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Project

Inflamm-aging and bone loss in a rodent model of spinal cord injury

Funder: Craig H Neilsen Foundation

Funding period
USD 300 K
Funding amount
Abstract
Approximately 80% of individuals living with spinal cord injury (SCI) are diagnosed with osteopenia or osteoporosis. Bone loss begins immediately after injury, continuing for at least the next 2 years. Studies vary, but is estimated that there is a 30-40% decrease in bone mineral density in the legs following SCI. As bone mineral density decreases, the risk of fractures increases. Patients with SCI are estimated to be 104 times more likely, than the general population, to have a fracture by the age of 50. Most of these fractures occur without known trauma; patients notice a symptom such as swelling that is later clinically diagnosed as a fracture. For the spinally injured, fractures have significant implications resulting in increased morbidity, mortality, and healthcare costs. Further, loss of bone mineral density and increased fracture risk significantly limits physical rehabilitation post injury. Unfortunately, current treatments for preventing and managing osteoporosis in the general population have not proven effective after SCI. We hypothesize that the inflammation inherent to SCI contributes to the rapid and exacerbated SCI-induced bone loss. Specifically, our preliminary studies suggest that TNF-alpha and IL-17 expression is increased on osteocytes following spinal cord injury. These pro-inflammatory cytokines have been shown to regulate osteoblast and osteoclast activity, decreasing bone formation and increasing bone resorption respectively. We will use FDA-approved and pre-clinical trial biologics (TNF-alpha inhibitor, Infliximab; VP254, a new ROR gamma t inhibitor to block differentiation of Th17 cells from naïve Th0 cells) to test whether these cytokines play a critical role in the bone loss observed after SCI. As inflammation increases with age, we also propose that bone loss in older individuals may be substantial. To address this, we will examine both proinflammatory osteocyte protein expression and bone loss in both young (2 month) and older (12 month) male Sprague-Dawley rats after SCI. We aim to identify factors that exacerbate bone loss after SCI and in the long-term develop therapeutic strategies that prevent and reverse SCI-induced osteoporosis. (CHN: SCIRTS chn:wdg)
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System

Categories
  • FOR (ANZSRC)

    1103 Clinical Sciences

  • RCDC

    Aging

  • RCDC

    Injury (total) Accidents/Adverse Effects

  • RCDC

    Injury - Trauma - (Head and Spine)

  • RCDC

    Osteoporosis

  • RCDC

    Mind and Body

  • RCDC

    Spinal Cord Injury

  • RCDC

    Neurodegenerative

  • HRCS HC

    Musculoskeletal

  • HRCS HC

    Injuries and Accidents

  • HRCS RAC

    2.1 Biological and endogenous factors

  • HRCS RAC

    5.1 Pharmaceuticals

  • Health Research Areas

    Biomedical

  • Broad Research Areas

    Clinical Medicine and Science