Adiposity and Bone Loss in Spinal Cord Injury

脊髓损伤中的肥胖和骨质流失

• 批准号: 8056504
• 负责人: Leslie R. Morse
• 金额: $ 61.38万
• 依托单位: SPAULDING REHABILITATION HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-05 至 2015-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8056504
• 关键词: Adipose tissue; Affect; Aging; Alcohol consumption; Amputation; Blood; Body Weight; Body mass index; Bone Density; Bone Resorption; Bone remodeling; Boston; Chronic; Chronic Phase; Clinical; Cross-Sectional Studies; Data; Decubitus ulcer; Distal; Enrollment; Equilibrium; Fatty acid glycerol esters; Femur; Fracture; General Population; Glosso-Sterandryl; Health; Health behavior; Hip Fractures; Hip region structure; Hormones; Impairment; Individual; Injury; Intervention; Knee; Left; Leg; Leptin; Link; Longitudinal Studies; Lower Extremity; Measures; Mechanical Stimulation; Mechanics; Mediating; Mediator of activation protein; Metaphysis; Modeling; Motor; Muscle; Natural History; Neurologic; Obesity; Osteocalcin; Osteogenesis; Osteomyelitis; Osteoporosis; Osteoporosis prevention; Paralysed; Participant; Pathogenesis; Pattern; Population; Postmenopausal Osteoporosis; Postmenopause; Protocols documentation; Risk; Scanning; Senile Osteoporosis; Severities; Site; Smoking; Source; Spinal cord injury; Testing; Trauma; Vertebral column; Visceral; adiponectin; arm; base; bone; bone disuse atrophy; bone loss; bone mass; bone metabolism; clinically relevant; design; disability; improved; innovation; long bone; medical complication; novel; osteoporosis with pathological fracture; prevent; programs; protective effect; public health relevance; response; tibia

DESCRIPTION (provided by applicant): Excessive bone loss occurs following spinal cord injury (SCI) leading to osteoporosis and an increased risk of low-impact fracture in up to 50% of all individuals with neurologically complete SCI. These fractures can be catastrophic as they limit mobility, worsen disability, and predispose to medical complications 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. In contrast, the metaphyses of the distal femur and proximal tibia (i.e., above and below the knee) are the most commonly fractured sites following SCI. Currently, little is known about the cause of, the natural history, or the specific factors that contribute to the severity of bone loss following SCI. Based on preliminary studies, we hypothesize that visceral fat is involved in the pathogenesis of SCI-induced bone loss and may be a mediator of osteoporosis severity and fracture risk in this population. We propose to investigate the relationship between visceral fat, circulating levels of fat derived hormones, and longitudinal change in bone mineral density in chronic SCI. 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. This study will be the first large longitudinal study of bone loss in chronic SCI, and is both significant and innovative because it will be the first to use SCI as a clinical model to characterize adipose mediated bone loss occurring in isolation from mechanical loading. Defining the rate of bone loss at the distal femur and proximal tibia and assessing relationships with visceral fat will have important implications for the management and prevention of osteoporosis in SCI. If confirmed, these findings will lay the groundwork for novel clinical programs that target excess body weight and to promote mechanical stimulation of bone to improve bone mass and prevent osteoporotic fractures. PUBLIC HEALTH RELEVANCE: This project seeks to understand bone loss triggered by spinal cord injury. 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 that injury severity and the amount of stored central (visceral) fat are important factors in determining how much bone is lost following spinal cord injury. We will test this hypothesis by determining the amount of bone lost in subjects with more severe injury, those with less severe injury, and those without injury. We will also determine if people with SCI and greater amounts of visceral fat lose more bone than those with SCI and less fat and assess relationships with bone loss and hormones in the blood that are related to fat.

描述（由申请人提供）：脊髓损伤 (SCI) 后会发生过度骨质流失，导致骨质疏松症，并且在所有患有神经学完全性 SCI 的个体中，高达 50% 的人发生低冲击性骨折的风险增加。这些骨折可能是灾难性的，因为它们限制了活动能力，加剧残疾，并容易出现医疗并发症。虽然这种骨质流失的根本原因仍有待澄清，但它的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。相反，股骨远端和胫骨近端（即膝盖上方和下方）的干骺端是 SCI 后最常见的骨折部位。目前，对于 SCI 后骨质流失严重程度的原因、自然史或具体因素知之甚少。根据初步研究，我们假设内脏脂肪参与了 SCI 引起的骨质流失的发病机制，并且可能是该人群骨质疏松严重程度和骨折风险的中介因素。我们建议研究慢性 SCI 中内脏脂肪、脂肪源性激素循环水平和骨矿物质密度纵向变化之间的关系。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。这项研究将是第一个关于慢性 SCI 中骨质流失的大型纵向研究，并且具有重要意义和创新性，因为它将是第一个使用 SCI 作为临床模型来表征与机械负荷无关的脂肪介导的骨质流失的特征。定义股骨远端和胫骨近端的骨丢失率并评估与内脏脂肪的关系将对 SCI 骨质疏松症的管理和预防产生重要影响。如果得到证实，这些发现将为针对超重并促进骨骼机械刺激以改善骨量和预防骨质疏松性骨折的新临床计划奠定基础。 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，使骨骼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，损伤严重程度和储存的中央（内脏）脂肪量是决定脊髓损伤后骨质流失量的重要因素。我们将通过确定损伤较严重、损伤较轻和未损伤的受试者的骨质流失量来检验这一假设。我们还将确定患有 SCI 和内脏脂肪较多的人是否比患有 SCI 和较少脂肪的人失去更多的骨质，并评估骨质流失与血液中与脂肪相关的激素的关系。