Liraglutide enhances bone regeneration in a critical-size calvarial defect model in male rats: A comparative study with autogenous grafts, allografts, and xenografts.

OBJECTIVE: Bone grafting materials are widely used in the treatment of critical-sized bone defects, and pharmacological agents with the potential to enhance their regenerative potential have been of great interest. The purpose of this study was to investigate the effect of the glucagon-like peptide-1 receptor agonist Liraglutide on bone regeneration when combined with different grafting materials. DESIGN: Critical-sized calvarial defects with a 5 mm diameter were created bilaterally in rats, and eight experimental groups were formed: Control, autogenous graft, allograft, xenograft, and the combination of each graft material with Liraglutide. Bone healing was evaluated through histomorphometric analyses and micro-computed tomography (micro-CT). ANALYSES: Immunohistochemical analyses for β-catenin, BMP-2, osterix, osteoprotegerin, RANKL, and Runx2 were performed. RESULTS: Histomorphometric data demonstrated that Liraglutide significantly enhanced the osteogenic performance of the grafts, resulting in greater new bone formation and defect closure (p < 0.05). The Liraglutide-Autogenous graft group showed the highest levels of new bone formation and defect closure. Immunohistochemical results revealed that Liraglutide promoted osteoblastic activity while suppressing osteoclastic activity. Micro-CT findings supported these outcomes, indicating significant improvements in bone volume, trabecular thickness, and structural integrity. CONCLUSION: Liraglutide enhances bone healing and exerts a synergistic effect when used in combination with bone grafts. These findings suggest that Liraglutide serves as a promising adjunct in bone tissue engineering and regenerative medicine.