Toriumi Shinya, Kobayashi Akinobu, Uesawa Yoshihiro
Department of Medical Molecular Informatics, Meiji Pharmaceutical University, Kiyose, Tokyo 204-8588, Japan.
Department of Pharmacy, National Hospital Organization Kanagawa Hospital, Hadano, Kanagawa 257-8585, Japan.
Pharmaceuticals (Basel). 2020 Dec 16;13(12):467. doi: 10.3390/ph13120467.
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.
药物相关性颌骨坏死（MRONJ）与多种药物有关，包括双膦酸盐（BP）。BP与非典型股骨骨折和外耳道骨坏死有关。因此，据报道许多药物会对骨骼产生不良反应。本研究旨在调查药物及患者背景对包括MRONJ在内的骨坏死相关副作用的影响。本研究使用了一个大型自愿报告数据库，即日本药品不良事件报告数据库。首先，我们使用火山图和逻辑回归分析寻找与MRONJ相关的危险因素。接下来，我们使用主成分分析和聚类分析寻找与骨坏死相关的副作用。与MRONJ显著相关的因素包括八种BP、地诺单抗、泼尼松龙、舒尼替尼、阿法骨化醇、雷洛昔芬、来曲唑、去氧氟尿苷、依西美坦、氯化镭、甲羟孕酮、女性、老年人和身材矮小。此外，抗吸收剂（即BP和地诺单抗）倾向于通过影响破骨细胞诱导MRONJ和非典型股骨骨折。我们相信这些发现将有助于医务人员管理多种药物的副作用。
