Abstract: We included five RCTs (1218 participants) in the review. Three trials focused on the prophylaxis of MRONJ. Two trials investigated options for the treatment of established MRONJ. The RCTs included only participants treated with bisphosphonates and, thus, did not cover the entire spectrum of medications associated with MRONJ. Prophylaxis of MRONJ One trial compared standard care with regular dental examinations in three-month intervals and preventive treatments (including antibiotics before dental extractions and the use of techniques for wound closure that avoid exposure and contamination of bone) in men with metastatic prostate cancer treated with zoledronic acid. The intervention seemed to lower the risk of MRONJ: RR 0.10; 95% CI 0.02 to 0.39 (253 participants; low-quality evidence). Secondary outcomes were not evaluated. As dentoalveolar surgery is considered a common predisposing event for developing MRONJ, one trial investigated the effect of plasma rich in growth factors (PRGF) for preventing MRONJ in people with cancer undergoing dental extractions. There was insufficient evidence to support or refute a benefit of PRGF on MRONJ incidence when compared with standard treatment (RR 0.08, 95% CI 0.00 to 1.51; 176 participants; very low-quality evidence). Secondary outcomes were not reported. In another trial comparing wound closure by primary intention with wound closure by secondary intention after dental extractions in people treated with oral bisphosphonates (700 participants), no cases of intraoperative complications or postoperative MRONJ were observed. QoL was not investigated. Treatment of MRONJ One trial analysed hyperbaric oxygen (HBO) treatment used in addition to standard care (antiseptic rinses, antibiotics, and surgery) compared with standard care alone. HBO in addition to standard care did not significantly improve healing from MRONJ compared with standard care alone (at last follow-up: RR 1.56; 95% CI 0.77 to 3.18; 46 participants included in the analysis; very low-quality evidence). QoL data were presented qualitatively as intragroup comparisons; hence, an effect estimate of treatment on QoL was not possible. Other secondary outcomes were not reported. The other RCT found no significant difference between autofluorescence- and tetracycline fluorescence-guided sequestrectomy for the surgical treatment of MRONJ at any timepoint (at one-year follow-up: RR 1.05; 95% CI 0.86 to 1.30; 34 participants included in the analysis; very low-quality evidence). Secondary outcomes were not reported. Prophylaxis of MRONJ One open-label RCT provided some evidence that dental examinations in three-month intervals and preventive treatments may be more effective than standard care for reducing the incidence of MRONJ in individuals taking intravenous bisphosphonates for advanced cancer. We assessed the certainty of the evidence to be low. There is insufficient evidence to either claim or refute a benefit of either of the interventions tested for prophylaxis of MRONJ (i.e. PRGF inserted into the postextraction alveolus during dental extractions, and wound closure by primary or secondary intention after dental extractions). Treatment of MRONJ Available evidence is insufficient to either claim or refute a benefit for hyperbaric oxygen therapy as an adjunct to conventional therapy. There is also insufficient evidence to draw conclusions about autofluorescence-guided versus tetracycline fluorescence-guided bone surgery.

Plain-language summary: Working with Cochrane Oral Health, we searched for studies that had been published up to November 2016. We found three studies that focused on the prevention of MRONJ and two studies that tested treatments for MRONJ. The studies involved 1218 adults, with the smallest study having 40 participants and the largest study having 700 participants. Most study participants were women, but one study was of men with prostate cancer receiving bisphosphonate infusions (given by drip into a vein). All studies included only participants treated with bisphosphonates (used to support treatment and reduce risk of fracture and bone pain), although several other drugs are also known to induce MRONJ. One study provided low-quality evidence that dental examinations at three-month intervals and preventive treatments (antibiotics before dental extractions and the use of techniques for wound closure that avoid exposure and contamination of bone) are more effective than standard care for reducing the number of cases with MRONJ in a group of people receiving intravenous bisphosphonates for cancer-related conditions. In the experimental group (which received preventive care consisting of antibiotics and specific wound closure), fewer people developed MRONJ (2 participants per 100 who underwent close monitoring) compared with the control group (23 participants per 100 who had standard care). There was insufficient evidence to conclude that the use of the other interventions investigated would reduce the risk of MRONJ or would improve healing of MRONJ. The quality of evidence was low or very low. This was due to limitations in how the studies were designed and run. For example, some participants changed groups during the study, some participants did not finish the study, and the outcomes were measured at different follow-up times.