Bone Density and Circulating Mediators of Bone Metabolism in Chronic SCI

慢性 SCI 中骨密度和骨代谢循环介质

• 批准号: 7591815
• 负责人: Leslie R. Morse
• 金额: $ 22.66万
• 依托单位: SPAULDING REHABILITATION HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-01 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7591815
• 关键词: Affect; Aging; Alcohol consumption; Autonomic Dysreflexia; Biological Markers; Biology; Blood; Bone Density; Bone Resorption; Boston; C-telopeptide; Cerebral Palsy; Chronic; Clinical; Clinical Trials; Data; Decubitus ulcer; Development; Diagnosis; Disease; Distal; Enrollment; Femur; Fracture; Future; Health; Health behavior; Hip region structure; Hypertensive Crisis; Individual; Injury; Intervention; Knee; Left; Lesion; Measures; Mediator of activation protein; Metaphysis; Minerals; Natural History; Nervous System Trauma; Neurologic; Osteocalcin; Osteoclasts; Osteomyelitis; Osteoporosis; Paralysed; Participant; Pathogenesis; Pathway interactions; Pattern; Persons; Population; Postmenopausal Osteoporosis; Prevention; Process; Prospective Studies; Protocols documentation; Quadriplegia; Recombinants; Risk; Scanning; Screening procedure; Secondary to; Serum; Severities; Severity of illness; Site; Smoking; Spinal cord injury; Stroke; TNFSF11 gene; Testing; Therapeutic; Trauma; Treatment Protocols; Tumor necrosis factor receptor 11b; Vertebral column; Work; base; bone; bone loss; bone metabolism; bone turnover; disability; improved; insight; medical complication; osteogenic; patient population; programs; public health relevance; response; skeletal; therapeutic target; tibia; treatment strategy

DESCRIPTION (provided by applicant): 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.

描述（由申请人提供）：脊髓损伤（SCI）后会发生过多的骨质流失，导致骨质疏松症和骨折风险增加。虽然这种骨质流失的根本原因仍有待澄清，但其严重程度和模式与其他已知的骨质疏松症原因（包括废用性和绝经后骨质疏松症）不同。目前，人们对这种骨质流失的原因、自然史以及导致其严重程度的具体因素知之甚少。根据初步研究，我们假设骨保护标志物骨保护素 (OPG) 参与 SCI 引起的骨质流失的发病机制，并且可能是该人群疾病严重程度和骨折风险的生物标志物。此外，如果得到证实，OPG 是预防和治疗神经源性骨质流失的潜在强大治疗靶点。 在这个探索性和发展性项目中，我们建议研究四肢瘫痪个体和脊髓损伤程度较轻个体的骨矿物质密度差异。我们将确定神经病变以下部位的骨矿物质密度与 OPG 循环水平之间的关系。因参加 VA 波士顿的一项纵向健康研究而已知其健康行为（吸烟、饮酒）和合并症的 SCI 参与者将接受研究。由于骨质疏松症在该患者群体中普遍存在，但目前治疗不足，我们希望有助于了解这种疾病的过程，以开发改进的临床干预措施。此外，这项工作将有助于了解神经损伤后的骨质流失，并对中风和脑瘫等健康状况产生更广泛的健康影响。 公共健康相关性：该项目旨在了解脊髓损伤引发的骨质流失。脊髓损伤后会发生快速、严重的骨质流失，使骨头变得脆弱且容易骨折。这种骨质流失尚不清楚。但是，它似乎与衰老引起的骨质流失不同，它对膝盖的影响大于对臀部和脊柱的影响。 我们认为瘫痪程度是决定脊髓损伤后骨质流失量的最重要因素。我们将通过测定损伤较严重和损伤较轻的受试者的骨密度来检验这一假设。我们还将检验这样的假设：神经损伤导致血液中已知可保护骨密度的分子缺乏。我们相信，患有最严重瘫痪的个体的这种分子（骨保护素或 OPG）水平较低，骨矿物质密度也较低。