Is it safe to place implants in patients at risk of MRONJ?

Data sources Four electronic databases, namely PubMed, Scopus, Web of Science and the Cochrane Central Register of Controlled Trials, were searched from their inception to 16 July 2019. The OpenGrey database was also used to identify unpublished studies.Study selection Eligible study designs included randomised controlled trials, cohort studies, case-control studies and case series with a retrospective, cross-sectional or prospective design related to implant placement in patients with a history of anti-angiogenic or antiresorptive medications. Selection was conducted by two independent reviewers; however, if a consensus was not reached, a third reviewer was involved. Studies required a minimum of five patients with a history of antiresorptive or anti-angiogenic drug therapy before implant placement and strict criteria were used to ensure studies reported sufficient data items for discussion. Only full papers in the English language were included.Data extraction and synthesis A total of 6,073 papers were initially identified following removal of duplicates and 29 of these met the inclusion criteria for this systematic review. Twenty-eight reported on bisphosphonates which included five cohort studies, six case-control studies and 17 case series. A single case series reported on denosumab and no studies were identified reporting on selective oestrogen receptor modulators, calcitonin or anti-angiogenics. The quality of the included cohort and case-control studies were assessed by applying the modified Newcastle-Ottawa scale while the case series were assessed according to the Joanna Briggs Institute critical appraisal checklist. A score of <50% was considered to indicate low quality, 50-70% moderate quality and >75% high quality. A standardised Microsoft Excel spreadsheet was used to extract data from the studies which included study design, number of cases, implants and controls, patient characteristics (systemic diseases/age/gender/smoking status), drug history (type of drug, indication, administration route, intake before implant placement), whether patients were taking the drug at the time of implant placement and follow-up, reported outcome and parameters (implant loss, failure, success, survival and incidence of medication-related osteonecrosis of the jaw [MRONJ]). Where data was missing, estimations were calculated and a qualitative synthesis of all data was performed.Results No single study reported all the relevant data required by the authors and the overall level of quality was moderate. Regarding implant failure, patients with a history of bisphosphonates for osteoporosis are not at increased risk. However, insufficient data was available for those with a history of bisphosphonates for cancer, or any other antiresorptive or anti-angiogenic medications. Comparing this to MRONJ, patients with a history of bisphosphonate treatment are at risk of developing MRONJ following implant placement, while those with a history of denosumab for osteoporosis have a negligible risk. There was insufficient data available to assess the risk of MRONJ for those with a history of denosumab for cancer or other antiresorptive or anti-angiogenic medications.Conclusions Patients with a history of bisphosphonate treatment are at risk of MRONJ following implant placement while patients who take bisphosphonates for osteoporosis are not at increased risk of implant failure. There is a negligible risk of developing MRONJ in those taking denosumab for osteoporosis. However, practitioners should bear in mind a lack of high-quality evidence regarding the safety of placing implants in patients with a history of antiresorptive or anti-angiogenic medications.