Evaluation of the effect of sodium ‐glucose cotransporter 2 inhibition on fracture risk: evidence from Mendelian randomization and genetic association study

This study aims to evaluate the causal effect of sodium-glucose cotransporter 2 (SGLT2) inhibition on bone mineral density (BMD), osteoporosis, and fracture risk using genetics. Two-sample Mendelian randomization (MR) analyses were performed utilizing two sets of genetic variants as instruments (six and two single-nucleotide polymorphisms [SNPs]) associated withSLC5A2 gene expression and glycated hemoglobin A1c levels. Summary statistics of BMD from the Genetic Factors for Osteoporosis (GEFOS) consortium (BMD for total body, n  = 66,628; femoral neck, n = 32,735; lumbar spine, n = 28,498; forearm, n = 8,143) and osteoporosis (6,303 cases, 325,717 controls) and 13 types of fracture (≤ 17,690 cases, ≤ 328,382 controls) data from the FinnGen study were obtained. One-sample MR and genetic association a nalyses were conducted in UK Biobank using the individual-level data of heel BMD (n = 256,286) and incident osteoporosis (13,677 cases, 430,262 controls) and fracture (25,806 cases, 407,081 controls). Using six SNPs as the instrument, genetically proxied SGLT2 inhibition showed little evidence o f association with BMD of total body, femoral neck, lumbar spine, and forearm (all P ≥ 0.077). Similar results were observed using two SNPs as instruments. Little evidence was found for the SGLT2 inhibition effect on osteoporosis (all P ≥ 0.112) or any 11 major types of fracture (all P ≥  0.094), except for a nominal significance for fracture of lower...
Source: Journal of Bone and Mineral Research - Category: Orthopaedics Authors: Tags: Research Article Source Type: research