Influence of Spinal Loading on Vertebral Fracture

项目概要/摘要 脊椎骨折（VF）困扰高达30-50%的50岁以上的成年人，并导致严重的发病率，增加 死亡率，在美国每年花费超过10亿美元。随着老年人口的增长， 预计到2050年，VF及其相关的个人、社会和经济负担将翻一番。骨矿物质 目前用于评估骨折风险的临床标准DXA骨密度（BMD）测试缺乏敏感性， 只有四分之一的VF患者通过BMD测试患有骨质疏松症。改善高风险患者的识别 骨折风险将使治疗针对那些最需要他们的人。生物力学原理决定了 当施加在骨头上的负荷超过其强度时就会发生骨折。然而，很少有人注意到 估计脊柱负荷。虽然可以使用人体的肌肉骨骼模型来估计在人体上的力， 肌肉、骨骼和关节在体内无法测量，迄今为止这些模型集中在四肢， 颈椎和腰椎，但在很大程度上忽略了胸部。这是一个主要的局限性， 骨折最常发生在脊柱的胸腰段和胸中段区域。最近我们 开发了新的肌肉骨骼模型，性别特异性，并纳入胸椎和肋骨架。 此外，我们还开发了创新方法，可以从3D医疗数据中有效创建特定对象的模型。 显像我们的长期目标是开发基于生物力学的方法，帮助临床医生识别 骨折风险高的人。我们目前提案的目标是验证我们的脊柱 肌肉骨骼模型，特别适用于进行动态日常生活活动的老年男性和女性，并 在以人群为基础的队列中，测试脊柱负荷的受试者特异性估计值是否能改善 脊椎骨折此外，我们还将确定影响脊柱负荷的因素，以便采用 将这些生物力学工具转化为临床实用工具的第一步 实践成功完成拟议的项目将通过提供一个 开源、解剖学上详细、完全连接且经过验证的胸腰椎肌肉骨骼模型 脊椎和肋骨的骨架。该模型和对患者特定建模的新见解 我们将产生将广泛用于翻译的肌肉骨骼模型的临床，从而提高 我们对多发性脊柱炎的生物力学机制和潜在治疗方法的理解， 影响大部分人口的疾病和状况。值得注意的是，我们将在以下方面取得进展： 脊柱建模通过在OpenSim（一个广泛使用的开源软件）中实现它们而广泛可用。 肌肉骨骼建模平台。

PROJECT SUMMARY/ABSTRACT Vertebral fractures (VF) afflict up to 30-50% of adults >50 years and lead to profound morbidity, increased mortality, and costs exceeding $1 billion in the US annually. With growth in the elderly population, the number of VF and associated personal, societal and financial burdens are predicted to double by 2050. Bone mineral density (BMD) testing by DXA, the current clinical standard for assessment of fracture risk, lacks sensitivity, as only a quarter of those with a VF have osteoporosis by BMD testing. Improved identification of patients at high risk for fracture will allow targeting of therapies to those who most need them. Biomechanical principles dictate that a fracture occurs when the loads applied to a bone exceed its strength. Yet, little attention is paid to estimating spinal loading. While musculoskeletal models of the human body can be used estimate forces on muscles, bones, and joints that not measurable in vivo, to date these models have focused on the extremities, cervical spine and lumbar spine, but have largely ignored the thorax. This is a major limitation as vertebral fractures occur most commonly in the thoracolumbar and mid-thoracic regions of the spine. Recently we have developed novel musculoskeletal models that are sex-specific and incorporate the thoracic spine and rib cage. Further, we have developed innovative methods to efficiently create subject-specific models from 3D medical imaging. Our long-term goal is to develop biomechanically-based approaches that will help clinicians to identify individuals at high risk for fracture. Our objectives of the current proposal are to validate our spine musculoskeletal model specifically in older men and women performing dynamic activities of daily living, and to test, in population-based cohorts, whether subject-specific estimates of spinal loading improve prediction of vertebral fractures. In addition, we will determine the factors that influence spinal loading, in order to take the first steps towards translating these biomechanical tools into ones that will be practical and useful in clinical practice. Successful completion of the proposed project will address a key gap in knowledge by providing an open source, anatomically detailed, fully articulated, and validated musculoskeletal model of the thoracolumbar spine and rib cage for older women and men. This model and the new insights into patient-specific modeling we will generate will be broadly useful for translation of musculoskeletal models to the clinic, thereby improving our understanding of the biomechanical mechanisms underlying, and potential treatments for, multiple spinal diseases and conditions that affect a large segment of the population. Notably, we will make our advances in spine modeling broadly available by implementing them in OpenSim, a widely used open source musculoskeletal modeling platform.