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

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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.