Clinical proxy for bone fracture risk in osteoporosis

今天，可能的骨折风险的临床指标是模糊的-目前骨质疏松症的诊断标准使数百万人的自主权和生活质量受到影响。本提案旨在解决基于临床断层成像的海绵状骨（最常受骨质疏松症影响）的表征问题。与传统使用的骨矿物质密度或骨体积参数相反，这将是第一次使用一组来自3D图像的海绵状（小梁）骨的新结构参数来为骨质疏松症患者提供可靠的预后。这个建议是基于最近的发现，健康的小梁骨符合拓扑原则，即用最少数量的相互连接的元素跨越最大的三维体积，类似于用几根均匀分布的绳子将帆桅杆固定在船甲板上，而不是用绳子向一个方向拉，或者用多余的大量绳子。这种拓扑原理反映了骨骼对不同负荷的有效重新分配和避免应力集中的适应性，两者都以最低的代谢成本进行。通过新型的骨小梁间角（ITA）分析，可以获得骨小梁的拓扑描述符。本项目主要研究健康及骨质疏松小梁骨的拓扑参数变化。我们有初步证据表明这种变异确实存在，并且可以量化。根据骨小梁结构拓扑稳定和不稳定之间的范围定义，进行临床成像模拟，设计医学断层扫描的自动化临床应用。该项目的设想最终结果将是一个直观的应用程序，为临床验证做好准备，并支持正常和病理骨骼3D图像的数据库。这对发达国家来说尤其重要，因为在这些国家，长寿人群容易受到久坐不动的生活方式和代谢疾病的影响。

Today, clinical indicators of a possible bone fracture risk are vague - the current diagnostic criteria ofosteoporosis leave the autonomy and life quality of millions of people to chance. This proposal aims to resolvethe problem of characterization of spongy bone (most commonly affected by osteoporosis) based on clinicaltomographic imaging. This will be the first time that a new set of architectural parameters of spongy(trabecular) bone derived from a 3D image are used to provide a reliable prognosis to osteoporosis patients, asopposed to the traditionally-used bone mineral density or bone volume parameters. The proposal is based onthe recent discovery that healthy trabecular bone conforms to the topological principle of spanning maximal 3Dvolume with the minimal number of interconnected elements, akin to securing a sail mast to a boat deck with afew evenly spread ropes, rather than with the ropes pulling in one direction, or with a redundantly high numberof ropes. This topological principle reflects the adaptation of bone for effective re-distribution of diverse loadsand avoiding stress concentrations, both at the lowest metabolic cost. The topological descriptors of trabecularbone can be accessed via the novel inter-trabecular angle (ITA) analysis. This project will focus on detectionand analysis of variation of the topological parameters in healthy and osteoporotic trabecular bone. We havepreliminary evidence that such variation does exist and can be quantified. Following the definition of the rangebetween topologically stable and unstable configurations of trabecular bone, simulation of clinical imaging willbe carried out and an automated clinical application for medical tomography will be designed. The envisionedend result of this project will be an intuitive application ready for clinical validation and a supporting databaseof normal and pathological bone 3D images. This is especially relevant for developed countries where thehigh-longevity population succumbs to sedentary life style and metabolic diseases.