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Ozone therapy as an adjunctive strategy for MRONJ in oncology patients: A systematic review and meta-analysis
Mailon Cury Carneiro1, Júlia França da Silva1, Tiago Carvalho Dos Santos1
1Department of Surgery, Stomatology, Pathology, and Radiology, Bauru School of Dentistry, University of São Paulo. Alameda Octávio Pinheiro Brisolla 9-75, Bauru, 17012-901, SP, Brazil.
Purpose:
Medication-related osteonecrosis of the jaw (MRONJ) is a serious complication associated with antiresorptive and antiangiogenic therapies, particularly in oncology patients. Ozone therapy has been proposed as a supportive treatment due to its antimicrobial and tissue-regenerative properties, but its clinical efficacy remains uncertain.
Methods:
This systematic review and meta-analysis, registered in PROSPERO (CRD42025631661), followed PRISMA 2020 guidelines. A comprehensive search was conducted in PubMed, Embase, Scopus, Web of Science, Cochrane Library, and gray literature. We included clinical studies using ozone therapy in adults with MRONJ. Studies combining ozone with other experimental interventions were excluded. Data on patient characteristics, protocols, and outcomes were extracted. A meta-analysis of proportions was performed using a random-effects model with logit transformation and Hartung-Knapp adjustment. Risk of bias was assessed using Joanna Briggs Institute tools.
Results:
Six studies involving 178 patients (65.7% female; mean age ~ 65.9 years) were included. Ozone therapy was administered in gaseous or oil-based formulations, with varied frequencies and application methods. The pooled clinical success rate was 71% (95% CI: 55%-84%), with moderate heterogeneity (I2 = 41.9%). Sensitivity analyses confirmed the robustness of the results. No adverse effects were reported. Improvements in pain and quality of life were frequently observed. All studies were classified as having low risk of bias.
Conclusions:
Ozone therapy may be associated with clinical benefits in MRONJ management. However, the evidence is of very low certainty due to methodological limitations and heterogeneity. Randomized clinical trials with standardized protocols are needed to clarify its role in supportive care.
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