Development and validation of novel image-based bone strength measures

骨质疏松症被定义为一种骨骼疾病，其特征是骨强度受损，易导致骨折风险增加。桡骨远端腕部骨折是老年女性最常见的骨折，也是未来桡骨远端骨折风险的早期指标。当外力作用在骨骼上（通常是由于跌倒造成的撞击）超过整个骨骼的强度时，就会发生手腕骨折。全骨强度只能通过体外破坏性力学测试直接确定。然而，骨结构和材料特性的替代测量可用于估计体内骨强度，并且通常通过医学成像和计算微有限元（microFE）建模获得。桡骨远端结构和材料特性的外周定量计算机断层扫描（pQCT）图像提供了估计体内骨强度的独特潜力。标准pQCT可用于计算强度指数，以使用基于工程的梁理论估计全骨强度。然而，常用的骨强度指标仅在胫骨（我们以前的工作），而不是桡骨远端的骨强度指标进行了验证。高分辨率pQCT（HR-pQCT）图像，具有小（82微米）各向同性体素，提供了骨微结构的详细信息，当与microFE建模相结合时，已用于估计承受轴向压缩载荷的桡骨远端整个或切除部分的失效载荷。这些强度估计的一个常见局限性是，它们已在仅涉及轴向压缩的机械测试场景中得到验证。然而，在摔倒时伸出的手所经历的载荷条件包括轴向压缩和“离轴”背侧和侧向力的组合，这些力产生弯曲。目前尚不清楚如何最好地预测骨强度抵抗离轴载荷。本研究项目的主要目的是开发和验证pQCT、HR-pQCT和microFE成像方法，以估计轴向压缩和离轴载荷联合作用下桡骨远端骨强度。我们将首先使用标准成像协议用pQCT和HR-pQCT扫描仪扫描15具女性尸体手臂的桡骨远端。然后，我们将在新型离轴载荷条件下对样本进行机械测试，并根据机械性能（失效载荷、应变）验证新的pQCT衍生强度指数和HR-pQCT microFE衍生失效载荷。使用猪模型的次要目的是开发经验证的pQCT衍生的肌肉组成评估。本研究项目的信息将增加对轴向压缩和离轴载荷组合下骨强度的基本理解。经验证的肌肉结果将补充未来的骨折风险评估模型。这一发现对骨骼研究、腕关节骨折的预防和治疗具有重要意义。

Osteoporosis is defined as a skeletal disorder characterized by compromised bone strength predisposing to an increased risk of fracture. Wrist fractures of the distal radius are the most common fractures in older women and early indicators of future osteoporotic fracture risk. Wrist fracture occurs when the external forces applied to bone—usually due to fall-related impact—exceeds whole bone strength. Whole bone strength can only be directly determined via destructive mechanical testing ex vivo. However, surrogate measures of bone structure and material properties can be used to estimate bone strength in vivo, and are commonly obtained by medical imaging and computational micro-finite element (microFE) modeling. Peripheral quantitative computed tomography (pQCT) images of distal radius structure and material properties offer unique potential to estimate bone strength in vivo. Standard pQCT can be used to calculate strength indices to estimate whole bone strength using engineering-based beam theory. However, commonly used bone strength indices have only been validated at the tibia (our previous work), not the fracture-prone distal radius. High resolution pQCT (HR-pQCT) images, with small (82 micron) isotropic voxels, provide detailed information of bone microarchitecture and when combined with microFE modeling, have been used to estimates failure load of the whole or excised sections of distal radius undergoing axial compressive loading. A common limitation in these strength estimates is that they have been validated in mechanical testing scenarios involving axial compression only. Loading conditions experienced during a fall on the outstretched hand, though, include a combination of axial compression and “off-axis” dorsal- and lateral-directed forces which create bending. It is unknown how to best predict bone strength resisting off-axis loading. The primary objective of this research program is to develop and validate pQCT, HR-pQCT and microFE imaging methods to estimate distal radius bone strength under combined axial compression and off-axis loading. We will first scan distal radii of 15 female cadaver arms with both pQCT and HR-pQCT scanners using standard imaging protocols. We will then mechanically test specimens in novel off-axis loading conditions and validate the new pQCT-derived strength indices and HR-pQCT microFE-derived failure load against mechanical properties (failure load, strain). The secondary objective, using a swine model, is to develop validated pQCT-derived muscle composition assessments. Information from this research program will add to the fundamental understanding of bone strength under combination of axial compression and off-axis loading. Validated muscle outcomes will complement future models of fracture risk assessment. Findings will be important for skeletal research, prevention and treatment of osteoporotic wrist fractures.