MON-817 Association of Semaglutide and Tirzepatide Use on Bone Density and Fracture Risk in Obese Patients with and without Diabetes

Abstract Disclosure: Y. Liu: None. D. Walzer: None. S. Schmitz: None. A. Shukla: None. S.R. Kashyap: None. D. D'Angelo: None. Introduction: Semaglutide and tirzepatide have potent benefits on glucose lowering, weight loss and nutritional changes that may impact skeletal health, but little is known about their effects on bone density and fracture risk. Method: We conducted a retrospective review to investigate the impact of bone mineral density (BMD) and incidence of fracture with semaglutide and tirzepatide use. We included patients aged 18 years or older with at least six months of semaglutide or tirzepatide use and two BMD scans done on the same machine, with the first scan occurring within three months of semaglutide or tirzepatide initiation. Patients were excluded if their body mass index (BMI) at the baseline scan and at the medication start date differed by more than ±3 kg/m². The primary outcome was the percentage change in BMD and its association with weight loss. Results: We included 255 patients (92% female, 63% white, average age of 68±9 years, weight of 82±16 kg, and a baseline BMI of 31.2±5.7 kg/m²). The cohort included 44% with diabetes mellitus (DM), of whom 10% were using insulin. At baseline, 75% patients had osteopenia or osteoporosis, with 27% with a previous history of fragility fracture. 27% of patients received osteoporosis treatment. After an average follow up of 34 months, weight decreased by 7.0%. A significant decline in BMD were noticed in all sites—lumbar spine (-1.6±7.3%), femoral neck (-1.8±6.6%) and total hip (TH, -2.8±4.9%, p<0.001 for all). The decline of TH BMD percentage was significantly associated with the amount of weight loss (Pearson r=0.35, p<0.001).33 patients (13%) developed a new fracture after starting semaglutide or tirzepatide. Fracture incidence was significantly higher in patients with DM than those without DM (20.5 vs 7.0%, p=0.0014). Conclusion: In patients at high risk for fractures receiving semaglutide or tirzepatide, greater weight loss was associated with a greater decline in total hip BMD, highlighting the potential skeletal risks of these medications. Further prospective, controlled studies are needed to confirm these findings and guide clinical management. Presentation: Monday, July 14, 2025