Abstract
Summary
Concerns have been raised among clinicians and patients whether or not bisphosphonates increase the risk of atrial fibrillation. In this large cohort study, increased risk of atrial fibrillation was not found to be associated with bisphosphonate. In fact, bisphosphonate even showed a protective effect against cardiac arrhythmia compared to other osteoporosis medications.
Introduction
Increased risk of atrial fibrillation among bisphosphonate users has been reported; however, the results from these studies are controversial. The purpose of this study was to evaluate the risk of atrial fibrillation associated with bisphosphonate use in older women.
Methods
We used the Korean Health Insurance Review and Assessment Service claims database from May 1, 2005 to June 30, 2006. Retrospective cohort analysis was conducted on women 65 years or older with newly diagnosed cases of osteoporosis (ICD 10 code: M80, M81) who had not previously taken any medications for osteoporosis. Bisphosphonate-exposed and non-exposed patients were followed until they were either diagnosed with atrial fibrillation (ICD 10 code: I48) or until the end of the study. The Cox proportional hazards model was used to calculate hazard ratios and the 95% confidence intervals.
Results
Atrial fibrillation was reported in 626 of the 120,319 patients (0.52%) treated with bisphosphonates and 66 of 9,863 patients (0.67%) treated with other osteoporosis medications. Overall hazard ratio for developing atrial fibrillation in the bisphosphonate-treated group was 0.52 (95% CIs, 0.29–0.91). In patients with a medication possession ratio greater than 0.7, the hazard ratio was lower (HR 0.41, 95% CIs 0.23–0.75). In the subgroup analysis, alendronate showed a statistically significant protective effect against the risk of atrial fibrillation with a hazard ratio of 0.75 (95% CI, 0.58–0.97).
Conclusion
Among older Korean women with osteoporosis, bisphosphonate was found to have a protective effect against atrial fibrillation.

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Acknowledgments
This study was supported by a grant from the Korean Food and Drug Administration (07072KFDA224).
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An erratum to this article can be found at http://dx.doi.org/10.1007/s00198-011-1841-5
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Rhee, C.W., Lee, J., Oh, S. et al. Use of bisphosphonate and risk of atrial fibrillation in older women with osteoporosis. Osteoporos Int 23, 247–254 (2012). https://doi.org/10.1007/s00198-011-1608-z
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DOI: https://doi.org/10.1007/s00198-011-1608-z