Statin Use and Clinical Osteoarthritis in the General Population: A Longitudinal Study

Abstract

BACKGROUNDOne hypothesis has posited whether abnormal lipid metabolism might be a causal factor in the pathogenesis of osteoarthritis (OA). Routine statin use in clinical practice provides the basis for a natural experiment in testing this hypothesis.OBJECTIVETo test the hypothesis that statins reduce the long-term occurrence of clinically defined OA.DESIGNCohort design with a 10-year follow-up.PARTICIPANTS16,609 adults cardiovascular disease cohorts aged 40 years and over from the UK General Practice Research Database with data available to 31 December 2006.INTERVENTIONStatins were summarised as annual mean daily dose and dose change over two-year time periods.MAIN MEASURESIncident episode of clinically defined osteoarthritis was assessed within 2 years, and at 4-year and 10-year follow-up time periods, using Cox and discrete time survival analysis. Covariates included age, gender, deprivation, body mass index, cholesterol level, pain-modifying drug co-therapies, and duration and severity of cardiovascular disease.KEY RESULTSHigher therapeutic dose of statin, with a treatment duration of at least 2 years was associated with a significant reduction in clinical OA compared to non-statin users in the follow-up time period. The estimated adjusted rate ratios were as follows: lowest statin dose quartile 1: 2.5 (95 % CI 2.3, 2.9); quartile 2: 1.3 (1.1, 1.5); quartile 3: 0.8 (0.7, 0.95); and highest statin dose quartile 4: 0.4 (0.3, 0.5). The largest statin dose increments were associated with significant reductions estimated at 18 % in OA outcome within 2 years and 40 % after 4 years, compared to non-statin users.CONCLUSIONSThis longitudinal study from a national clinical practice setting provides evidence that higher statin dose and larger statin dose increments were associated with a reduction in clinically defined OA outcome.

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

“…Riddle et al found no association between statin use and knee pain in a sample of 2,207 men and women with or at high risk of OA (12). However, 2 studies that examined associations between statin use and symptomatic radiographic OA did find significant associations (9,10). In these 2 studies, more frequent use and higher dose were associated with reduced risks of symptomatic radio- 16 …”

“…graphic OA (9,10). A potential explanation for the lack of an association between statin use and joint pain/stiffness is that our question was not specific enough.…”

“…In the same study, however, no associations were found between statin use and symptomatic radiographic OA in participants with Ͼ5 years of followup (9). Kadam et al found that high (10 -18.4 mg/day: hazard ratio [HR] 0.82, 99% CI 0.7-0.9) and very high (Ն18.5 mg/day: HR 0.41, 99% CI 0.3-0.5) dosage users had reduced risks of symptomatic radiographic OA compared with non-users, while low (0.01-4.6 mg/day: HR 2.55, 99% CI 2.3-2.9) and medium (4.7-9.9 mg/day: HR 1.31, 99% CI 1.1-1.5) dosage users had increased risks of symptomatic radiographic OA (10). It may be that opposing effects of dose and duration resulted in no effect in the current study by combining duration and dose in the cumulative dose variable; however, differences in sample characteristics, study design, and definitions of statin use and outcomes hamper a direct comparison of results.…”

“…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).…”

Statin Use and Osteoarthritis

“…1 However, the data also contributes to a growing evidence base supporting the pleiotropic effects of statins, which has been a topic of interest for vascular biologists and clinicians alike. Clearly, the potential public health impact of increasing the use of these well-established agents is vast.…”