Exploring the regulatory mechanisms of antidiabetic drugs on osteoporosis and Bone mineral density.

BACKGROUND

Osteoporosis is the leading cause of fractures, characterized by reduced bone formation and increased bone resorption. Exploring the potential mechanisms of antidiabetic drugs in the treatment of OP provides valuable clinical insights for the future pharmacological management of osteoporosis patients.

METHODS

This study employed a comprehensive analytical pipeline utilizing cis-MR, SMR, and colocalization methods to assess the causal relationships between antidiabetic drug target genes and 12 phenotypes related to OP and BMD. The analysis incorporated genome-wide association study (GWAS) data from the GEnetic Factors for Osteoporosis (GEFOS) Consortium website and FinnGen consortium, as well as gene expression data from the eQTLGen and Genotype-Tissue Expression database.

RESULTS

Among 41 drug target genes across 8 classes of drugs, 9 genes were identified to have causal relationships with OP and BMD phenotypes. These genes included PPARG and GSTP1, which are targets for thiazolidinediones; KCNJ11, CPT1A, TRPM4, and VEGFA, which are targets for Sulfonylureas; GPD1 and ETFDH, which are targets for Metformin; and IGFBP7, which is a target for Insulin.

CONCLUSIONS

Certain antidiabetic drugs had potential regulatory effects on OP and BMD, and specific antidiabetic medications significantly altered the progression of OP. These findings provide clinical insights for future drug management in OP patients.