Severe damage to the jaw can happen in some people as a reaction to some medicines used in the treatment of cancer and osteoporosis. Osteoporosis is a disease that makes bones fragile. Damage to the jaws caused by this reaction is known as medication-related osteonecrosis of the jaws (MRONJ). MRONJ is a painful condition that can be difficult to treat. MRONJ occurs rarely in people taking medicines for osteoporosis. However, some of these medicines are also used at higher doses for cancer‐related conditions. The risk of MRONJ may be higher in cancer patients. It has been reported to occur in up to five in 100 individuals. It is important to identify effective preventive measures to reduce the risk of MRONJ, and to test better treatments for those who have it.
This is an update of our review first published in 2017. It is based on a search for articles that was conducted most recently in June 2021.
What was the research?
A systematic review to find out the effects of different interventions to either prevent or treat MRONJ. The review compared interventions with each other or with no treatment or a placebo.
Who conducted the research?
The research was conducted by a team led by Natalie H. Beth-Tasdogan of Ulm University, Ulm, Germany on behalf of Cochrane Oral Health. Benjamin Mayer, Heba Hussein, Oliver Zolk and Jens-Uwe Peter were also on the team.
What evidence was included in the review?
We searched for randomised controlled trials, published up to June 2021. We found five studies that focused on the prevention of MRONJ and eight studies that tested treatments for MRONJ. The studies involved 1,668 adults, with the smallest study having 13 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 but two 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. Two trials also included patients treated with bisphosphonates or denosumab.
What did the evidence say?
One study provided very low‐certainty evidence that dental examinations at three‐month intervals and preventive treatments are more effective than standard care for reducing the number of cases of MRONJ in people receiving bisphosphonates for cancer‐related conditions. The treatments to prevent MRONJ that were tested in this study were antibiotics before dental extractions and the use of techniques for wound closure that avoid exposure and contamination of bone. In the experimental group, which received preventive care consisting of antibiotics and specific wound closure, fewer people developed MRONJ. Two participants per 100 who underwent close monitoring developed MRONJ compared to 23 participants per 100 in the control group (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.
How good was the evidence?
The certainty 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. Most of the studies had only a small number of participants.
What are the implications for dentists and the general public?
One study provided very low‐certainty evidence that dental examinations at three‐month intervals plus preventive treatments are more effective than standard care in reducing the incidence of MRONJ. Our conclusion from the study is that people receiving bisphosphonates for advanced cancer should have regular dental check-ups. The check-ups should include a check of oral hygiene, periodontal diseases, cavities, and effective infection control. For the other treatments studied in this review, there was not enough evidence to show if they were effective. We cannot draw any conclusions about them.
What should researchers look at in the future?
Future research should look at preventing MRONJ in people undergoing dental surgery and whether a “drug holiday” could help to prevent MRONJ. In terms of treating MRONJ, future trials should look at whether surgery is effective, and what type of surgery is most effective. Other treatments should also be studied, including laser therapy and ozone therapy. Further research may be difficult as MRONJ is rare. Studies should be set up in different places throughout the world to capture the most number of cases.
Link
Beth-Tasdogan NH, Mayer B, Hussein H, Zolk O, Peter J-U. Interventions for managing medication‐related osteonecrosis of the jaw. Cochrane Database of Systematic Reviews 2022, Issue 7. Art. No.: CD012432. DOI: 10.1002/14651858.CD012432.pub3.
This post is an extended version of the review’s plain language summary, compiled by Anne Littlewood at the Cochrane Oral Health Editorial Base.
Cochrane Oral Health 