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Canine Cancellous Bone Microarchitecture after One Year of High-Dose Bisphosphonates

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Abstract

We examined the effects of one-year high-dose bisphosphonates (risedronate 0.5 mg/kg/day or alendronate 1.0 mg/kg/day) on the three-dimensional (3-D) microstructural and mechanical properties of canine cancellous bone. A high-resolution micro-CT scanner was used to scan cubic specimens produced from the first lumbar vertebrae. Microstructural properties of the specimens were calculated directly from the 3-D datasets and the mechanical properties of the specimens were determined. Our data demonstrate significant microarchitectural changes in the bisphosphonate-treated cancellous bone that was typically plate-like, denser, with thicker and more trabeculae compared with those of the controls. Consistent with architectural changes, the Young’s moduli of cancellous bone increased in all three directions with the greatest increase in primary axial loading (cephalo-caudal) direction after treatment. Our results suggest a bone remodeling-adaptation mechanism stimulated by bisphosphonates that increases bone volume fraction, thickens trabeculae, changes trabeculae towards more plate-like, and increases mechanical properties. The secondary degree of anisotropy contributed significantly to the explained variance in bone strength, and the primary or tertiary degree of anisotropy improved the explanation of variances for Young’s moduli, i.e., 79% of strength variances or 74–83% of modulus variances could be explained by the combined anisotropy and bone volume fraction. These significant improvements of cancellous bone architecture provide a rationale for the clinical observation that fracture risk decreased by 50% in the first year of bisphosphonate therapy with only a 5% increase in bone mineral density. We conclude that bisphosphonates enhance mechanical properties and reduce fracture risk by improving architectural anisotropy of cancellous bone 3-D microarchitecture.

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Acknowledgements

We thank European Commission Research Directorates for a Senior Fellowship for M. Ding (EU grant QLRT-1999-02024, MIAB). The authors thank Anette Milten and Jane Pauli for technical assistance. This study was supported by NIH grants 2PO1 AG05793, 46225, and AR14685 and AR42862 and from NWO/MW. Risedronate and alendronate were kindly provided by Procter and Gamble Pharmaceuticals, Inc. and Merck and Co., Inc., respectively.

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Authors and Affiliations

  1. Orthopaedic Research Laboratory, Department of Orthopaedics, Aarhus University Hospital, Aarhus C, Denmark

    M. Ding & I. Hvid

  2. Orthopaedic Research Laboratory, Erasmus University Rotterdam, Rotterdam, The Netherlands

    J. S. Day & H. Weinans

  3. Departments of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, Indiana, USA

    D. B. Burr, T. Mashiba & T. Hirano

  4. Departments of Anatomy and Orthopaedics, Rush Medical College, Chicago, Illinois, USA

    D. R. Sumner

  5. Department of Orthopaedics, Aalborg University Hospital, Aalborg, Denmark

    I. Hvid

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  1. M. Ding
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Correspondence to M. Ding.

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Ding, M., Day, J., Burr, D. et al. Canine Cancellous Bone Microarchitecture after One Year of High-Dose Bisphosphonates . Calcif Tissue Int 72, 737–744 (2003). https://doi.org/10.1007/s00223-002-2066-6

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  • DOI: https://doi.org/10.1007/s00223-002-2066-6

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