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Comparative gastrointestinal safety of weekly oral bisphosphonates

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Abstract

Summary

Weekly bisphosphonates are the primary agents used to treat osteoporosis. Although these agents are generally well tolerated, serious gastrointestinal adverse events, including hospitalization for gastrointestinal bleed, may arise. We compared the gastrointestinal safety between weekly alendronate and weekly risedronate and found no important difference between new users of these agents.

Introduction

Weekly bisphosphonates are the primary agents prescribed for osteoporosis. We examined the comparative gastrointestinal safety between weekly bisphosphonates.

Methods

We studied new users of weekly alendronate and weekly risedronate from June 2002 to August 2005 among enrollees in a state-wide pharmaceutical benefit program for seniors. Our primary outcome was hospitalization for upper gastrointestinal bleed. Secondary outcomes included outpatient diagnoses for upper gastrointestinal disease, symptoms, endoscopic procedures, use of gastroprotective agents, and switching between therapies. We used Cox proportional hazard models to compare outcomes between agents within 120 days of treatment initiation, adjusting for propensity score quintiles. We also examined composite safety outcomes and stratified results by age and prior gastrointestinal history.

Results

A total of 10,420 new users were studied, mean age = 79 years (SD, 6.9), and 95% women. We observed 31 hospitalizations for upper gastrointestinal bleed (0.91 per 100 person-years) within 120 days of treatment initiation. Adjusting for covariates, there was no difference in hospitalization for upper gastrointestinal bleed among those treated with risedronate compared with alendronate (HR, 1.12; 95%CI, 0.55 to 2.28). Risedronate switching rates were lower; otherwise, no differences were observed for secondary or composite outcomes.

Conclusions

We found no important difference in gastrointestinal safety between weekly oral bisphosphonates.

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Acknowledgments

The authors thank Dr. Sebastian Schneeweiss, MD, ScD, Director for Drug Evaluation and Outcomes Research, Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women’s Hospital, for helpful comments and discussions.

Grant support

Dr Brookhart is supported by the National Institute on Aging (K25 AG027400), Dr Cadarette was supported by the Canadian Institutes of Health Research (Post-Doctoral Fellowship), Dr Katz is supported by the National Institute of Arthritis and Muskuloskeletal and Skin Diseases (K24 AR02123 and P60 AR47782), Dr Solomon is supported by the Arthritis Foundation and the National Institutes of Health (K24 AR055989, R21 AG027066, and P60 AR47782), and Dr. Stürmer is supported by the National Institute on Aging (RO1 AG023178) and the UNC-GSK Center for Excellence in Pharmacoepidemiology and Public Health.

Conflicts of interest

Co-authors have received salary support in the last 5 years from research grants to the Brigham and Women’s Hospital for unrelated work from: Amgen (Dr Brookhart), GlaxoSmithKline (Dr Stürmer), Merck (Drs. Solomon and Stürmer), Novartis (Dr Katz), Pfizer, Procter & Gamble, and Savient (Dr Solomon). There was no pharmaceutical industry support for this study.

Author information

Authors and Affiliations

  1. Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    S. M. Cadarette, M. A. Brookhart, T. Stürmer, M. R. Stedman, R. Levin & D. H. Solomon

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

    S. M. Cadarette

  3. Division of Rheumatology, Immunology and Allergy, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    J. N. Katz & D. H. Solomon

  4. Department of Orthopaedic Surgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    J. N. Katz

  5. Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    T. Stürmer

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  1. S. M. Cadarette
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Corresponding author

Correspondence to S. M. Cadarette.

Appendix

Appendix

Table 3 Study outcome coding (diagnoses and procedures)
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Table 4 Definition and coding of variables included in logistic regression model used to create propensity scores
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Table 5 Cohort characteristics within propensity score quintiles for risedronate prescribing by drug received, overlapping propensity scores (N = 10,416)
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Appendix Figure
figure 3

Sensitivity analysis of residual confounding using the array approach for our primary outcome (hospitalization for upper gastrointestinal bleed). To facilitate interpretation by the reader, we have maintained the notation used in the explanatory article and Excel program that we modified (available at www.drugepi.org) to produce this figure [29]. ARR apparent exposure relative risk, i.e., the relative risk (hazard ratio) observed in the current study (risedronate versus alendronate), fixed at 1.12. P C0 prevalence of counfounder among unexposed (alendronate), fixed at 20% in this example. P C1 prevalence of confounder among exposed (risedronate) group, varied from 0% to 50% in the figure. RR CD association between confounder and disease outcome, varied from 1.0 to 5.5 in figure. RR fully adjusted or “true” exposure relative risk. Blue line no confounding present, prevalence of confounder same among alendronate and risedronate recipients

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Cadarette, S.M., Katz, J.N., Brookhart, M.A. et al. Comparative gastrointestinal safety of weekly oral bisphosphonates. Osteoporos Int 20, 1735–1747 (2009). https://doi.org/10.1007/s00198-009-0871-8

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  • DOI: https://doi.org/10.1007/s00198-009-0871-8

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