Bone Material Properties in Trabecular Bone From Human Iliac Crest Biopsies After 3- and 5-Year Treatment With Risedronate

Authors

  • Erich Durchschlag,

    1. Ludwig Boltzmann Institute of Osteology at the Hanusch Hospital WGKK and AUVA Trauma Centre Meidling, 4th Medical Department, Hanusch Hospital, Vienna, Austria
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  • Eleftherios P Paschalis,

    Corresponding author
    1. Ludwig Boltzmann Institute of Osteology at the Hanusch Hospital WGKK and AUVA Trauma Centre Meidling, 4th Medical Department, Hanusch Hospital, Vienna, Austria
    • Eleftherios P Paschalis, PhD Ludwig Boltzmann Institute of Osleology Hanusch Hospital Heinrich-Collin Str 30 Vienna A-1140, Austria
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  • Ruth Zoehrer,

    1. Ludwig Boltzmann Institute of Osteology at the Hanusch Hospital WGKK and AUVA Trauma Centre Meidling, 4th Medical Department, Hanusch Hospital, Vienna, Austria
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  • Paul Roschger,

    1. Ludwig Boltzmann Institute of Osteology at the Hanusch Hospital WGKK and AUVA Trauma Centre Meidling, 4th Medical Department, Hanusch Hospital, Vienna, Austria
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  • Peter Fratzl,

    1. Department of Biomaterials, Max Planck Institute of Colloids and Interfaces, Berlin, Germany
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  • Robert Recker,

    1. Osteoporosis Research Center, Creighton University, Omaha, Nebraska, USA
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  • Roger Phipps,

    1. Procter & Gamble Pharmaceuticals, Mason, Ohio, USA
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  • Klaus Klaushofer

    1. Ludwig Boltzmann Institute of Osteology at the Hanusch Hospital WGKK and AUVA Trauma Centre Meidling, 4th Medical Department, Hanusch Hospital, Vienna, Austria
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  • Dr Paschalis has received research grants from Procter & Gamble Pharmaceuticals, Eli Lilly & Co., and Osteotech. He has received consultancies from Procter & Gamble Pharmaceuticals, Eli Lilly & Co., Osteotech, and Novartis. Dr Roschger holds consultancies with Procter & Gamble Pharmaceuticals and MSD. Dr Klaushofer holds consultancies with Amgen, Procter & Gamble Pharmaceuticals, MSD, Roche, and Novartis. Dr Recker receives consultancies and speaker fees from Merck & Co., Eli Lilly & Co., Wyeth, Procter & Gamble Pharmaceuticals, Amgen, Roche, GSK, Novartis, and NPS Allelix. Dr Phipps is a full-time employee of Procter & Gamble Pharmaceuticals. All other authors state that they have no conflicts of interest.

  • Published online on July 10, 2006;

Abstract

Long-term effects of risedronate on bone mineral maturity/crystallinity and collagen cross-link ratio in triple iliac crest biopsies of osteoporotic women were evaluated. In this double-blinded study, 3- and 5-year treatment with risedronate arrested the tissue aging encountered in untreated osteoporosis and in osteoporosis treated with other antiresorptives. This effect may be contributing to risedronate's antifracture efficacy.

Introduction: Risedronate is widely used in the treatment of osteoporosis. It reduces bone turnover, increases BMD, and decreases fracture risk. To date, there are no data available on the long-term effects of risedronate on bone material properties in humans.

Materials and Methods: Osteoporotic women enrolled in the VERT-NA trial received either risedronate (5 mg/day, orally) or placebo for up to 5 years. All subjects received calcium. They also received vitamin D supplementation if deficient at baseline. Triple iliac crest biopsies were collected from a subset of these subjects at baseline, 3 years, and 5 years. Mineral maturity/crystallinity and collagen cross-link ratio was measured in these biopsies using Fourier transform infrared imaging.

Results: Patients that received placebo exhibited increased mineral maturity/crystallinity and collagen cross-link ratio after 3 and 5 years compared with baseline values. On the contrary, patients that received risedronate retained baseline values in both bone material indices throughout. A more spatially detailed analysis revealed that this was achieved mainly through beneficial effects on active bone-forming areas. Surprisingly, patients that received risedronate achieved premenopausal values at bone-forming areas in both indices after 5 years of treatment.

Conclusion: Long-term treatment with risedronate affects bone material properties (mineral maturity/crystallinity and collagen cross-link ratio) and arrests the tissue aging apparent in untreated osteoporosis. These changes at the material level of the bone matrix may contribute to risedronate's rapid and sustained antifracture efficacy in osteoporotic patients.

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