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The relation between bisphosphonate use and non-union of fractures of the humerus in older adults

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Abstract

Summary

While nitrogen-containing bisphosphonates have been shown to reduce fracture risk in postmenopausal women and men, their safety in the period after a fracture is unclear. In fully adjusted multivariable regression models, bisphosphonate use in the post-fracture period was associated with an increased probability of non-union [odds ratio (OR) 2.37, 95% confidence interval (CI) 1.13–4.96]. Clinicians might consider waiting for several months before introduction of a bisphosphonate after a fracture.

Introduction

While nitrogen-containing bisphosphonates have been shown to reduce fracture risk in postmenopausal women and men, their safety in the period after a fracture is unclear. We examined the risk of non-union associated with post-fracture bisphosphonate use among a group of older adults who had experienced a humerus fracture.

Methods

We conducted a nested case–control study among subjects who had experienced a humerus fracture. From this cohort, cases of non-union were defined as those with an orthopedic procedure related to non-union 91–365 days after the initial humerus fracture. Bisphosphonate exposure was assessed during the 365 days prior to the non-union among cases or the matched date for controls. Multivariable logistic regression models were examined to calculate the OR and 95% CI for the association of post-fracture bisphosphonate use with non-union.

Results

From the cohort of 19,731 patients with humerus fractures, 81 (0.4%) experienced a non-union. Among the 81 cases, 13 (16.0%) were exposed to bisphosphonates post-fracture, while 69 of the 810 controls (8.5%) were exposed in the post-fracture interval. In fully adjusted multivariable regression models, bisphosphonate use in the post-fracture period was associated with an increased odds of non-union (OR 2.37, 95% CI 1.13–4.96). Albeit limited by small sample sizes, the increased risk associated with bisphosphonate use persisted in the subgroup of patients without a history of osteoporosis or prior fractures (OR 1.91, 95% CI 0.75–4.83).

Conclusions

In this study of older adults, non-union after a humerus fracture was rare. Bisphosphonate use after the fracture was associated with an approximate doubling of the risk of non-union.

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Conflicts of interest

There is no specific support for this project. Dr. Solomon receives salary support from the NIH (AR 047782, AR 055989, AG 027066, DA 022600) and AHRQ. He has served as an unpaid member of an Advisory Board to Amgen for a non-osteoporosis-related product. He provides epidemiologic consulting to CORRONA. Dr. Hochberg receives salary support from the NIH and the Department of Veterans Affairs and is a consultant to the following companies that have products in the field of osteoporosis: Amgen, Merck & Co., Inc., Novartis Pharma A.G., Proctor & Gamble Pharmaceutical Co., and Roche Pharmaceutical Co. Dr. Schneeweiss is Principal Investigator of the Brigham and Women’s Hospital DEcIDE Research Center on comparative effectiveness research funded by the Agency of Healthcare Research and Quality.

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Authors and Affiliations

  1. Division of Pharmacoepidemiology, Harvard Medical School, Boston, MA, USA

    D. H. Solomon, H. Mogun & S. Schneeweiss

  2. Division of Rheumatology, Immunology, and Allergy, Harvard Medical School, Boston, MA, USA

    D. H. Solomon

  3. Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    D. H. Solomon, H. Mogun & S. Schneeweiss

  4. Division of Rheumatology and Clinical Immunology, University of Maryland School of Medicine, Baltimore, MD, USA

    M. C. Hochberg

  5. Department of Medicine and Division of Gerontology, University of Maryland School of Medicine, Baltimore, MD, USA

    M. C. Hochberg

  6. Department of Epidemiology and Preventive Medicine, University of Maryland School of Medicine, Baltimore, MD, USA

    M. C. Hochberg

  7. Division of Rheumatology, Brigham and Women’s Hospital, 75 Francis Street, Boston, MA, 02115, USA

    D. H. Solomon

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  1. D. H. Solomon
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  2. M. C. Hochberg
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  3. H. Mogun
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  4. S. Schneeweiss
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Correspondence to D. H. Solomon.

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Solomon, D.H., Hochberg, M.C., Mogun, H. et al. The relation between bisphosphonate use and non-union of fractures of the humerus in older adults. Osteoporos Int 20, 895–901 (2009). https://doi.org/10.1007/s00198-008-0759-z

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  • DOI: https://doi.org/10.1007/s00198-008-0759-z

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