Osteoporosis: more than fractures alone : an epidemiological approach

The main purposes of this thesis are to study the incidence of and risk factors for vertebral fractures and to evaluate the interrelations between bone mineral density, atherosclerosis and breast cancer, all of which are considered to be influenced by estrogen exposure. We will look into fracture prevention; are the current methods for identifying subjects at risk for fractures adequate and should men and women be treated equally. Finally, the results of these studies are combined in a model on cost-effectiveness of fracture prevention In Chapter 2, vertebral fractures are investigated in both men and women. In chapter 2.1, the incidence of vertebral fractures will be described. In addition, the associations of incident vertebral fractures with both BMD and the presence of baseline prevalent vertebral fractures are studied. In chapter 2.2, we extended the analyses on risk factors for incident vertebral fractures for men and women. At first, we evaluated potential risk factors univariately for an association \Vith incident vertebral fractures. Then, we evaluated whether univariately sigoificant risk factors were independent from BMD, prevalent vertebral fractures and from each other. In Chapter 3, we study the value of a T -score of BMD in fracture prevention. In Chapter 3.1 it is evaluated whether the current criterion for osteoporosis, as defined by the 'WHO, of a T-score at or below -2.5, is useful in accurately identifying women who will fracture within the coming years. Chapter 3.2 discusses whether the association between BMD and fractures is similar for both men and women and if so, whether using a gender specific T -score of BMD is useful in describing the problem of osteoporosis in men. Chapter 4 describes the associations between BMD and diseases other than osteoporosis that are also considered to be influenced by estrogen exposure. First, in Chapter 4.1, the association between BMD and peripheral arterial disease, which is a measure for generalised atherosclerosis, is described. Chapter 4.2 then shows the association between BMD and incident breast cancer in women. Following the associations between BMD and morbidity, the association between femoral neck BMD and overall mortality is described for both men and women in Chapter 5. The results of a mathematical model on the cost-effectiveness of fracture prevention are discussed in Chapter 6. This model is an example of how the results as described in the previous chapters can be used to evaluate the costeffectiveness of fracture prevention. In this model, different treatment strategies ofHRT, SERMs and bisphosphonates are compared. Finally, in Chapter 7 the overall results of this thesis are placed in perspective in a general discussion. We further discuss pitfalls, as well as the clinical relevance of the research that was presented in this thesis. The general discussion ends with some suggestions for further research.