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Comparative gastrointestinal safety of bisphosphonates in primary osteoporosis: a network meta-analysis

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Abstract

Summary

We completed a network meta-analysis of published papers to compare bisphosphonate gastrointestinal safety. We found that zoledronic acid had the highest chance of causing gastrointestinal adverse events. Etidronate had the highest chance of discontinuation due to an adverse event. No difference was found for serious adverse events.

Introduction

Bisphosphonates are first-line treatment for osteoporosis. Gastrointestinal (GI) adverse events (AE) are the primary reason for non-adherence. Little is known about the comparative GI safety of bisphosphonates.

Purpose

Leverage published clinical trial data to examine the comparative GI safety of bisphosphonates.

Methods

We completed a systematic review of all English-language clinical trials that assessed bisphosphonate safety and/or efficacy in primary osteoporosis through to 2012. Randomized, blinded, and controlled studies were eligible. The primary outcome was any GI-related AE. Subanalyses were completed for upper GI symptoms, serious GI, nausea, esophageal-related events, and discontinuation due to AE. A Bayesian-based network meta-analysis was completed to allow for indirect comparisons. Results were reported as the probability that a specific drug had the highest number of events.

Results

We identified 50 studies: 32 alendronate, 12 risedronate, 5 etidronate, and 7 zoledronic acid. Zoledronic acid had the highest probability of having the highest number of any GI AE (91 %) and nausea (70 %). Etidronate (70 %) and zoledronic acid (28 %) had the highest probability of having the greatest attrition due to AE. Etidronate had the highest probability (56 %) of having the greatest number of upper GI symptoms among oral bisphosphonates.

Conclusion

Zoledronic acid had the highest probability of causing the greatest number of GI AE, possibly related to nausea. These results question the assumption that annual zoledronic acid will translate into better adherence. Little difference was found between alendronate and risedronate for serious AE. More research into real-world implications of the comparative safety of bisphosphonates is needed.

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Acknowledgments

This research was supported by a research grant to Dr. Cadarette from the Ontario Ministry of Research and Innovation Early Researcher Award (ER09-06-043). Dr. Cadarette is supported by a Canadian Institutes of Health Research (CIHR) New Investigator Award in Aging and Osteoporosis (MSH-95364), and Dr. Tadrous is supported by a CIHR Fredrick Banting and Charles Best Canada Graduate Scholarship Doctoral Award (GSD-11342). Dr. Mamdani has served as an advisory board member for the following pharmaceutical companies: Astra Zeneca, Bristol-Myers Squibb, Eli Lilly and Company, Glaxo Smith Kline, Hoffman La Roche, Novartis, Novo Nordisk and Pfizer.

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Authors and Affiliations

  1. Leslie Dan Faculty of Pharmacy, University of Toronto, 144 College Street, Toronto, ON, M5S 3M2, Canada

    M. Tadrous, L. Wong, M. M. Mamdani, M. D. Krahn & S. M. Cadarette

  2. Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada

    M. M. Mamdani & M. D. Krahn

  3. Applied Health Research Centre, Li Ka Shing Knowledge Institute, St. Michael’s Hospital, Toronto, ON, Canada

    M. M. Mamdani

  4. Sunnybrook Research Institute, Toronto, ON, Canada

    D. N. Juurlink

  5. Toronto Health Economics and Technology Assessment (THETA) Collaborative, Toronto, ON, Canada

    M. D. Krahn

  6. Department of Community Health and Epidemiology, Queen’s University, Kingston, ON, Canada

    L. E. Lévesque

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Tadrous, M., Wong, L., Mamdani, M.M. et al. Comparative gastrointestinal safety of bisphosphonates in primary osteoporosis: a network meta-analysis. Osteoporos Int 25, 1225–1235 (2014). https://doi.org/10.1007/s00198-013-2576-2

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