The effect of abaloparatide on new bone formation in critical bone defects in the calvaria of post-menopausal rats

Objective: This study examined the effect of locally administered abaloparatide (ABL), alone or combined with autogenous graft, on new bone formation in critical-sized calvarial defects in postmenopausal rats. Method: Thirty-two ovariectomised female rats were divided into 4 equal groups: Control (C), abaloparatide (ABL), autogenous (O), abaloparatide + autogenous (ABL+O). An 8 mm diameter calvarial defect was created with a trephan drill in all rats. After eight weeks, bone regeneration was evaluated using micro-CT and histologic analyses. Alkaline phosphatase (ALP), beta-catenin (β-catenin), bone morphogenetic protein-2 (BMP-2), collagen 1, osteocalcin, osteonectin, osterix (OST), osteoprotegerin (OPG), receptor ligand for nuclear factor-kappa B (RANKL), transforming growth factor-beta (TGF-β) and vascular endothelial growth factor (VEGF) were evaluated immunohistochemically. Result: Significant improvements were found in the parameters related to bone healing in the ABL and O groups compared to the K group. ABL+O group reached the highest values in terms of total healing area, defect closure rate and new bone formation. Histomorphometric analysis showed that the ABL+O group had the highest number of osteoblasts and the lowest number of osteoclasts. Immunohistochemical analysis showed that ALP, β-catenin, BMP-2, collagen-1, osteocalcin, osteonectin, OST, OPG, RUNX2, TGF-β and VEGF expressions were significantly increased in the ABL+O group, while RANKL expression was highest in the K group. Micro-CT analysis showed that the ABL+O group had the best results in terms of bone density (BV/TV), trabecular thickness (Tb.Th) and trabecular number (Tb.N). Conclusion: ABL+O showed a high therapeutic potential on bone regeneration by optimizing the healing of critical-sized bone defects in post-menopausal rats. These findings suggest that ABL+O may be an effective treatment option in clinical applications. Keywords: Calvarial defect, Rat, Autogenous graft, Abaloparatide