Investigating the Relationship Between Glucagon-Like Peptide-1 Receptor Agonist Use and Incidence of Vertebral Fractures in Female Patients Aged Over 50 Years With Osteoporosis: A Propensity-Matched Analysis.

Abstract

Retrospective cohort. To investigate the relationship between GLP-1 receptor agonist exposure and incidence of vertebral fracture and surgical intervention for these injuries in patients with osteoporosis. Vertebral fractures are relatively common in patients with osteoporosis and frequently result in substantial morbidity, such as persistent pain and functional deficit. Although primarily indicated for the management of type 2 diabetes mellitus and obesity, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have demonstrated positive effects on bone mineral density (BMD) in the lumbar spine. However, it remains unknown if this effect translates to positive clinical outcomes for patients with osteoporosis. This study utilized the TriNetX database to identify female patients aged over 50 years diagnosed with osteoporosis without a current pathologic fracture within the 10-year period ended January 1, 2025. The study group included patients with a history of GLP-1 RA use after osteoporosis diagnosis compared with a control group with no GLP-1 RA exposure. Cohorts were propensity-matched based on baseline demographic characteristics, BMI, HbA1c, eGFR, medical comorbidities, osteoporotic medication use, and serum calcium, phosphate, and vitamin D levels. Primary outcomes included incidence of vertebral collapse and vertebral augmentation within the 10-year study period. There were 56,142 matched pairs. The rate of vertebral fracture in the experimental group was ∼1.9% compared with 4.3% in the control group (RR: 0.434, 95% CI: 0.404-0.467, P<0.001). In addition, GLP-1 RA exposure was associated with a lower incidence of kyphoplasty or vertebroplasty (RR: 0.453, 95% CI: 0.381-0.538, P<0.001). Glucagon-like peptide-1 receptor agonist use is associated with a lower incidence of vertebral fracture and osteoporotic fracture intervention in female patients aged 50+ with osteoporosis. These findings underscore the potential protective effects of GLP-1 receptor agonists in patients with poor bone quality. Level III.