The Emu as a Model for Necrotic Femoral Head Collapse

鸸鹋作为股骨头坏死模型

• 批准号: 6869624
• 负责人: THOMAS DUDLEY BROWN
• 金额: $ 41.64万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-04-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6869624
• 关键词: Aves; biomechanics; bone necrosis; computed axial tomography; disease /disorder model; dogs; femur; hip; magnetic resonance imaging; model design /development; orthopedics; osteocytes; pathologic process; skeletal stress

DESCRIPTION (provided by applicant): Femoral head osteonecrosis remains a major unsolved problem in orthopedic surgery of the hip. Because total hip replacement often proves unsatisfactory for patients with this disorder, means are needed to forestall necrotic femoral head collapse. Much could be learned from an animal model reliably mimicking the human disorder's natural history of structural collapse. Existing quadrupedal models fail to replicate this key aspect of the pathogenesis, presumably owing to unduly benign biomechanical demand. Cryogenically-induced osteonecrosis in the emu, a large and very active biped, shows great promise for overcoming this difficulty. The central goal of the proposed work is to bring this new emu model optimally into concordance with human disorder. Aim 1 is to establish quantitative linkage between cryo-insult parameters and resulting distributions of osteocyte death. This will involve thermal finite element analysis of temperature fields produced by a specially developed cryo-insult probe, and prediction of corresponding patterns of osteocyte death. Validation will be provided by osteocyte death distributions resulting from corresponding insults delivered intraoperatively. Aim 2 is to quantify the functional similarity of femoral head mechanical load transmission in emus versus humans. In vivo joint loading of the emu hip will be determined from force plate and optoelectronic recordings. Bench tests will be performed to measure hip joint contact stress distributions, and to map cancellous bone stiffness distributions. A whole-gait-cycle structural finite element model of the emu femoral head will be developed, for comparison with corresponding data for the human. Aim 3 is to compare the pathogenesis of osteonecrosis in emus with that in a (non-collapsing) canine model. Parameters of interest include the speed and patterns of revascularization, cell types, histomorphometric alterations of the trabecular lattice, and mechanical compromise. Aim 4 is to correlate the speed and severity of collapse in the emu osteonecrosis model with quantifiable structural compromise. This will again involve the structural finite element model, coupled with CT-based assessments of bony structural degradation. At the project's conclusion, we expect to have filled a longstanding need in the field of osteonecrosis research: an animal model suitable for systematic study of human-implementable interventions to forestall femoral head collapse.

描述（由申请人提供）：股骨头骨坏死仍然是髋部骨科手术中的一个主要问题。由于总髋关节置换通常证明对这种疾病患者不满意，因此需要减少坏死性股骨头塌陷的手段。从动物模型中可以汲取很多东西，可以可靠地模仿人类混乱的结构崩溃的自然史。现有的四倍模型无法复制发病机理的这一关键方面，这可能是由于过度良性的生物力学需求。在EMU中，较大且非常活跃的emu造成的骨坏死在克服这一困难方面表现出巨大的前景。拟议工作的核心目标是将这种新的EMU模型最佳地与人类混乱一致。目的1是在冷冻参数和骨细胞死亡的分布之间建立定量联系。这将涉及由特殊开发的冷冻探测器产生的温度场的热元素分析，以及对骨细胞死亡的相应模式的预测。验证将由术中相应损伤产生的骨细胞死亡分布提供。 AIM 2是量化EMUS与人类股骨头机械载荷传递的功能相似性。 EMU髋关节的体内关节载荷将根据力板和光电记录确定。将进行台式测试以测量髋关节接触应力分布，并绘制取消骨刚度分布。将开发股骨头的全基因周期结构有限元模型，以与人类的相应数据进行比较。目的3是将EMU中骨坏死的发病机理与（非colla犬）模型中的骨坏死的发病机理。感兴趣的参数包括血运重建的速度和模式，细胞类型，小梁晶格的组织形态变化以及机械折衷。目的4是将EMU截骨模型中塌陷的速度和严重程度与可量化的结构妥协相关联。这将再次涉及结构有限元模型，再加上基于CT的骨结构降解评估。在该项目的结论中，我们预计在骨质症研究领域的长期需求：一种适合系统地研究人类无能干预以防止股骨头倒塌的动物模型。