Comprehensive Study of the Risk Factors for Medication-Related Osteonecrosis of the Jaw Based on the Japanese Adverse Drug Event Report Database

Medication-related osteonecrosis of the jaw (MRONJ) is associated with many drugs, including bisphosphonates (BPs). BPs are associated with atypical femoral fractures and osteonecrosis of the external auditory canal. Thus, many drugs are reported to cause adverse effects on bone. This study aimed to investigate the effects of drugs and patient backgrounds regarding osteonecrosis-related side effects, including MRONJ. This study used a large voluntary reporting database, namely, the Japanese Adverse Drug Event Report database. First, we searched for risk factors related to MRONJ using volcano plots and logistic regression analysis. Next, we searched for bone-necrosis-related side effects using principal component and cluster analysis. Factors that were significantly associated with MRONJ included eight types of BPs and denosumab, prednisolone, sunitinib, eldecalcitol, raloxifene, letrozole, doxifluridine, exemestane, radium chloride, medroxyprogesterone, female, elderly, and short stature. Furthermore, antiresorptive agents (i.e., BPs and denosumab) tended to induce MRONJ and atypical femoral fractures by affecting osteoclasts. We believe these findings will help medical personnel manage the side effects of many medications.