3-D Visualization and Prediction of Vertebral Fractures

描述（由申请人提供）：椎体骨折是最常见的骨质疏松性骨折类型，50岁以上的女性中有三分之一，男性中有六分之一。尽管它们的发病率很高，但对椎体骨折风险的敏感和具体估计仍然难以捉摸。目前估计椎体强度和骨折风险的方法严重依赖于平均骨矿物质密度（BMD）的测量，这些方法的局限性已被广泛认识。然而，与“平均骨密度”方法相比，替代方法缺乏验证和明确的优势。我们最近的数据通过展示使用定量计算机断层扫描（QCT）进行临床可行的测量来增强对椎体衰竭的预测，解决了知识和翻译方面的这一关键差距。通过qct测量骨组织在整个椎体中的分布，我们发现BMD的椎体内异质性的大小提供了更好的椎体强度预测，并且在有椎体骨折的女性中比没有骨折的女性更低。这些数据还表明，椎体内骨密度的多重、特征性空间分布（“模式”）可以赋予较高的骨强度，这些模式和强度之间的关联可能受到邻近椎间盘退变的严重程度的调节。我们现在建议在基于人群的研究和补充性的离体研究中定义骨密度、椎体衰竭和IVD退变的椎内异质性之间的关系。目的1将采用病例对照研究设计，对Framingham心脏研究（FHS）多检测器QCT研究中登记的男性和女性进行先前获得的QCT扫描，以验证异质性程度降低与普遍骨折风险增加相关的假设。目标2将使用来自FHS QCT队列的年龄和性别分层的随机样本来确定BMD空间分布与IVD健康之间的关联，然后进行离体研究，确定这些关联如何影响椎体强度。我们在Aim #2中的双重假设是，骨密度的空间模式与IVD健康有关，而椎体强度取决于空间骨密度模式与IVD提供的负荷分布之间的一致性。Aim 3将通过一种新颖的实验方法继续我们以临床为重点的生物力学研究，为基于qct的椎体衰竭有限元模型的准确性提供急需的评估。这一目标将检验一个假设，即通过纳入临床可获得的IVD健康评估，FE预测的准确性得到提高。总之，这些目标是减少椎体骨折负担的重要一步。这项工作与一项具有成本效益的研究合作，在社区居住人群中进行椎体内异质性现象的研究，并对这种异质性的生物力学后果进行病例对照和实验室研究。研究结果将提供一种广泛适用的、综合的椎体健康评估方法，并配有可翻译的工具，为估计骨折风险制定新的标准。

DESCRIPTION (provided by applicant): 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 accurac 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.