3-D Visualization and Prediction of Vertebral Fractures

脊椎骨折是最常见的脊椎骨折类型，三分之一的女性和四分之一的女性患有脊椎骨折。 六个50岁以上的男人尽管其患病率很高，但对椎体骨折的敏感性和特异性评估 风险仍然难以捉摸。当前评估椎体强度和骨折方法的局限性 严重依赖于平均骨矿物质密度（BMD）测量的骨密度风险被广泛认可。 然而，替代方法在验证和明显优于 “平均BMD”方法。我们最近的数据解决了知识和翻译方面的这一关键差距， 证明使用定量计算机断层扫描进行的临床可行测量 (QCT)扫描以增强对脊椎衰竭的预测。使用QCT衍生的分布测量， 我们已经发现，在整个椎骨的骨组织中， BMD提供了更好的椎骨强度预测，并且在有椎骨的女性中比没有椎骨的女性更低。 骨折这些数据还表明，骨密度的多个、特征性空间分布（“模式”）， 脊椎骨可以赋予高骨强度，这些模式和强度之间的关联可能是 受相邻椎间盘（IVD）退变严重程度的调节。我们现建议 明确BMD椎体内异质性、椎体失效和IVD退变之间的关系， 基于人群的研究和补充的离体研究。目标1将采用病例对照研究设计， 入组Frachial Heart研究（FHS）的男性和女性既往获得的QCT扫描 多探测器QCT研究，以检验异质性程度降低与 普遍骨折的风险增加。目标2将使用来自FHS的年龄和性别分层随机样本 QCT队列研究，以确定BMD空间分布与IVD健康之间的相关性， 体内研究确定这些关联如何影响椎骨强度。我们在Aim中的双重假设 #2是BMD的空间模式与IVD健康相关，椎骨强度取决于 空间BMD模式和IVD提供的载荷分布之间的一致性。目标#3将 继续我们的临床重点，生物力学研究通过一种新的实验方法，提供 急需对基于QCT的椎骨失效有限元（FE）模型的准确性进行评估。这 目的是检验假设，即FE预测的准确性通过将临床 可获得的IVD健康评估。这些目标合在一起，是朝着减轻妇女负担迈出的重要一步。 脊椎骨折这项工作合作伙伴的成本效益研究的现象，椎体内异质性 在社区居住人群中进行病例对照和生物力学实验室研究， 这种异质性的后果。结果将提供一个广泛适用的综合评估， 脊椎健康，配有可翻译的工具，为评估骨折风险设定了新的标准。

Vertebral fractures are the most common type of osteoporotic fracture, afflicting one in three women and one in six men over the age of 50. Despite their high prevalence, sensitive and specific estimates of vertebral fracture risk have remained elusive. The limitations of current approaches for estimating vertebral strength and fracture risk, which rely heavily on measurement of the average bone mineral density (BMD), are widely recognized. However, alternative methods have been lacking with respect to validation and clear advantages over the “average BMD” approach. Our recent data address this critical gap in knowledge and translation by demonstrating the use of clinically feasible measurements made from quantitative computed tomography (QCT) scans to enhance predictions of vertebral failure. Using QCT-derived measures of the distribution of bone tissue throughout the vertebra, we have found that the magnitude of the intra-vertebral heterogeneity in BMD provides improved predictions of vertebral strength and is lower in women with vs. without vertebral fracture. These data also indicate that multiple, characteristic spatial distributions (“patterns”) of BMD within the vertebra can confer high bone strength, and that the associations between these patterns and strength may be modulated by the severity of degeneration in the adjacent intervertebral discs (IVDs). We now propose to define relationships among intra-vertebral heterogeneity in BMD, vertebral failure, and IVD degeneration in population-based studies and complementary ex vivo studies. Aim #1 will use a case-control study design with previously acquired QCT scans in men and women enrolled in the Framingham Heart Study (FHS) Multidetector QCT study to test the hypothesis that decreased magnitude of heterogeneity is associated with increased risk of prevalent fracture. Aim #2 will use an age- and sex-stratified, random sample from the FHS QCT cohort to determine associations between the spatial distribution of BMD and IVD health, followed by ex vivo studies that define how these associations can influence vertebral strength. Our dual hypotheses in Aim #2 are that the spatial patterns of BMD are associated with IVD health and that vertebral strength depends on the congruence between the spatial BMD pattern and the load distribution supplied by the IVDs. Aim #3 will continue our clinically focused, biomechanical investigations via a novel experimental approach that provides much-needed evaluation of the accuracy of QCT-based finite element (FE) models of vertebral failure. This aim will test the hypothesis that the accuracy of the FE predictions is improved by incorporating clinically obtainable assessments of IVD health. Together, these Aims are a major step towards reducing the burden of vertebral fracture. This work partners a cost-effective study of the phenomenon of intra-vertebral heterogeneity in a community-dwelling population with case-control and laboratory studies of the biomechanical consequences of this heterogeneity. The results will provide a widely applicable, integrated assessment of vertebral health, complete with translatable tools to set a new standard for estimation of fracture risk.