Evaluation of the Effect of Sodium-Glucose Cotransporter 2 Inhibition on Fracture Risk: Evidence From Mendelian Randomization and Genetic Association Study
Authors' conclusion
Therefore, this study does not support an effect of genetically proxied SGLT2 inhibition on fracture risk.
Study context
- Population
- GWAS summary statistics (Genetic Factors for Osteoporosis consortium, FinnGen) and UK Biobank individual-level data; instruments: 6 and 2 SNPs associated with SLC5A2 expression and HbA1c
- Comparison
- Genetically proxied SGLT2 inhibition
- Outcome
- BMD, osteoporosis and fracture risk
Methodological detailstwo-sample Mendelian randomization (MR), one-sample MR
- Two-sample MR
- One-sample MR
Main finding
As reported in the abstract
BMD, osteoporosis and fracture (two-sample MR)
- Little evidence of association with bone mineral density (BMD) of total body, femoral neck, lumbar spine and forearm (6 SNPs); similar with 2 SNPs
- all p ≥ 0.077
- Little evidence of effect on osteoporosis
- all p ≥ 0.112
- Little evidence of effect on 11 major fracture types
- all p ≥ 0.094
- Nominal significance: fracture of lower leg
- p = 0.049
- Nominal significance: fracture of shoulder and upper arm
- p = 0.029
Further findings
Heel BMD, osteoporosis and fracture (one-sample MR and genetic association, UK Biobank)
- Weighted genetic risk scores (6 and 2 SNPs) not causally associated with heel BMD, osteoporosis and fracture
- all p ≥ 0.387
Original publication
Evaluation of the Effect of Sodium-Glucose Cotransporter 2 Inhibition on Fracture Risk: Evidence From Mendelian Randomization and Genetic Association Study. J Bone Miner Res. Published 27 July 2023. doi:10.
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