Association between sclerostin and bone density in chronic spinal cord injury

Authors

  • Leslie R Morse,

    1. Department of Physical Medicine and Rehabilitation, Harvard Medical School, Boston, MA, USA
    2. Spaulding-Harvard Spinal Cord Injury Model System, Spaulding Rehabilitation Hospital, Boston, MA, USA
    3. Department of Cytokine Biology, The Forsyth Institute, Cambridge, MA, USA
    4. Spinal Cord Injury Service, VA Boston Healthcare System, Boston, MA, USA
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  • Supreetha Sudhakar,

    1. Spaulding-Harvard Spinal Cord Injury Model System, Spaulding Rehabilitation Hospital, Boston, MA, USA
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  • Valery Danilack,

    1. Programs in Research at VA Boston, Harvard Medical School, Boston, MA, USA
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  • Carlos Tun,

    1. Rehabilitation Medicine Service, VA Boston Healthcare System, Boston, MA, USA
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  • Antonio Lazzari,

    1. Primary Care Section, VA Boston Healthcare System and Boston University School of Medicine, Boston, MA, USA
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  • David R Gagnon,

    1. VA Cooperative Studies Program, VA Boston Healthcare System, Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA
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  • Eric Garshick,

    1. Pulmonary and Critical Care Medicine Section, Medical Service, VA Boston Healthcare System, Boston, MA, USA
    2. Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
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  • Ricardo A Battaglino

    Corresponding author
    1. Department of Cytokine Biology, The Forsyth Institute, Cambridge, MA, USA
    2. Department of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Boston, MA, USA
    • Department of Cytokine Biology, The Forsyth Institute, 245 First Street, Cambridge, MA 02142.
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Abstract

Spinal cord injury (SCI) results in profound bone loss due to muscle paralysis and the inability to ambulate. Sclerostin, a Wnt signaling pathway antagonist produced by osteocytes, is a potent inhibitor of bone formation. Short-term studies in rodent models have shown increased sclerostin in response to mechanical unloading that is reversed with reloading. These studies suggest that complete spinal cord injury, a condition resulting in mechanical unloading of the paralyzed lower extremities, will be associated with high sclerostin levels. We assessed the relationship between circulating sclerostin and bone density in 39 subjects with chronic SCI and 10 without SCI. We found that greater total limb bone mineral content was significantly associated with greater circulating levels of sclerostin. Sclerostin levels were reduced, not elevated, in subjects with SCI who use a wheelchair compared with those with SCI who walk regularly. Similarly, sclerostin levels were lower in subjects with SCI who use a wheelchair compared with persons without SCI who walk regularly. These findings suggest that circulating sclerostin is a biomarker of osteoporosis severity, not a mediator of ongoing bone loss, in long-term, chronic paraplegia. This is in contrast to the acute sclerostin-mediated bone loss shown in animal models of mechanical unloading in which high sclerostin levels suppress bone formation. Because these data indicate important differences in the relationship between mechanical unloading, sclerostin, and bone in chronic SCI compared with short-term rodent models, it is likely that sclerostin is not a good therapeutic target to treat chronic SCI-induced osteoporosis. © 2012 American Society for Bone and Mineral Research

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