Li Jie, Bao Li, Dai Can, He Miao
Department of Orthopedic Surgery, Chongqing Emergency Medical Center, Chongqing University Central Hospital, Chongqing, People's Republic of China.
Orthop Res Rev. 2025 Apr 13;17:147-157. doi: 10.2147/ORR.S508155. eCollection 2025.
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.
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.
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.
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.
骨质疏松症与类风湿关节炎（RA）常同时出现，但它们之间是否存在因果遗传关系仍不清楚。本研究采用两样本孟德尔随机化（MR）方法来探究这种因果关系。
从已发表的全基因组关联研究（GWAS）中获取骨质疏松症和RA的遗传工具变量。我们选择了具有全基因组显著性（p < 5×10-8）和独立变异（r2 < 0.001）的单核苷酸多态性（SNP）。使用逆方差加权（IVW）方法评估因果关系，并使用 Cochr an's Q检验、MR-Egger截距和留一法敏感性分析来检验异质性、多效性和稳健性。
MR分析显示骨密度（BMD）降低对RA风险有因果效应（总骨密度：比值比[OR]=1.094，95%置信区间[CI]=1.023 - 1.170，P = 0.009；股骨颈骨密度：OR = 1.159，95% CI = 1.019 - 1.320，P = 0.025；腰椎骨密度：OR = 1.175，95% CI = 1.070 - 1.291，P = 0.001）。不同部位和年龄组的骨质疏松症对RA有显著影响，而RA对骨质疏松症无显著影响。敏感性分析证实了结果的稳健性。
我们的研究表明骨质疏松症与RA之间存在潜在的因果关系，提示骨质疏松症可能使个体易患RA。需要进一步研究以了解其机制并在不同人群中证实这些发现。
