Bisphosphonates are drugs very similar to pyrophosphate (a normal substance found in bone). They are used to lessen symptoms and complications due to the spread of cancer to the bones, and to prevent and treat fragile bones in osteoporosis (a conditon where tiny holes in the bones makes them brittle). These drugs can cause a rare but serious condition called bisphosphonate-related osteonecrosis of the jaw or ‘BRONJ’. BRONJ affects the healing of bone damage by interrupting the process of removing dead bone and laying down new bone. When this happens, parts or all of the jaw bone becomes friable (a bit like chalk), and eventually this dead bone can be exposed. This makes it difficult for people to eat, speak or brush their teeth, and it often causes severe pain. Many different treatments are currently used for BRONJ. They can be categorised as non-invasive treatments (such as antibiotics and mouth rinses), surgical approaches or “add-on” treatments used to enhance usual care (for example, ozone therapy or use of blood plasma that has been enriched with platelets). Different treatments may be combined.
What was the research?
A systematic review on the effectiveness of treatments for bisphosphonate-related osteonecrosis of the jaw bones, or ‘BRONJ’. How well do they work and how safe are they?
Who conducted the research?
The research was conducted by a team led by Victoria Rollason of Geneva University Hospitals on behalf of the Cochrane Oral Health Group. Alexandra Laverrière, Laura C.I. MacDonald, Tanya Walsh, Martin R. Tramèr and Nicole B. Vogt-Ferrier were also on the team.
What evidence was included in the review?
Review authors, working with the Cochrane Oral Health Group, carried out a thorough search up to 15 December 2015 for studies that randomly allocated participants to different treatments for BRONJ (or to a ‘placebo’ that has no active treatment). These studies are known as randomised controlled trials. We only found one relevant completed study and two ongoing studies. The completed study compared people with BRONJ being treated with surgery, antibiotics and mouth rinses to people receiving the same ‘standard care’ with an add-on treatment called hyperbaric oxygen therapy, which is thought to increase bone renewal. There were 49 participants, most of whom had cancer.
What did the evidence say?
The study found that the participants in the hyperbaric oxygen therapy group were more likely than the standard care group participants to have an improvement in their osteonecrosis at three months, but there was no clear difference between the groups when they were evaluated at six, 12 and 18 months and last contact. There was no clear difference between the groups at any time point for complete healing. These results are not reliable as the quality of the evidence is very low. The study did not assess whether there were any side effects of the treatment.
How good was the evidence?
The study had several important flaws: for example, there was a very small number of participants, some participants changed groups during the study and there was a loss of participants during the study.
What are the implications for dentists and the general public?
There is a lack of evidence from randomised controlled trials to guide treatment of bisphosphonate-related osteonecrosis of the jaw (BRONJ). Treatment should be determined for each individual situation based on clinical judgement and patient preference.
What should researchers look at in the future?
Two trials are currently underway to evaluate teriparatide treatment for BRONJ. This systematic review has identified the need for well-designed, adequately powered randomised controlled trials to assess the benefits of all proposed treatments for BRONJ. Future studies should use standardised, reproducible scales; they should use randomisation to assign participants to treatment and report how groups were randomised in sufficient detail. Participants and personnel should be “blinded” as to which treatment is being administered to which group. There should be a follow up period after the trial of at least six months.There is currently no ‘gold standard’ of treatment for BRONJ. Three broad categories of interventions have been described: classical conservative wound healing management, surgery and “add-on” adjuvant treatments. All of these should be explored to find out which treatment is most effective.
Rollason V, Laverrière A, MacDonald LCI, Walsh T, Tramèr MR, Vogt-Ferrier NB. Interventions for treating bisphosphonate-related osteonecrosis of the jaw (BRONJ). Cochrane Database of Systematic Reviews 2016, Issue 2. Art. No.: CD008455. DOI: 10.1002/14651858.CD008455.pub2.
This post is an extended version of the review’s plain language summary, compiled by Anne Littlewood at the Cochrane Oral Health Group Editorial Base.