Abstract: Objective：To establish bisphosphonate-related osteonecrosis of the jaw (BRONJ) model in rats and to make preliminary analysis of its etiological mechanisms. Methods: A BRONJ model was established in rats using pamidronate, dexamethasone combined with alveolar bone trauma (tooth extraction) method, and the ratios of CD4+ and CD90+ lymphocytes in splenocytes were also analyzed by flow cytometry in each group. For in vitro studies, the effects of pamidronate and dexamethasone on the proliferation of human osteosarcoma cell line MG-63 and mouse preosteoclasts cell line Raw 264.7 were investigated using CCK-8 assay. Results: The rat BRONJ model was successfully established using the method described above. Flow cytometry results showed that the ratios of CD4+ and CD90+ lymphocytes in splenocytes were much lower in the pamidronate and dexamethasonetreated rats than those in either pamidronte alone- or dexamethasone alone-treated rats. CCK-8 assay results showed that pami-dronate could inhibit the proliferation of both MG-63 and Raw 264.7 cell lines, while dexamethasone could enhance the inhibitory effect of pamidronate on Raw 264.7 cells. Conclusion: This study successfully established the BRONJ model in rats and verified that dexamethasone could enhance the inhibitory effect of pamidronate on preosteoclasts in vitro. At least three factors including alveolar bone trauma, infection and immune response induced by dexamethasone could be involved in the process of BRONJ.

Key words: Bisphosphonate-related osteonecrosis of the jaw, Models, animal, Pamidronate, Dexa-methasone, Immune system