Treatment of bisphosphonate induced osteonecrosis of jaw in rats using an angiogenesis factor (A-Heal) and ABMDO (Autologous Bone Marrow Derived Osteoblasts)

Abstract

Background and objective: The aims of this study were to create Bisphonates Related Osteonecrosis of the Jaw (BRONJ) in rats and treat them with an angiogenesis factor (A-Heal) and ABMDO (Autologous Bone Marrow Derived Osteoblasts). Materials and methods: Thirty female Wistar rats were procured. Rats were labeled as Group I to III. Group I = Osteoblast group, Group II = A-Heal and Group III Control group. In Groups I-III, BRONJ was created and treated in Group I with ABMDO, Group II with A-Heal and Group III was the control group. At the end of the four weeks post treatment, all the animals were humanely killed. The intact maxillae were removed in total. Histopathological and radiological examinations were carried out with physicians blinded to the groups. Results: Computerized tomography revealed that Groups I and II demonstrated the presence of dense osteosclerosis, intralesional calcifications, and adequate healing of the overlying soft tissues compared to Group III, which showed the presence of bone erosions at the alveolar ridge with a lack of intralesional calcifications and ulceration of the overlying soft tissues. Histologically, H&E staining Group 1 and Group 2 both showed marked reactive bone formation. Group 2 additionally revealed the most prominent vascular proliferation (also highlighted by Factor VIII, an endothelial cell marker) among all groups. Group 3 showed cartilaginous proliferation with less reactive bone formation, implicating decreased endochondral ossification compared to Groups 1 and 2. Conclusion: This study shows that angiogenesis factor (A-Heal) and ABMDO were successful in the treatment of experimentally created BRONJ in an animal model.

Keywords

• Bisphosphonate-associated osteonecrosis of the jaw
• Osteoblasts
• Angiogenesis factor
• Osteoporosis
• Bisphosphonates
• Stem cell