Bone Density and Circulating Mediators of Bone Metabolism in Chronic SCI

描述（由申请人提供）：脊髓损伤（SCI）后发生过度骨丢失，导致骨质疏松症和骨折风险增加。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。目前，人们对这种骨质流失的原因或导致其严重程度的自然史和特定因素知之甚少。基于初步研究，我们假设骨保护标志物骨保护素（OPG）参与SCI诱导的骨丢失的发病机制，可能是该人群疾病严重程度和骨折风险的生物标志物。此外，如果得到证实，OPG是预防和治疗神经源性骨丢失的潜在强大治疗靶点。 在这个探索性和发展性的项目中，我们建议调查四肢瘫痪患者和那些较轻程度的SCI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OPG循环水平之间的关系。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。由于骨质疏松症在这一患者人群中很普遍，但目前治疗不足，我们希望有助于了解这种疾病的过程，以改善临床干预措施的发展。此外，这项工作将有助于了解神经损伤后的骨质流失，并将对从中风到脑瘫的健康状况产生更广泛的健康影响。 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。 我们认为瘫痪的程度是决定脊髓损伤后骨丢失量的最重要因素。我们将通过测定受试者的骨密度来检验这一假设，受试者中有较严重的损伤，也有较不严重的损伤。我们还将测试神经损伤导致血液中已知保护骨密度的分子缺乏的假设。我们认为，最严重的瘫痪患者的这种分子（骨保护素或OPG）水平较低，骨密度较低。

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.