I–3 Bisphosphonate-Related Osteonecrosis of the Jaw (BRONJ)

Abstract

Objective: We proposed a site-specific mechanism of mouse mandibular bone remodeling in which osteoblasts express RANKL and BCL-2 only when mechanically loaded. Gene expression is regulated by α5β1 integrin, as a cellular defense mechanism against exposure to oral bacteria that would otherwise induce bone resorption through production of inflammatory cytokines (Exp Cell Res 2011). We hypothesize that loss of occlusal force caused by tooth extraction and bacterial infection increases the risk of bisphosphonate-related osteonecrosis of the jaw (BRONJ). If mechanical stimulation is required to sustain remodeling and prevent osteoblast apoptosis, then tooth extraction will induce BRONJ. The aim of this study is to induce BRONJ in a rat model through tooth extraction and to test whether LIPUS exposure can prevent BRONJ. Methods: To evaluate the effect of LIPUS exposure, we removed maxillary first molars from female ovariectomized rats following 4 weeks of subcutaneous alendronate administration. In addition, Porphyromonas gingivalis was topically applied to the molar during the last 3 weeks. LIPUS was applied extrabuccally to the extraction socket 5 times a week for 4 weeks in LIPUS-treated cells and was not applied in non-LIPUS-treated cells. Results and Discussion: In rats given alendronate and not LIPUS, delayed healing of the epithelium and alveolar bone was observed in the socket. In addition, there were involucrum sequestra in which the epithelial invaginations contained pieces of necrotic bone. In rats given alendronate with LIPUS, wounds healed normally, as judged by the restored activity of TRAP and ALP. In this rat model, we showed that tooth removal resulted in BRONJ-like pathology. LIPUS exposure can prevent BRONJ, perhaps by providing an alternative mechanical stimulus which inhibited inflammation. LIPUS normalized the healing process in the wound and the alveolar bone.