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An evaluation of the Fracture Risk Assessment Tool (FRAX®) as an indicator of treatment efficacy: the effects of bazedoxifene and raloxifene on vertebral, nonvertebral, and all clinical fractures as a function of baseline fracture risk assessed by FRAX®

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Abstract

Summary

The relationship between baseline Fracture Risk Assessment Tool (FRAX®) and treatment efficacy was evaluated using data from a pivotal phase 3 study. Relative risk of vertebral, nonvertebral, and all clinical fractures decreased with increasing probability of fracture for bazedoxifene (BZA) versus placebo but remained generally constant for raloxifene (RLX).

Introduction

To determine whether the FRAX® predicts osteoporosis treatment efficacy, we evaluated reductions in fracture incidence associated with BZA and RLX according to baseline fracture risk determined by FRAX® using data from a phase 3 osteoporosis treatment study.

Methods

Hazard ratios (HRs) for effects of BZA and RLX versus placebo on incidence of vertebral, nonvertebral, and all clinical fractures were calculated using a Cox regression model. Cox regression analyses were performed in subgroups at or above 10-year fracture probability thresholds determined by FRAX®.

Results

HRs for the risk of vertebral, nonvertebral, and all clinical fractures versus placebo decreased with increasing 10-year fracture probability for BZA, while those for RLX remained stable. In all 10-year fracture probability subgroups, all BZA doses significantly reduced vertebral fracture risk versus placebo (HR = 0.22–0.66). BZA at 20, 40, and 20/40 mg significantly reduced risk of nonvertebral fractures (HR = 0.45, 0.44, and 0.45, respectively) and all clinical fractures (HR = 0.38, 0.41, and 0.40, respectively) for ≥20.0 % fracture probability. Vertebral fracture risk reductions for RLX 60 mg versus placebo were significant in subgroups at lower fracture probabilities (≥2.5– ≥ 10.0 %), but not higher (≥12.5 %), and in no subgroups for nonvertebral or all clinical fractures.

Conclusion

The antifracture efficacy of BZA increased with increasing baseline FRAX® score, but there was no clear relationship between RLX and baseline FRAX®. These findings provide independent confirmation of current literature, suggesting that the relationship between FRAX® and treatment efficacy varies for different agents.

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Acknowledgments

This study was sponsored by Pfizer. Medical writing assistance for this manuscript was provided by Lisa Shannon, PharmD, and Katie Gersh, Ph.D. of MedErgy, and was funded by Pfizer.

Conflicts of interest

J.-M. Kaufman reports consulting fees, paid advisory boards, lecture fees, and/or grant support from Amgen, Eli Lilly, GlaxoSmithKline, Merck Sharp & Dohme, Novartis, Roche, Sanofi-Aventis, Servier, and Warner Chilcott as well as investigator fees from Wyeth (presently Pfizer) for the clinical trial described in the present manuscript. S. Palacios has been a symposium speaker or advisory board member for Servier, Pfizer, Pierre-Fabre, Bayer Schering Pharma, GlaxoSmithKline, and Amgen and has received research grants and/or consulting fees from Pfizer, Servier, Amgen, Bayer Schering Pharma, and Teva. S. Sutradhar is a current employee of Pfizer Inc. A.A. Chines is a stockholder and former employee of Pfizer. S. Silverman has no relevant disclosures to report.

Author information

Authors and Affiliations

  1. Department of Endocrinology and Unit for Osteoporosis and Metabolic Bone Diseases, Ghent University Hospital, Ghent, Belgium

    J.-M. Kaufman

  2. Instituto Palacios, Salud y Medicina de la Mujer, Madrid, Spain

    S. Palacios

  3. Cedars-Sinai Medical Center and University of California, Los Angeles, CA, USA

    S. Silverman

  4. Pfizer, Collegeville, PA, USA

    S. Sutradhar & A. Chines

Authors
  1. J.-M. Kaufman
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  2. S. Palacios
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  3. S. Silverman
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  4. S. Sutradhar
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  5. A. Chines
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Correspondence to J.-M. Kaufman.

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A. Chines is no longer affiliated with Pfizer.

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Kaufman, JM., Palacios, S., Silverman, S. et al. An evaluation of the Fracture Risk Assessment Tool (FRAX®) as an indicator of treatment efficacy: the effects of bazedoxifene and raloxifene on vertebral, nonvertebral, and all clinical fractures as a function of baseline fracture risk assessed by FRAX® . Osteoporos Int 24, 2561–2569 (2013). https://doi.org/10.1007/s00198-013-2341-6

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  • DOI: https://doi.org/10.1007/s00198-013-2341-6

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