Toriumi Shinya, Kobayashi Akinobu, Sueki Hitoshi, Yamamoto Munehiro, Uesawa Yoshihiro
Department of Medical Molecular Informatics, Meiji Pharmaceutical University, Kiyose 204-8588, Japan.
Department of Pharmacy, National Hospital Organization Kanagawa Hospital, Hadano 257-8585, Japan.
Pharmaceuticals (Basel). 2021 Dec 13;14(12):1299. doi: 10.3390/ph14121299.
Fractures occur when bones become fragile and are subjected to external forces as occurring during falls. The use of drugs that increase bone fragility or fall risk increases the risk of fracture. This study investigates drug-induced fractures reported in the Japanese Adverse Drug Event Report (JADER) database in patients using 4892 drugs. Atypical femur fracture was the most frequently reported fracture, and 58 other fractures were also reported. Using Volcano plots and multiple logistic regression analysis, we identified the risk factors for drug-induced fractures as being female, of older age, higher body mass index, and using one of 90 drugs. The drug groups significantly associated with drug-induced fractures included bone resorption inhibitors, antiviral drugs, dopaminergic drugs, corticosteroids, and sleep sedatives. Principal component analysis was used to examine the relationship between the use of specific drugs and the site of drug-induced fracture. Bone resorption inhibitors and corticosteroids were associated with atypical femur fractures, jaw fractures, and ulna fractures through an osteoclast-mediated process. Other drugs were found to increase fracture risk via non-osteoclast-mediated mechanisms. These findings suggest that many drugs can result in drug-induced fractures through a variety of mechanisms.
当骨骼变得脆弱并受到如跌倒时所产生的外力作用时，就会发生骨折。使用会增加骨骼脆弱性或跌倒风险的药物会增加骨折风险。本研究调查了使用4892种药物的患者在日本药品不良反应报告（JADER）数据库中报告的药物性骨折情况。非典型股骨骨折是报告最频繁的骨折类型，还报告了其他58种骨折。通过火山图和多元逻辑回归分析，我们确定药物性骨折的风险因素为女性、年龄较大、体重指数较高以及使用90种药物中的一种。与药物性骨折显著相关的药物类别包括骨吸收抑制剂、抗病毒药物、多巴胺能药物、皮质类固醇和镇静催眠药。主成分分析用于研究特定药物的使用与药物性骨折部位之间的关系。骨吸收抑制剂和皮质类固醇通过破骨细胞介导的过程与非典型股骨骨折、颌骨骨折和尺骨骨折相关。发现其他药物通过非破骨细胞介导的机制增加骨折风险。这些发现表明，许多药物可通过多种机制导致药物性骨折。
