Bisphosphonates and osteonecrosis of the jaw: pathogenetic hypothesis and new preventive measures

BRONJ is a serious oral complication of BP treatment involving the exposure of necrotic maxillary or mandibular bone. We investigated the pathogenetic hypothesis and new preventive measures for BRONJ in patients with bone metastases who received BP zoledronic acid (ZOL) and chemotherapy combined with the antiangiogenic agent bevacizumab (BEV). The pathogenesis of BRONJ is uncertain: the type of BP, duration of the drug use and the occurrence of tooth extractions or other invasive dental procedures during treatment seem to play a major role. A theory that BRONJ is a form of avascular necrosis similar to osteoradio-necrosis also has been proposed. It maybe hypothesized that the combination of the antiangiogenic agent BEV with ZOL can lead to the enhancement of bone tissue avascularization (reduction of vascularization), which can account for a potentially higher incidence of ONJ in patients with bone metastases [to the bone] who receive this type of treatment.In order to better understand the problem we followed up a total of 121 patients for a period of 3 years. Methods: Patients were divided into 2 groups: group PA (preventive approach, 78 patients) and group OB (observation, 63 patients). Group PA patients had never been previously treated with BP, and group OB patients had already undergone therapy with BP. All patients received a complete oral and dental examination and a panoramic radiograph. If necessary, oral hygiene, restorative and rehabilitation therapy were offered to patients. All patients participated in regular checkups every 3 months. Group PA patients underwent oral surgical procedures, as needed. Group OB patients underwent less invasive procedures (restorative treatment) or root canal and surgical procedures, as needed. Results:In group OB is interesting to note that the 16 patients with root canal treatment have not developed BRONJ, suggesting that a mini invasive procedure is highly reccomended for patients who have already stareted ZOL + BEV, while 14% of patients, who underwent oral surgical procedures, presented with BRONJ during the 18 month follow up period. No patients in group PA had ONJ. Conclusion: Current evidence suggests that root canal therapy in cancer patients is a safe procedure and may reduce the incidence of ONJ.