A systematic review of oxygen therapy for the management of Medication-Related Osteonecrosis of the Jaw (MRONJ)

Roberto Sacco, Racheal Leeson, Joseph Nissan, Sergio Olate, Carlos Henrique Bettoni Cruz de Castro, Alessandro Acocella, Anand Lalli

Research output: Contribution to journalReview articlepeer-review


Background: Medication-related osteonecrosis of the jaw (MRONJ) can be a life changing iatrogenic complication of antiresorptive and antiangiogenic drug therapy. It is most often associated with high doses of these medications that are used to prevent skeletal-related events in patients with cancer and bone pathologies. Unfortunately, managing MRONJ lesions has proven difficult and remains a major challenge for clinicians. Due to the lack of efficacy in treating MRONJ by surgical modalities (local debridement and free flap reconstruction), the nonsurgical management of MRONJ is still advocated to aid healing or avoid disease progression. The aim of this systematic review is to identify, analyse and understand the published evidence related to the success of oxygen therapies such as ozone (OT) and hyperbaric oxygen (HBO) in treating MRONJ. Material and methods: A multi-database (PubMed, MEDLINE, EMBASE, CINAHL and Cochrane CENTRAL) systematic search was performed by three authors. The identified articles were independently assessed for their risk of bias. Any type of study evaluating humans treated with antiresorptive and antiangiogenic drugs were considered. The aim is primarily to evaluate the success of OT and HBO in resolving MRONJ and secondarily to identify any improvements in quality of life (QoL), rate of complications, time-to-event and severity of side effects related to these treatments. Results: In total, just 13 studies were eligible for analysis. A pooled total of 313 patients (HBO group n = 82; OT group n = 231) described in these studies have shown good tolerance for oxygen therapies. Complete resolution of MRONJ was reported in 44.58% of OT patients but only 5.17% of the HBO group. Progression of MRONJ was reported only in the HBO studies in 10.34% of cases (6 patients). The quality of evidence was low or very low in all studies. This was due to limitations in how the studies were designed, run and reported. Conclusions: Based on the limited data available, it is difficult to suggest OT is better or worse than HBO or whether it is better than a placebo. As the level of evidence available is low, this necessitates larger well-designed trials to justify these interventions for patients affected by MRONJ.

Original languageEnglish
Article number1026
JournalApplied Sciences (Switzerland)
Issue number5
StatePublished - 2019


  • Antiangiogenic drugs
  • Antiresorptive drugs
  • Bisphosphonate-related osteonecrosis of the jaw
  • Hyperbaric oxygen therapy
  • Osteonecrosis
  • Ozone therapy


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