The Effect of Abaloparatide on New Bone Formation in Critical Calvarial Defectsin a Postmenopausal Model

We examined the effect of locally administered abaloparatide (ABL), alone or combined with an autogenous graft, on new bone formation in critical-sized calvarial defects in postmenopausal rats.

Thirty-two ovariectomized rats were divided into 4 equal groups: control (C), ABL, autogenous (O), and ABL+O. Each rat received an 8-mm calvarial defect with a trephine drill. After 8 weeks, rats were sacrificed and bone regeneration was evaluated using microCT and histologic analyses. Alkaline phosphatase (ALP), β-catenin, bone morphogenetic protein 2 (BMP-2), collagen-1, osteocalcin, osteonectin, osterix (OST), osteoprotegerin (OPG), receptor ligand for nuclear factor-kappaB (RANKL), transforming growth factor-beta (TGF-β), and vascular endothelial growth factor (VEGF) were evaluated immunohistochemically.

Significant improvements were found in bone healing in the ABL and O groups, compared with the C group. The ABL+O group reached the highest values in terms of total healing area, defect closure rate, and new bone formation. Histopathologic analysis showed that the ABL+O group had the most osteoblasts and the fewest osteoclasts. Immunohistochemical analysis showed that ALP, β-catenin, and BMP-2. Collagen-1, osteocalcin, osteonectin, OST, OPG, RUNX2, TGF-β, and VEGF expressions were increased in the ABL+O group, and RANKL expression was highest in the C group. Micro-CT analysis showed that the ABL+O group had the best results in terms of bone density, trabecular thickness, and trabecular number.

Abaloparatide+O showed a high therapeutic potential in bone regeneration by optimizing the healing of critical-sized bone defects in postmenopausal rats. These findings suggest that ABL+O may be an effective treatment option in clinical applications.