RESUMO
Introduction: Bisphosphonates are widely used in the treatment of osteoporosis; however, they are associated with the serious adverse event of bisphosphonate-related osteonecrosis of the jaw (BRONJ). Aim: The aim of this study is to assess the effects of nitrogen-containing bisphosphonates (N-PHs) on the synthesis of IL-1ß, TNF-α, sRANKL, cathepsin K, and annexin V in bone cells cultured in vitro. Materials and Methods: Osteoblasts and bone marrow-derived osteoclasts were cultured in vitro, subjected to treatment with alendronate, risedronate, or ibandronate at a concentration of 10-5 M for 0 to 96 h and then assayed for IL-1ß, sRANKL, and TNF-α production by ELISA. Cathepsin K and Annexin V-FITC staining in osteoclasts were assessed by flow cytometry. Results: There was significant downregulation of IL-1ß, sRANKL, and TNF-α in experimental osteoblasts compared to control cells, and there was upregulation of IL-1ß and downregulation of RANKL and TNF-α in experimental osteoclasts. Furthermore, in osteoclasts, cathepsin K expression was downregulated at 48-72 h with alendronate treatment, while risedronate treatment resulted in upregulated annexin V expression at 48 h compared to the control treatment. Conclusion: Bisphosphonates added to bone cells inhibited osteoclastogenesis, which led to the downregulation of cathepsin K and induction of apoptosis in osteoclasts; these changes limited the capacity of bone remodelling and healing that may contribute to BRONJ induced by surgical dental procedures.
