Biomechanics of Vertebral Fractures: The Framingham QCT Study

描述（由申请人提供）：椎体骨折（VF）是老年人中最常见的骨折，困扰着20-35%的女性和15-25%的男性，在50岁以下，导致严重的发病率，死亡率增加，在美国每年的成本超过10亿美元。有强有力的证据表明，除了低骨密度（BMD）外，其他因素也会影响室性房颤的风险。然而，导致骨折的生物力学因素了解甚少。从力学角度来看，当施加在椎骨上的载荷超过其强度时，就会发生VF。因此，在这个竞争性的更新中，我们的目标是研究我们最近的工作表明与VF风险相关的几个因素，无论是通过影响椎体负荷和/或椎体强度。我们将在我们之前的横断面研究结果的基础上，研究两个特征明确的队列中可能导致椎体骨折的几个新因素：弗雷明汉心脏研究多探测器CT研究和年龄、基因/环境易感性-雷克雅未克研究（AGES）。在上一个资助期内，我们发现椎体负荷的估计对几个因素高度敏感，即脊柱弯曲、躯干肌肉大小和躯干肌肉密度的变化，这些因素在我们（和其他人）之前的研究中没有考虑到，可能导致体内椎体负荷的估计出现错误。我们的初步数据还表明，即使在调整了骨密度后，椎体内骨密度分布的异质性的新测量方法也与尸体标本中的椎体强度和普遍的VF相关。因此，我们建议对事件VF进行前瞻性研究，以确定1)脊柱弯曲，2)躯干肌肉的大小和质量；3)椎体内骨密度到VF的分布。此外，我们将测试使用最先进的方法来估计椎体强度和体内脊柱负荷的患者特异性风险因素（即负荷-强度比）是否比单独使用aBMD或FRAX更好地预测VF事件。总之，这个项目意义重大，因为它解决了减轻VF日益增加的负担的需要。该建议是高度创新和高效的，通过使用现有的QCT和来自具有良好特征的前瞻性人群队列的临床数据，以及经验丰富的团队和多学科方法来获得关于VF病因的知识。这项工作的完成将最终改变目前VF病因学的范式“超越BMD”，从而指出识别骨折风险的新方法和减少VF发生的新干预措施。

DESCRIPTION (provided by applicant): Vertebral fractures (VF) are the most common fracture among older persons, afflicting 20-35% of women and 15-25% of men >50 yrs, and leading to profound morbidity, increased mortality, and costs exceeding $1 billion in the US annually. There is strong evidence that factors other than low bone mineral density (BMD) influence VF risk. Yet, the biomechanical factors that contribute to fractures are poorly understood. From a mechanical perspective, a VF occurs when loads applied to the vertebrae exceed its strength. Thus, in this competing renewal, we aim to study several factors that our recent work indicates are related to VF risk, either by affecting vertebral loading and/or vertebra strength. We will build upon our prior cross-sectional findings by studying several novel factors that may contribute to incident vertebral fractures in two, well-characterized cohorts: the Framingham Heart Study Multidetector CT Study and the Age, Gene/Environment Susceptibility- Reykjavik Study (AGES). In the last funding period, we showed that estimates of vertebral loading are highly sensitive to several factors, namely variations in spine curvature, trunk muscle size and trunk muscle density that were not accounted for in our (and others') prior studies and likely led to errors in the in vivo estimates of vertebral loading. Our preliminary dat also show that a novel measure of heterogeneity in the distribution of bone density within the vertebral body is associated with vertebral strength in cadaveric specimens and with prevalent VF, even after adjusting for BMD. Thus we propose to conduct a prospective study of incident VF to determine the contribution of 1) spinal curvature, 2) the size and quality of trunk muscles; and 3) the distribution of bone density within the vertebral body to VF. Further, we will test whether a patient-specific factor-of-risk (ie, load-to-strength ratio) that uses state-of-the art approaches to estimate vertebral strength and in vivo spinal loading predicts incident VF better than aBMD or FRAX alone. In summary, this project is significant because it addresses the need to reduce the growing burden of VF. The proposal is highly innovative and efficient by using existing QCT and clinical data from well-characterized prospective population- based cohorts, along with an experienced team and multidisciplinary approach to gain knowledge about the etiology of VF. Completion of the proposed work will ultimately shift the current paradigm for VF etiology "beyond BMD", thereby pointing towards new approaches to identify those at risk for fracture and novel interventions to reduce the occurrence of VF.