Analysis of the time-to-onset of osteonecrosis of jaw with bisphosphonate treatment using the data from a spontaneous reporting system of adverse drug events

Mitsuhiro Nakamura; Ryogo Umetsu; Junko Abe; Toshinobu Matsui; Natsumi Ueda; Yamato Kato; Sayaka Sasaoka; Kohei Tahara; Hirofumi Takeuchi; Yasutomi Kinosada

doi:10.1186/s40780-015-0035-2

Analysis of the time-to-onset of osteonecrosis of jaw with bisphosphonate treatment using the data from a spontaneous reporting system of adverse drug events

J Pharm Health Care Sci. 2015 Dec 22:1:34. doi: 10.1186/s40780-015-0035-2. eCollection 2015.

Authors

Affiliations

¹ Laboratory of Drug Informatics, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu, 501-1196 Japan.
² Laboratory of Drug Informatics, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu, 501-1196 Japan ; Present address: Clinical Research, Innovation and Education Center, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba Ward, Sendai, Miyagi 980-8574 Japan.
³ Laboratory of Drug Informatics, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu, 501-1196 Japan ; Medical Database Co., LTD, 3-11-10 Higashi, Shibuya-ku, Tokyo 150-0011 Japan.
⁴ Laboratory of Pharmaceutical Engineering, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu, 501-1196 Japan.
⁵ United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, 1-1 Yanagido, Gifu, 501-1194 Japan.

Abstract

Background: Bisphosphonates (BPs) are potent antiresorptive agents used to treat osteoporosis and the complications associated with malignant bone metastasis. The aim of this study was to evaluate the incidence of bisphosphonate-related osteonecrosis of the jaw (BRONJ) using the Japanese Adverse Drug Event Report (JADER) database. In particular, we focused on the time-to-onset profile of BRONJ.

Findings: We analyzed reports of BRONJ in the JADER database and calculated the reporting odds ratio (ROR) of BPs potentially associated with BRONJ. We applied the weibull shape parameter to time-to-event data in JADER. The drugs selected for this investigation were seven BPs approved in Japan (alendronate [intraveneous, I.V.], pamidronate, and zoledronate as I.V. BPs; and alendronate (oral), etidronate, minodronate, and risedronate as oral BPs). We analyzed reports of BRONJ events associated with BPs in the JADER database from April 2004 to November 2014. The median value of BRONJ cases caused by alendronate (I.V.), pamidronate, zoledronate, alendronate (oral), etidronate, minodronate, and risedronate were 1342, 812, 486, 863, 1461, 432, and 730 days, respectively. The lower 95 % confidence interval of the Weibull-shape parameter β for I.V. BPs (pamidronate and zoledronate) exceeded 1. The risk of BRONJ with I.V. BPs increased over time.

Conclusion: Thus, the incidence of BRONJ with BP treatment should be closely monitored for a 3-year period. Further studies are required to draw conclusions, and we believe that this information about BRONJ induced by BPs will prove beneficial to patients and pharmacists.

Keywords: Bisphosphonate; Japanese adverse drug event report database; Osteonecrosis of jaw.

Publication types

Case Reports