| Objective This study used Mendelian randomization analysis to investigate the causal relationship between 1400 blood metabolites and the risk of osteoporosis. Methods Genomewide association study data on 1400 blood metabolites and osteoporosis were obtained. Single nucleotide polymorphisms (SNPs) were used as instrumental variables for analysis. Two-sample Mendelian randomization analysis was performed using IVW, WM, and MR-Egger regression methods to examine the causal relationship between the 1400 blood metabolites and osteoporosis. The sensitivity and multiplicity tests were conducted. Results Six blood metabolites were significantly associated with osteoporosis. Mendelian randomization analysis results showed that the IVW OR values for GCST90199879, GCST90200092, GCST90200368, GCST90200656, GCST90200664, and GCST90200973 were 0.973 (95%CI: 0.954-0.991, P=0.004), 0.883 (95%CI: 0.805-0.968, P=0.008), 1.111(95%CI: 1.030-1.197, P=0.006), 1.147 (95%CI: 1.038-1.267, P=0.007), 1.069 (95%CI: 1.022-1.119, P=0.004), and 0.741 (95%CI: 0.602-0.914, P=0.005), respectively, indicating a causal relationship between blood metabolites and osteoporosis. Cochran Q tests for IVW (P>0.05) and MR-Egger regression (P>0.05) indicated no heterogeneity in the SNPs. The Egger intercept of the MR-Egger method showed no significant statistical difference from 0 (P>0.05), indicating no horizontal pleiotropy in the SNPs. Conclusion This study suggests a causal relationship between 6 blood metabolites and osteoporosis, providing new insights into the pathogenesis of osteoporosis mediated by blood metabolites. |