Aromatase inhibitors and medication-related osteonecrosis of the jaw: Friends, foes, or bystanders?

Since the 1980s, aromatase inhibitors (AI) have been a cornerstone in the management of hormone receptor-positive breast cancer. However, because of their frequent co-prescription with antiresorptive agents, concerns have been raised regarding the potential contribution of AI to medication-related osteonecrosis of the jaw (MRONJ). We conducted a scoping review to investigate the possible association between AI use and MRONJ. Electronic searches were performed across five databases and supplemented with manual screening and gray literature. Observational studies and clinical trials were included. Fifty-four studies comprising 1,613,480 individuals (45,121 AI users) from 17 countries were analyzed. Most samples consisted of women with breast cancer/metastatic breast cancer in pre- and/or postmenopausal stages. Letrozole was the most frequently prescribed AI, followed by anastrozole and exemestane. MRONJ was reported in 43 studies, with 1147 cases among 45,121 AI users (2.5 % of AI users in the included samples), the majority of whom were concomitantly treated with zoledronic acid and/or denosumab. Three studies documented MRONJ in patients receiving AI monotherapy. Data demonstrate the difficulty of disentangling the effects of AI from those of antiresorptive therapy in MRONJ pathogenesis. Future research should consider AI as potential confounders in analytical studies to clarify their independent contribution, if any, to observed MRONJ occurrences.