Statin use is associated with reduced incidence and progression of knee osteoarthritis in the Rotterdam study

Abstract

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 ...

Vitamin D status modifies the association between statin use and musculoskeletal pain: A population based study

“…Adding to our prior analyses, however, is that (1) among persons without arthritis, statin use in the setting of low vitamin D status demonstrated an even higher odds for risk of musculoskeletal pain than found in our main models, and (2) among those with arthritis, statin use in the setting of 25(OH)D ≥15ng/mL was associated with significantly lower odds for risk of musculoskeletal pain. Regarding the second finding, other studies have reported similar observations regarding a possible protective effect of statin on reducing the risk or progression of arthritis [13,14]. However, vitamin D supplementation, on its own, was not found to improve symptoms or prevent progression of osteoarthritis [15].…”

Is Statin Use Associated With New Joint‐Related Symptoms, Physical Function, and Quality of Life? Results From Two Population‐Based Cohorts of Women

“…The results from Clockaerts et al suggest that, compared with non-users, long-term statin users (Ͼ365 days) had reduced risks of radiographic knee OA (OR 0.49, 95% CI 0.26 -0.92) (8). Similarly, Chodick et al found that among statin * OR ϭ odds ratio; 99% CI ϭ 99% confidence interval; DDD ϭ cumulative defined daily dosage; NA ϭ not applicable; PF ϭ physical functioning subscale score.…”

“…The DDD for each medication was defined according to the World Health Organization Anatomical Therapeutic Chemical/DDD index 2013 (18). The cumulative dose was categorized as Ͻ120, 120 -365, and Ն365 DDD, corresponding to 1 DDD per day for Ͻ4 months, 4 -12 months, and Ն12 months in agreement with categories used by Clockaerts et al (8).…”

“…A number of studies have examined associations between statin use and OA. One study found that statin use was associated with a reduced incidence and structural progression of radiographic knee OA (8), and 2 studies re-ported reduced incidence of symptomatic radiographic OA diagnosis (all sites) (9,10). Another study found that statin use was associated with an increased risk of radiographic hip OA (11).…”

“…The following variables were included as potential confounders: age, area of residence, level of education, smoking status, body mass index (BMI), diabetes mellitus, heart disease, and hypertension (8,12). Level of education was assessed at the 1996 survey as the highest qualification completed as follows: no formal qualification, school certificate, high school certificate, trade/ apprenticeship/diploma, university, or higher degree.…”