[Show abstract][Hide abstract] ABSTRACT: Objective:
The aim of this study was to compare the effect of standing frame and electrical stimulation on bone quality in a rodent transection model of spinal cord injury (SCI).
Seven-week-old male Wistar rats were divided into four groups: sham, n = 10; SCI, n = 7; SCI + standing frame, n = 7; and SCI + electrical stimulation, n = 7. Complete SCI was generated by surgical transection of the cord at the T10 level. Therapies were initiated 3 days after the surgery, 3 days/wk, 20 mins/day, for 30 days. Animals were killed on day 33 postinjury.
No treatment preserved bone mineral density at any skeletal site tested (P = 0.08-0.99). Standing frame therapy preserved maximal load at the lumbar vertebral body (14% vs. 37% reduction, P = 0.01) and prevented SCI-induced loss of stiffness at both the femur (8% vs. 37% reduction, P = 0.03) and the tibia (35% vs. 56% reduction, P < 0.0001). Electrical stimulation therapy reduced SCI-induced loss of stiffness at the tibia only (40% vs. 56% reduction, P = 0.003).
Standing frame and electrical stimulation may have potential as future therapeutic modalities to treat or prevent bone loss after SCI.
American journal of physical medicine & rehabilitation / Association of Academic Physiatrists 03/2013; 92(5). DOI:10.1097/PHM.0b013e318287697c · 2.20 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective:
The aim of this study was to determine the association between participation in organized sports programs and employment in adults with chronic spinal cord injury.
This is a cross-sectional study of 149 adults with chronic spinal cord injury. Motor level and completeness of injury were confirmed by physical examination. Information related to demographics, employment, level of education, body mass index, duration of injury, participation in individually planned exercise, and participation in organized sports was obtained using a standardized questionnaire. Multivariable logistic regression analyses were used to assess factors associated with employment.
In univariate analyses, employment was associated with younger age (P = 0.001) and a higher level of education (P = 0.01), whereas obesity decreased the likelihood of employment (P = 0.04). Participation in organized sports approached significance (P = 0.06). In the multivariable analysis and after adjusting for age, education, and body mass index, participation in organized sports was significantly associated with employment (odds ratio, 2.4; P = 0.04). Sex, duration of injury, wheelchair use, and participation in individually planned exercise were not significantly associated with employment (P = 0.16-0.94).
In the adults with chronic spinal cord injury, participation in organized sports was positively associated with employment. Further studies are necessary to determine the causative nature of this association and how various factors related to sports participation may contribute.
American journal of physical medicine & rehabilitation / Association of Academic Physiatrists 03/2013; 92(5). DOI:10.1097/PHM.0b013e3182876a5f · 2.20 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Autoimmunity is thought to contribute to poor neurological outcomes following spinal cord injury (SCI). However, there are few mechanism-based therapies designed to reduce tissue damage and neurotoxicity after SCI because the molecular and cellular bases for SCI-induced autoimmunity are not completely understood. Recent ground-breaking studies in rodents indicate that B cells are responsible for SCI-induced autoimmunity. This novel paradigm, if confirmed in humans, could aid in the design of neuroprotective immunotherapies. The aim of this study was to investigate the molecular signaling pathways and mechanisms by which autoimmunity is induced after spinal cord injury, with the goal of identifying potential targets in therapies designed to reduce tissue damage and inflammation in the chronic phase of SCI. To that end we performed an exploratory microarray analysis of circulating monocytes to identify differentially expressed genes in chronic SCI. We identified a gene network associated with lymphoid tissue structure and development that was composed of 29 distinct molecules and five protein complexes, including two cytokines (APRIL and BAFF) and one receptor (BMCA) involved in B cell development, proliferation, activation, and survival. qPCR analysis from RNA samples confirmed upregulation of these three genes in SCI. To our knowledge, this is the first report that circulating monocytes produce increased levels of BAFF and APRIL in chronic SCI. This finding provides evidence of systemic regulation of SCI-autoimmunity via APRIL and BAFF mediated activation of B cells through BMCA and points towards these molecules as potential targets of therapies designed to reduce neuroinflammation after SCI.
Journal of neurotrauma 10/2012; DOI:10.1089/neu.2012.2501 · 3.71 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We assessed several circulating proteins as candidate biomarkers of bone status in men with chronic spinal cord injury. We report that sclerostin is significantly associated with bone mineral content and bone density at all skeletal sites tested. We found no association between bone and any other tested biomarker. INTRODUCTION: Spinal cord injury results in severe osteoporosis. To date, no circulating biomarker of spinal cord injury (SCI)-induced osteoporosis has been identified. We recently reported that circulating sclerostin is associated with bone density in chronic SCI. In this study, we assessed several circulating proteins as candidate biomarkers of bone in men with chronic SCI. METHODS: We assessed the relationship between bone mineral content or bone density and the following circulating bone-related proteins: sclerostin, DKK-1, soluble receptor activator of nuclear factor kappa B ligand, osteoprotegerin, osteocalcin, and c-telopeptide in 39 men with chronic SCI and 10 men with no SCI. RESULTS: After adjusting for age, lower sclerostin levels were significantly associated with lower bone mineral content and bone density at all skeletal sites tested (p = 0.0002-0.03). No other circulating protein was associated with bone mineral content or bone mineral density (p = 0.18-0.99). CONCLUSION: These findings suggest that circulating sclerostin reflects the severity of bone loss and is a candidate biomarker of osteoporosis severity in chronic SCI.
Osteoporosis International 07/2012; 24(3). DOI:10.1007/s00198-012-2072-0 · 4.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Spinal cord injury (SCI) causes profound bone loss due to muscle paralysis resulting in the inability to walk. Sclerostin, a Wnt signaling pathway antagonist produced by osteocytes, is a potent inhibitor of bone formation. Short-term studies in rodent models have demonstrated increased sclerostin in response to mechanical unloading that is reversed with reloading. Although sclerostin inhibition has been proposed as a potential therapy for bone loss, it is not known if sclerostin levels vary with duration of SCI in humans. We analyzed circulating sclerostin in 155 men with varying degrees of SCI who were 1 year or more post-injury. We report that sclerostin levels are greatest in subjects with short-term SCI (≤5 years post-injury) and decrease significantly over the first 5 years post-injury. There was no association between sclerostin and injury duration in subjects with long-term SCI (>5 years post-injury). In subjects with long-term SCI, sclerostin levels were positively associated with lower extremity bone density and bone mineral content. These data suggest that sclerostin levels are initially increased after SCI in response to mechanical unloading. This response is time-limited and as bone loss progresses, circulating sclerostin is lowest in subjects with severe osteoporosis. These findings support a dual role for sclerostin after SCI: a therapeutic target in acute SCI, and a biomarker of osteoporosis severity in chronic SCI.
Bone 05/2012; 51(3):600-5. DOI:10.1016/j.bone.2012.04.019 · 3.97 Impact Factor
[Show abstract][Hide abstract] 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.
Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 02/2012; 27(2):352-9. DOI:10.1002/jbmr.546 · 6.83 Impact Factor