Adverse effects of hyperlipidemia on bone regeneration and strength

Authors

  • Flavia Pirih,

    1. Division of Diagnostic and Surgical Sciences, School of Dentistry, University of California, Los Angeles, Los Angeles, CA, USA
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  • Jinxiu Lu,

    1. Department of Physiology, University of California, Los Angeles, Los Angeles, CA, USA
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  • Fei Ye,

    1. Division of Cardiology, Department of Medicine, University of California, Los Angeles, Los Angeles, CA, USA
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  • Olga Bezouglaia,

    1. Division of Diagnostic and Surgical Sciences, School of Dentistry, University of California, Los Angeles, Los Angeles, CA, USA
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  • Elisa Atti,

    1. Division of Diagnostic and Surgical Sciences, School of Dentistry, University of California, Los Angeles, Los Angeles, CA, USA
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  • Maria-Grazia Ascenzi,

    1. Department of Orthopedic Surgery, University of California, Los Angeles, Los Angeles, CA, USA
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  • Sotirios Tetradis,

    1. Division of Diagnostic and Surgical Sciences, School of Dentistry, University of California, Los Angeles, Los Angeles, CA, USA
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  • Linda Demer,

    1. Department of Physiology, University of California, Los Angeles, Los Angeles, CA, USA
    2. Division of Cardiology, Department of Medicine, University of California, Los Angeles, Los Angeles, CA, USA
    3. Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA, USA
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    • Senior coauthors.

  • Tara Aghaloo,

    1. Division of Diagnostic and Surgical Sciences, School of Dentistry, University of California, Los Angeles, Los Angeles, CA, USA
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  • Yin Tintut

    Corresponding author
    1. Division of Cardiology, Department of Medicine, University of California, Los Angeles, Los Angeles, CA, USA
    • Division of Cardiology, David Geffen School of Medicine, University of California, Los Angeles, Center for the Health Sciences A2-237, 10833 Le Conte Ave, Los Angeles, CA 90095-1679, USA.
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    • Senior coauthors.


Abstract

Hyperlipidemia increases the risk for generation of lipid oxidation products, which accumulate in the subendothelial spaces of vasculature and bone. Atherogenic high-fat diets increase serum levels of oxidized lipids, which are known to attenuate osteogenesis in culture and to promote bone loss in mice. In this study, we investigated whether oxidized lipids affect bone regeneration and mechanical strength. Wild-type (WT) and hyperlipidemic (Ldlr−/−) mice were placed on a high-fat (HF) diet for 13 weeks. Bilateral cranial defects were introduced on each side of the sagittal suture, and 5 weeks postsurgery on the respective diets, the repair/regeneration of cranial bones and mechanical properties of femoral bones were assessed. MicroCT and histological analyses demonstrated that bone regeneration was significantly impaired by the HF diet in WT and Ldlr−/− mice. In femoral bone, cortical bone volume fraction (bone volume [BV]/tissue volume [TV]) was significantly reduced, whereas cortical porosity was increased by the HF diet in Ldlr−/− but not in WT mice. Femoral bone strength and stiffness, measured by three-point bending analysis, were significantly reduced by the HF diet in Ldlr−/−, but not in WT mice. Serum analysis showed that the HF diet significantly increased levels of parathyroid hormone, tumor necrosis factor (TNF)-α, calcium, and phosphorus, whereas it reduced procollagen type I N-terminal propeptide, a serum marker of bone formation, in Ldlr−/−, but not in WT mice. The serum level of carboxyl-terminal collagen crosslinks, a marker for bone resorption, was also 1.7-fold greater in Ldlr−/− mice. These findings suggest that hyperlipidemia induces secondary hyperparathyroidism and impairs bone regeneration and mechanical strength. © 2012 American Society for Bone and Mineral Research

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