Vertebral fracture risk: Combined assessment through clinical 2D-osteodensitometry tools and experimental high-resolution micro-CT analyses to pinpoint regional 3D bone quality characteristics

脊椎骨折是衰老的常见并发症，通常发生在习惯性负荷过程中。然而，在骨折发生之前预测它仍然是具有挑战性的。目前，骨折危险性的预测依赖于金标准方法--双能X线骨密度仪(DXA)。然而，由于DXA是一种低分辨率的方法，而且是基于三维物体的二维投影，越来越多的研究表明，DXA技术仅具有有限的描述骨折风险的能力。因此，引入了额外的参数(即骨结构指数(BSI)和骨小梁评分(TBS))，以增加临床影像数据的预测价值，并更好地识别高骨折风险个体。然而，尽管这些2D参数被期望反映骨骼微结构作为骨强度的重要决定因素，但高分辨率的3D成像方法，如微型计算机断层扫描(Micro-CT)，对于深入了解与年龄相关的骨脆性的微观结构起源是必需的。在这个项目中，我们想要检验一种假设，即衰老过程损害了3D骨骼微结构和椎骨的力学性能，并且随着年龄的增加，骨微结构和力学性能的恶化在单个椎骨的不同亚区有所不同。预计椎体内不同的骨丢失模式可以解释其特定的解剖亚区在加载过程中崩溃的原因，从而导致不同的骨折模式(如楔形骨折等)。我们的目标将通过这些目标来实现：i)使用Micro-CT和机械测试来评估不同椎体区域的3D骨微结构和骨力学性能随年龄的恶化，ii)通过临床成像方法(DXA和全椎体数字摄影)评估反映椎体骨折风险(BMD、TBS、BSI)的2D参数的年龄相关变异性，以及iii)展示临床2D成像信息和实验评估的高分辨率3D骨微结构和椎体区域的力学特性之间的关系。为了扩展DXA提供的有限信息，改善临床环境中对个人脊柱骨折风险的评估，该项目将使用和整合临床可用的2D诊断信息(基于DXA技术)和通过实验性高分辨率Micro-CT成像获得的3D微架构数据。提高对骨折风险的了解并通过医学成像加强对骨折风险的评估对于改善老年人口的骨骼保健至关重要。

Vertebral fractures are a common complication of aging and usually occur during habitual loading. However, predicting a fracture before it happens is still challenging. Currently, fracture risk prediction relies on the gold standard method Dual-energy X-ray Absorptiometry (DXA). Yet, as it is a low-resolution method and based on a two-dimensional projection of a three-dimensional object, an increasing number of studies showed that DXA technology has only a limited ability to depict fracture risk. Therefore, additional parameters were introduced (i.e. Bone Structure Index (BSI) and Trabecular Bone Score (TBS)) to increase the predictive value of clinical imaging data and better identify individuals at a high fracture risk. Still, although these 2D parameters are expected to reflect bone microarchitecture as an important determinant of bone strength, high-resolution 3D imaging methods such as micro-computed tomography (micro-CT) are mandatory to gain in-depth knowledge of the microstructural origins of age-related bone fragility. In this project we want to test the hypothesis that aging processes impair 3D bone microarchitecture and mechanical properties of vertebrae, and that age-dependent deterioration of bone microarchitecture and mechanical properties varies between different subregions of individual vertebrae. It is expected that different patterns of bone loss in vertebral bodies can explain why their specific anatomical subregions collapse during loading which leads to distinguishable fracture patterns (e.g. wedge fracture, etc). Our aims will be accomplished through these objectives: i) assessment of age-related deterioration in 3D bone microarchitecture and bone mechanical properties in different vertebral subregions using micro-CT and mechanical testing, ii) evaluation of the age-related variability in 2D parameters reflecting vertebral fracture risk (BMD, TBS, BSI) by clinical imaging methods (DXA and digital radiography of the whole vertebra), and iii) demonstration of the relationship between clinical 2D-imaging information and experimentally evaluated high-resolution 3D bone microarchitecture and mechanical properties at the vertebral subregions. In order to extend the limited information provided by DXA and improve the assessment of individuals vertebral fracture risk in clinical settings, this project will use and consolidate clinically available 2D diagnostic information (based on DXA technology) and 3D microarchitecture data obtained by experimental high-resolution micro-CT imaging. Improved understanding of fracture risk and its enhanced assessment through medical imaging is essential for improving skeletal healthcare of the elderly population.