Osteoarthritis (OA) refers to a heterogeneous group of conditions. This thesis focuses on OA with a hereditary background; Familial OA at multiple joint sites and radiological hand OA at middle age... Show moreOsteoarthritis (OA) refers to a heterogeneous group of conditions. This thesis focuses on OA with a hereditary background; Familial OA at multiple joint sites and radiological hand OA at middle age. The main objective is to identify risk factors that play a role in the development of OA in order to gain further insight in the aetiology of OA. The secondary objective is to investigate factors that determine the outcome in OA. This thesis provides evidence that familial clustering of symptomatic OA is most prominent for hand and hip OA. In search for genetic risk factors, we present data suggesting that a proportion of the genetic susceptibility for OA at multiple sites is encoded by variation in innate cytokine activity. Further, we find HLA-DR antigens to be associated with radiological hand OA. In addition to genetic risk factors, this thesis demonstrates that other systemic risk factors such as hormonal status and local factors, to be important in the susceptibility of familial OA at multiple sites, underscoring the multicausal etioliology of this phenotype. Finally, this thesis addresses the resulting disability from OA. Using the International Classification of Functioning, Disability and Health as framework, we show illness perceptions and mental health to be important modifying factors in OA in the hands and lower extremities. Show less
Osteoarthritis of the knee is a chronic progressive joint disease leading to pain and loss of function in a considerable proportion of patients with great impact and consequences in the ageing... Show moreOsteoarthritis of the knee is a chronic progressive joint disease leading to pain and loss of function in a considerable proportion of patients with great impact and consequences in the ageing population of the industrialized world. Clinical symptoms and radiographs of the knee are normally used to monitor osteoarthritic changes in the knee. However, the correlation between radiographic osteoarthritic findings and clinical features is poor. Does MR imaging of the knee tell us more about the relation between osteoarthritic structural findings and clinical features? According to the present thesis, the answer is “No”. Most of the data presented in this thesis is based on a 1.5T longitudinal MR study called the “Genetica, Artrose & Progressie” (GARP) study. In the GARP study MR imaging findings were associated with clinical features of patients with OA, and it was concluded that there were no strong associations between the most important OA imaging findings and clinical features of patients with OA. These controversial findings are important findings with regards to future clinical trials, as it urges conservatism with regards to the idea of BME being an outcome measure for progression of the disease. Therefore, the current theses also strongly recommend a further quest to identify ideal parameters to quantify the progression of the disease. Show less
