Suppressed Bone Turnover by Bisphosphonates Increases Microdamage Accumulation and Reduces Some Biomechanical Properties in Dog Rib

Authors

  • Tasuku Mashiba,

    1. Departments of Anatomy and Cell Biology, and Orthopaedic Surgery, Biomechanics and Biomaterials Research Center, Indiana University School of Medicine, Indianapolis, Indiana, U.S.A.
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  • Toru Hirano,

    1. Departments of Anatomy and Cell Biology, and Orthopaedic Surgery, Biomechanics and Biomaterials Research Center, Indiana University School of Medicine, Indianapolis, Indiana, U.S.A.
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  • Charles H. Turner,

    1. Departments of Anatomy and Cell Biology, and Orthopaedic Surgery, Biomechanics and Biomaterials Research Center, Indiana University School of Medicine, Indianapolis, Indiana, U.S.A.
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  • Mark R. Forwood,

    1. Department of Anatomical Sciences, The University of Queensland, Brisbane, Queensland, Australia
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  • C. Conrad Johnston,

    1. Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, U.S.A.
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  • David B. Burr Ph.D.

    Corresponding author
    1. Departments of Anatomy and Cell Biology, and Orthopaedic Surgery, Biomechanics and Biomaterials Research Center, Indiana University School of Medicine, Indianapolis, Indiana, U.S.A.
    • Department of Anatomy and Cell Biology Medical Sciences Building 5035 Indiana University School of Medicine Indianapolis, IN 46202, U.S.A.
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Abstract

It has been hypothesized that suppression of bone remodeling allows microdamage to accumulate, leading to increased bone fragility. This study evaluated the effects of reduced bone turnover produced by bisphosphonates on microdamage accumulation and biomechanical properties of cortical bone in the dog rib. Thirty-six female beagles, 1–2 years old, were divided into three groups. The control group (CNT) was treated daily for 12 months with saline vehicle. The remaining two groups were treated daily with risedronate (RIS) at a dose of 0.5 mg/kg per day or alendronate (ALN) at 1.0 mg/kg per day orally. After sacrifice, the right ninth rib was assigned to cortical histomorphometry or microdamage analysis. The left ninth rib was tested to failure in three-point bending. Total cross-sectional bone area was significantly increased in both RIS and ALN compared with CNT, whereas cortical area did not differ significantly among groups. One-year treatment with RIS or ALN significantly suppressed intracortical remodeling (RIS, 53%; ALN, 68%) without impairment of mineralization and significantly increased microdamage accumulation in both RIS (155%) and ALN (322%) compared with CNT. Although bone strength and stiffness were not significantly affected by the treatments, bone toughness declined significantly in ALN (20%). Regression analysis showed a significant nonlinear relationship between suppressed intracortical bone remodeling and microdamage accumulation as well as a significant linear relationship between microdamage accumulation and reduced toughness. This study showed that suppression of bone turnover by high doses of bisphosphonates is associated with microdamage accumulation and reduced some mechanical properties of bone.

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