Effects of glucagon‑like peptide‑1 receptor agonists on fracture healing in a rat osteoporotic model

Abstract

Osteoporosis is a common disease characterized by reduced bone mass, microstructural deterioration, fragility and consequent fragility fractures and is particularly prevalent among the elderly population. Although glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have positive effects on bones, their role in the prevention of osteoporotic fractures remains to be elucidated. The present study assigned female Sprague Dawley rats with osteoporotic fractures into variectomized osteoporosis (OVX), OVX + liraglutide (LIRA) (50 µg/kg/day subcutaneous LIRA) and control groups. At 3 and 6 weeks postoperatively, X-ray, tartrate-resistant acid phosphatase (TRAP) staining, histological and biomechanical assays and assessment of femoral bone mineral density (BMD) were performed. Compared with the OVX group, GLP-1 RA treatment improved the formation of calluses and osseous union. TRAP staining showed significantly fewer osteoclasts in the OVX + LIRA group compared with the OVX group. In the osteoporotically fractured rats, LIRA improved bone strength at the femoral diaphysis, stiffness, ultimate load and femoral trabecular BMD Compared with the OVX group. GLP-1 RA treatment inhibited osteoclast formation and improved trabecular bone architecture and mass in osteoporotic fracture model rats, leading to improved biomechanical strength. GLP-1 RAs may be used as novel anti-osteoporotic fracture agents.