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: Huajie Dai,
Longyi Zheng,
Zheng Zhu,
Xin Geng,
Tianzhichao Hou,
Qi Wang,
Yijie Zhu,
Hong Lin,
Shuangyuan Wang,
Ruizhi Zheng,
Zhiyun Zhao,
Mian Li,
Jieli Lu,
Yu Xu,
Tiange Wang,
Jianmin Liu,
Guang Ning,
Weiqing Wang,
Yufang Bi,
Jie Zheng Tags: Research Article Source Type: research
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