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

椎体骨折是老年人常见的并发症，通常发生在习惯性负荷期间。然而，在骨折发生之前预测它仍然具有挑战性。目前，骨折风险预测依赖于金标准方法双能X射线吸收法（DXA）。然而，由于它是一种低分辨率的方法，并且基于三维物体的二维投影，越来越多的研究表明，DXA技术在描述骨折风险方面的能力有限。因此，引入了其他参数（即骨结构指数（BSI）和骨小梁评分（TBS）），以增加临床成像数据的预测价值，并更好地识别高骨折风险个体。尽管如此，尽管这些2D参数预计将反映骨微结构作为骨强度的重要决定因素，但高分辨率3D成像方法（如微计算机断层扫描（micro-CT））对于深入了解年龄相关性骨脆性的微结构起源是必需的。在这个项目中，我们要测试的假设，即老化过程损害三维骨微结构和力学性能的椎骨，骨微结构和力学性能的年龄依赖性恶化不同的个体椎骨的不同亚区之间的变化。预计椎体中不同的骨丢失模式可以解释为什么在加载过程中其特定的解剖亚区塌陷，导致可区分的骨折模式（例如楔形骨折等）。我们将通过以下目标实现我们的目标：i）使用微CT和机械测试评估不同椎骨亚区中3D骨微结构和骨机械特性的年龄相关恶化，ii）评估反映椎骨骨折风险的2D参数的年龄相关变异性（BMD、TBS、BSI）通过临床成像方法（DXA和整个椎骨的数字X射线摄影），以及iii）证明临床2D成像信息与实验评估的高-分辨率3D骨微结构和椎骨亚区的机械性能。为了扩展DXA提供的有限信息并改善临床环境中对个体椎骨骨折风险的评估，该项目将使用并整合临床可用的2D诊断信息（基于DXA技术）和通过实验性高分辨率微CT成像获得的3D微结构数据。通过医学影像学提高对骨折风险的认识和增强评估对于改善老年人群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.