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Oral bisphosphonates and upper gastrointestinal toxicity: a study of cancer and early signals of esophageal injury

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Abstract

Summary

We evaluated the association between bisphosphonate use and (1) upper gastrointestinal cancer, (2) upper endoscopy, (3) incident Barrett’s esophagus, and (4) prescription antacid initiation among Medicare beneficiaries. We found no bisphosphonate-cancer association and negative bisphosphonate-Barrett’s association.

Introduction

Bisphosphonates can irritate the esophagus; a cancer association has been suggested. Widespread bisphosphonates use compels continued investigation of upper gastrointestinal toxicity.

Methods

Using a 40 % Medicare random sample denominator, inpatient, outpatient (2003–2011), and prescription (2006–2011) claims, we studied patients age 68 and older with osteoporosis and/or oral bisphosphonate use. Inverse propensity weighting estimated marginal structural models for the effect of bisphosphonate intensity (pills per month) and cumulative bisphosphonate pills received on upper gastrointestinal cancer risk. Secondary analyses of sub-cohorts without past bisphosphonates or upper endoscopy assessed bisphosphonate initiation and risk of (1) upper endoscopy, (2) incident Barrett’s esophagus, and (3) prescription antacid initiation.

Results

The cohort included 1.64 million beneficiaries: 87.9 % women, mean age, 76.8 (standard deviation (SD) 9.3); mean follow-up, 39.6 months; 38.1 % received oral bisphosphonates. Cumulative bisphosphonate receipt, among users, ranged from 4 to 252 pills (5th to 95th percentile). We identified 2,308 upper gastrointestinal cancers (0.43/1000 person years). We found no association between cumulative bisphosphonate pills and cancer, odds ratio (OR) for each additional pill 1.00 (95 % confidence interval (CI) 1.00, 1.00). In sub-cohorts, compared to none, lowest cumulative bisphosphonate use (one to nine pills) was associated with higher risk of endoscopy (OR 1.11, 95 % CI 1.08–1.14) and antacid initiation (OR 1.13, 95 % CI 1.10–1.16); higher intensity conferred no increased risk. Higher intensity and higher cumulative bisphosphonate category were associated with lower Barrett’s risk.

Conclusions

We found no bisphosphonate-cancer association and negative bisphosphonate-Barrett’s association. Bisphosphonate initiation appears to identify patients susceptible to early irritating effects; clinicians might offer alternatives and delay endoscopy or antacids.

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Funding

National Institutes on Aging K23AG035030 (Morden) and P01 AG019783

Robert Wood Johnson Foundation Dartmouth Atlas Project

National Institute of Arthritis and Musculoskeletal and Skin Diseases P60AR062799

Conflicts of interest

Nancy E. Morden, Jeremy Smith, Todd A. Mackenzie, Stephen K. Liu, and Anna N A Tosteson declare that they have no conflict of interest. Dr. Munson received payment from GlaxoSmithKline for consulting on the design and analysis of a research study.

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Authors and Affiliations

  1. The Dartmouth Institute for Health Policy & Clinical Practice, Geisel School of Medicine at Dartmouth, 35 Centerra Parkway, Room 3088, Lebanon, NH, 03766, USA

    N. E. Morden, J. C. Munson, J. Smith, T. A. Mackenzie, S. K. Liu & A. N. A. Tosteson

  2. Norris Cotton Cancer Center, Dartmouth Hitchcock Medical Center, Lebanon, NH, 03766, USA

    N. E. Morden, T. A. Mackenzie, S. K. Liu & A. N. A. Tosteson

  3. Community and Family Medicine, Geisel School of Medicine at Dartmouth, 1 Rope Ferry Rd., Hanover, NH, 03755, USA

    N. E. Morden

  4. Department of Medicine, Geisel School of Medicine at Dartmouth, 1 Rope Ferry Rd., Hanover, NH, 03755, USA

    J. C. Munson, T. A. Mackenzie & S. K. Liu

Authors
  1. N. E. Morden
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  2. J. C. Munson
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Correspondence to N. E. Morden.

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Morden, N.E., Munson, J.C., Smith, J. et al. Oral bisphosphonates and upper gastrointestinal toxicity: a study of cancer and early signals of esophageal injury. Osteoporos Int 26, 663–672 (2015). https://doi.org/10.1007/s00198-014-2925-9

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  • DOI: https://doi.org/10.1007/s00198-014-2925-9

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