Efficacy and tolerability of medical ozone gas insufflations in patients with osteonecrosis of the jaw treated with bisphosphonates-Preliminary data Medical ozone gas insufflation in treating ONJ lesions

Osteonecrosis of the Jaw (ONJ) is an adverse event reported especially in patients receiving cancer treatments regimen, bisphosphonates (BPs), and denosumab. We performed an open-label, prospective study in patients treated with zoledronic acid who developed ONJ lesions > 2.5 cm, and had no benefit after the treatment with the standard therapy, to evaluate the efficacy and tolerability of medical ozone (O₃) treatment delivered as gas insufflations on each ONJ lesions. Twenty-four patients (mean age 62.5, range 41-80; 12 female) with bone metastases due to breast (11), prostate (4)and lung (4)cancers, myeloma (2), or osteoporosis (3), previously treated with zoledronic acid and not underwent dental preventive measures and with ONJ lesions > 2.5 cm, were observed and treated with topical O₃ gas insufflation every third day for a minimum of 10 for each pathological area or till necrotic bone sequestrum or surgery. We used a special insufflation bell-shaped device adjusted to the specific characteristics of the patient, capable of eliminating any residue of O₃ diffusion by degrading it and releasing O ₂ into the air. Azithromicin 500 mg/day was administered for 10 days in all patients before the first three gas insufflation although they had previously received various cycles of antibiotics. Ten patients required more than 10 O₃ gas insufflations due to multiple lesions and/or purulent sovrainfections; one patient received two further O₃ insufflations while waiting the day of surgery. Six of 24 patients interrupted the O ₃ gas therapy for oncological disease progression (five patients) and for fear of an experimental therapy (one patient). Six patients had the sequestrum and complete or partial (one patient) spontaneous expulsion of the necrotic bone followed by oral mucosa re-epithelization after a range of 4-27 of O₃ gas insufflations. No patient reported adverse events. In 12 patients with the largest and deeper ONJ lesions, O₃ gas therapy produced the sequestrum of the necrotic bone after 10 to 38 insufflations; surgery was necessary to remove it (11 patients). Of interest, removal was possible without the resection of healthy mandible edge because of the presence of bone sequestrum. All together the response rate was 75.0% (95% CI, 53.3-90.2%) in ITT analysis and 100% (95% CI, 81.5-100%) in the PP analysis. In all patients treated with O₃ gas ± surgery, no ONJ relapse appeared (follow-up mean 18 months, range 1-3 years). Medical O₃ gas insufflations is an effective and safe treatment for patients treated with BPs who developed ONJ lesions > 2.5 cm.