Although osteoarthritis is a common disease, there are currently no disease-modifying availible. For a long time osteoarthritis was considered a purely degenerative disease without inflammation of... Show moreAlthough osteoarthritis is a common disease, there are currently no disease-modifying availible. For a long time osteoarthritis was considered a purely degenerative disease without inflammation of the synovium (synovitis). However, recent research has shown that synovitis is of importance in patients with osteoarthritis. Therefore, this thesis aimed to understand the role synovitis in ossteoarthritis. In the first part of this thesis, we investigated the nature of synovitis by examining the synovium of osteoarthritis patients using differnt laboratory techniques. Furthermore, we validated a new synovitis scoring system on MRI with contrast. In the second part of this thesis, we investigated role of synovitis in relation to clinical characteristics such as pain and structural damage. This thesis shows that synovial inflammation in osteoarthritis is not only frequently present, but may also play a role in the pathophysiology of osteoarthritis and development of clinical features. Results presented in this thesis provide insight into different aspects of synovial inflammation aimed at increasing our understanding of the pathophysiology of OA and aiding to the development of disease-modifying drugs in OA. Show less
Osteoarthritis (OA) is an age related disorder of the joints characterized by pain, crepitus, and stiffness resulting in decreased mobility. Pathophysiology consists of cartilage degeneration and... Show moreOsteoarthritis (OA) is an age related disorder of the joints characterized by pain, crepitus, and stiffness resulting in decreased mobility. Pathophysiology consists of cartilage degeneration and bone remodeling, however, knowledge of OA etiology is still limited. Due to the growing population of elderly, OA prevalence rapidly increases. The fact that no reliable clinical markers are available for diagnosis, monitoring and progression is a major impediment in OA disease management and incurs high costs in drug development and clinical trials. Molecular markers were studied in OA affected cartilage compared to unaffected cartilage of the same joint (chapter 2) and in blood of OA patients (chapter 3). Perturbation of the application of traditional biochemical markers sCOMP and uCTX2 in the clinic due to genetic factors that, independent of OA, affect innate levels was investigated (chapter 4). Furthermore, we have tried to go beyond the results of molecular epidemiological studies to increase insights into underlying mechanisms (chapter 6 & 7). This shows how functional genomics can be achieved by combining genetic and functional data and will facilitate translation of knowledge of genetic variants to the needs of OA patients and thus to application in the clinic. Show less
In the first part an update of a guideline for the physiotherapy treatment of patients with hip and knee OA is described. Then a set of quality indicators for the physiotherapy management is... Show moreIn the first part an update of a guideline for the physiotherapy treatment of patients with hip and knee OA is described. Then a set of quality indicators for the physiotherapy management is developed to be used as an instrument to measure guideline adherence. Subsequently the effect of educational strategies to enhance their uptake by physiotherapists in daily clinical practice is investigated. An interactive approach with patient colaboration and following a proces of clinical reasoning has shown to be the most effective strategy. The second part describes the extent of the provision of physiotherapy before and after joint replacement surgery from the physiotherapists__ and patients__ perspective. Results showed a large variation in provided interventions before and after surgery, although evidence for physiotherapy before joint replacement surgery is lacking. This indicates that more research is necessary focussing on effectiveness for specific groups of patients. In addition it was concluded that the presence of severe back pain in THA and dizziness in THA and TKA, should maybe ascertained before surgery and if present be treated if possible in order to decrease the chance of unfavourable outcome, although the predictive value of dizziness should be confirmed in a study with a prospective design. Show less
Osteoarthritis is a prevalent disease causing pain and disability. It__s aetiology is unknown and no curative treatment is available. Osteoarthritis research is complicated due to heterogeneity of... Show moreOsteoarthritis is a prevalent disease causing pain and disability. It__s aetiology is unknown and no curative treatment is available. Osteoarthritis research is complicated due to heterogeneity of the disease, slow progression and poor association of clinical features with radiographic abnormalities, imaging modality of choice until now. In this thesis the role of synovitis in osteoarthritis is studied in relationship with clinical features and structural damage. The studies described made especially use of data derived a prospective follow-up study in symptomatic hand osteoarthritis patients. Synovitis detected on ultrasound was associated with clinical features and with progression of structural damage after 2.3 years in hand osteoarthritis. In erosive osteoarthritis, a subtype of hand osteoarthritis, more synovitis was found in all hand joints, even in non-erosive joints, when compared to joints of patients without erosive osteoarthritis. Also, associations were found between synovitis and erosive development at follow-up. All analyses were performed on joint level, using GEE analyses, thereby taking into account patient effects. Associations were poor/absent when analyses were done on patient level. This is important for further research. These results indicate that synovitis plays a role in pain and in development of structural damage in osteoarthritis and could be a therapeutic target. Show less
