Medication-induced osteonecrosis of the jaw: a review of cases from the Food and Drug Administration Adverse Event Reporting System (FAERS)

Abstract

Background Osteonecrosis of the jaw (ONJ) is a rare but serious adverse drug reaction (ADR) commonly associated with bisphosphonate and denosumab therapy. Prior research utilized an online, public FDA Adverse Event Reporting System (FAERS) Database to explore this ADR. This data identified and described several novel medications associated with ONJ. Our study aims to build upon the prior findings, reporting trends of medication induced ONJ over time and identifying newly described medications. Methods We searched the FAERS database for all reported cases of medication related osteonecrosis of the jaw (MRONJ) from 2010 to 2021. Cases lacking patient age or gender were excluded. Only adults (18 +) and reports from Healthcare Professions were included. Duplicate cases were removed. The top 20 medications were identified and described for April 2010-December 2014 and April 2015-January 2021. Results Nineteen thousand six hundred sixty-eight cases of ONJ were reported to the FAERS database from 2010–2021. 8,908 cases met inclusion criteria. 3,132 cases were from 2010–2014 and 5,776 cases from 2015–2021. Within the cases from 2010–2014, 64.7% were female and 35.3% were male, and the average age was 66.1 ± 11.1 years. Between 2015–2021, 64.3% were female and 35.7% were male, and the average age was 69.2 ± 11.5 years. Review of the 2010–2014 data identified several medications and drug classes associated with ONJ not previously described. They include lenalidomide, corticosteroids (prednisolone and dexamethasone), docetaxel and paclitaxel, letrozole, methotrexate, imatinib, and teriparatide. Novel drugs and classes described between 2015–2021 include palbociclib, pomalidomide, radium 223, nivolumab, and cabozantinib. Discussion While stricter inclusion criteria and removal of duplicate cases led to fewer overall identified cases of MRONJ when compared to prior research, our data represents a more reliable analysis of MRONJ reports to the FAERS database. Denosumab was the most frequently reported medication associated with ONJ. While unable to imply incidence rates from our data due to the nature of the FAERS database, our findings provide further description of the various medications associated with ONJ and elucidate patient demographics associated with the ADR. Additionally, our study identifies cases of several newly described drugs and drug classes that have not been previously described in literature.

Osteonecrosis of the jaw after radiation followed by bevacizumab

“…Other medications reported to be associated with ONJ include other anti-vascular endothelial growth factor agents, such as sunitinib and aflibercept, antireceptor activator of nuclear factor kappa-Β ligand (RANKL) antibody denosumab, lenalidomide, corticosteroid (prednisolone and dexamethasone), docetaxel, letrozole, methotrexate, everolimus, paclitaxel, imatinib, sorafenib, and nivolumab [6]. There are three case reports on ONJ associated with ipilimumab [7] and two case reports on pembrolizumab-related ONJ [8] as of May 22, 2023.…”

Post-marketing risk analysis of bendamustine: a real-world approach based on the FAERS database

“…Given the limitations of the FAERS database, specifically the absence of denominator data, we cannot directly calculate the incidence of AEs. However, disproportionality analysis serves as a robust method in pharmacovigilance to detect signals of disproportionate reporting related to bendamustine ( Ahdi et al, 2023 ). In our study, we applied both Bayesian and Frequentist approaches to assess the association between bendamustine and AEs.…”

Endocrine system-related adverse events associated with PD-1/PD-L1 inhibitors: data mining from the FDA adverse event reporting system

“…In addition, sensitivity analysis cannot be performed in the current proportion imbalance method, and the impact of combined drug use on the outcome is difficult to predict,other research methods can be explored to evaluate the impact in the future. Fourth, due to a lack of information on the total number of people used, the incidence of specific adverse events cannot be calculated ( 37 ), therefore, the intensity of the association between drugs and adverse events was measured.…”