The causal relationship between metformin and bone mineral density: A Two- Sample Mendelian randomization study

[Background] Metformin is a widely used hypoglycemic agent with Excellent hypoglycemic capacity. Many studies have shown that bone metabolism is altered in diabetes. Therefore, understanding the effect of metformin, a commonly used hypoglycemic agent, on bone mineral density has positive implications for advising diabetic patients about exercise and nutritional intake. [Method] The Bone mineral density (BMD) dataset was derived from the GEFOS Consortium and the UK Biobank's GWAS meta-analysis study and categorized for classification according to the site (heel, forearm (F), femoral neck (FN) and lumbar spine (LS)) and age (15–30,30–45,45–60 and over 60). Data for metformin were obtained from the MRC-IEU consortium and included people of European ancestry (11,552 cases and 451,381 controls). We investigated the causal relationship between metformin and BMD by two-sample Mendelian randomization. Metformin was the exposure factor, and BMD was the outcome variable. Mendelian randomization was performed using inverse variance weighting (IVW), MR-Egger, weighted median (WM), simple mode, and weighted mode methods, and tests for heterogeneity, horizontal multivariate analysis, and sensitivity analyses were performed. [Results] In terms of results, no significant data suggested that oral metformin improved BMD. However, conclusions of the data on heel bone mineral density (Heel-BMD: Beta = 1.178, 95%CI = 0.3579–1.9974, P = 0.0049)) and bone mineral density in patients over 60 years (Over 60 BMD: (Beta = 1.980, 95%CI = 0.6759–3.2848, P = 0.0029)) suggest there is an association between metformin use and elevated levels of bone mineral density. [Conclusion] This MR study found that in a European population, while oral metformin had a beneficial effect on whole-body BMD in the 60 + age group and heel BMD, there was no causal effect on the rest of the age group and the rest of the site. The potential exists for metformin to improve BMD, but more extensive clinical trials are still needed to validate this. It can be recommended in elderly patients with diabetes combined with osteoporosis.