BMP-2 Local Administration for MRONJ-mice Induced Partial Bone Regeneration

Objectives: The pathogenesis of medication-related osteonecrosis of the jaw (MRONJ) still remains unclear, and no clear treatment has yet been established. On the other hand, BMP-2, which is widely known as a strong inducer of bone formation, has been applied in the clinical setting. This study aimed to investigate the effect of BMP-2 on the regeneration of tooth extraction sockets in a mouse MRONJ model.
Methods: To produce MRONJ model mice (MRONJ-mice, n=3), females aged 8-12 weeks were administered Zoledoronic Acid Hydrate (0.05 mg/kg) subcutaneously or cyclophosphamide (150 mg/kg) intraperitoneally twice a week during the entire experimental period. Control mice (n=3) were injected saline solution in the same fashion. Three weeks after administration, the maxillary first molar was extracted, and a mixture of 2.5 μg of rhBMP-2 and 1.5 mg of β-TCP was transplanted into the tooth extraction socket. HE-staining-based histological analysis of the tooth extraction socket was performed after 14 days and 56 days.
Results: In control mice, the extraction sockets were almost completely regenerated 14 days after extraction. However, almost no bone regeneration was observed in the extraction sockets of MRONJ-mice, in which sparse tissues with few cellular components were seen. On the other hand, the extraction sockets with rhBMP-2/β-TCP transplantation presented bone regeneration at the deep apexes, with the surrounding area filled by connective tissues and dense cell components. Quantitative analysis of bone regeneration as mean area percentage showed 0.25% and 14.6% in the extraction sockets in MRONJ-mice without and with rhBMP-2/β-TCP, respectively (P<0.05, t-test). Fifty six days after extraction, regenerated bone could also be observed at the apexes of extraction sockets in MRONJ-mice with rhBMP-2/β-TCP and the mean regeneration area percentage was 15.6%.
Conclusions: BMP-2 could induce a partial bone healing at the deep apex of the tooth extraction socket in this mouse MRONJ model.