Targeting cortical bone quality by ultrasound biomarkers - relations to porosity, stiffness and strength

骨质疏松症（OP）是我们老龄化人口中最重要的全球性健康问题之一，它降低了流动性和生活质量，增加了死亡率，并给医疗保健系统带来了巨大的负担。OP和其他退行性骨病变是由骨吸收和骨形成之间的不平衡引起的，导致小梁网的稀疏化，以及部分再填充的基本多细胞单位（BMU）在皮质组织中的积累。后者导致骨皮质变薄、孔隙率增加、骨皮质硬度改变，从而导致骨强度降低。OP被认为是最容易被漏诊的疾病之一。除了电离辐射用于纵向筛查的有限适用性之外，现在广泛接受的是双能X射线吸收测定法（DXA），其是用于测量骨矿物质密度的已建立的诊断工具，并且仅预测约60%的个体骨折。骨强度评估长期以来集中在松质骨，其忽略了皮质骨的衰退在骨脆性的发病机理中以及在65岁或以上的女性和男性的骨折发生率中的作用。最近的研究指出了皮质骨的重要性，这表明诊断和风险评估应该包括对皮质骨的准确评估。皮质骨丢失很难通过基于X线的技术来捕获。最近，定量超声的创新基础研究已经转向使用导波和后向散射波测量皮质骨。复杂的方法，目前正在探索，其中，通过解决一个反问题，有效的刚度系数，皮质内孔隙率，和皮质厚度可以提供单独为每个patient.The的目的，这个协调项目是建立新的超声生物标志物的皮质骨丢失，这使得定量评估皮质厚度，刚度，和孔隙度，并将这些超声生物标志物与测量部位处的局部皮质骨强度相关联（组织衰竭，mm长度标度）和股骨近端强度（器官衰竭）。将在人类供体的股骨-胫骨对中进行离体测量。将通过最先进的技术，如扫描声学显微镜、微型计算机断层扫描、共振超声光谱和机械失效测试，确定胫骨中段、股骨干近端和股骨颈皮质骨组织的结构、弹性和失效特性。股骨近端强度将在两种机械载荷配置下通过实验确定，并通过基于有限元分析的高分辨率定量CT确定。有针对性的超声生物标志物有望在骨病理的诊断和纵向监测中开辟前景。

Osteoporosis (OP) is one of the most important global health problems of our aging population, which reduces mobility and quality of life, increases mortality, and sets dramatic burden to the healthcare system. OP and other degenerative bone pathologies are caused by a dis-balance between bone resorption and bone formation, leading to a rarefication of the trabecular network, and accumulation of partially refilled basic multicelluar units (BMUs) in cortical tissue. The latter result in cortical thinning, increased porosity, alterations of cortical bone stiffness and subsequently, to a reduction of bone strength.OP is considered as one of the most underdiagnosed diseases. Besides the limited applicability of ionizing radiations for longitudinal screening, it is now well accepted that dual X-ray absorptiometry (DXA), the established diagnostic tool for measuring bone mineral density and predicts only ~60% of the individual fracture.Bone strength assessment has long focused on trabecular bone, which has neglected the role of the decay of cortical bone in the pathogenesis of bone fragility and in the incidence of fractures in women and men aged 65 years or more. Recent studies are pointing towards the importance of cortical bone, suggesting that diagnosis and risk assessment should include accurate evaluation of cortical bone.Cortical bone loss is poorly captured by X-ray based techniques. Recently, innovative basic research on quantitative ultrasound has shifted towards measurements of cortical bone using guided and backscattered waves. Sophisticated approaches are currently explored in which, by solving an inverse problem, effective stiffness coefficients, intra-cortical porosity, and cortical thickness could be provided individually for each patient.The aims of this concerted project are to establish novel ultrasound biomarkers of cortical bone loss, which allow quantitative assessment of cortical thickness, stiffness, and porosity using guided waves propagation by multidirectional axial transmission and high-frequency backscatter measurement analyses, respectively, and to relate these ultrasound biomarkers to local cortical bone strength at the measurement sites (tissue failure, mm-length scale) and to proximal femur strength (organ failure). Measurements will be conducted ex-vivo in femur-tibia pairs from human donors. Structure, elastic and failure properties of cortical bone tissue will be determined at tibia midshaft, proximal femoral shaft and femoral neck by means of state-of-the art techniques, such as scanning acoustic microscopy, micro-computed tomography, resonance ultrasound spectroscopy, and mechanical failure testing. Proximal femur strength will be determined experimentally, in two mechanical loading configurations, and by high-resolution quantitative CT based finite element analysis. The targeted ultrasound biomarkers are anticipated to open perspectives in the diagnosis and longitudinal monitoring of bone pathologies.