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Association between timing of zoledronic acid infusion and hip fracture healing

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Abstract

Summary

Patients in the Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly (HORIZON) Recurrent Fracture Trial were assessed for evidence of delayed hip fracture healing. No association was observed between zoledronic acid (ZOL) and delayed healing. We conclude that ZOL has no clinically evident effect on fracture healing, even when the drug is infused in the immediate postoperative period.

Introduction

Intravenous zoledronic acid 5 mg (ZOL) given after a hip fracture reduces secondary fracture rates and mortality. It has been postulated that bisphosphonates may affect healing if given soon after a fracture. We sought to determine whether the timing of ZOL infusion affected the risk of delayed hip fracture healing.

Methods

In the HORIZON Recurrent Fracture Trial, patients were randomized within 90 days of a low-trauma hip fracture to receive either once-yearly ZOL (n = 1,065) or placebo (n = 1,062). Clinical symptoms of delayed hip fracture healing were sought at randomization, 6 months and 12 months after fracture; if present, a central adjudication committee blinded to treatment assignment reviewed radiographs and clinical records. Median follow-up was 1.9 years.

Results

The overall incidence of delayed healing was 3.2% (ZOL) and 2.7% (placebo; odds ratio [OR], 1.17; 95% confidence interval [CI], 0.72–1.90; p = 0.61). Logistic regression models revealed no association between ZOL and delayed healing even after adjusting for other risk factors (OR, 1.21; 95% CI, 0.74–1.99; p = 0.44). There was no interaction by timing of infusion, and nonunion rates were similar even when ZOL was given within 2 weeks of hip fracture repair. NSAID use was significantly associated with delayed fracture healing (OR, 2.55; 95% CI, 1.49–4.39; p < 0.001).

Conclusions

ZOL has no clinically evident effect on fracture healing, even when the drug is infused in the immediate postoperative period.

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Acknowledgements

The authors thank Vikrant Pallapotu (MSCD-India, Novartis) and Holly Gilbert-Jones (BioScience Communications) for their editorial assistance.

Conflicts of interest

Dr. Colón-Emeric serves as a consultant for Novartis and Amgen. Dr. Nordsletten has no conflicts of interest. Dr. Olson has no conflicts of interest. Dr. Major has no conflicts of interest. Dr. Boonen has received research funding and consulting fees from Novartis. Dr. Haentjens has no conflict of interest. Dr. Mesenbrink is an employee of Novartis and owns stock in the company. Dr. Magaziner serves as a consultant for Novartis, Eli Lilly and Amgen, and has research grants from Novartis and Merck. Dr. Adachi serves as a consultant/advisor for Amgen, Astra Zeneca, Eli Lilly, Glaxo Smith Kline (GSK), Merck, Novartis, Nycomed, Pfizer, Procter & Gamble, Roche, Sanofi-Aventis, Servier, Wyeth, Bristol-Myers Squibb. Dr. Lyles serves as a consultant for Novartis, Procter & Gamble, Merck, Amgen, Kirin Pharmaceutical, GTx, Lilly, GSK, Bone Medical Ltd., Wyeth and Osteologix, and receives research support from Novartis, Alliance for Better Bone Health and Amgen. Dr. Hyldstrup serves as a consultant for Novartis, Nycomed, Unilabs and Amgen.Dr. Bucci-Rechtweg is an employee of Novartis and owns stock in the company. Dr. Recknor serves as a consultant/advisor for Roche, GSK, Lilly, Procter & Gamble, Merck, Novartis, Amgen, NPS and Zelos.

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Authors and Affiliations

  1. Duke University Medical Center and the Geriatrics Research Education and Clinical Center, Veterans Affairs Medical Center, Durham, NC, USA

    C. Colón-Emeric, S. Olson & K. W. Lyles

  2. Ullevål University Hospital, Oslo, Norway

    L. Nordsletten

  3. Hospital of the University of Pennsylvania, Philadelphia, PA, USA

    N. Major

  4. Division of Gerontology and Geriatrics, Leuven University, Leuven, Belgium

    S. Boonen

  5. Centre for Outcomes Research and Laboratory for Experimental Surgery, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels, Belgium

    P. Haentjens

  6. Novartis Pharmaceuticals, East Hanover, NJ, USA

    P. Mesenbrink & C. Bucci-Rechtweg

  7. The University of Maryland, Baltimore, MD, USA

    J. Magaziner

  8. McMaster University, Hamilton, ON, Canada

    J. Adachi

  9. Hvidovre Hospital, Hvidovre, Denmark

    L. Hyldstrup

  10. United Osteoporosis Centers, Gainesville, GA, USA

    C. Recknor

  11. Duke University Medical Center and the Durham VA GRECC, 508 Fulton St. GRECC 182, Durham, NC, 27705, USA

    C. Colón-Emeric

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  1. C. Colón-Emeric
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  2. L. Nordsletten
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  3. S. Olson
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  4. N. Major
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  10. K. W. Lyles
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  12. C. Bucci-Rechtweg
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  13. C. Recknor
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for the HORIZON Recurrent Fracture Trial

Corresponding author

Correspondence to C. Colón-Emeric.

Additional information

This study is supported by Novartis Pharma AG.

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Colón-Emeric, C., Nordsletten, L., Olson, S. et al. Association between timing of zoledronic acid infusion and hip fracture healing. Osteoporos Int 22, 2329–2336 (2011). https://doi.org/10.1007/s00198-010-1473-1

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  • DOI: https://doi.org/10.1007/s00198-010-1473-1

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