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Ten-year fracture probability identifies women who will benefit from clodronate therapy—additional results from a double-blind, placebo-controlled randomised study

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Abstract

Summary

Fracture risk prediction can be enhanced by the concurrent assessment of other clinical risk factors. This study demonstrates that the estimation of an individual’s 10-year probability of fracture by the FRAX® algorithm identifies patients at high risk of fracture who will respond to bisphosphonate therapy.

Introduction

Treatments for osteoporosis are targeted largely to patients with low bone density (BMD) or a prior fragility fracture. Fracture risk prediction can be enhanced by the concurrent assessment of other clinical risk factors, but it is important to determine whether the risk so identified can be reduced by intervention. We determined the effect of a bisphosphonate on fracture rates when risk was calculated using a new risk algorithm (FRAX®).

Methods

Women aged 75 years or more were recruited to a randomised, double-blind controlled trial of 800 mg oral clodronate (Bonefos®) daily over 3 years. Baseline clinical risk factors were entered in the FRAX® model to compute the 10-year probability of major osteoporotic fractures with or without input of femoral neck BMD. The interaction between fracture probability and treatment efficacy was examined by Poisson regression.

Results

In 3,974 women, the interaction between fracture probability and treatment efficacy was significant when probability was assessed without BMD (p = 0.043), but not when BMD was included (p = 0.10). Efficacy was more evident in those deemed at highest risk. For example women lying at the 75th percentile of fracture probability in the absence of BMD (10-year probability 24%) treatment reduced fracture risk by 27% (HR 0.73, 95%CI 0.58–0.92). In those with a fracture probability of 30% (90th percentile), the fracture risk reduction was 38% (HR 0.62, 0.46–0.84).

Conclusions

The estimation of an individual’s 10-year probability of fracture by the FRAX® algorithm identifies patients at high risk of fracture who will respond to bisphosphonate therapy.

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Acknowledgements

We would like to acknowledge the Medical Research Council, London, UK and Bayer Schering Pharma Oy, Helsinki, Finland for funding the original study from which this analysis is derived.

Conflicts of interest

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Authors and Affiliations

  1. WHO Collaborating Centre for Metabolic Bone Diseases, University of Sheffield, Beech Hill Road, Sheffield, S10 2RX, UK

    E. V. McCloskey, H. Johansson, A. Oden, S. Vasireddy, K. Kayan, K. Pande & J. A. Kanis

  2. Bayer Schering Pharma Oy, Helsinki, Finland

    T. Jalava

  3. Metabolic Bone Centre Sorby Wing Northern General Hospital, Herries Road, Sheffield, S5 7AU, UK

    E. V. McCloskey

Authors
  1. E. V. McCloskey
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  2. H. Johansson
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  3. A. Oden
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  4. S. Vasireddy
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  5. K. Kayan
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  6. K. Pande
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  7. T. Jalava
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  8. J. A. Kanis
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Correspondence to E. V. McCloskey.

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McCloskey, E.V., Johansson, H., Oden, A. et al. Ten-year fracture probability identifies women who will benefit from clodronate therapy—additional results from a double-blind, placebo-controlled randomised study. Osteoporos Int 20, 811–817 (2009). https://doi.org/10.1007/s00198-008-0786-9

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  • DOI: https://doi.org/10.1007/s00198-008-0786-9

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