Adiposity and Bone Loss in Spinal Cord Injury

描述（由申请人提供）：脊髓损伤（SCI）后发生过度骨质流失，导致骨质疏松症和低冲击骨折的风险增加，在所有神经完全性SCI患者中高达50%。这些骨折可能是灾难性的，因为它们限制了活动能力，加重了残疾，并易导致医学并发症。虽然这种骨质流失的潜在原因尚不清楚，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）是脊髓损伤后最常见的骨折部位。目前，对脊髓损伤后骨质流失的原因、自然历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诱导的骨质流失的发病机制，并可能是该人群骨质疏松严重程度和骨折风险的中介。我们建议研究慢性脊髓损伤患者内脏脂肪、循环脂肪源性激素水平和骨密度纵向变化之间的关系。脊髓损伤患者的健康行为（吸烟、饮酒）和合并症由于在VA Boston的纵向健康研究登记而已知，将被研究。这项研究将是慢性脊髓损伤中骨质流失的第一个大型纵向研究，具有重要意义和创新性，因为它将首次使用脊髓损伤作为临床模型来表征脂肪介导的骨质流失，而不受机械负荷的影响。确定股骨远端和胫骨近端骨质流失率，并评估与内脏脂肪的关系，将对脊髓损伤骨质疏松症的管理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，以超重为目标，促进骨的机械刺激，以改善骨量，预防骨质疏松性骨折。

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.