OA. Patients who had received a corticosteroid injection had a 2.7-fold chance of recovery after 5 years, as compared with patients who had not received an injection. CONCLUSION: Trochanteric pain is shown to be a chronic disease in a substantial number of patients. The disorder is associated with much impairment when conducting daily activities.

Acute wrist trauma: value of a short dedicated extremity MR imaging examination in prediction of need for treatment (Article)

2005-01-01T00:00:00Z

PURPOSE: To assess predictive value of a short magnetic resonance (MR) imaging examination in addition to or instead of radiography in patients with acute wrist trauma to identify patients who require additional treatment versus those who do not and can be discharged without further follow-up. MATERIALS AND METHODS: Informed consent was obtained from all participating patients; the institutional review board approved the randomized controlled trial and use of data to create prediction models. Of 90 patients (37 female, 53 male; mean age, 40.0 years), 87 with acute wrist trauma were randomized to undergo radiography (n = 43) or radiography and a short MR imaging examination with low-field-strength dedicated extremity MR system (n = 44). Age, sex, trauma mechanism, presence of tenderness of the anatomic snuffbox, radiographic results, MR imaging results, and treatment data were collected. Univariable and multivariable logistic regression analysis was used to create four models for prediction of treatment need. RESULTS: Thirty-six patients had one or more fractures; one patient had a marked soft-tissue lesion. In univariable analysis, age (odds ratio, 1.02; 95% confidence interval: 1.00, 1.05), anatomic snuffbox tenderness (odds ratio, 2.31; 95% confidence interval: 0.90, 5.96), radiographic results (odds ratio, 31.2; 95% confidence interval: 8.90, 109), and positive MR imaging results versus MR imaging not performed (odds ratio, 1.86; 95% confidence interval: 0.57, 6.06) were significantly predictive of treatment need. In multivariable analysis, radiographic results (odds ratio, 24.7; 95% confidence interval: 6.59, 93.1) and positive MR imaging results (odds ratio, 6.28; 95% confidence interval: 1.27, 31.0) were significantly predictive of treatment need. Negative MR imaging results were not significantly predictive (odds ratio, 0.87; 95% confidence interval: 0.20, 3.82). CONCLUSION: A short MR imaging examination with a low-field-strength MR imaging system following radiography in initial evaluation of patients with acute wrist trauma has additional value in prediction of treatment need; it does not have value in identification of patients who can be discharged without further follow-up.

Acute knee trauma: value of a short dedicated extremity MR imaging examination for prediction of subsequent treatment (Article)

2005-01-01T00:00:00Z

PURPOSE: To assess the predictive value of a short magnetic resonance (MR) imaging examination, in addition to or instead of radiography, performed in patients with acute knee trauma to identify those who require additional treatment versus those who do not and can be discharged without further follow-up. MATERIALS AND METHODS: The randomized controlled trial and use of collected data for prediction modeling were approved by the institutional review board; informed consent was obtained. Patients with recent knee injury were included in the trial if radiography was ordered. They were randomized into a group undergoing only radiography and a group undergoing radiography plus immediate MR imaging. A 0.2-T dedicated extremity MR imager and four short pulse sequences were used. Univariable and multivariable logistic regression analysis was used to evaluate patient characteristics, trauma mechanism, and findings at radiography and MR imaging for their value in prediction of need for subsequent treatment within the 6-month follow-up. RESULTS: Data in 189 patients (123 male patients, 66 female patients; mean age, 33.4 years), 109 of whom underwent treatment after their initial visit, were analyzed. Age of 30 years or older, indirect trauma mechanism, radiographic results, and MR imaging results were significant predictors of need for treatment in univariable and multivariable analyses (P < .05). In the multivariable analysis, only abnormal MR imaging results were significantly predictive of need for treatment, and only when MR imaging replaced radiography (odds ratio, 2.61; 95% confidence interval: 1.12, 6.06). CONCLUSION: Implementation of a dedicated extremity MR imaging examination, in addition to or instead of radiography, performed in patients with traumatic knee injury improves prediction of the need for additional treatment but does not significantly aid in identification of patients who can be discharged without further follow-up. Value of a short MR imaging examination in the initial stage after knee trauma is limited.

Acute ankle trauma: value of a short dedicated extremity MR imaging examination in prediction of need for treatment (Article)

2005-01-01T00:00:00Z

PURPOSE: To assess predictive value of a short magnetic resonance (MR) imaging examination with or instead of radiography performed in patients with acute ankle trauma to identify those who require additional treatment versus those who do not and can be discharged without further follow-up. MATERIALS AND METHODS: Informed consent was obtained from all participating patients, and the institutional review board approved the randomized controlled trial and use of data to create prediction models. In a prospective controlled trial, 197 patients with recent ankle trauma (92 women, 105 men) were randomized into two groups: those who underwent radiography and those who underwent a combination of radiography and MR imaging. Data about side of injury, trauma mechanism, and results of radiography and MR imaging were collected. Additional treatment was necessary in 109 of 197 patients after their initial hospital visit. With univariable and multivariable regression analysis, four models were created for prediction of treatment. RESULTS: In univariable analysis, age (odds ratio [OR], 1.02; 95% confidence interval: 1.00, 1.04), radiographic results (OR, 7.92; 95% confidence interval: 3.17, 19.8), and positive or uncertain results in patients who underwent MR imaging versus patients who did not (OR, 2.42; 95% confidence interval: 1.25, 4.70) were predictive of treatment. In the multivariable analysis, positive or uncertain MR imaging results (OR, 2.61; 95% confidence interval: 1.28, 5.30) contributed significantly to prediction of subsequent treatment. Negative MR imaging results did not contribute significantly (OR, 0.66; 95% confidence interval: 0.27, 1.61). CONCLUSION: A limited MR imaging examination in initial evaluation of acute ankle injury with radiography has additional predictive value in identification of patients who need treatment but does not add significant information in identification of those who can be discharged without further follow-up. A limited MR imaging examination cannot replace radiography for prediction of need for additional treatment.

Does this patient have an instability of the shoulder or a labrum lesion? (Article)

2004-10-27T00:00:00Z

CONTEXT: History taking and clinical tests are commonly used to diagnose shoulder pain. Unclear is whether tests and history accurately diagnose instability or intra-articular pathology (IAP). OBJECTIVE: To analyze the accuracy of clinical tests and history taking for shoulder instability or IAP. DATA SOURCES: Relevant studies identified through PubMed, EMBASE, CINAHL, and bibliographies of known primary and review articles. STUDY SELECTION: Studies comparing the performance of history items or physical examination with a reference standard were included. Studies on fibromyalgia, fractures, or systemic disorders were excluded. Of 1449 articles, 35 were eligible, and 17 were selected. DATA EXTRACTION: Data were extracted on study population, clinical tests, reference tests, and outcome. The studies' methodological quality (patient spectrum, verification, blinding, and replication) was assessed with the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) checklist. DATA SYNTHESIS: Six tests showed positive likelihood ratios (LRs) and confidence intervals (CIs). Tests favoring the diagnosis for establishing instability included: relocation (LR, 6.5; 95% CI, 3.0-14.0) and anterior release (LR, 8.3; 95% CI, 3.6-19). Tests showing promise for establishing labral lesions included: the biceps load I and II (LR, 29; 95% CI, 7.3-115.0 and LR, 26; 95% CI, 8.6-80.0), respectively, pain provocation of Mimori (LR, 7.2; 95% CI, 1.6-32.0), and internal rotation resistance strength (LR, 25; 95% CI, 8.1-76.0). The apprehension, clunk, release, load and shift, and sulcus sign tests proved less useful. Results should be cautiously interpreted because studies were completed in select populations in orthopedic practice, mostly assessed by the test designers, and evaluated in single studies only. No accuracy studies were found for history taking or for clinical tests in primary care. CONCLUSIONS: Shoulder complaints are frequently recurrent. Instability might cause some of these complaints. Best evidence supports the value of the relocation and anterior release tests. Symptoms related to IAP (labral tears) remain unclear. Most promising for establishing labral tears are currently the biceps load I and II, pain provocation of Mimori, and the internal rotation resistance strength tests.

Stretch-induced phosphorylation of ERK1/2 depends on differentiation stage of osteoblasts (Article)

2004-10-01T00:00:00Z

The goal of this study was to investigate the effect of mechanical loading on osteoblasts and extracellular signal-regulated kinase (ERK1/2) signaling in relation to osteoblast differentiation and mineralization. A human osteoblast cell line (SV-HFO) was triggered to differentiate to the advanced state of mineralization by addition of the osteogenic factors dexamethasone and beta-glycerophosphate. Osteoblasts were subjected to cyclic, equibiaxial stretch for 5, 15, or 60 min at different stages of differentiation (days 7, 14, and 21). Baseline (static) phosphorylated ERK1/2 and total ERK1/2 levels gradually increased during osteoblast differentiation. Cyclic stretch induced a rapid increase in ERK1/2 phosphorylation with a maximum between 5 and 15 min. Prolonged stretching for 60 min resulted in a decrease of phosphorylated ERK1/2 towards baseline level, suggesting a desensitization mechanism. The effect of stretch on ERK1/2 phosphorylation was strongest at later stages of differentiation (days 14 and 21). At day 21, the increase of ERK1/2 phosphorylation in response to stretch was significantly lower in non-differentiating than in differentiating osteoblasts. This could not be explained by differences in cell density, but did correlate with the formation of extracellular matrix, collagen fibrils. Mineralization of the extracellular matrix did not lead to a further increase of ERK1/2 phosphorylation. In conclusion, the current study demonstrates that the extent of activation of the ERK1/2 pathway is dependent on the differentiation or functional stage of the osteoblast. The presence of an extracellular matrix, but not per se mineralization, seems to be the predominant determinant of osteoblastic response to strain.

Work-related risk factors for the incidence and recurrence of shoulder and neck complaints among nursing-home and elderly-care workers (Article)

2004-08-01T00:00:00Z

OBJECTIVES: This study assessed the differences and similarities in the incidence and recurrence of shoulder and neck complaints with respect to work-related physical, psychosocial, and personal risk factors. METHODS: A prospective cohort study was carried out among 769 workers of nursing homes and homes for the elderly. At baseline, a questionnaire was used to collect data on personal characteristics, physical workload, psychosocial workload, and the presence of shoulder and neck complaints. After 1 and 2 years, follow-up data were collected on shoulder and neck complaints. Generalized estimation equations were used for analyzing risk factors for the participants with at least one follow-up measurement available (N=556, 72%). RESULTS: In the multivariate model, adjusted for age and gender, obesity [odds ratio (OR) 2.12, 95% confidence interval (95%CI) 1.23-3.65] was related to the incidence of shoulder complaints. The incidence of neck complaints was increased for obesity (OR 1.81, 95% CI 1.07-3.05), work in awkward postures (OR 1.76, 95% CI 1.11-2.78), and poor or fair general health (OR 1.53, 95% CI 1.02-2.31). The recurrence of both shoulder and neck complaints was associated with chronic complaints at baseline (shoulder: OR 1.91, 95% 1.36-2.67; neck: OR 1.71, 95% 1.14-2.55) but not with work-related risk factors. CONCLUSIONS: The results suggest that there are differences in risk factors for the incidence and recurrence of shoulder and neck complaints.

Fibroblast growth factor-2 in serum-free medium is a potent mitogen and reduces dedifferentiation of human ear chondrocytes in monolayer culture (Article)

2004-07-01T00:00:00Z

The loss of the differentiated phenotype (dedifferentiation) during the expansion culture of donor chondrocytes remains a large problem in cartilage tissue engineering. Dedifferentiated chondrocytes produce other matrix components and therefore the tissue produced will be of less suitable quality. Previously, the addition of fibroblast growth factor-2 (FGF2) to a serum-containing medium (SCM) during expansion culture was shown to have positive effects on the phenotype of articular chondrocytes. In the present study, we focused on a more defined, serum-free medium (SFM), to expand chondrocytes in monolayer culture for the purpose of cartilage tissue engineering. Adult human ear chondrocytes were expanded in serum-free medium supplemented with 100 ng/ml FGF2. Expansion culture in a conventional serum-containing medium (10% FCS) served as control. The cell yield during expansion culture in serum-free medium with FGF2 was significantly higher compared to serum-containing medium. In addition, chondrocytes expanded in the serum-free medium with FGF2 expressed a more differentiated phenotype at the end of monolayer culture, as indicated by higher gene expression ratios of collagen type II to collagen type I and aggrecan to versican. Also, a higher gene expression of Sox9 was found. Next, suspension in alginate and subsequent culture in vitro or subcutaneous implantation in nude mice was used to evaluate the capacity of the chondrocytes, expanded in either medium, to re-express the differentiated phenotype (redifferentiation) and to form cartilage. The observed beneficial effects of the serum-free medium with FGF2 on the chondrocyte phenotype at the end of monolayer culture were sustained on both transcriptional and extracellular level throughout both redifferentiation methods.

Altered tissue properties induce changes in cancellous bone architecture in aging and diseases (Article)

2004-03-01T00:00:00Z

The mechanical properties of cancellous bone depend on its architecture and the tissue properties of the mineralized matrix. The architecture is continuously adapted to external loads. In this paper, it was assumed that changes in tissue properties leading to changes in tissue deformation can induce adaptation of the architecture. We asked whether changes in cancellous bone architecture with aging and in e.g. early osteoarthrosis can be explained from changes in tissue properties.This was investigated using computer models in which the cancellous architecture was adapted to external loads. Bone tissue with deformations below a certain threshold was resorbed, deformations above another threshold induced formation. Deformations between these two boundaries, in the 'lazy zone', did not induce bone adaptation. The effects of changes in bone tissue stiffness on bone mass, global stiffness and architecture were investigated. The bone gain (40-60%) resulting from a 50% decrease in tissue stiffness (simulating diseased tissue) was much larger than the bone loss (2-30%) resulting from a 50% increase in tissue stiffness (simulating highly mineralized, old tissue). The adaptation induced by a decrease in tissue stiffness resulted in an almost constant stiffness in the main load bearing direction, but the transversal stiffness decreased. An increased tissue stiffness resulted in a higher stiffness in the main direction and overcompensation in the transversal directions: the global stiffness could become even smaller than the stiffness of the original model. Concluding, we showed that changes in trabecular bone in aging and diseases can be partly explained from changes in tissue properties.

Role of first ray hypermobility in the outcome of the Hohmann and the Lapidus procedure. A prospective, randomized trial involving one hundred and one feet (Article)

2004-03-01T00:00:00Z

BACKGROUND: The role of hypermobility of the first tarsometatarsal joint in the etiology of hallux valgus deformity is controversial. Consequently, the need to include an arthrodesis of this joint in the surgical treatment of hallux valgus has been questioned. We designed a study to evaluate the role of arthrodesis of the first tarsometatarsal joint on the outcome of surgical treatment of hallux valgus. METHODS: A prospective, blinded, randomized study was performed to compare the results of a distal osteotomy of the first metatarsal (the Hohmann procedure) with those of an arthrodesis of the first tarsometatarsal joint combined with a soft-tissue procedure of the first metatarsophalangeal joint (the Lapidus procedure) for correction of a symptomatic hallux valgus deformity. One hundred and one feet of eighty-seven patients were included in the study. Fifty feet had a Hohmann procedure, and fifty-one had a Lapidus procedure. The mobility of the first tarsometatarsal joint was assessed in the preoperative clinical examination. On the basis of this examination, two subgroups were identified: sixty-eight feet with a hypermobile first tarsometatarsal joint and thirty-three feet with a nonhypermobile first tarsometatarsal joint. The patients were assessed clinically and radiographically at two years after the operation. RESULTS: There was a significant improvement in the score on the great toe metatarsophalangeal-interphalangeal scale of the American Orthopaedic Foot and Ankle Society and in the pain score following both procedures (p < 0.001). With the numbers available, no significant difference between the two procedures or between the subgroups of feet with a hypermobile first tarsometatarsal joint and those with a nonhypermobile joint could be identified. The patient satisfaction rating did not differ either between the two procedures or between the two subgroups. The radiographic results of the two methods were also similar, except for shortening of the first metatarsal, which was significantly greater (p < 0.001) in the Hohmann group, and plantar flexion of the first metatarsal, which was greater in the Lapidus group. CONCLUSIONS: These short-term results were satisfactory and were comparable with those in previous isolated reports on these two procedures. As no significant differences between the two procedures or between the two subgroups (feet with a hypermobile first tarsometatarsal joint and those with a nonhypermobile joint) were found on clinical assessment, the theory that patients with hallux valgus and a hypermobile first tarsometatarsal joint should be managed with a Lapidus procedure was not supported. Level of Evidence: Therapeutic study, Level I-1a (randomized controlled trial [significant difference]). See Instructions to Authors for a complete description of levels of evidence.

Multiplication of human chondrocytes with low seeding densities accelerates cell yield without losing redifferentiation capacity (Article)

2004-02-01T00:00:00Z

To treat a cartilage defect with tissue-engineering techniques, multiplication of donor cells is essential. However, during this multiplication in monolayer expansion culture chondrocytes will lose their phenotype and produce matrix of inferior quality (dedifferentiation). Dedifferentiation occurs more extensively with low seeding densities and passaging. To obtain cartilage of good quality it is important that the multiplicated cells regain their cartilaginous phenotype (redifferentiation capacity). A "gold standard" for the multiplication of chondrocytes in monolayer, with respect to seeding density and passaging, is lacking. In numerous available studies, various cell densities have been used, making comparison of the results of these studies difficult. Therefore, we performed a comparative study to gain insight concerning the effect of seeding density and passaging on the capacity of cells to redifferentiate. From the resulting data we deduced the seeding density in monolayer culture for which cell expansion is both sufficient and fast, while the cells retain a capacity to redifferentiate. As a guideline we calculated that, at minimum, 20-fold multiplication is needed to fill an average cartilage defect of 4 cm(2) with the amount of donor chondrocytes we obtained. For this study we used isolated ear chondrocytes from five children. Four different seeding densities in monolayer culture were used, ranging from 3500 to 30000 cells/cm(2). The cells were cultured for four passages. The capacity of the expanded chondrocytes to redifferentiate (redifferentiation capacity) was studied after an additional 3-week culture in alginate beads and was assessed by glycosaminoglycan production and immunohistochemical stainings for collagen type I, collagen type II, elastin, and a fibroblast marker (11-fibrau). In general, we found that both passaging and decreasing seeding density yielded an increase in expanded chondrocytes, but at the same time decreased the dedifferentiation capacity. In further analyzing our data according to the proposed guidelines we found that with lower seeding densities sufficient multiplication (20 times) was reached in less time and with less passaging than at higher seeding densities. Importantly, the redifferentiation capacity of these chondrocytes was preserved. It was equal to or even surpassed that of chondrocytes multiplied 20 times at higher seeding densities, which required more time and more passages in monolayer culture. Thus, for cartilage tissue-engineering purposes we propose that expansion culture with low seeding densities is preferable.

Detecting and tracking local changes in the tibiae of individual rats: a novel method to analyse longitudinal in vivo micro-CT data (Article)

2004-01-01T00:00:00Z

In this study we present the analysis of in vivo micro-CT scans using a new method based on image registration that accurately evaluates longitudinal micro-CT studies. We tested if detailed changes in the bone architecture could be detected and tracked in individual animals. A prototype in vivo micro-CT scanner (Skyscan 1076) was developed in which tibiae of rats that are lying on a bed under gas anaesthesia were scanned. For this study, three female Wistar rats were used: a sham-operated rat, an ovariectomised (OVX) rat and one rat that served as a reproducibility control. The reproducibility control rat was scanned twice in 1 day. The other animals were scanned at week 0, just before surgery, at week 4 and at week 14 after surgery. Architectural changes over time were detected by overlaying two data sets made at different time points using an algorithm that uses mutual information for optimal registration. The scans were segmented into binary data sets using a local thresholding algorithm. The reproducibility test showed small errors of less than 3% in bone volume measurements and errors less than 0.5% in measurements of trabecular thickness. The sham-operated rat showed no changes in total bone volume, though thinning and eventual loss of some small trabeculae could be detected, which could be related to the age of the animal. The OVX rat lost much trabecular bone volume, especially in the metaphysis (60% at week 4, 75% at week 14). The remaining trabeculae slowly increased in thickness. Following the different scans in time showed the forming of new trabecular structures. Additionally, small longitudinal growth at the growth plate could be detected after the first 4 weeks. Further, the OVX rat showed extensive modelling at the proximal endosteal lateral cortex. We have shown a new method that can detect and track changes in the local bone architecture and individual trabeculae in time, in an individual living animal. This method enables longitudinal in vivo micro-CT studies and has the potential to greatly contribute to experimental rat or mouse studies on pharmacological intervention and transgenic models.

Osteotomie ter hoogte van de knie voor jonge patienten met gonartrose (Article)

2004-01-01T00:00:00Z

Young patients with gonarthrosis that does not respond adequately to conservative therapy can be treated by corrective osteotomy. Osteoarthritis of one compartment more often has a mechanical aetiology than osteoarthritis of the entire knee. Patients with osteoarthritis of the medial compartment often have a genu varum (bow-legs) while patients with osteoarthritis of the lateral compartment often have a genu valgum (knock-knees). The goal of corrective osteotomy is to transfer the load bearing to the normal compartment, which will reduce the symptoms and permit arthroplasty to be postponed. In retrospective studies, the procedure resulted in less pain, improved knee function or postponement of knee arthroplasty in 28-87% of the patients. Possible complications include pseudarthrosis, thromboembolism, contracture of the patellar tendon, paresis of the N. peroneus, compartment syndrome. The outcome of osteotomy for gonarthrosis depends on careful patient selection, the stage of osteoarthritis, and the achievement and maintenance of the correction of the load axis that was calculated before the operation.

Influence of hip dysplasia on the development of osteoarthritis of the hip (Article)

2004-01-01T00:00:00Z

BACKGROUND: It has been suggested that in some patients with primary hip osteoarthritis (OA), the disease occurs as a consequence of acetabular dysplasia or hip dysplasia (HD). OBJECTIVE: To carry out a systematic review to investigate the association between acetabular dysplasia and hip OA. METHODS: A database search of Medline, Embase, and the Cochrane library was carried out, and articles that aimed at studying the relationship between HD and hip OA were identified. The methodological quality of the selected studies was assessed using a standardised set of criteria, and a best evidence synthesis was used to summarise the results from the individual studies. RESULTS: Five cohort studies and four case-control studies were included in this review. One cohort study had the correct design to answer the question and was considered to be a high quality study. This study reported a positive association between HD and hip OA. Overall, limited evidence was found for a positive association between HD and hip OA. Most studies included older people. In younger age groups the relation between HD and OA or hip complaints may be much higher. CONCLUSION: The evidence for the influence of HD on the occurrence of hip OA, at age 50-60 or older, is limited.

Improved cartilage integration and interfacial strength after enzymatic treatment in a cartilage transplantation model (Article)

2004-01-01T00:00:00Z

The objective of the present study was to investigate whether treatment of articular cartilage with hyaluronidase and collagenase enhances histological and mechanical integration of a cartilage graft into a defect. Discs of 3 mm diameter were taken from 8-mm diameter bovine cartilage explants. Both discs and annulus were either treated for 24 hours with 0.1% hyaluronidase followed by 24 hours with 10 U/ml collagenase or left untreated (controls). Discs and annulus were reassembled and implanted subcutaneously in nude mice for 5 weeks. Integration of disc with surrounding cartilage was assessed histologically and tested biomechanically by performing a push-out test. After 5 weeks a significant increase in viable cell counts was seen in wound edges of the enzyme-treated group as compared with controls. Furthermore, matrix integration (expressed as a percentage of the total interface length that was connected; mean +/- standard error) was 83 +/- 15% in the treated samples versus 44 +/- 40% in the untreated controls. In the enzyme-treated group only, picro-Sirius Red staining revealed collagen crossing the interface perpendicular to the wound surface. Immunohistochemical analyses demonstrated that the interface tissue contained cartilage-specific collagen type II. Collagen type I was found only in a small region of fibrous tissue at the level of the superficial layer, and collagen type III was completely absent in both groups. A significant difference in interfacial strength was found using the push-out test: 1.32 +/- 0.15 MPa in the enzyme-treated group versus 0.84 +/- 0.14 MPa in the untreated controls. The study shows that enzyme treatment of cartilage wounds increases histological integration and improves biomechanical bonding strength. Enzymatic treatment may represent a promising addition to current techniques for articular cartilage repair.

Living cells in 1 of 2 frozen femoral heads (Article)

2003-12-01T00:00:00Z

Allogeneic, frozen bone is now the most commonly grafted tissue (Norman-Taylor and Villar 1997). Tissue banks collect bone material according to protocols developed with the aim of maintaining osseoinductive properties of grafts as well as preventing transmission of viral or bacterial diseases (Standards from the American Association of Tissue Banks (AATB) or from the European Association for Musculo-skeletal Transplanting (EAMST)). Standard procedures include cryopreservation of tissue at -80 degrees C, which is generally considered to devitalize the bone by killing all cells present, resulting in reduced immunogenicity of the graft. The osseoinductive properties of frozen, allogeneic bone grafts have therefore mainly been attributed to the dead bone matrix, that may provide osteoblast-stimulating growth factors and other essential proteins, and/or an osteoclast substrate to direct bone remodeling (Aspenberg et al. 1996, Kingsmill et al. 1999). Recently however, it was suggested that some cells in bone biopsies may survive standard bone bank freezing procotols. It is unclear whether vital cells are present in other bone banks and whether these cells can contribute to the clinical outcome of frozen allogeneic bone grafting. In this report, we show that frozen bone biopsies, obtained from the Erasmus Medical Center bone bank may contain living cells that can be cultured in vitro. These cultured cells were found to originate from the donor by genotyping.

The whole leg radiograph: standing versus supine for determining axial alignment (Article)

2003-10-01T00:00:00Z

The whole leg radiograph (WLR), the standard technique for determining axial alignment, is usually taken in a standing position, although some prefer the supine position. To determine the difference between these two positions, we performed a standing and a supine WLR in 20 patients with a varus alignment. We found an average of 2 degrees more varus deviation in the standing position than in the supine position.

A simulation model at trabecular level to predict effects of antiresorptive treatment after menopause (Article)

2003-09-23T00:00:00Z

Antiresorptive drugs are widely used to prevent osteoporotic fractures in men and women. Large clinical trials have shown vertebral fracture risk reductions up to 50%, resulting from relatively small increases of 3-8% in bone mineral density (BMD). We developed a computer model that mimics bone turnover in human vertebral cancellous bone during menopause and antiresorptive treatment. This model links cell activity in trabeculae to changes in bone volume and mechanical properties. We asked whether treatment started shortly after menopause is better than treatment started late after menopause. In order to answer this question we used the model to simulate menopause and 5 years of anti-resorptive treatment with two different agents: one incorporated in the tissue, one not incorporated. We found that late treatment can result in almost the same bone mass as early treatment, but early treatment is much better in conserving the strength and stiffness of the cancellous bone. The effect of the incorporation of drugs in the tissue (giving the drugs a long half-life) was small. After discontinuation of treatment, bone was lost slower, but after 20 years the difference between the incorporated and the not incorporated drug in stiffness and bone volume was below 3%. This kind of simulation model may be used to preclinically test new pharmaceuticals and treatment protocols and to predict long-term effects of treatment before patient data become available.

Techniques for measuring weight bearing during standing and walking (Article)

2003-08-01T00:00:00Z

OBJECTIVE: To classify and assess techniques for measuring the amount of weight bearing during standing and walking. BACKGROUND: A large variety of weight bearing measuring techniques exists. This review describes their advantages and limitations to assist clinicians and researchers in selecting a technique for their specific application in measuring weight bearing. METHODS: A literature search was performed in Pubmed-Medline, CINAHL, and EMBASE. Measurement techniques were classified in 'clinical examination', 'scales', 'biofeedback systems', 'ambulatory devices' and 'platforms', and assessed on aspects of methodological quality, application, and feasibility. RESULTS: A total of 68 related articles was evaluated. The clinical examination technique is a crude method to estimate the amount of weight bearing. Scales are useful for static measurements to evaluate symmetry in weight bearing. Biofeedback systems give more reliable, accurate and objective data on weight bearing compared to clinical examination and scales, but the high costs could limit their use in physical therapy departments. The ambulatory devices can measure weight bearing with good accuracy and reliability in the hospital and at home. Platforms have the best methodological quality, but are mostly restricted to a gait laboratory, need trained personnel, and are expensive. CONCLUSIONS: The choice of a technique largely depends upon the criteria discussed in this review; however the clinical utilisation, the research question posed, and the available budget also play a role. The new developments seen in the field of 'ambulatory devices' are aimed at extending measuring time, and improved practicality in data collection and data analysis. For these latter devices, however, mainly preliminary studies have been published about devices that are not (yet) commercially available.

Placebochirurgie in gerandomiseerd onderzoek: soms wel uitvoerbaar en ethisch verantwoord (Article)

2003-03-08T00:00:00Z

Randomised clinical trials in surgery are relatively rare. There are many problems associated with the comparison of two types of surgical treatment. Comparison of surgical treatment and a non-operative approach is difficult because patient and surgeon are not blinded. In a recent study, the outcomes after arthroscopic lavage or debridement were no better than those after a placebo arthroscopic procedure. This placebo treatment appears ethically justified, because the risks to participants of this study were limited. Placebo surgery may help to resolve longstanding debates about several surgical procedures.

Tissue-engineered cartilage using serially passaged articular chondrocytes. Chondrocytes in alginate, combined in vivo with a synthetic (E210) or biologic biodegradable carrier (DBM) (Article)

2003-03-01T00:00:00Z

In vitro multiplication of isolated autologous chondrocytes is required to obtain an adequate number of cells to generate neo-cartilage, but is known to induce cell-dedifferentiation. The aim of this study was to investigate whether multiplied chondrocytes can be used to generate neo-cartilage in vivo. Adult bovine articular chondrocytes, of various differentiation stages, were suspended in alginate at densities of 10 or 50 million/ml, either directly after isolation (P0) or after multiplication in monolayer for one (P1) or three passages (P3). Alginate with cells was seeded in demineralized bovine bone matrix (DBM) or a fleece of polylactic/polyglycolic acid (E210) and implanted in nude mice for 8 weeks. The newly formed tissue was evaluated by Alcian Blue and immunohistochemical staining for collagen type-II and type-I. Structural homogeneity of the tissue, composed of freshly isolated as well as serially passaged cells, was found to be enhanced by high-density seeding (50 million/ml) and the use of E210 as a carrier. The percentage of collagen type-II positive staining P3-cells was generally higher when E210 was used as a carrier. Furthermore, seeding P3-chondrocytes at the highest density (50 million/ml) enhanced collagen type-II expression. This study shows promising possibilities to generate structurally regular neo-cartilage using multiplied chondrocytes in alginate in combination with a fleece of polylactic/polyglycolic acid.

Wat is er bekend over de werkzaamheid van 'Sonocur Plus'? (Letter To Editor)

2003-03-01T00:00:00Z

Letter by Dalhuisen with a response from Verhaar

Luxatie van totaleheupprothese; risicofactoren en behandeling (Article)

2003-02-15T00:00:00Z

Primary hip prostheses dislocate in 0.4 to 8.7% of the cases. Revision hip prostheses dislocate in 5 to 20% of the cases. High age, female sex, co-morbidity and alcoholism increase the risk of dislocation. The surgical approach of the hip and the experience of the surgeon are important factors in the operation technique. The anterior approach causes the least dislocations, but a disadvantage of this approach is that patients are more likely to walk with a limp afterwards. The selected implant also influences the dislocation risk. The smaller the head, the narrower the neck must be. Furthermore, the femur must not come to be too close to the pelvis. If necessary, a cup can be used with a raised anterior edge. Treatment of a primary dislocation is usually conservative and is based on providing the patient with guidelines. An abduction brace can be prescribed if a patient is not able or willing to comply with these rules. If dislocation is a recurring problem, revision of the prosthesis is often the only solution.

Acute renal failure after local gentamicin treatment in an infected total knee arthroplasty (Article)

2002-10-01T00:00:00Z

Local gentamicin treatment in revision surgery for infected hip and knee prostheses is well established. It is a safe and effective method compared with the systemic use of aminoglycosides. Although nephrotoxic side effects are uncommon, we report a case of acute renal failure after 2-stage revision treatment of an infected knee prosthesis with gentamicin-impregnated beads and block spacers. The combined use of beads and a cement block spacer, both gentamicin impregnated, may have induced this severe complication. Use of this procedure in elderly patients warrants careful follow-up of renal function.

Prognostic factors of progress of hip osteoarthritis: a systematic review (Article)

2002-10-01T00:00:00Z

Joint space narrowing and relationship with symptoms and signs in adults consulting for hip pain in primary care (Article)

2002-08-01T00:00:00Z

OBJECTIVE: To study whether clinical symptoms and signs can predict radiological osteoarthritis (OA) of the hip in primary care patients with hip pain. METHODS: Consecutive patients (n = 220) aged 50 years or older consulting the general practitioner for hip pain and referred for radiological investigation underwent a standardized history, radiological, laboratory, and physical examination. Radiological OA was confirmed with joint space < or = 2.5 mm. Additionally, a more stringent definition was used (< or = 1.5 mm). The relationship between radiological OA and possible clinical symptoms/signs of OA was tested. Combinations of clinical symptoms/signs that had shown an independent relationship with radiological OA in multivariate analyses were tested for their predictive value. RESULTS: Radiological OA (joint space < or = 2.5 mm) of the (more) symptomatic hip was present in 35.5% of the study population and more severe OA (joint space < or = 1.5 mm) in 11.4%. Presence of 4 specific symptoms/signs from history and examination showed a positive predictive value (PPV) of 73% (specificity 91%, sensitivity 45%) for radiological OA. When 5 specific symptoms/signs were present, the PPV for the more severe radiological OA was 82% (specificity 98%, sensitivity 72%), and when 6 or 7 specific symptoms/signs were present the PPV was 100% (specificity 100%, sensitivity 40% and 8%, respectively). Negative predictive values were high for almost all combinations. CONCLUSION: In primary care patients with hip pain, clinical symptoms and signs can to a moderate extent predict radiological OA and to a large extent more severe radiological OA.

Serum-free medium supplemented with high-concentration FGF2 for cell expansion culture of human ear chondrocytes promotes redifferentiation capacity (Article)

2002-08-01T00:00:00Z

For tissue engineering of autologous cartilage, cell expansion is needed to obtain the cell numbers required. Standard expansion media contain bovine serum. This has several disadvantages, that is, the risk of transmitting diseases and serum-batch variations. The aim of this study was to find a serum-free medium with at least the same potential to expand cell numbers as serum-containing media. Ear chondrocytes of three young children were expanded in either serum-containing medium (SCM; DMEM with 10% fetal calf serum) or serum-free medium (SFM; DMEM with ITS+) supplemented with 5 or 100 ng/mL fibroblast growth factor-2 (FGF2). To promote cell adherence onto the culture flask, the serum-free conditions were cultured with 10% serum for 1 day after each trypsinization. After the fourth passage, the chondrocytes were encapsuled in alginate beads and redifferentiated in a SFM (DMEM with ITS+, hydrocortisone, and L-ascorbic acid) supplemented with 10 ng/mL IGF-I and 10 ng/mL TGFbeta-2. Results showed that expansion in SFM with 100 ng/mL FGF2 was comparable to expansion in SCM. Redifferentiation with SFM with IGF-I and TGFbeta-2 showed high collagen type II expression and high GAG/DNA production regardless of which expansion medium had been used. However, chondrocytes expanded in SFM with 100 ng/mL FGF2 resulted in less positive cells for collagen type I and 11-fibrau (a fibroblast membrane marker). The present study shows that it is possible to use serum-free medium for tissue engineering of cartilage. Expansion of immature ear chondrocytes in SFM supplemented with high-concentration FGF2 resulted in high cell numbers, which in addition had better redifferentiation capacity than cells expanded in medium with 10% serum.

Migration of the femoral stem after impaction bone grafting (Article)

2002-08-01T00:00:00Z

We report the initial results of an ongoing randomised, prospective study on migration of the Exeter and Elite Plus femoral stems after impaction allografting, as measured by radiostereometry. Clinically, the impaction technique gave good results for both stems. The mean subsidence in the first year was 1.30 mm and 0.20 mm for the Exeter and the Elite Plus stems, respectively. In the second year, the Exeter stem continued to subside further by a mean of 0.42 mm, while the Elite Plus stem did not do so. Subsidence of the Exeter stem correlated with deficiency of bone stock as graded on the Gustilo and Pasternak scale. This correlation was not found for the Elite Plus stem. None of the other parameters which were studied predisposed to subsidence. There was no significant association between the amount of subsidence and the radiological appearance of the graft for either stem. Our findings do not support the theory that radial compression, due to subsidence of the Exeter stem, is the essential stimulus for remodelling in impaction allografting.

Specific enzymatic treatment of bovine and human articular cartilage: implications for integrative cartilage repair (Article)

2002-04-01T00:00:00Z

OBJECTIVE: Chondrocyte death in articular cartilage wound edges and the subsequent lack of matrix-producing cells in the interface area are considered to be a major cause of impaired cartilage wound healing and poor integrative cartilage repair. This study was undertaken to investigate whether enzymatic matrix digestion can be used to stimulate integrative cartilage repair via a mechanism of local increase in the amount of vital chondrocytes in cartilage wound edges. METHODS: Full-thickness bovine articular cartilage samples were cultured in vitro for 14 days in standard medium. Samples were either left untreated or treated for 48 hours with 0.3% hyaluronidase or 30 units/ml highly purified collagenase VII. Nuclear and cytoplasmic changes were analyzed to determine cell viability, and the number of vital chondrocytes in wound edges was determined. Subsequently, we investigated whether increased chondrocyte density in the lesion edges resulted in better wound healing. Finally, full-thickness human tibial plateau cartilage explants were tested with similar enzyme treatment protocols to determine the clinical value of our results. RESULTS: In bovine explants a rapid onset of chondrocyte death was observed in wound edges in all treatment groups. This led to low chondrocyte density in a band of 0-150 microm from the lesion edges in untreated and hyaluronidase-treated explants. Treatment with 30 units/ml collagenase resulted in a significant increase in chondrocyte density in this area. The integration experiments demonstrated improved integration of the lesion edges after treatment with collagenase. In human articular cartilage an increase in chondrocyte density at the lesion edges could also be achieved, but only when proteoglycans were depleted from the wound edges prior to collagenase treatment. CONCLUSION: Treatment with highly purified collagenase improves integrative cartilage repair, possibly by increasing the cell density at cartilage wound edges.

Fracture of an exeter stem 3 years after impaction allografting--a case report (Article)

2002-03-23T00:00:00Z

Alginate as a chondrocyte-delivery substance in combination with a non-woven scaffold for cartilage tissue engineering (Article)

2002-03-01T00:00:00Z

For tissue engineering of cartilage, chondrocytes can be seeded in a scaffold and stimulated to produce a cartilage-like matrix. In the present study, we investigated the effect of alginate as a chondrocyte-delivery substance for the construction of cartilage grafts. E210 (a non-woven fleece of polyglactin) was used as a scaffold. When bare' E210 (without alginate and without chondrocytes) was implanted subcutaneously in nude mice for 8 weeks. the explanted tissue consisted of fat and fibrous tissue only. When E210 with alginate but without chondrocytes was implanted in nude mice, small areas of newly formed cartilage were found. Alginate seems to stimulate chondrogenesis of ingrowing cells. When chondrocytes were seeded in E210, large amounts of cartilage were found, independent of the use of alginate. This was expressed by a high concentration of glycosaminoglycans (30 microg/mg w.w.) and the presence of collagen type II (1.5 microg/mg w.w.). Macroscopically the grafts of E210 without alginate were shrunk and warped, whereas the grafts with alginate had kept their original shape during the 8 weeks of implantation. The use of alginate did not lead to inflammatory reactions nor increased capsule formation. In conclusion, the use of alginate to seed chondrocytes in E210 does not influence the amount of cartilage matrix proteins produced per tissue wet weight. However, it provides retention of the graft shape.

Growth factors in cartilage tissue engineering (Article)

2002-01-01T00:00:00Z

Tissue engineering of cartilage consists of two steps. Firstly, the cells from a small biopsy of patient's own tissue have to be multiplied. During this multiplication process they lose their cartilage phenotype. In the second step, these cells have to be stimulated to re-express their cartilage phenotype and produce cartilage matrix. Growth factors can be used to improve cell multiplication, redifferentiation and production of matrix. The choice of growth factors should be made for each phase of the tissue engineering process separately, taking into account cell phenotype and the presence of extracellular matrix. This paper demonstrates some examples of the use of growth factors to increase the amount, the quality and the assembly of the matrix components produced for cartilage tissue engineering. In addition it shows that the "culture history" (e.g., addition of growth factors during cell multiplication or preculture period in a 3-dimensional environment) of the cells influences the effect of growth factor addition. The data demonstrate the potency as well as the limitations of the use of growth factors in cartilage tissue engineering.

Influence of obesity on the development of osteoarthritis of the hip: a systematic review (Article)

2002-01-01T00:00:00Z

OBJECTIVE: To evaluate the evidence for the influence of obesity as a risk factor for the occurrence of osteoarthritis (OA) of the hip. METHODS: A bibliographical search of Medline, EMBASE and the Cochrane library until April 2000 was carried out. Articles describing studies of the relationship between obesity and the occurrence of hip OA were selected. The quality of the studies was assessed with a standardized set of criteria. The outcome of the studies was compared with respect to study characteristics and the quality score for the study. A best-evidence synthesis was used to summarize the results of the individual studies. RESULTS: Five longitudinal and seven cross-sectional studies were included in this review. There was no association between outcome and study design or methodological quality. The associations between obesity and hip OA were, however, stronger in studies in which the diagnosis of hip OA was based not only on radiological criteria but also on clinical symptoms. Overall, moderate evidence was found for a positive association between obesity and the occurrence of hip OA, with an odds ratio of approximately 2. CONCLUSION: The evidence for a positive influence of obesity on the development of hip OA is moderate.

Trabecular bone's mechanical properties are affected by its non-uniform mineral distribution (Article)

2001-12-01T00:00:00Z

The bone remodeling process takes place at the surface of trabeculae and results in a non-uniform mineral distribution. This will affect the mechanical properties of cancellous bone, because the properties of bone tissue depend on its mineral content. We investigated how large this effect is by simulating several non-uniform mineral distributions in 3D finite element models of human trabecular bone and calculating the apparent stiffness of these models. In the 'linear model' we assumed a linear relation between mineral content and Young's modulus of the tissue. In the 'exponential model' we included an empirical exponential relation in the model. When the linear model was used the mineral distribution slightly changed the apparent stiffness, the difference varied between an 8% decrease and a 4% increase compared to the uniform model with the same BMD. The exponential model resulted in up to 20% increased apparent stiffness in the main load-bearing direction. A thin less mineralized surface layer (28 microm) and highly mineralized interstitial bone (mimicking mineralization resulting from anti-resorptive treatment) resulted in the highest stiffness. This could explain large reductions in fracture risk resulting from small increases in BMD. The non-uniform mineral distribution could also explain why bone tissue stiffness determined using nano-indentation is usually higher than finite element (FE)-determined stiffness. We conclude that the non-uniform mineral distribution in trabeculae does affect the mechanical properties of cancellous bone and that the tissue stiffness determined using FE-modeling could be improved by including detailed information about mineral distribution in trabeculae in the models.

Hip problems in older adults: classification by cluster analysis (Article)

2001-11-01T00:00:00Z

No validated classification system of hip disorders in primary care is available. This study explores whether it is possible to obtain such a classification with the method of cluster analyses. A total of 224 consecutive patients aged 50 years or older, consulting the general practitioner for pain in the hip region, and referred for X-ray investigation of the hip, underwent a standardized examination. Ward's cluster analysis with variables from history and physical examination of the hip region resulted in a classification with nine different clusters. These clusters were reproduced in 10 random subsamples and with an alternative cluster analysis. Significant relationships of various external variables (radiological and sonographic signs and variables of low-back and knee examination) with the distinctive clusters were found. Twenty of the approached experts recognized the symptoms in seven clusters as identifiable syndromes. However, further validation of the achieved classification system, especially with respect to the clinical importance, is needed before introducing it into clinical practice.

Monoclonal antibody 11-fibrau: a useful marker to characterize chondrocyte differentiation stage (Article)

2001-10-14T00:00:00Z

The aim of this study was to determine the feasibility of discriminating between differentiated and dedifferentiated chondrocytes by using the Mab 11-fibrau. Mab 11-fibrau did not bind to differentiated chondrocytes in cartilage of human knee joint, auricle, or nasal septum. During monolayer culture, when cells dedifferentiate, the number of 11-fibrau positive cells gradually increased and reached up to 100% after 4 passages. When differentiated chondrocytes were cultured in alginate, most (90--95%) of the cells remained 11-fibrau negative, in accordance with previous studies demonstrating that differentiated chondrocytes cultured in alginate keep their phenotype. Dedifferentiated (11-fibrau positive) cells were subjected to different redifferentiation regimes. As a well-known fact, cultures in alginate in medium where FCS was replaced by IGF1 and TGF beta 2 results in increased collagen type II formation, indicative for redifferentiation. However, the cells remained 11-fibrau positive, suggesting they are not (yet) fully redifferentiated. On the other hand, when dedifferentiated cells (after 4 passages in monolayer culture) were seeded in a biomaterial and implanted subcutaneously in a nude mouse, the newly formed cartilage matrix contained collagen type II and the 11-fibrau staining on the cells had disappeared. Our results indicate that 11-fibrau may be a reliable and sensitive marker of chondrocyte phenotype.

Tendon interposition arthroplasty versus arthrodesis for the treatment of trapeziometacarpal arthritis: a retrospective comparative follow-up study (Article)

2001-09-01T00:00:00Z

Long-term subjective and objective outcomes of 24 tendon interposition arthroplasties in 17 patients and 32 trapeziometacarpal (TMC) arthrodeses in 26 patients were compared retrospectively in a standardized manner. Tendon interposition arthroplasty led to complications less often (27%) than TMC arthrodesis (39%). Patients in the tendon interposition arthroplasty group reported significantly less pain, less temperature intolerance, and better thumb mobility and were more satisfied with pain symptoms than patients in the arthrodesis group. Patients undergoing tendon interposition arthroplasty had better thumb opposition, interphalangeal joint mobility, and radial and palmar TMC joint range of motion. No statistically significant differences were found in tip pinch, key pinch, and grip strength between the 2 groups. Proximal first metacarpal collapse occurred in the tendon interposition patients without affecting subjective or objective outcome. Seven of 25 patients with TMC arthrodesis had pseudarthrosis. Tendon interposition arthroplasty seems to be preferable to TMC joint arthrodesis for the treatment of TMC arthritis.

Growth factor expression in cartilage wound healing: temporal and spatial immunolocalization in a rabbit auricular cartilage wound model (Article)

2001-05-01T00:00:00Z

OBJECTIVE: The ability of cartilage to regenerate following injury is limited, potentially leading to osteoarthritis. Integrative cartilage repair, necessary for durable restoration of cartilage lesions, can be regarded as a wound healing process. Little is known about the effects of growth factors regulating acute cartilage wound healing in vivo. In this study the temporal expression patterns of growth factors and proteoglycan content in cartilage wound edges in vivo were studied. DESIGN: Cartilage wounds were created in rabbit ear cartilage using a 6 mm biopsy punch. Specimens were subsequently harvested 1, 3, 7, 14 and 28 days after surgery. Paraffin sections were thionin stained to visualize proteoglycan loss and replacement. Immunohistochemical staining of TGFbeta1, TGFbeta3, IGF-1, IGF-II and FGF-2 was used to define growth factor expression at the cartilage wound sites. RESULTS: Almost no effect of cartilage wounding was observed one day after surgery. A decrease of proteoglycan content, with a maximal loss at day 7, and a subsequent restoration was observed at the wound edges. Growth factor expression increased simultaneously. Maximal immunostaining for IGF1, IGFII, FGF2 and TGF-beta3 was observed at day 7, followed by a gradual decrease. Increased expression of TGFbeta1 lasted from day 3 until day 14. CONCLUSION: We have demonstrated the ability of chondrocytes to increase growth factor expression and to restore the rapid decrease in proteoglycan content in the initial phase following acute wounding. A temporal increase in intracellular growth factor expression suggests an autocrine and/or paracrine metabolic stimulation, which can be regarded a sign of chondrocytes repair capacity.

Magnetic resonance imaging of multiple epiphyseal dysplasia (type 2) of the knee (Article)

2001-04-23T00:00:00Z

Purpose: The aim of this study was to determine the additional value of magnetic resonance imaging (MRI) in the knee joint of patients with multiple epiphyseal dysplasia (MED) type 2 compared with conventional radiographic examination. Methods: Six individuals with MED (mean age 12.7 years) underwent investigation of their knee joints with conventional radiography and MRI. Results: As in conventional radiographs, MRI images showed irregular and delayed ossification of the epiphyses; articular cartilage had a normal appearance. Conclusion: Magnetic resonance imaging did not reveal specific abnormalities in patients with MED type 2 compared with conventional radiographs. The indications for MRI in patients with MED are the same as in patients without this condition.

A three-dimensional simulation of age-related remodeling in trabecular bone (Article)

2001-04-01T00:00:00Z

After peak bone mass has been reached, the bone remodeling process results in a decrease in bone mass and strength. The formation deficit, the deficit of bone formation compared with previous resorption, results in bone loss. Moreover, trabeculae disconnected by resorption cavities probably are not repaired. The contributions of these mechanisms to the total bone loss are unclear. To investigate these contributions and the concomitant changes in trabecular architecture and mechanical properties, we made a computer simulation model of bone remodeling using microcomputed tomography (micro-CT) scans of human vertebral trabecular bone specimens. Up to 50 years of physiological remodeling were simulated. Resorption cavities were created and refilled 3 months later. These cavities were not refilled completely, to simulate the formation deficit. Disconnected trabeculae were not repaired; loose fragments generated during the simulation were removed. Resorption depth, formation deficit, and remodeling space were based on biological data. The rate of bone loss varied between 0.3% and 1.1% per year. Stiffness anisotropy increased, and morphological anisotropy (mean intercept length [MIL]) was almost unaffected. Connectivity density increased or decreased, depending on the remodeling parameters. The formation deficit accounted for 69-95%, disconnected trabeculae for 1-21%, and loose fragments for 1-17% of the bone loss. Increasing formation deficit from 1.8% to 5.4% tripled bone loss but only doubled the decrease in stiffness. Increasing resorption depth from 28 to 56 microm slightly increased bone loss but drastically decreased stiffness. Decreasing the formation deficit helps to prevent bone loss, but reducing resorption depth is more effective in preventing loss of mechanical stiffness.

Mechanical consequences of bone loss in cancellous bone (Article)

2001-03-01T00:00:00Z

The skeleton is continuously being renewed in the bone remodeling process. This prevents accumulation of damage and adapts the architecture to external loads. A side effect is a gradual decrease of bone mass, strength, and stiffness with age. We investigated the effects of bone loss on the load distribution and mechanical properties of cancellous bone using three-dimensional (3D) computer models. Several bone loss scenarios were simulated. Bone matrix was removed at locations of high strain, of low strain, and random throughout the architecture. Furthermore, resorption cavities and thinning of trabeculae were simulated. Removal of 7% of the bone mass at highly strained locations had deleterious effects on the mechanical properties, while up to 50% of the bone volume could be removed at locations of low strain. Thus, if remodeling would be initiated only at highly strained locations, where repair is likely needed, cancellous bone would be continuously at risk of fracture. Thinning of trabeculae resulted in relatively small decreases in stiffness; the same bone loss caused by resorption cavities caused large decreases in stiffness and high strain peaks at the bottom of the cavities. This explains that a reduction in the number and size of resorption cavities in antiresorptive drug treatment can result in large reductions in fracture risk, with small increases in bone mass. Strains in trabeculae surrounding a cavity increased by up to 1,000 microstrains, which could lead to bone apposition. These results give insight in the mechanical effects of bone remodeling and resorption at trabecular level.

Impaction bone-grafting of severely defective femora in revision total hip surgery: 21 hips followed for 41-85 months (Article)

2000-04-01T00:00:00Z

We performed a prospective study to evaluate the application of impacted allograft bone particles at revision surgery of severely defective femora. According to the Endo-Klinik classification, 21 hips had grade III or IV femoral defects, of which 4 had a preoperative fracture. No femoral re-revisions had been necessary after a mean follow-up of 60 (41-85) months. The mean Harris Hip Score improved by 39 points to 78 points. 2 fractures occurred postoperatively, 1 of which needed reoperation with osteosynthesis. 1 patient needed a closed reduction after dislocation. 4 stems showed significant subsidence (> 10 mm) in the follow-up radiographs. In total hip revision surgery, even severely damaged femora can be successfully treated by impaction allografting.

Fixation-dependent immunolocalization shift and immunoreactivity of intracellular growth factors in cartilage (Article)

2000-01-01T00:00:00Z

The effects of fixation on immunolocalization and immunoreactivity in cartilage tissues were studied using monoclonal antibodies against peptides that can effectively stimulate chondrocytes in vitro and have been shown to play a role in musculoskeletal tissue regeneration: transforming growth factor β1, transforming growth factor β3, insulin-like growth factor I, insulin-like growth factor II and fibroblast growth factor 2. Paraffin sections fixed in buffered formalin, buffered paraformaldehyde, Carnoy and methacarn, as well as cryosections, were tested. A strong immunoreaction was observed in tissue fixed in formaldehyde-based fixatives, with a resemblance to that in cryopreserved tissues. Immunoreactivity was reduced in alcohol-fixed tissues. Furthermore, a striking intracellular immunolocalization shift from cytoplasm to nucleus was observed using alcohol-based fixatives as compared to cryopreserved or formaldehyde-based fixatives. We concluded that, for the detection and localization of growth factors in cartilage tissues, fixation in buffered formalin or paraformaldehyde is optimal.

Sonography for hip joint effusion in adults with hip pain (Article)

2000-01-01T00:00:00Z

OBJECTIVE: To study the prevalence of ultrasonic hip joint effusion and its relation with clinical, radiological and laboratory (ESR) findings in adults with hip pain. METHODS: Patients (n = 224) aged 50 years or older with hip pain, referred by the general practitioner for radiological investigation, underwent a standardised examination. The distance between the ventral capsule and the femoral neck, an increase in which represents joint effusion, was measured sonographically. Joint effusion was defined in three different ways: "effusion" according to Koski's definition, "major effusion", and "asymmetrical effusion" based on only individual side differences. RESULTS: "Effusion" was present in 80 (38%), "major effusion" in 20 (9%), and "asymmetrical effusion" in 47 (22%) patients. Pain in the groin or medial thigh, pain aggravated by lying on the side, decreased extension/internal rotation/abduction/flexion, painful external rotation, and pain on palpation in the groin showed a significant relation (adjusted for age and radiological osteoarthritis of the hip) with ultrasonic hip joint effusion. "Major effusion" showed a significant relation with an increased ESR. When patients with bilateral pain and increased ESR were excluded, a side difference in the range of motion of extension of the hip was shown to be a good predictor for "asymmetrical effusion" (positive predictive value: 71%, negative predictive value: 80%). CONCLUSION: This study showed a relatively high prevalence of ultrasonic joint effusion in adults with hip pain in general practice. Furthermore the results indicate a relation between joint effusion and clinical signs.

The limited value of radionuclide imaging at symptomatic knee prosthesis (Article)

1999-09-01T00:00:00Z

Objective: Determination of the value of bone scanning in symptomatic total knee arthroplasties. Setting: Academic Hospital Maastricht and Maasland Hospital Sittard. Design: Retrospective clinical investigation. Method: The clinical reports of 27 patients, who underwent a bone scintigraphic study, were investigated for complaints and analysis of diagnostic decision making. These patients had persistent symptoms after total knee arthroplasty. In addition, conventional radiographs and the isotope scans were studied without knowledge of the clinical records. Based on these data we evaluated in which cases isotope scanning of the knee had contributed decisively to the further treatment. Results: Isotope scanning did not contribute to the treatment planning if physical examination or conventional radiographs had not led to a clinical diagnosis. This comprised 37% of the patients in our series. If a clinical diagnosis was present, isotope scanning did influence decision making in 65% of the patients. However in the remaining patients with a clinical diagnosis (35%) this was not the case. Conclusion: Radionuclide imaging is of limited value in the diagnostic process of symptomatic total knee arthroplasty. It may support or reject a clinical diagnosis, but in the absence of abnormal findings at physical examinations or radiologic studies, it seldom will induce a change in treatment.

Distorsie of enkelbandruptuur? (Article)

1999-01-01T00:00:00Z

In the Netherlands, almost 500,000 patients visit a physician each year because of an ankle inversion trauma. Most people are seen by a general practitioner, but a considerable number go directly to an emergency department. Recently a nation-wide accepted strategy for diagnosis and treatment of these lesions was formulated. This strategy includes the use of the Ottawa ankle rules, a second physical examination after four to five days if there is severe swelling of the ankle and functional treatment with inelastic tape bandage or brace application in case of an established rupture of the lateral band complex. At present, however, the efficacy of a second physical examination in primary health care has not been analysed and the economic consequences of the new strategy are unknown. From a scientific point of view none of the types of conservative treatment is preferable to another. Further scientific studies are needed.

Limited value of arthroscopic evaluation and treatment of painful knee prostheses: a retrospective study of 27 cases (Article)

1998-11-01T00:00:00Z

Twenty-seven painful knee replacements were evaluated arthroscopically. The diagnostic and therapeutic value of these arthroscopic procedures was studied retrospectively. In 5 of the 27 cases, the arthroscopy revealed no diagnosis for the pain. Some form of arthroscopic treatment was performed in 20 cases; in 6 of these 20 cases, however, the treatment did not reduce the pain. Based on these findings, we conclude that the indications for arthroscopic evaluation and treatment of painful knee prostheses are limited.

Prognose van de totaleheupprothese (Article)

1998-06-20T00:00:00Z

The prognosis of total hip arthroplasty is excellent and as many publications show, the survival of a good type of implant is well above 90 per cent at the 10-year follow-up. The results of the average orthopaedic surgeon may not match those obtained by the experts who have published these results. Therefore, in 1979 a prospective multicentre study was started in Sweden to evaluate the outcome of total hip arthroplasty. This National Hip Register has shown that the outcome is related to type of prosthesis, patient selection and operative technique. The results from one orthopaedic department to another differed considerably. The feedback from the Register resulted in improvements of the overall outcome and decrease of the differences between the orthopaedic departments in Sweden A Dutch National Implant Register is needed.

Honderd jaar orthopedie in Nederland. I. Inleiding (Article)

1998-05-01T00:00:00Z

One hundred years ago, on 1 May 1898, the Netherlands Orthopaedic Association was founded. This was prompted by the view that general surgeons paid insufficient attention to the treatment of the locomotor system; they were permitted to join the new association, however, at any rate until 1947. It was especially in the last 30 years that orthopaedic surgery underwent major changes. The most striking novelty was arthroplastic surgery. There have also been developments in the treatment of spinal abnormalities, rheumatological surgery, sports medicine, oncology and traumatology.

Honderd jaar orthopedie in Nederland. V. Artroscopie (Article)

1998-05-01T00:00:00Z

Since the early eighties arthroscopy has become an important part of orthopaedics. Virtually every joint can be examined with an arthroscope. Apart from the diagnostic possibilities, an increasing number of arthroscopically guided surgical operations are possible. Knee arthroscopy can be used therapeutically for many conditions, including meniscal lesions, refractory synovitis, cruciate ligament lesions, tibial plateau fractures and osteochondral defects; in the shoulder it can be applied to lesions of the glenoid lip or the rotator cuff; in the ankle and foot, for osteochondral fractures and creation of an arthrodesis; in the wrist, for treatment of instability, intra-articular distal fractures of the radius and the carpal tunnel syndrome; in the hip, for removal of loose bodies and in the spine, for the performance of discectomy. Advantages over conventional open operations are smaller proportions of complications (< 2%), shorter hospital stay and more rapid rehabilitation. The areas of indication are defined in guidelines issued by the orthopaedic societies themselves; most orthopaedic surgeons follow these guidelines. A possibility for the future is use of laser in interventions on joints.

Orthopaedie: beeld en verbeelding (Inaugural Lecture)

1996-04-19T00:00:00Z

Local corticosteroid injection versus Cyriax-type physiotherapy for tennis elbow (Article)

1996-01-01T00:00:00Z

We performed a prospective, randomised trial on 106 patients to compare the effects of local corticosteroid injections with physiotherapy as advocated by Cyriax in the treatment of tennis elbow. The main outcome measures were the severity of pain, pain provoked by resisted dorsiflexion of the wrist, and patient satisfaction. At six weeks 22 of 53 patients in the injection group were free from pain compared with only three in the physiotherapy group. In the corticosteroid-treated group 26 patients had no pain on resisted dorsiflexion of the wrist compared with only three in the physiotherapy group. Thirty-five patients who had injections and 14 who had physiotherapy were satisfied with the outcome of treatment at six weeks. At the final assessment there were 18 excellent and 18 good results in the corticosteroid group and one excellent and 12 good results in the physiotherapy group. There was a significant increase in grip strength in both groups but those with injections had a significantly better result. After one year there were no significant differences between the two groups. Half of the patients, however, had received only the initial treatment, 20% had had combined therapy and 30% had had surgery. We conclude that at six weeks, treatment with corticosteroid injections was more effective than Cyriax physiotherapy and we recommend it because of its rapid action, reduction of pain and absence of side-effects.

Dislocation of the coccyx: a case report (Article)

1995-09-01T00:00:00Z

Een gevaarlijk stijve nek bij ziekte van Bechterew (Article)

1990-01-01T00:00:00Z

De botbank; een actuele benadering (Article)

1990-01-01T00:00:00Z

Recurrent medial swivel dislocation of the foot (Article)

1990-01-01T00:00:00Z