Abstract
OBJECTIVE: This study comprehensively evaluated the causal relationship between different types of statins use and knee/hip osteoarthritis (OA) using a two-sample and multivariate Mendelian randomization (MR) method. METHODS: MR analysis was conducted using publicly available summary statistics data from genome-wide association studies (GWAS) to assess the causal associations between total statins use (including specific types) and knee/hip OA. The primary analysis utilized the inverse variance-weighted (IVW) method, with sensitivity analysis conducted to assess robustness. Multivariable MR (MVMR) analysis adjusted for low-density lipoprotein cholesterol (LDL-C), intermediate-density lipoprotein cholesterol (IDL-C), high-density lipoprotein cholesterol (HDL-C), and body mass index (BMI). RESULTS: The MR analysis revealed a significant inverse association between genetically predicted total statins use and the risk of knee OA (OR = 0.950, 95%CI: 0.920-0.982, p = 0.002) as well as hip OA (OR = 0.932, 95%CI: 0.899-0.966, p <0.001). Furthermore, this study highlighted a reduced risk of knee/hip OA with the use of atorvastatin and simvastatin. Rosuvastatin use was associated with a decreased risk of hip OA but showed no association with knee OA. MVMR results indicated no correlation between exposure factors and outcomes after adjusting for LDL-C or IDL-C. HDL-C may not significantly contribute to statin-induced osteoarthritis, while BMI may play an important role. CONCLUSION: This study provides compelling evidence of the close relationship between statin use and a reduced risk of knee/hip OA, particularly with atorvastatin and simvastatin. LDL-C and IDL-C may mediate these effects. These findings have important implications for the clinical prevention and treatment of knee/hip OA.