Adiposity and Bone Loss in Spinal Cord Injury

描述（由申请人提供）： 脊髓损伤（SCI）后发生过度骨丢失，导致骨质疏松症，并增加了高达50%的神经学完全SCI患者发生低冲击性骨折的风险。这些骨折可能是灾难性的，因为它们限制了活动性，使残疾恶化，并易患医疗并发症。虽然这种骨丢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。相反，股骨远端和胫骨近端的干骺端（即，膝盖以上和以下）是SCI后最常见的骨折部位。目前，对SCI后骨丢失的原因、自然史或导致严重性的具体因素知之甚少。基于初步研究，我们假设内脏脂肪参与SCI诱导的骨丢失的发病机制，并且可能是该人群中骨质疏松症严重程度和骨折风险的介导者。我们建议研究慢性SCI患者内脏脂肪、循环中脂肪源性激素水平和骨密度纵向变化之间的关系。将研究因在VA波士顿的纵向健康研究中登记而已知其健康行为（吸烟，饮酒）和共病疾病的SCI受试者。这项研究将是第一项关于慢性SCI骨丢失的大型纵向研究，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隔离发生的脂肪介导的骨丢失。明确股骨远端和胫骨近端的骨丢失率并评估其与内脏脂肪的关系，将对SCI患者骨质疏松症的治疗和预防具有重要意义。如果得到证实，这些发现将为新的临床项目奠定基础，这些项目针对超重，促进骨骼的机械刺激，以改善骨量并预防骨质疏松性骨折。 公共卫生相关性： 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，使骨骼变脆，容易骨折。这种骨质流失还没有得到很好的理解。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，损伤的严重程度和储存的中央（内脏）脂肪量是决定脊髓损伤后骨丢失量的重要因素。我们将通过确定受试者中骨丢失的量来检验这一假设，这些受试者有更严重的损伤，那些有较轻的损伤，以及那些没有损伤。我们还将确定SCI患者和内脏脂肪量较大的人是否比SCI患者和脂肪较少的人失去更多的骨骼，并评估与骨骼丢失和血液中与脂肪相关的激素的关系。

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.