Efficacy and safety of medical ozone (O(3)) delivered in oil suspension applications for the treatment of osteonecrosis of the jaw in patients with bone metastases treated with bisphosphonates: Preliminary results of a phase I-II study.

Osteonecrosis of the jaw (ONJ) is an adverse event that has been reported in patients receiving cancer treatment regimens, including bevacizumab, bisphosphonates, and denosumab. We performed a preliminary open label, prospective phase I-II study in patients treated with bisphosphonate to evaluate the treatment effect and tolerability of medical ozone (O(3)) delivered in an oil suspension on BONJ lesions ≤2.5cm. Ten consecutive patients with BONJ lesions not responsive to conservative treatment were pre-treated with 10days of antibiotics to reduce purulent secretions on the gum. The exposed bone lesion and osteomucosal edge was cleaned with an ultrasonic scaler. The BONJ lesion was treated with 10 local applications of medical O(3) delivered in an oil suspension for 10min. In all patients, mucosal lesions resolved with complete reconstitution of oral and jaw tissue, with 3-10 applications. No toxicity was reported. Unexpectedly, total sequestration of the necrotic bone, with spontaneous expulsion in eight patients and new bone formation around the necrotic area in two patients was observed. No patient required surgical intervention. In two patients with pre-and post-treatment X-rays, no residual bone lesions were observed after treatment. These preliminary results show the efficacy and tolerability of O(3) delivered in an oil suspension applied directly to BONJ lesions ≤2.5cm, thus indicating that BONJ can be a manageable and potentially curable condition.