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
Conclusion: Baseline structural damage and bone turnover activity, as reflected by BMLs, seem to be involved in knee OA progression. Moreover, progression in PFJ and TFJ seems to be related. (C)... Show moreConclusion: Baseline structural damage and bone turnover activity, as reflected by BMLs, seem to be involved in knee OA progression. Moreover, progression in PFJ and TFJ seems to be related. (C) 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved. Show less
Bomer, N.; Hollander, W. den; Ramos, Y.F.M.; Meulenbelt, I. 2015
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
Visser, A.W.; Boyesen, P.; Haugen, I.K.; Schoones, J.W.; Heijde, D.M. van der; Rosendaal, F.R.; Kloppenburg, M. 2014
The aim of this thesis was to investigate the limitations in daily life, outcome measures, clinical outcomes with the emphasis on patient satisfaction, and economic aspects of the treatment of hand... Show moreThe aim of this thesis was to investigate the limitations in daily life, outcome measures, clinical outcomes with the emphasis on patient satisfaction, and economic aspects of the treatment of hand osteoarthritis (OA). Patients with hand OA report severe restrictions in daily life, in particular in opening food packaging. We defined guidelines for the industry on the production of easy-to-open food packaging to make life easier for patients in the future. For evaluating the outcome of an intervention, numerous patient-reported outcome measures are used at present with questionable measurement properties. We could show that the Michigan Hand Outcomes Questionnaire demonstrates good measurement properties in patients with trapeziometacarpal (TMC) OA. Many variables determine patient satisfaction with treatment; expectations being fulfilled, relief of pain or symptoms, and the restoration of hand function are the most important determinants. Evaluation of the outcomes of conservative and surgical management in patients with TMC OA showed that surgery leads to significantly improved hand function after one year, while conservative treatment is most effective in the first 6 months. From an economic point of view, surgery is associated with considerably higher costs than conservative treatment, with respect to both healthcare costs and loss of productivity. Show less
This thesis investigates the role of adipose tissue inflammation in joint diseases such as osteoarthritis (OA) and rheumatoid arthritis (RA) . In the first part, we show that baseline levels of... Show moreThis thesis investigates the role of adipose tissue inflammation in joint diseases such as osteoarthritis (OA) and rheumatoid arthritis (RA) . In the first part, we show that baseline levels of circulating adiponectin can predict radiographic progression in patients with early RA. In contrast, in patients with hand OA, this association appears protective. Therefore, to obtain insight into the mechanisms underlying these associations, we investigated the high-molecular-weight isoform of adiponectin (hmwAPN), which is one of the most biologically active isoforms of adiponectin. We show that the associations of total adiponectin with radiographic progression are not mediated by hmwAPN, in either RA or HOA. In the second part, we present the immunological characterization of the infrapatellar fat pad (IFP), a joint associated adipose tissue, in patients with advanced knee OA. We observed profound differences in secreted inflammatory factors and immune cell composition between the IFP and paired subcutaneous adipose tissue samples. Interestingly, we observed obesity-related changes in the IFP phenotype, and in macrophages and adipocytes, Therefore, we investigated the modulatory effects of adipocytes on the phenotype of human macrophages in vitro and we observed that adipocyte-derived lipids can mediate the obesity-related changes in the phenotype of adipose tissue macrophages in humans Show less
