Int J Med Sci 2020; 17(4):471-479. doi:10.7150/ijms.39523

Research Paper

Association between oral anticoagulants and osteoporosis: Real-world data mining using a multi-methodological approach

Satoshi Yokoyama1✉, Shoko Ieda2, Mirai Nagano1, Chihiro Nakagawa1, Makoto Iwase1, Kouichi Hosomi1, Mitsutaka Takada1

1. Division of Clinical Drug Informatics, School of Pharmacy, Kindai University, 3-4-1 Kowakae, Higashi-osaka, Osaka 577-8502, Japan
2. Department of Pharmacy, Kindai University Hospital, 377-2 Ohno-higashi, Osaka-Sayama, Osaka 589-8511, Japan

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Citation:
Yokoyama S, Ieda S, Nagano M, Nakagawa C, Iwase M, Hosomi K, Takada M. Association between oral anticoagulants and osteoporosis: Real-world data mining using a multi-methodological approach. Int J Med Sci 2020; 17(4):471-479. doi:10.7150/ijms.39523. Available from http://www.medsci.org/v17p0471.htm

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Abstract

Introduction: Warfarin and direct oral anticoagulants (DOACs) have been widely used in antithrombotic therapy. Although warfarin use has been suspected to be associated with osteoporosis risk, several studies have shown otherwise. Conversely, a few reports have found an association between DOACs and osteoporosis. This study therefore clarifies the association between oral anticoagulants and osteoporosis by analyzing real-world data using different methodologies, algorithms, and databases.

Methods: Real-world data from the US Food and Drug Administration Adverse Event Reporting System (FAERS; 2004-2016) and Japanese administrative claims database (2005-2017; JMDC Inc., Tokyo) were used. Reporting odds ratio (ROR) and information component (IC) were calculated through disproportionality analysis (DPA) using reports recorded in the FAERS. Sequence symmetry analysis (SSA) was employed to calculate the adjusted sequence ratio (SR) using the JMDC Claims Database. For the adjusted SR and ROR, a significant signal was detected when the lower limit of the two-sided 95% confidence interval (CI) was more than 1. For the IC, a significant signal was detected when the lower limit of the 95% CI was more than 0.

Results: DPA for warfarin found significant signals for osteoporosis in ROR (1.43, 95% CI: 1.32-1.54) and IC (0.50, 95% CI: 0.39-0.61). SSA showed a significant association between warfarin use and osteoporosis or bisphosphonate use. Moreover, a significant association was observed in males and females, albeit only for warfarin.

Conclusion: Multi-methodological data mining revealed that warfarin use, not DOACs, is significantly associated with osteoporosis regardless of sex difference.

Keywords: warfarin, direct oral anticoagulant, osteoporosis, disproportionality analysis, sequence symmetry analysis, data mining