Osteoprotegerin Abrogates Chronic Alcohol Ingestion-Induced Bone Loss in Mice

Authors

  • Jian Zhang,

    1. Unit for Laboratory Animal Medicine, University of Michigan, Ann Arbor, Michigan, USA
    2. Department of Pathology, University of Michigan, Ann Arbor, Michigan, USA
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  • Jinlu Dai,

    1. Unit for Laboratory Animal Medicine, University of Michigan, Ann Arbor, Michigan, USA
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  • Din-Lii Lin,

    1. Unit for Laboratory Animal Medicine, University of Michigan, Ann Arbor, Michigan, USA
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  • Paula Habib,

    1. Unit for Laboratory Animal Medicine, University of Michigan, Ann Arbor, Michigan, USA
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  • Peter Smith,

    1. Unit for Laboratory Animal Medicine, University of Michigan, Ann Arbor, Michigan, USA
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  • Jill Murtha,

    1. Unit for Laboratory Animal Medicine, University of Michigan, Ann Arbor, Michigan, USA
    2. Department of Pathology, University of Michigan, Ann Arbor, Michigan, USA
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  • Zheng Fu,

    1. Program in Immunology, University of Michigan, Ann Arbor, Michigan, USA
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  • Zhi Yao,

    1. Department of Immunology, Tianjin Medical University, Tianjin, China
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  • Yinghua Qi,

    1. Lab of Cellular and Molecular Biology, Department of Internal Medicine, Tianjin Third Municipal Hospital, Tianjin, China
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  • Evan T. Keller D.V.M., Ph.D.

    Corresponding author
    1. Unit for Laboratory Animal Medicine, University of Michigan, Ann Arbor, Michigan, USA
    2. Department of Pathology, University of Michigan, Ann Arbor, Michigan, USA
    3. Program in Immunology, University of Michigan, Ann Arbor, Michigan, USA
    4. Institute of Gerontology, University of Michigan, Ann Arbor, Michigan, USA
    5. Program in Comparative Integrative Genomics, University of Michigan, Ann Arbor, Michigan, USA
    • Room 5304 CCGCB, Box 0940, 1500 East Medical Center Drive, Ann Arbor, MI 48109-0940, USA
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  • The authors have no conflict of interest.

Abstract

To investigate the role of osteoprotegerin (OPG) on alcohol (ethanol)-mediated osteoporosis, we measured a variety of bone remodeling parameters in mice that were either on a control diet, an ethanol (5%) diet, or an ethanol (5%) diet plus OPG administration. OPG diminished the ethanol-induced (1) decrease in bone mineral density (BMD) as determined by dual-energy densitometry, (2) decrease in cancellous bone volume and trabecular width and the increase of osteoclast surface as determined by histomorphometry of the femur, (3) increase in urinary deoxypyridinolines (Dpd's) as determined by ELISA, and (4) increase in colony-forming unit-granulocyte macrophage (CFU-GM) formation and osteoclastogenesis as determined by ex vivo bone marrow cell cultures. Additionally, OPG diminished the ethanol-induced decrease of several osteoblastic parameters including osteoblast formation and osteoblast culture calcium retention. These findings were supported by histomorphometric indices in the distal femur. Taken together, these data show that OPG diminishes ethanol-induced bone loss. Furthermore, they suggest that OPG achieves this through its ability to abrogate ethanol-induced promotion of osteoclastogenesis and promote osteoblast proliferation.

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