http://repub.eur.nl/res/aut/17896/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/39936/ 2013-04-22T00:00:00Z Objectives: Age-related changes in articular cartilage are likely to play a role in the etiology of osteoarthritis (OA). One of the major age-related changes in cartilage is the accumulation of advanced glycation end products (AGEs). The present study evaluates whether pentosidine can predict radiographic progression and/or burden over 5 years follow-up in a cohort of early knee and/or hip OA. Design: The 5 years follow-up data of 300 patients from cohort hip & cohort knee (CHECK) were used. Radiographic progression and burden were assessed by X-rays of both knees and hips (Kellgren and Lawrence (K&L) and Altman scores). Baseline pentosidine levels (and urinary CTXII as a comparator) were measured by high-performance-liquid-chromatography (HPLC) and enzyme linked immunosorbent assay (ELISA). Univariable and multivariable associations including baseline radiographic damage, age, gender, body mass index (BMI) and kidney function were performed. Results: Both pentosidine and urinary C-terminal telopeptide of type II collagen (uCTXII) correlated with radiographic progression and burden. In general pentosidine did not have an added predictive value to uCTXII for progression nor burden of the disease. The best prediction was obtained for burden of radiographic damage (R2= 0.60-0.88), bus this was predominantly determined by baseline radiographic damage (without this parameter R2= 0.07-0.17). Interestingly, pentosidine significantly added to prediction of osteophyte formation, whereas uCTXII significantly added to prediction of JSN in multivariable analysis. Conclusion: Pentosidine adds to prediction of radiographic progression and burden of osteophyte formation and uCTXII to radiographic progression and burden of JSN, but overall skin pentosidine did not perform better that uCTXII in predicting radiographic progression or burden. Burden of damage over 5 years is mainly determined by radiographic joint damage at baseline. http://repub.eur.nl/res/pub/37393/ 2012-11-01T00:00:00Z Objective: To investigate cross-sectional and predictive associations of plasma adipokines with biochemical markers of systemic joint metabolism and radiographic signs of early-stage knee osteoarthritis (OA). Design: The adipokines pLeptin, pAdiponectin, and pResistin, the cartilage markers C-terminal telopeptide of type II collagen (uCTX-II), N-terminal propeptide of type IIA procollagen (sPIIANP), chondroitin sulfate 846 (sCS846), and cartilage oligomeric matrix protein (sCOMP), and the synovial markers hyaluronic acid (sHA) and N-terminal propeptide of type III procollagen (sPIIINP) were assessed by enzyme-linked immunosorbent assay or radioactive immunoassay in baseline samples of Cohort Hip and Cohort Knee (CHECK), a cohort of 1002 subjects with early-stage symptomatic knee and/or hip OA. Knee radiographs were obtained at baseline and after 2 and 5 years and scored according to Kellgren and Lawrence. Results: pLeptin showed positive associations with uCTX-II, sCOMP, sPIIANP, sHA, and sPIIINP, and with presence and progression of radiographic knee OA. Associations expectedly disappeared after adjustment for body mass index. pResistin showed positive associations with sPIIINP and present and incident radiographic knee OA that were largely independent of BMI. pAdiponectin showed positive associations with uCTX-II and sCOMP. Furthermore, pAdiponectin did not show associations with radiographic knee OA on itself, but associations of pResistin with present radiographic knee OA were stronger in higher pAdiponectin tertiles (P = 0.024 for interaction between pAdiponectin and pResistin). Although statistically significant, all associations were weak. Conclusions: Adipokines may have aggravating, although may be minor, structural effects in early-stage knee OA. http://repub.eur.nl/res/pub/20656/ 2010-07-01T00:00:00Z In osteoarthritis (OA), cartilage degradation is accompanied by subchondral bone changes. The pathogenesis and physiology of bone changes in OA are still unclear. The changes in subchondral bone architecture and cartilage damage were compared in differently induced experimental models of OA. Experimental OA was induced bilaterally by anterior cruciate ligament transection (ACLT) or by cartilage trauma (Groove model); bilateral sham surgery served as control. Lysylpyridinoline (LP, bone resorption) and C-telopeptide of type II collagen (CTX-II, cartilage breakdown) were measured over time. At 20 weeks after surgery, the subchondral cortical plate and trabecular bone of the tibia were analyzed by micro-computed tomography (μCT) and cartilage degeneration was analyzed histologically and biochemically. In both models, cartilage degeneration and cortical subchondral plate thinning were present. CTXII levels were elevated over time in both models. Subchondral trabecular bone changes were observed only in the ACLT model, not in the Groove model. Correspondingly, LP levels were elevated over time in the ACLT model and not in the Groove model. Interestingly, the trabecular bone changes in the ACLT model were extended to the metaphyseal area. The early decrease in plate thickness, present in both models, as was cartilage damage, suggests that plate thinning is a phenomenon that is intrinsic to the process of OA independent of the cause/induction of OA. On the other hand, trabecular changes in subchondral and metaphyseal bone are not part of a common pathway of OA development and may be induced biomechanically in the destabilized and less loaded ACLT joint. http://repub.eur.nl/res/pub/20707/ 2010-05-01T00:00:00Z Abstract OBJECTIVE: The pathogenesis of osteoarthritis (OA) includes cartilage degeneration, synovial inflammation, and bone changes. Slowly, the sequence and inter-relationship of these features is becoming clearer. Early models of OA suggest thinning of the subchondral plate in addition to trabecular bone changes. In the present study subchondral bone changes were studied in the canine anterior cruciate ligament transection (ACLT)-meniscectomy model. This model is characterized by intra-joint variability with respect to cartilage damage (predominantly medial) and loading (lateral unloading due to a shifted axis). METHODS: In 13 Labrador dogs, OA was induced by transection of the anterior cruciate ligament and removal of the medial meniscus. Twelve weeks later, cartilage integrity was evaluated histologically using the modified Mankin score (0-11), and proteoglycan content was determined by Alcian Blue assay. Bone architecture of the tibia was quantified by micro-CT. RESULTS: Cartilage damage was severe in the medial compartment (Mankin score +3.5, glycosaminoglycan (GAG) content -28%) and mild in the lateral compartment (Mankin score +1.6, GAG content -15%). Thinning and porosity of the subchondral plate were only present on the medial side (-21%, +87%, respectively). Interestingly, changes in trabecular bone structure did almost not occur in the medial compartment (volume fraction -7%) but were clear in the lateral compartment (-20%). CONCLUSION: Thinning of the subchondral plate is a localized phenomenon related to cartilage degeneration while trabecular bone changes are related to mechanical (un)loading. The different mechanisms responsible for bone changes in OA should be taken in account when designing and interpreting studies interfering with bone turnover in the treatment of OA. http://repub.eur.nl/res/pub/15160/ 2008-02-01T00:00:00Z BACKGROUND: This study evaluates changes in peri-articular bone in two canine models for osteoarthritis: the groove model and the anterior cruciate ligament transection (ACLT) model. METHODS: Evaluation was performed at 10 and 20 weeks post-surgery and in addition a 3-weeks time point was studied for the groove model. Cartilage was analysed, and architecture of the subchondral plate and trabecular bone of epiphyses was quantified using micro-CT. RESULTS: At 10 and 20 weeks cartilage histology and biochemistry demonstrated characteristic features of osteoarthritis in both models (very mild changes at 3 weeks). The groove model presented osteophytes only at 20 weeks, whereas the ACLT model showed osteophytes already at 10 weeks. Trabecular bone changes in the groove model were small and not consistent. This contrasts the ACLT model in which bone volume fraction was clearly reduced at 10 and 20 weeks (15-20%). However, changes in metaphyseal bone indicate unloading in the ACLT model, not in the groove model. For both models the subchondral plate thickness was strongly reduced (25-40%) and plate porosity was strongly increased (25-85%) at all time points studied. CONCLUSION: These findings show differential regulation of subchondral trabecular bone in the groove and ACLT model, with mild changes in the groove model and more severe changes in the ACLT model. In the ACLT model, part of these changes may be explained by unloading of the treated leg. In contrast, subchondral plate thinning and increased porosity were very consistent in both models, independent of loading conditions, indicating that this thinning is an early response in the osteoarthritis process.