Medication-related osteonecrosis of the jaw: Analysing the range of implicated drugs from the Australian database of adverse event notifications

Aims Medication-related osteonecrosis of the jaw (MRONJ) is an uncommon but potentially debilitating condition, characterised by nonhealing jawbone, with or without mucosal exposure, in the presence of certain drugs. Those already strongly associated with MRONJ include antiresorptives denosumab and bisphosphonates; however, a growing range of other non-antiresorptive drugs is implicated. The aim of this study was to analyse all case reports of MRONJ submitted to the publicly available Database of Adverse Event Notification from the Therapeutic Goods Administration in Australia.

Methods The Therapeutic Goods Administration was contacted on 6 January 2020 and asked for all reports containing the words "osteonecrosis of the jaw". This was provided in a spreadsheet of de-identified reports received from commencement of the database in 1971 until 1 October 2019.

Results The drugs implicated in the 419 cases were divided by established drugs with MRONJ and secondary drugs that possibly contribute to MRONJ development. While the majority of cases were associated with denosumab or bisphosphonates (n = 405), there were 14 reports where secondary agents that directly or indirectly affect bone turnover, were also implicated. Some of these secondary drugs, including adalimumab, etanercept, methotrexate and rituximab have previously been associated with MRONJ in published case reports.

Conclusions This study contributes to the sparse but growing literature associating an increasing number of drugs with MRONJ, and underscores the importance of considering all possible drugs that elevate a patient's MRONJ risk.