Potential Benefits of Statin Therapy in Reducing Osteoarthritis Risk: A Mendelian Randomization Study

Abstract

Objective: The purpose of this study was to determine the causal effect of statins on osteoarthritis (OA) risk using Mendelian randomization (MR).

Methods: Single nucleotide polymorphism-based genome-wide association analyses of statins were collected from the UK Biobank and FinnGen dataset, and OA data were collected from the UK Biobank and Arthritis Research UK Osteoarthritis Genetics (arcOGEN) study. Two-sample MR analyses were performed using the inverse-variance weighted (IVW) technique. MR-Egger, weighted median, and weighted mode served as supplementary analyses. MR-Egger regression, Cochran's Q test, and Mendelian Randomization Pleiotropy Residual Sum and Outlier analysis were performed as sensitivity analyses. Hydroxymethylglutaryl-coenzyme A reductase (HMGCR) expression and OA risk were evaluated using summary data-based MR (SMR).

Results: MR analyses consistently supported a causal connection between statin use and OA risk. A causal effect was observed for atorvastatin (IVW: β = -2.989, P = 0.003) and rosuvastatin (IVW: β = -14.141, P = 0.006) treatment on hip OA. Meta-analysis showed the association between atorvastatin and knee OA was statistically significant (odds ratio 0.15; P = 0.004). Simvastatin use exhibited a protective effect against knee (IVW: β = -1.056, P = 0.004) and hip OA (IVW: β = -1.405, P = 0.001). Statin medication showed a protective effect on hip OA (IVW: β = -0.054, P = 0.013). HMGCR correlated significantly with a reduced risk of knee OA (β = -0.193, P_SMR = 0.017), rather than hip OA (β = 0.067, P_SMR = 0.502), which suggested that statins' protective effect on OA may not be related to its lipid-lowering effect.

Conclusion: This MR study provides compelling evidence that statin treatment may be a protective factor for OA. Further research is required to clarify its underlying mechanism.