Osteoinductive potential of recombinant BMP-9 in bone defects of mice treated with antiresorptive agents

Abstract

The aim of the present study was to investigate the effects of recombinant human (rh)BMP-9 on bone regenerative potential in a mouse model of antibody-mediated antiresorptive therapy (AMART). A monoclonal anti-murine receptor activator of nuclear factor-kappa B ligand (RANKL) antibody (mAb) was used to create an AMART model in mice. rhBMP-9 combined with collagen membrane was implanted in calvarial defects in mAb-treated mice. After 4 weeks, the bone formative potential in the defects was evaluated by micro-computed tomography and histological approaches. The groups implanted with rhBMP-9-containing collagen membranes demonstrated substantial osteopromotive potential, with significantly greater new bone volume (Sham + BMP-9 group; 0.86 ± 0.29 mm³ and mAb + BMP-9 group; 0.64 ± 0.16 mm³) than control PBS-membranes (Sham + PBS group; 0.44 ± 0.29 mm³ and mAb + PBS group; 0.24 ± 0.12 mm³) in both sham and mAb-treated mice. In line with in vivo study, bone marrow cells isolated from both sham and mAb-treated mice confirmed greater osteogenic potential upon stimulation with rhBMP-9 in vitro. These findings suggest for the first time that local rhBMP-9 administration might be a strategy to accelerate bone regeneration in the context of AMART.

Keywords: BMP-9; antiresorptive agents; bone morphogenetic proteins; bone regeneration; denosumab.