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Insights into the bisphosphonate holiday: a preliminary FTIRI study

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Abstract

Summary

Bone composition evaluated by FTIRI analysis of iliac crest biopsies from post-menopausal women treated with alendronate for 10 years, continuously or alendronate for 5 years, followed by a 5-year alendronate-holiday, only differed with the discontinued biopsies having increased cortical crystallinity and heterogeneity of acid phosphate substitution and decreased trabecular crystallinity heterogeneity.

Introduction

Bisphosphonates (BP) are the most commonly used and effective drugs to prevent fragility fractures; however, concerns exist that prolonged use may lead to adverse events. Recent recommendations suggest consideration of a BP “holiday” in individuals taking long-term BP therapy not at high risk of fracture. Data supporting or refuting this recommendation based on bone quality are limited. We hypothesized that a “holiday” of 5 years would cause no major bone compositional changes.

Methods

We analyzed the 31 available biopsies from the FLEX-Long-term Extension of FIT (Fracture Intervention Trial) using Fourier transform infrared imaging (FTIRI). Biopsies from two groups of post-menopausal women, a “Continuously treated group” (N = 16) receiving alendronate for ~ 10 years and a “Discontinued group” (N = 15), alendronate treated for 5 years taking no antiresorptive medication during the following 5 years. Iliac crest bone biopsies were provided at 10 years.

Results

Key FTIRI parameters, mineral-to-matrix ratio, carbonate-to-phosphate ratio, acid phosphate substitution, and collagen cross-link ratio as well as heterogeneity of these parameters were similar for Continuously treated and Discontinued groups in age-adjusted models. The Discontinued group had 2% greater cortical crystallinity (p = 0.01), 31% greater cortical acid phosphate heterogeneity (p = 0.02), and 24% lower trabecular crystallinity heterogeneity (p = 0.02).

Conclusions

Discontinuation of alendronate for 5 years did not affect key FTIRI parameters, supporting the hypothesis that discontinuation would have little impact on bone composition. Modest differences were observed in three parameters that are not likely to affect bone mechanical properties. These preliminary data suggest that a 5-year BP holiday is not harmful to bone composition.

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Acknowledgments

Supported by NIH AR041325 (ALB). The parent study was supported by contracts with Merck & Co. (Rahway, NJ) and was designed jointly by non-Merck investigators and Merck employees. Study drug was manufactured and packaged by Merck.

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Authors and Affiliations

  1. Hospital for Special Surgery, New York, NY, USA

    A. L. Boskey & L. Spevak

  2. The George Washington University, Washington, DC, USA

    Y. Ma & H. Wang

  3. University of California San Francisco, San Francisco, CA, USA

    D. C. Bauer, D. M. Black & A. V. Schwartz

Authors
  1. A. L. Boskey
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  2. L. Spevak
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  3. Y. Ma
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  7. A. V. Schwartz
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Corresponding author

Correspondence to A. V. Schwartz.

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Conflicts of interest

Boskey, Spevak, Ma, Wang, Bauer, and Schwartz have no conflicts of interest. Black reports conflicts.

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A. L. Boskey died May 2, 2017

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Boskey, A.L., Spevak, L., Ma, Y. et al. Insights into the bisphosphonate holiday: a preliminary FTIRI study. Osteoporos Int 29, 699–705 (2018). https://doi.org/10.1007/s00198-017-4324-5

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  • DOI: https://doi.org/10.1007/s00198-017-4324-5

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