Exploring the Causal Relationship Between Osteoporosis and Rheumatoid Arthritis: A Bidirectional Mendelian Randomization Study

Jie Li, Li Bao, Can Dai, Miao He Department of Orthopedic Surgery, Chongqing Emergency Medical Center, Chongqing University Central Hospital, Chongqing, People’s Republic of ChinaCorrespondence: Miao He; Can Dai, Email [email protected]; [email protected]: Osteoporosis and rheumatoid arthritis (RA) are commonly associated, but whether there is a causal genetic relationship between them remains unclear. This study used a two-sample Mendelian randomization (MR) approach to investigate this causal relationship.Methods: Genetic instruments for osteoporosis and RA were obtained from published genome-wide association studies (GWAS). We selected SNPs with genome-wide significance (p < 5× 10− 8) and independent variation (r2 < 0.001). Causality was assessed using the inverse variance weighted (IVW) method, and heterogeneity, pleiotropy, and robustness were tested using Cochran’s Q test, MR-Egger intercept, and leave-one-out sensitivity analysis.Results: The MR analysis revealed a causal effect of decreased bone mineral density (BMD) on RA risk (TB-BMD: OR = 1.094, 95% CI = 1.023– 1.170, P = 0.009; FA-BMD: OR = 1.159, 95% CI = 1.019– 1.320, P = 0.025; LS-BMD: OR: 1.175, 95% CI = 1.070– 1.291, P = 0.001). Osteoporosis at different sites and age groups significantly influenced RA, while RA did not significantly affect osteoporosis. Sensitivity analyses confirmed the robustness of the results.Conclusion: Our study suggests a potential causal relationship between osteoporosis and RA, suggesting that osteoporosis may predispose individuals to RA. Further research is needed to understand the mechanisms and to confirm these findings across diverse populations.Keywords: osteoporosis, rheumatoid arthritis, Mendelian randomization, GWAS