The pathogenesis of OA is largely unknown; however, several risk factors are known to contribute to disease development. Treatment modalities are currently limited to alleviation of symptoms. In... Show moreThe pathogenesis of OA is largely unknown; however, several risk factors are known to contribute to disease development. Treatment modalities are currently limited to alleviation of symptoms. In order to develop better treatment modalities, increase of the understanding of the underlying mechanisms leading to OA development may provide targets for disease modification. Furthermore, knowledge regarding appropriate outcome measures that can be applied in OA research has to be increased for adequate assessment of potential treatment effects. Therefore, part I of this thesis describes studies aiming to increase the understanding of mechanisms underlying the association between known risk factors and OA, especially focussing on obesity in relation to OA in weight-bearing and non-weight-bearing joints. Furthermore, it was investigated which specific structural abnormalities on specific locations within the knee joint could best discriminate presence of symptomatic OA, and impact of knee OA and its modifiable or preventable risk on health-related quality of life was evaluated. Part II of this thesis describes two systematic reviews, assessing available instruments for measurement of the domains pain, physical function, patient global assessment and imaging in hand OA in order to enable recommendations for use in clinical trials. Show less
