循环炎症细胞因子与药物引起的骨质疏松性骨折的双向孟德尔随机化研究OA

Objective To assess whether there is a causal association between circulating inflammatory cytokine levels and drug-induced osteoporotic fractures(DOPF)using a two-sample bidirectional Mendelian randomisation(MR)approach.Methods A bidirectional MR analysis was conducted,with 91 circulating inflammatory cytokines and DOPF serving as exposure and outcome variables,respectively.Genetic data were obtained from a genome-wide association study(GWAS)database.Instrumental variables were selected following screening for genome-wide significance(P＜5×10-6 for inflammatory cytokines and P＜5×10-8 for DOPF),linkage independence(r2＜0.1 with SNP distance of 500 kb for in-flammatory cytokines and 1 000 kb for DOPF),a strong tool test(F＞10),and screening for horizontal pleiotropy.The in-verse variance weighted(IVW)method was employed as the primary analysis approach,supplemented by MR-Egger re-gression and the weighted median method to assess causal effects.The reliability of the analysis was validated through het-erogeneity,sensitivity,and horizontal pleiotropy analyses.Results CCL19(OR=1.392,95%CI:1.032-1.878,P=0.030),CXCL10(OR=1.762,95%CI:1.213-2.559,P=0.003),CXCL6(OR=1.471,95%CI:1.149-1.883,P=0.002),IL-10(OR=1.549,95%CI:1.092-2.196,P=0.014),IL-10Rα(OR=1.648,95%CI:1.053-2.578,P=0.029),IL-12β(OR=1.266,95%CI:1.018-1.574,P=0.034),and IL-17C(OR=1.948,95%CI:1.305-2.91,P=0.001)were identified as risk factors for DOPF,while CXCL5(OR=0.699,95%CI:0.514-0.951,P=0.023),GDNF(OR=0.601,95%CI:0.377-0.959,P=0.033),and IL-8(OR=0.642,95%CI:0.427-0.966,P=0.034)were protective.Sensitivity analyses showed no significant heterogeneity or horizontal pleiotropy.The reverse MR found no evidence of reverse causality.Conclusion Genetic evidence supports causal associations between multiple circulating inflammatory cytokines and drug-induced osteoporotic fractures,suggesting that inflammatory responses play an important role in the pathogenesis of DOPF.