EDTA Could Prevent Bisphosphonates-Related Osreonecrosis of Jaw after Traumatic Injury

Abstract

The pathophysiological mechanism underlying Bisphosphonates related osteonecrosis of Jaw (BRONJ) remains poorly understood. Bisphosphonates localize to sites of osteoclast activity as Bisphosphonates bind Ca+2 in Tridentate manner. The aims of this study is to 1) prove the feasibility of in-vivo targeted removal of bisphosphonates from bone using chelating agents, and 2) use the targeted chelation to prevent BRONJ in rats. First, we tested whether local application of EDTA will reduce the bisphosphonate content in alveolar bone. Then, we tested the effect of EDTA in preventing BRONJ in eight Sprague Dawley rats that were treated intravenously for 12 weeks by Zoledronate [80 mg/kg; once per week]. Immediately after the last dose, the mandibular first and second molars were extracted on both sides, followed by application to the extraction site of EDTA on one side and saline on the other side in each animal for 10 minutes. Four weeks later, animals were sacrificed, and mandibles harvested for micro CT analysis and Extraction sites analysis. Exposure and necrosis of alveolar bone were evident on the PBS-treated extraction sites. Contralateral extraction sites treated with EDTA showed significantly improved mucosal covering and the signs of bone necrosis were significantly diminished both clinically and with micro-CT. We concluded that application of local chelating agents after tooth extraction maybe a new way for improving bone healing and preventing BRONJ.