Inada Ayaka, Hosohata Keiko, Oyama Saki, Niinomi Iku, Mori Yasuhiro, Yamaguchi Yuki, Uchida Mayako, Iwanaga Kazunori
Education and Research Center for Clinical Pharmacy, Osaka University of Pharmaceutical Sciences, Takatsuki, Osaka 569-1094, Japan,
Ther Clin Risk Manag. 2018 Dec 24;15:59-64. doi: 10.2147/TCRM.S176620. eCollection 2019.
Bisphosphonates (BPs) and denosumab are widely used to treat osteoporosis and complications associated with bone metastases. However, medication-related osteonecrosis of the jaw (MRONJ) is a serious problem.
The objective of this study was to evaluate the frequency, outcome, and characteristics of patients with drug-induced MRONJ.
Retrospective pharmacovigilance disproportionality analysis was conducted using the Japanese Adverse Drug Event Report (JADER) database from the Pharmaceuticals and Medical Devices Agency. Adverse event reports submitted to JADER between 2004 and 2017 were analyzed, and the reporting odds ratio (ROR) was calculated.
Among the BPs that cause MRONJ, zoledronate was the most common; therefore, we compared the characteristics of cases of MRONJ induced by zoledronate with those induced by denosumab. Among the 3,875 (68.1% women) cases of MRONJ, zoledronate-related MRONJ accounted for 1,283 (56.0% women) and denosumab-related MRONJ accounted for 322 (55.3% women). MRONJ was more frequent after 70 years of age regardless of the use of either zoledronate or denosumab; onset occurred after 1 year from the denosumab treatment, but it is unknown when onset occurred after zoledronate treatment. The outcomes for MRONJ were poor, with 406 reports on zoledronate (31.6%) and 152 reports on denosumab (47.2%) demonstrating nonrecovery. Zoledronate (ROR: 319.3, 95% CI: 296.0-344.4) had the highest ROR among BP agents. Denosumab had a high ROR (ROR: 155.2, 95% CI: 136.5-176.3). Zoledronate and denosumab were used in similar patient backgrounds, and their use resulted in a similar frequency of MRONJ.
The findings of this comprehensive evaluation of MRONJ using the JADER database will be helpful for prescribing medications to elderly patients.
双膦酸盐（BPs）和地诺单抗被广泛用于治疗骨质疏松症及与骨转移相关的并发症。然而，药物相关性颌骨坏死（MRONJ）是一个严重问题。
本研究旨在评估药物性MRONJ患者的发生率、结局及特征。
使用日本药品和医疗器械管理局的日本药品不良事件报告（JADER）数据库进行回顾性药物警戒不均衡性分析。分析了2004年至2017年期间提交至JADER的不良事件报告，并计算报告比值比（ROR）。
在导致MRONJ的双膦酸盐中，唑来膦酸盐最为常见；因此，我们比较了唑来膦酸盐诱导的MRONJ病例与地诺单抗诱导的MRONJ病例的特征。在3875例MRONJ病例中（68.1%为女性），唑来膦酸盐相关的MRONJ占1283例（56.0%为女性），地诺单抗相关的MRONJ占322例（55.3%为女性）。无论使用唑来膦酸盐还是地诺单抗，MRONJ在70岁以后更为常见；地诺单抗治疗1年后开始发病，但唑来膦酸盐治疗后何时发病尚不清楚。MRONJ的结局较差，唑来膦酸盐有406份报告（31.6%）和地诺单抗有152份报告（47.2%）显示未恢复。唑来膦酸盐（ROR：319.3，95%CI：296.0 - 344.4）在双膦酸盐类药物中ROR最高。地诺单抗的ROR也较高（ROR：155.2，95%CI：136.5 - 176.3）。唑来膦酸盐和地诺单抗用于相似的患者背景，且它们的使用导致MRONJ的发生率相似。
使用JADER数据库对MRONJ进行的这项综合评估结果将有助于为老年患者开药。
