Causal association of metformin and osteoporosis: A 2-sample Mendelian randomization study

To investigate the causal relationship between metformin use and osteoporosis and different subtypes of osteoporosis using a 2-sample Mendelian randomization method. Data from genome-wide association studies were analyzed, with the exposure factor being metformin and the outcome variables being osteoporosis and different subtypes. Mendelian randomization was performed using Inverse Variance Weighted (IVW), MR-Egger, and weight median (WM) methods, and heterogeneity tests, horizontal multivariate analyses, and sensitivity analyses were performed. The IVW method analysis with metformin and osteoporosis showed P = 1.53E-04, OR (95%CI) = 1.81E-02 (2.27E-02-1.44E-01); the IVW method analysis with metformin and postmenopausal osteoporosis with pathologic fracture showed P = 2.22E-01, OR (95%CI) = 4.89E-02 (3. 83E-04-6.23E + 00); the IVW method using metformin with osteoporosis with pathological fracture showed that P = 2.14E-01, OR (95%CI) = 1.64E + 00(5.78E-02-6.44E-04); the IVW method using metformin with pharmacological osteoporosis with pathological fracture showed that P = 9. 83E- 01, OR (95%CI) = 1.11E + 00 (3.99E-05-3.11E + 04); IVW method of metformin use and pharmacological osteoporosis showed that P = 5.99E-01, OR (95%CI) = 2.27E + 01 (2.00E-04-2.57E + 06); there is a causal relationship between metformin use and osteoporosis, but there is no causal relationship between metformin use and postmenopausal osteoporosis with pathological fracture, osteoporosis with pathological fracture, pharmacological osteoporosis, and pharmacological osteoporosis with pathological fracture, and metformin use is a protective factor for osteoporosis.