Excessive bone loss occurs following spinal cord injury (SCI) leading to osteoporosis and an increased risk of fracture. While the underlying cause of this bone loss remains to be clarified, it is distinct in severity and pattern from other known causes of osteoporosis including disuse and postmenopausal osteoporosis. Currently, little is known about the cause of this bone loss or the natural history and specific factors that contribute to its severity. Based on preliminary studies, we hypothesize the osteoprotective marker osteoprotegerin (OPG) is involved in the pathogenesis of SCI-induced bone loss and may be a biomarker of disease severity and fracture risk in this population. Furthermore, if confirmed, OPG is a potentially powerful therapeutic target in the prevention and treatment of neurogenic bone loss. In this exploratory and developmental program, we propose to investigate differences in bone mineral density in individuals with tetraplegia and in those with lesser degrees of SCI. We will determine the relationship between bone mineral density at sites below the neurological lesion and circulating levels of OPG. Participants with SCI whose health behaviors (smoking, alcohol use) and comorbid illnesses are known due to enrollment in a longitudinal health study at VA Boston will be studied. As osteoporosis is prevalent in this patient population but currently under-treated, we expect to contribute to the understanding of this disease process for the development of improved clinical interventions. Furthermore, this work will contribute to the understanding of bone loss following neurological injury and will have broader health implications for health conditions ranging from stroke to cerebral palsy.

Public Health Relevance

This project seeks to understand bone loss triggered by spinal cord injury. A rapid, severe bone loss occurs after the spinal cord injury leaving the bones brittle and easy to fracture. This bone loss is not well understood. But, it appears to be different from bone loss seen with aging in that it affects the knees more than the hips and spine. We believe the degree of paralysis is the most important factor in determining how much bone is lost following spinal cord injury. We will test this hypothesis by determining bone density in subjects with more severe injury and those with less severe injury. We will also test the hypothesis that neurological injury causes a deficiency of a molecule in the blood known to protect bone density. We believe individuals with the most severe form of paralysis will have lower levels of this molecule (osteoprotegerin or OPG) and lower bone mineral density.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Exploratory/Developmental Grants (R21)
Project #
3R21HD057030-02S1
Application #
7935766
Study Section
Neurological, Aging and Musculoskeletal Epidemiology (NAME)
Program Officer
Nitkin, Ralph M
Project Start
2009-09-30
Project End
2011-09-29
Budget Start
2009-09-30
Budget End
2011-09-29
Support Year
2
Fiscal Year
2009
Total Cost
$136,902
Indirect Cost
Name
Spaulding Rehabilitation Hospital
Department
Type
DUNS #
079520862
City
Charlestown
State
MA
Country
United States
Zip Code
02129
Hart, Jaime E; Morse, Leslie; Tun, Carlos G et al. (2016) Cross-sectional associations of pulmonary function with systemic inflammation and oxidative stress in individuals with chronic spinal cord injury. J Spinal Cord Med 39:344-52
Doherty, Ashley L; Battaglino, Ricardo A; Donovan, Jayne et al. (2014) Adiponectin is a candidate biomarker of lower extremity bone density in men with chronic spinal cord injury. J Bone Miner Res 29:251-9
Saltzman, Jonah W; Battaglino, Ricardo; Stott, Helen et al. (2013) Neurotoxic or Neuroprotective? Current Controversies in SCI-Induced Autoimmunity. Curr Phys Med Rehabil Rep 1:
Morse, L R; Sudhakar, S; Lazzari, A A et al. (2013) Sclerostin: a candidate biomarker of SCI-induced osteoporosis. Osteoporos Int 24:961-8
Saltzman, Jonah W; Battaglino, Ricardo A; Salles, Loise et al. (2013) B-cell maturation antigen, a proliferation-inducing ligand, and B-cell activating factor are candidate mediators of spinal cord injury-induced autoimmunity. J Neurotrauma 30:434-40
Battaglino, Ricardo A; Sudhakar, Supreetha; Lazzari, Antonio A et al. (2012) Circulating sclerostin is elevated in short-term and reduced in long-term SCI. Bone 51:600-5
Morse, Leslie R; Sudhakar, Supreetha; Danilack, Valery et al. (2012) Association between sclerostin and bone density in chronic spinal cord injury. J Bone Miner Res 27:352-9
Morse, Leslie R; Geller, Andrew; Battaglino, Ricardo A et al. (2009) Barriers to providing dual energy x-ray absorptiometry services to individuals with spinal cord injury. Am J Phys Med Rehabil 88:57-60
Morse, L R; Battaglino, R A; Stolzmann, K L et al. (2009) Osteoporotic fractures and hospitalization risk in chronic spinal cord injury. Osteoporos Int 20:385-92
Morse, Leslie R; Lazzari, Antonio A; Battaglino, Ricardo et al. (2009) Dual energy x-ray absorptiometry of the distal femur may be more reliable than the proximal tibia in spinal cord injury. Arch Phys Med Rehabil 90:827-31

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