Adipose-derived stem cells and platelet-rich plasma for preventive treatment of bisphosphonate-related osteonecrosis of the jaw in a murine model

Abstract

Objectives: The main challenge in treating bisphosphonate-related osteonecrosis of the jaw (BRONJ) is the absence of an effective established treatment. We aimed to compare different potentially preventive treatments for BRONJ after dental extractions in zoledronic acid (ZA)-treated animals. We studied the local application of different combinations of adipose-derived stem cells (ASCs) with or without previous stimulation with bone morphogenetic protein 2 (BMP-2) and platelet-rich plasma (PRP) in rats.

Material and methods: Fifty-six male Wistar rats were treated with ZA for 9 weeks. Dental extractions were performed in the eighth week, and the animals were divided into 4 groups. In group 1 (n = 14), alveolar coverage with mucoperiosteal flap was performed. In group 2 (n = 14), PRP was applied over the sockets and covered with the flap. In group 3 (n = 15), allogeneic ASCs with PRP were applied and covered with the flap. In group 4 (n = 13), animals were treated with ASCs cultured with BMP-2, PRP, and flap coverage. Histologic, fluorescence, and radiologic studies of the maxillae were performed.

Results: ASC-treated animals showed lower frequency of osteonecrosis (14% vs 50%, p = 0.007) and greater bone turnover (p = 0.024) and osteoclast count (p = 0.045) than those not receiving the ASC treatment.

Conclusions: In this high-risk model, ASC-based treatments seem to prevent BRONJ more effectively than mucosal flap with or without PRP. The combination of ASCs and PRP appears to be synergistic, and the addition of BMP-2 could further improve the results.

Keywords: Adipose-derived stem cells; Bisphosphonate-related osteonecrosis of the jaw; Platelet-rich plasma; Zoledronic acid.