Determination of Pediatric Osteogenesis Imperfecta Bone Material Properties

儿童成骨不全骨材料特性的测定

• 批准号: 10217432
• 负责人: JESSICA M FRITZ
• 金额: $ 6.3万
• 依托单位: MEDICAL COLLEGE OF WISCONSIN
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-01 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10217432
• 关键词: Affect; Age; Behavior; Biopsy; Bone Density; Bone Diseases; Bone Tissue; Caring; Chicago; Child; Childhood; Clinical; Clinical Data; Clinical Treatment; Clinical assessments; Collagen Type I; Complex; DNA Sequence Alteration; Data; Development; Disease; Elements; Engineering; Etiology; Failure; Femoral Fractures; Femur; Finite Element Analysis; Fracture; Goals; Hereditary Disease; Heritability; Image; Image Analysis; Incidence; Individual; Link; Location; Lower Extremity Fracture; Measures; Mechanics; Methodology; Methods; Modeling; Modulus; Operative Surgical Procedures; Orthopedics; Osteogenesis Imperfecta; Osteotomy; Patients; Porosity; Prevention; Prevention approach; Production; Property; Proteins; Rare Diseases; Risk Assessment; Sampling; Severities; Specimen; Stress; Structure; Techniques; Testing; United States National Institutes of Health; Validation; Work; base; bone; bone fragility; bone imaging; bone mass; bone strength; clinical decision-making; computerized tools; cortical bone; effectiveness evaluation; fracture risk; long bone; mechanical properties; microCT; nanoindentation; novel strategies; reconstruction; tibia; tool; treatment planning

PROJECT SUMMARY/ABSTRACT Osteogenesis imperfecta (OI) is the most frequent heritable bone fragility disorder in children and is most commonly caused by genetic mutations affecting type I collagen production, which is the primary protein of bones. OI is common in pediatric orthopaedic centers, as affected individuals frequently require orthopaedic care during their growing years. Long bone fracture is common in children with OI. Bone strength assessment is critical in evaluating the effectiveness of current and new preventions and treatments of fractures in OI. Clinical decision-making could be put on a firmer basis if there was a more objective, quantitative way to assess a bone's capacity to withstand loading. The goal of the present project is to develop a micro-FE model of OI bone mini beams and a model to predict strength from clinical bone mineral density data. Very little data is yet available to describe bone material properties in OI. The first characterization studies of OI bone done by our team used nanoindentation to measure elastic moduli at the microstructural scale in small biopsies or surgical specimens of OI bones. Within that scale, the elastic modulus of bone tissues was found to be higher in children with severe OI vs age-matched controls, and to be slightly higher in children with mild vs severe OI. Our team developed a methodology using larger specimens of OI cortical bone. Using this technique, it was found that OI diaphyseal specimens had reduced material strength compared to normal pediatric bone. In addition, our team also imaged bone mini beams using micro-computed tomography (micro-CT). This allowed for the examination of cortical bone porosity. Imaging analyses provide microstructural detail that would otherwise be unknown. This data contributes to our knowledge of bone strength and fracture risk. A more detailed method for assessing bone strength is finite element analysis (FEA), a computational tool widely used in engineering to evaluate stresses and strains (i.e., internal local loading and deformation) within a complex structure by dividing it into smaller, simpler parts (elements). Using patient-specific geometric information and accurate mechanical properties of OI bone, FEA can simulate the behavior of long bones and assess fracture risk. The study PI has previously assessed femur fracture risk in OI by using approximate reconstruction methods to create bowing in the femur along with estimated OI bone tissue properties. This work also showed increased fracture risks with increased bowing as well as increased OI severity. However, this model cannot be validated as that would require knowing the exact force magnitude and location required to break the femur. Developing micro-FE models of the OI bone specimen mini beams will provide the first validation of OI bone strength modeling and answer questions about relationships between microstructure, macrostructure, vBMD, clinical data and whole bone strength.

项目摘要/摘要 成骨不完美（OI）是儿童中最常见的遗传骨脆弱性障碍，是最常见的 通常是由影响I型胶原蛋白产生的基因突变引起的，这是 骨头。 OI在小儿骨科中心很常见，因为受影响的个体经常需要骨科护理 在他们的成长中。长骨骨折在OI儿童中很常见。骨骼强度评估是 评估OI当前和新骨折治疗的有效性至关重要。临床 如果有一种更客观的定量方法来评估骨骼 承受负载的能力。本项目的目的是开发OI骨迷你的微型FE模型 梁和模型可预测临床骨矿物质密度数据的强度。很少有数据可用 描述OI中的骨骼材料特性。我们团队所做的OI骨骼的首次表征研究 在小型活检或手术标本的微观结构尺度上测量弹性模量的纳米构造 Oi骨头。在该尺度内，发现骨组织的弹性模量在严重的儿童中较高 OI与年龄匹配的对照，在轻度与严重OI的儿童中要稍高。我们的团队开发了一个 使用较大的OI皮质骨标本的方法。使用此技术，发现oi diaphyseal 与正常的小儿骨相比，标本的材料强度降低。此外，我们的团队还成像 使用微型层析成像（Micro-CT）的骨迷你束。这允许检查皮质 骨孔隙度。成像分析提供了微观结构细节，否则这些细节将是未知的。这个数据 有助于我们对骨骼强度和骨折风险的了解。一种评估骨骼的更详细的方法 强度是有限元分析（FEA），这是一种在工程中广泛用于评估应力的计算工具 通过将其分为较小， 更简单的零件（元素）。使用患者特异性的几何信息和OI的准确机械性能 骨，FEA可以模拟长骨的行为并评估断裂风险。研究PI以前具有 通过使用近似重建方法来评估OI中股骨骨折的风险，以在股骨中鞠躬 以及估计的OI骨组织特性。这项工作还显示骨折风险增加，随着增加的增加 鞠躬以及OI严重程度增加。但是，该模型无法验证，因为需要知道 破坏股骨所需的确切力量和位置。开发OI骨的微型FE模型 标本迷你光束将提供OI骨强度建模的首次验证，并回答有关 微观结构，宏观结构，VBMD，临床数据和整个骨骼强度之间的关系。