Development and validation of novel image-based bone strength measures

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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.