These data are consistent with the hypothesis that the IPFP is an osteoarthritic joint tissue capable of modulating inflammatory and destructive responses in knee-OA.

Objective. In osteoarthritis (OA), changes occur in both cartilage and subchondral bone. The subchondral bone plate facilitates normal cross-talk between articular cartilage and trabecular subchondral bone, and adaptive changes in the plate due to OA may therefore disturb cross-talk homeostasis. To investigate these changes over time, we examined the cartilagesubchondral bone interface using a combined approach of histologic analysis and in vivo microfocal computed tomography.Methods. Sixteen-week-old male C57BL/6 mice (n ‫؍‬ 32) received intraarticular injections of collagenase in 1 joint to induce instability-related OA and received saline injections in the contralateral knee joint (control joint). At 2, 4, 6, 10, and 14 weeks after injection, changes in the tibial subchondral bone plate and subchondral trabeculae were analyzed.Results. Two weeks after injection, collagenaseinjected joints had significantly more cartilage damage and osteophytosis than did control joints. Osteoclast activity directly underneath the subchondral bone plate was significantly elevated in collagenase-injected joints compared to control joints (mean ؎ SEM osteoclast surface/bone surface 11.07 ؎ 0.79% versus 7.60 ؎ 0.81%), causing the plate to become thinner and creating a large increase in subchondral bone plate porosity In osteoarthritis (OA), changes in bone are thought to accompany cartilage deterioration, although it remains unclear which process is responsible for the initial homeostatic disturbance. Located directly underneath the articular cartilage, the subchondral bone plate provides structural support and acts as a portal for biochemical interactions between the cartilage layer and bone marrow and/or subchondral trabecular bone (1-5). Therefore, any changes in its structure may well have an effect on the overlying cartilage as well as on the underlying subchondral bone. In OA, subchondral bone is hypomineralized and of inferior quality as a consequence of abnormally high turnover (6-10). The exact cause of this increased bone turnover is as yet unknown, but the involvement of changes in the overlying articular cartilage is proposed as the principal cause (11-13). In contrast, other studies have shown that the OA process starts with an increase in subchondral bone turnover, which in turn, initiates cartilage damage (12-15). Whichever theory is true, extensive interaction between carti-

Background Osteoarthritis is the most frequent chronic joint disease causing pain and disability. Besides biomechanical mechanisms, the pathogenesis of osteoarthritis may involve infl ammation, vascular alterations and dysregulation of lipid metabolism. As statins are able to modulate many of these processes, this study examines whether statin use is associated with a decreased incidence and/or progression of osteoarthritis. Methods Participants in a prospective populationbased cohort study aged 55 years and older (n=2921) were included. x-Rays of the knee/hip were obtained at baseline and after on average 6.5 years, and scored using the Kellgren and Lawrence score for osteoarthritis. Any increase in score was defi ned as overall progression (incidence and progression). Data on covariables were collected at baseline. Information on statin use during follow-up was obtained from computerised pharmacy databases. The overall progression of osteoarthritis was compared between users and non-users of statins. Using a multivariate logistic regression model with generalised estimating equation, OR and 95% CI were calculated after adjusting for confounding variables. Results Overall progression of knee and hip osteoarthritis occurred in 6.9% and 4.7% of cases, respectively. The adjusted OR for overall progression of knee osteoarthritis in statin users was 0.43 (95% CI 0.25 to 0.77, p=0.01). The use of statins was not associated with overall progression of hip osteoarthritis. Conclusions Statin use is associated with more than a 50% reduction in overall progression of osteoarthritis of the knee, but not of the hip.Osteoarthritis is the most common form of arthropathy. It affects 9.6% of men and 18% of women aged 60 years or older and is the leading cause of disability in older people. 1 2 The aetiology of osteoarthritis is not completely understood. Besides genetic variation and biomechanical mechanisms, infl ammation can lead to cartilage matrix breakdown, synovial hypertrophy, subchondral bone sclerosis and osteophyte formation. [3][4][5] The pathogenesis of osteoarthritis might also involve altered lipid metabolism and vascular pathology. [6][7][8] Current treatment of osteoarthritis consists of exercise therapy and lifestyle adjustment, with pharmacotherapeutic treatment of symptoms when needed. However, the therapeutic effi cacy of this treatment is small to moderate. 9 Until now, there is no disease-modifying compound for osteoarthritis. 5 9 In the past few decades, drug research and development has mainly focused on articular cartilage, even though the whole joint is affected in osteoarthritis and the disease process may also be infl uenced by systemic factors.In addition to lowering the circulating level of low-density lipoproteins, statins have a broad range of biological effects including anti-infl ammatory properties in different cell types. In-vitro studies revealed that statins have antioxidative effects, decrease the production of matrix metalloproteinases, interleukins and increase the production of ...