Non-antiresorptive drugs associated with the development of medication-related osteonecrosis of the jaw: a systematic review and meta-analysis.

OBJECTIVE: The aim of this systematic review was to provide evidence related to the association between non-antiresorptive medications and MRONJ. MATERIALS AND METHODS: The following three electronic databases were screened: PubMed, EMBASE, and Web of Science from December 2020 until April 2021. Two reviewers independently performed the study selection, data extraction, and quality assessment of the included studies. The Newcastle-Ottawa Scale (NOS) was used for assessing the risk of bias. A meta-analysis was performed for assessing the relationship between MRONJ and non-antiresorptive medications. RESULTS: The search strategy retrieved 996 articles. Following removal of duplicates, title, and abstract screening and full-text reading, 58 publications were eligible to be included in the review. A total of 867 cases of MRONJ were included (33% female, 55% male, 12% no gender reported). The mean age of the patients when MRONJ was diagnosed was 61 years (range 19-100 years) and the average time of diagnosis was 10 months following non-antiresorptive drug therapy. Patients with a history of corticosteroids (0.61, 95% CI 0.39, 0.82, p = < 0.001) and chemotherapy (0.59, 95% CI 0.51, 0.67, p = < 0.001) showed the highest significant effect size (ED) compared to the control group for MRONJ occurrence. CONCLUSION: A significant association existed between MRONJ and non-antiresorptive drugs. However, considering limited evidence, findings should be interpreted with caution. CLINICAL RELEVANCE: The non-antiresorptive drugs might allow the dentist to apply the principle of "drug holiday" following concurrence from the drug prescribing clinician. PROSPERO REGISTRATION NUMBER: CRD42020173891.