Exenatide, a glucagon-like peptide-1 receptor agonist, may negatively impact bone healing in rats: histopathological, biochemical, and in silico findings

BACKGROUND: This study evaluates the effects of exenatide (EXE), a glucagon-like peptide-1 (GLP-1) receptor agonist, on bone healing in rats using a single radius cortical defect model and histopathological, biochemical, and in silico methods. METHODS: ), phosphorus (P), alkaline phosphatase (ALP), osteocalcin (OC), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) in each specimen were measured. Radius samples were examined histopathologically using hematoxylin and eosin (H however, these changes may not have been due to EXE administration. No significant negative effect on bone healing was observed in the groups that received subcutaneous EXE after the bone defect was created. By contrast, it was observed that for the treatment group that received EXE for 7 consecutive days before the bone defect was created on Day 7, bone healing progressed more slowly than in the groups treated with saline. Regarding the binding of EXE to the other target receptors, root mean square deviation (RMSD) values were low, bruised surface area (BSA) was high, and electrostatic interactions were strong, indicating that the ligand (i.e., EXE) binds to the selected receptor surfaces. CONCLUSION: Although the data obtained from the in vitro analyses in this study were verified using molecular docking, it should be noted that its design is preclinical. Given the widespread clinical use of GLP-1 receptor agonists in the management of type 2 diabetes mellitus (T2DM), our research findings may have translational relevance. Although derived from an experimental animal model, these results suggest that GLP-1 agonists such as EXE can exert additional effects on bone healing and inflammatory processes, thus warranting further studies, including controlled clinical investigations, to elucidate the potential implications for patient care.