Development and validation of novel image-based bone strength measures

拟议研究的总体目标是开发和验证新的肌肉骨骼成像方法和模型(数学、有限元)，以结合体内肌肉特性可靠地估计骨强度(即抵抗骨折的能力)。这项研究计划将重点放在上肢，特别是最常见的骨折部位(桡骨远端)和前臂肌肉特性。为了提高我们对肌肉骨骼发育和退化的了解，对骨强度的可靠估计和关于增强或恶化骨强度的因素的信息是必不可少的。标准外周定量计算机断层扫描(PQCT)是一种广泛应用于肌肉骨骼研究的成像工具，它可以测量四肢的骨骼和肌肉特性(因此得名外周)，并利用基本射束理论和周围肌肉组织的结构和组成信息提供非侵入性骨强度估计。高分辨率pQCT(HR-pQCT)可以测量小(80微米)体素的腕部骨骼。近年来，HR-pQCT结合微观有限元模拟，通过估算破坏载荷，提供了新的桡骨远端强度估算方法。重要的是，使用pQCT和HR-pQCT估计的桡骨远端强度与轴向压缩载荷条件有关。这些估计没有考虑骨骼的抗弯能力，这对于对手腕进行建模非常重要，因为在跌落到伸展的手上时，骨骼会受到轴向压缩和弯曲(由于“离轴”力)的组合。关于肌肉，越来越多的证据表明，肌肉的大小和密度(通过pQCT评估)都提供了肌肉力量和质量的信息。尽管有这些证据，pQCT得出的肌肉密度尚未相对于组织脂肪的成分测量(例如甘油三酯含量)进行验证，也尚未用于获得“无脂肪”肌肉大小以更好地估计肌肉力量(收缩能力)。由于骨骼和肌肉组织之间的密切关系(例如，负荷适应、损伤的病因和治疗)，有效的措施很重要。目的：拟议的研究计划旨在解决以下短期目标(5年)：1.开发和验证基于pQCT的新的数学模型，以评估轴向和离轴载荷下的桡骨远端的力学特性。建立并验证了一种新的基于HR-pQCT的轴向和离轴载荷作用下的桡骨远端有限元模型。3.开发和验证基于pQCT的肌肉成分和力量的测量方法。长期目标是将这些经过验证的成像结果应用于肌肉骨骼研究和特定对象的生物力学肌肉骨骼模型，以全面研究肌肉骨骼的变化、适应和支撑骨骼发育和恶化的机制。

The overall goal of the proposed research is to develop and validate new musculoskeletal imaging methods and models (mathematical, finite element) to reliably estimate bone strength (i.e., ability to resist fracture) in combination with muscle properties in vivo. This program of studies will focus on the upper limb, specifically the most common fracture site (distal radius) and forearm muscle properties. Reliable estimates of bone strength and information on factors that enhance or deteriorate bone strength are imperative for investigations aiming to improve our understanding of musculoskeletal development and degeneration. Standard peripheral quantitative computed tomography (pQCT), a widely-used imaging tool for musculoskeletal research, can measure bone and muscle properties of limbs (hence the name peripheral') and offer non-invasive bone strength estimates using basic beam theory and information of structure and composition of surrounding muscle tissue. High resolution pQCT (HR-pQCT) can measure the bones of the wrist with a small (80micron) voxels. In recent years, HR-pQCT combined with micro-finite element modeling has offered novel estimates of distal radius strength by estimating failure load. Importantly, distal radius strength estimates using pQCT and HR-pQCT pertain to axial compressive loading conditions. These estimates do not take into account bone's resistance to bending, which is important for modeling the wrist as it is subjected to a combination of axial compression and bending (due to “off-axis” forces) during falling onto the outstretched hand. With regards to muscle, expanding evidence suggests that both muscle size and density (assessed via pQCT) provide information of muscle strength and quality. Despite this evidence, pQCT-derived muscle density has not yet been validated against compositional measures of tissue fatness (e.g., triglyceride content) or used to obtain "fat-free" muscle size to better estimate muscle strength (contractile capacity). Validated measures are important due to the close relationship between bone and muscle tissue (e.g., loading adaptation, etiology and treatment of injuries). OBJECTIVES:The proposed research program aims to address the following short-term objectives (5 years):1. Develop and validate a new pQCT-based mathematical model to estimate distal radius mechanical properties under both axial and off-axis loading.2. Develop and validate a new HR-pQCT-based finite element model of the distal radius under axial and off-axis loading. 3. Develop and validate pQCT-based measures of muscle composition and force.The long-term objective is to employ these validated imaged-outcomes in musculoskeletal research and subject-specific biomechanical musculoskeletal models to comprehensively investigate musculoskeletal changes, adaptation and mechanisms underpinning bone development and deterioration.