Effect of Blood Lipids and Lipid-lowering Therapies on Osteoarthritis Risk: A Mendelian Randomization Study

Background: We aimed to investigate the effects of blood lipids and lipid-lowering agents on osteoarthritis (OA) risk.

Materials And Methods: We performed Mendelian randomization (MR) analyses to estimate the causal effect of blood low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG) levels on knee and hip OA. Single nucleotide polymorphisms (SNPs) were selected from large genome-wide association studies (GWASs) of individuals of European ancestry as genetic instruments for blood lipid levels. The associations of selected genetic instruments with knee and hip OA were estimated in a recent GWAS of the UK Biobank and arcOGEN datasets. Univariate and multivariate MR analyses were performed to detect and adjust for potential pleiotropy. Furthermore, genetic instruments in , and regions were used to mimic LDL-C-lowering effects of statin, ezetimibe, and evolocumab, respectively.

Results: Genetically determined LDL-C increments led to reduced risks of both knee OA (OR = 0.91 per 1-SD increment, 95% CI: 0.86-0.95, = 6.3 × 10) and hip OA (OR = 0.92, 95% CI: 0.85-0.99, = 0.027). Multivariate MR analysis proved that the effect was independent of HDL-C, TG, and body mass index. TG increment was associated with reduced risks of hip OA in the univariate MR analysis; however, this was not supported by the multivariate MR analysis. Genetically proxied LDL-C-lowering effects of statins are related to increased risks of knee OA but not hip OA.

Conclusions: The findings suggested that LDL-C increments have independent protective effects on both knee and hip OA. LDL-C-lowering effects of statins may increase the risk of knee OA.