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Effect of osteoporosis treatments on risk of non-vertebral fractures: review and meta-analysis of intention-to-treat studies

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Abstract

Most osteoporosis treatments have proven efficacy in reducing the risk of vertebral fractures, whereas evidence is less straightforward for prevention of non-vertebral fractures. Conclusions as to the efficacy of a treatment should be based primarily on analyses of the intention to treat (ITT) population rather than on exploratory subgroup analyses; however, non-vertebral anti-fracture efficacy has been largely derived by post-hoc subgroup analyses. This review and meta-analysis was performed to assess non-vertebral anti-fracture efficacy of several osteoporosis therapies, including a more stringent assessment of the ITT populations. Data on non-vertebral anti-fracture efficacy, a defined endpoint of the ITT analyses and confirmed by radiographs, were obtained from randomized, placebo-controlled, phase III clinical trials of at least 3-year duration. Meta-analyses were performed for the two bisphosphonates, alendronate and risedronate. Relative risks (RR), 95% confidence intervals (CI) and statistical significance for active treatment compared with placebo were calculated. Eleven clinical trials met the criteria for review, three of which showed statistically significant ( P ≤0.05) non-vertebral anti-fracture efficacy in the ITT population: two trials with risedronate and one trial with strontium. A meta-analysis showed significant reductions in the relative risk of non-vertebral fracture for both alendronate (RR=0.86; 95% CI: 0.76–0.97, P =0.012) and risedronate (RR=0.81; 95% CI: 0.71–0.92, P =0.001). Risedronate and strontium ranelate were the only treatments to show non-vertebral anti-fracture efficacy in this robust assessment of anti-fracture efficacy of osteoporosis therapy using ITT populations in trials of 3 years or more in duration. Risedronate was the only agent shown to demonstrate efficacy in more than one trial. Meta-analysis showed that both alendronate and risedronate provide non-vertebral anti-fracture efficacy.

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Acknowledgements

Dr. S. Boonen is senior clinical investigator of the Fund for Scientific Research, Flanders, Belgium (F.W.O., Vlaanderen) and holder of the Leuven University Chair for Metabolic Bone Diseases. This study was supported by grant G.0171.03 N from the Fund for Scientific Research, Flanders, Belgium (F.W.O., Vlaanderen). The authors thank Christine Gilchrist for performing the Medline, EMBASE and BIOL electronic literature searches.

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Authors and Affiliations

  1. Division of Geriatric Medicine, Center for Metabolic Bone Diseases, Catholic University of Leuven, Herestraat 49, 3000, Leuven, Belgium

    Steven Boonen

  2. Department of Rheumatology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands

    Roland F. Laan

  3. Procter and Gamble Pharmaceuticals, Egham, UK

    Ian P. Barton

  4. College of Medicine, University of Cincinnati, Cincinnati, OH, USA

    Nelson B. Watts

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  1. Steven Boonen
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  2. Roland F. Laan
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  4. Nelson B. Watts
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Correspondence to Steven Boonen.

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Boonen, S., Laan, R.F., Barton, I.P. et al. Effect of osteoporosis treatments on risk of non-vertebral fractures: review and meta-analysis of intention-to-treat studies. Osteoporos Int 16, 1291–1298 (2005). https://doi.org/10.1007/s00198-005-1945-x

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  • DOI: https://doi.org/10.1007/s00198-005-1945-x

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