Biomechanics of the Vertebral Fracture Cascade

描述(申请人提供)：脊椎骨折是骨质疏松症最常见的并发症，与显著的发病率和增加的死亡率有关。据估计，50岁以上的人中有30%-50%至少有一次脊椎骨折，与年龄和骨密度(BMD)匹配、但没有既往骨折的其他骨质疏松患者相比，首次骨折的存在会使后续骨折的风险增加5-12倍。这种现象被称为“脊椎骨折级联”，尽管脊椎骨折对老年人的健康和福祉有很大的负面影响，但导致未来骨折风险增加的机制尚不清楚。本研究的目的是探讨生物力学改变在脊柱骨折级联中的作用。我们的假设是，最初的脊柱骨折改变了脊柱的几何形状，使得脊柱在日常生活活动中的压缩负荷增加，从而增加了随后脊柱骨折的风险。为了验证我们的假设，我们将使用一个大型社区队列的CT成像数据来量化脊柱骨折对脊柱曲率的影响，该队列由大约3500名年龄在31-83岁的个人组成，然后使用一个新的胸腰椎模型来探索脊柱骨折的几何形状如何影响脊柱的机械负荷和骨折风险。对椎体骨折级联机制的了解将有助于通过以下方式改进骨质疏松症患者的临床治疗：1)通过了解骨密度以外的因素如何导致骨折，可能更好地估计骨折风险；以及2)研究结果将使人们更好地了解针对维持正常脊椎曲度的干预措施的可能有效性，如运动和/或椎体增大。

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.