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: 7935766
• 负责人: Leslie R. Morse
• 金额: $ 13.69万
• 依托单位: SPAULDING REHABILITATION HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2011-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7935766
• 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)导致骨质疏松和骨折风险增加后，会发生过度的骨丢失。虽然骨丢失的潜在原因仍有待阐明，但它的严重程度和模式与其他已知的骨质疏松症原因不同，包括废用和绝经后骨质疏松症。目前，人们对这种骨丢失的原因或导致其严重程度的自然病史和具体因素知之甚少。根据初步研究，我们假设骨保护性标记物OPG参与了脊髓损伤所致骨丢失的发病机制，并可能是该人群疾病严重程度和骨折风险的生物标记物。此外，如果得到证实，OPG在预防和治疗神经源性骨丢失方面是一个潜在的强大的治疗靶点。 在这一探索性和发展性计划中，我们建议调查四肢瘫痪患者和脊髓损伤程度较轻的患者的骨密度差异。我们将确定神经病变下方部位的骨密度与循环中OPG水平的关系。由于参加了弗吉尼亚波士顿大学的一项纵向健康研究，已知其健康行为(吸烟、饮酒)和共病的SCI参与者将被研究。由于骨质疏松症在这一人群中普遍存在，但目前未得到治疗，我们希望有助于了解这一疾病的过程，以开发改进的临床干预措施。此外，这项工作将有助于理解神经损伤后的骨丢失，并将对从中风到脑瘫的各种健康状况具有更广泛的健康影响。 公共卫生相关性：这个项目试图了解脊髓损伤引发的骨丢失。脊髓损伤后会发生快速、严重的骨丢失，导致骨骼脆性和容易骨折。这种骨质流失的原因还不是很清楚。但是，它似乎与随着年龄增长而出现的骨质流失不同，因为它对膝盖的影响比对臀部和脊柱的影响更大。 我们认为瘫痪的程度是决定脊髓损伤后骨丢失的最重要因素。我们将通过测定损伤程度较重和损伤程度较轻的受试者的骨密度来验证这一假设。我们还将测试一种假设，即神经损伤导致血液中一种已知的保护骨密度的分子缺乏。我们认为，最严重的瘫痪形式的个体会有较低的这种分子(骨保护素或OPG)水平和较低的骨密度。

项目成果

Sclerostin: a candidate biomarker of SCI-induced osteoporosis.

• DOI: 10.1007/s00198-012-2072-0
• 发表时间: 2013-03
• 期刊: OSTEOPOROSIS INTERNATIONAL
• 影响因子: 4
• 作者: Morse, L. R.;Sudhakar, S.;Lazzari, A. A.;Tun, C.;Garshick, E.;Zafonte, R.;Battaglino, R. A.
• 通讯作者: Battaglino, R. A.

Neurotoxic or Neuroprotective? Current Controversies in SCI-Induced Autoimmunity.

• DOI: 10.1007/s40141-013-0021-2
• 发表时间: 2013-09
• 期刊: Current physical medicine and rehabilitation reports
• 影响因子: 1.1
• 作者: Saltzman JW;Battaglino R;Stott H;Morse LR
• 通讯作者: Morse LR

Association between sclerostin and bone density in chronic spinal cord injury.

• DOI: 10.1002/jbmr.546
• 发表时间: 2012-02
• 期刊: JOURNAL OF BONE AND MINERAL RESEARCH
• 影响因子: 6.2
• 作者: Morse, Leslie R.;Sudhakar, Supreetha;Danilack, Valery;Tun, Carlos;Lazzari, Antonio;Gagnon, David R.;Garshick, Eric;Battaglino, Ricardo A.
• 通讯作者: Battaglino, Ricardo A.

B-cell maturation antigen, a proliferation-inducing ligand, and B-cell activating factor are candidate mediators of spinal cord injury-induced autoimmunity.

• DOI: 10.1089/neu.2012.2501
• 发表时间: 2013-04
• 期刊: Journal of neurotrauma
• 影响因子: 4.2
• 作者: Jonah W Saltzman;R. Battaglino;L. Salles;P. Jha;Supreetha Sudhakar;E. Garshick;H. Stott;R. Zafonte;L. Morse