The association between GLP-1 receptor agonists and fractures: a nationwide Danish nested case-control study

Abstract

Summary: To examine whether GLP1-RA is associated with increased fracture risk, we compared 337,648 people with fractures to 675,296 people without fractures. Our adjusted analysis found that people with fractures tended to use GLP1-RA less often than people without fractures. This suggests that GLP1-RA may reduce fracture risk. Background: Glucagon-like peptide-1 (GLP-1) receptor agonists were introduced as a treatment for type 2 diabetes mellitus with weight loss as a beneficial side effect. Since then, the medications have been approved as weight-loss medication. However, rapid and substantial weight loss can lead to bone loss and increased fracture risk. Methods: We identified persons aged 30–90 years with a fracture between 2017 and 2021 and matched them 1:2 with fracture-free controls by sex and year of birth. Conditional logistic regression models were used to estimate odds ratios (ORs) for any fracture and major osteoporotic fracture (MOF) associated with GLP-1 receptor agonist use. Analyses were adjusted for relevant risk factors. Results: A total of 337,648 fracture cases and 675,296 fracture-free controls were included. In the unadjusted analyses, GLP-1 receptor agonist use did not differ between cases and controls (any fracture OR [confidence intervals (CI)], 1.00 [0.97–1.04]; MOF OR [CI], 0.96 [0.90–1.02]). In the adjusted analyses, GLP-1 receptor agonists were used less frequently in the group that sustained any fracture (OR [CI], 0.94 [0.90–0.97]) or MOF (OR [CI], 0.88 [0.83–0.94]) compared to the controls. Conclusion: GLP-1 receptor agonists may reduce fracture risk, suggesting a potential protective effect on bone health.