Adiposity and Bone Loss in Spinal Cord Injury

描述(申请人提供)：在所有神经功能完全的脊髓损伤患者中，高达50%的人在脊髓损伤(SCI)后会发生过度的骨丢失，导致骨质疏松和低冲击性骨折风险增加。这些骨折可能是灾难性的，因为它们限制了活动，恶化了残疾，并容易发生医学并发症。虽然这种骨丢失的根本原因尚不清楚，但其严重程度和模式与其他已知的骨质疏松原因不同，包括废用和绝经后骨质疏松症。相比之下，股骨远端和胫骨近端(即膝盖上方和下方)的干骺端是脊髓损伤后最常见的骨折部位。目前，对脊髓损伤后骨丢失的原因、自然病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脊髓损伤导致的骨丢失的发病机制，并可能是该人群骨质疏松严重程度和骨折风险的介体。我们建议研究慢性脊髓损伤患者内脏脂肪、循环中脂肪衍生激素水平和骨密度纵向变化之间的关系。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。这项研究将是第一个关于慢性脊髓损伤中骨丢失的大型纵向研究，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与机械负荷无关的脂肪介导性骨丢失。明确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，将对脊髓损伤后骨质疏松的管理和预防具有重要意义。如果得到证实，这些发现将为针对超重体重的新型临床计划奠定基础，并促进对骨骼的机械刺激，以改善骨量和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.