Biomechanics of Vertebral Fractures: The Framingham QCT Study

项目摘要 椎体骨折(VF)是老年人最常见的骨折，20%-35%的女性和 15%-25%的男性&>50岁，并导致严重的发病率、增加的死亡率和超过10亿美元的成本 每年在美国。有强有力的证据表明，低骨密度(BMD)以外的其他因素也会影响 VF风险。然而，导致骨折的生物力学因素却知之甚少。从一个机械设备 从角度来看，当施加在椎骨上的负荷超过其强度时，就会发生室颤。因此，在这场竞争中， 更新，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，或者通过 影响脊椎负荷和/或脊椎强度。我们将在之前的横断面研究结果的基础上，通过 研究了两个可能导致椎体骨折的新因素 队列：Framingham心脏研究多层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，我们显示了对脊椎负荷的估计很高 对几个因素敏感，即脊柱曲率、躯干肌肉大小和躯干肌肉密度的变化 这在我们(和其他人)之前的研究中没有被考虑到，并可能导致体内估计的错误 脊椎负荷。我们的初步数据还表明，在分布上的异质性的一个新的衡量标准 在身体标本中，椎体内的骨密度与椎体强度有关， 流行的室颤，即使在调整了BMD之后也是如此。因此，我们建议对VF事件进行前瞻性研究，以 确定1)脊柱弯曲的贡献，2)躯干肌肉的大小和质量；以及3) 椎体内的骨密度分布到VF。此外，我们将测试特定于患者的 风险系数(即负荷强度比)，使用最先进的方法来估计脊椎强度和 在活体脊柱负荷预测室颤事件比单独使用BMD或FRAX更好。总而言之，这个项目是 意义重大，因为它满足了减少VF日益增长的负担的需要。这项提议非常有说服力 通过使用现有的QCT和来自具有良好特征的潜在人群的临床数据，实现创新和高效- 基于队列，以及经验丰富的团队和多学科方法，以获得关于 室颤的病因学。拟议工作的完成将最终改变目前室颤病因学的范式 “超越骨密度”，从而指出了识别骨折风险的新方法和新的 减少室颤发生的干预措施。

Project Summary 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 vertebral 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 data 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.