Biomechanics of the Vertebral Fracture Cascade

描述（由申请人提供）：椎体骨折是骨质疏松症最常见的并发症，与显著的发病率和死亡率增加有关。据估计，30-50%的50岁以上的人至少有一次椎体骨折，与年龄和骨密度（BMD）相匹配的其他骨质疏松症患者相比，初次骨折的存在会使随后骨折的风险增加5-12倍，但没有先前骨折。这种现象被称为“椎体骨折级联”，尽管椎体骨折对老年人的健康和福祉有很大的负面影响，但未来骨折风险增加的机制尚不清楚。本研究的目的是探讨改变的生物力学对椎体骨折级联的贡献。我们的假设是，最初的椎体骨折改变了脊柱的几何形状，从而在日常生活活动中增加了脊柱的压缩负荷，从而增加了随后椎体骨折的风险。为了验证我们的假设，我们将使用来自大约3500名年龄在31 - 83岁之间的大型社区队列的CT成像数据来量化椎体骨折对脊柱弯曲的影响，然后使用一个新的胸椎和腰椎模型来探索脊柱骨折几何形状如何影响脊柱的机械载荷和骨折风险。了解椎体骨折级联机制将有助于改善骨质疏松症患者的临床管理：1)通过了解骨矿物质密度以外的因素如何导致骨折，可以更好地估计骨折风险；2)研究结果将提高对干预措施（如运动和/或椎体增强术）可能效果的理解，这些干预措施旨在维持正常的脊柱曲度。

DESCRIPTION (provided by applicant): Vertebral fractures are the most common complication of osteoporosis and are associated with significant morbidity and increased mortality. It is estimated that 30-50% of individuals over age 50 have at least one vertebral fracture, and the presence of an initial fracture increases risk of subsequent fracture 5-12 fold relative to other osteoporotic individuals matched for age and bone mineral density (BMD), but with no pre-existing fracture. This phenomenon is known as the 'vertebral fracture cascade', and despite the large negative impact of vertebral fractures on the health and well being of the elderly population, the mechanisms underlying the increased risk of future fracture are unclear. The aim of this study is to investigate the contribution of altered biomechanics to the vertebral fracture cascade. Our hypothesis is that an initial vertebral fracture alters the geometry of the spine such that spinal compressive loading is increased during activities of daily living, thereby increasing risk of subsequent vertebral fracture. To test our hypothesis, we will quantify the effect of vertebral fracture on spinal curvature using CT imaging data from a large-community based cohort consisting of approximately 3500 individuals age 31 - 83, and then use a novel model of the thoracic and lumbar spine to explore how fractured spinal geometries affect mechanical loading and fracture risk in the spine. Knowledge of the mechanisms underlying the vertebral fracture cascade will contribute to improved clinical management of individuals with osteoporosis in the following ways: 1) Fracture risk may be better estimated by understanding how factors other than bone mineral density contribute to fracture; and 2) The results will provide improved understanding of possible efficacy of interventions, such as exercise and/or vertebral augmentation, directed at maintaining normal spinal curvature.