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: 9808982
• 负责人: JESSICA M FRITZ
• 金额: $ 7.65万
• 依托单位: MARQUETTE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-01 至 2020-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9808982
• 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; Effectiveness; Elements; Engineering; Etiology; Failure; Femoral Fractures; Femur; Finite Element Analysis; Fracture; Goals; Heritability; 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; X-Ray Computed Tomography; base; bone; bone fragility; bone imaging; bone mass; bone strength; clinical decision-making; computerized tools; cortical bone; 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.

项目总结/摘要 成骨不全（OI）是儿童中最常见的遗传性骨脆性疾病， 通常由影响I型胶原蛋白产生的基因突变引起，I型胶原蛋白是胶原蛋白的主要蛋白质， 骨头由于受影响的个体经常需要骨科护理，因此OI在儿科骨科中心很常见 在他们成长的岁月里。长骨骨折在OI儿童中很常见。骨强度评估是 在评价现有和新的预防和治疗OI骨折的有效性方面至关重要。临床 如果有一种更客观、定量的方法来评估骨骼的健康状况， 承受负荷的能力。本课题的目的是建立一个骨质疏松症骨微生物力学模型 梁和模型来预测强度从临床骨矿物质密度数据。只有很少的数据可用于 描述OI中的骨材料特性。我们的团队对OI骨进行的第一次表征研究使用了 纳米压痕法测量小活检或手术标本微观结构尺度的弹性模量 的骨头。在该范围内，发现骨组织的弹性模量在患有严重骨质疏松症的儿童中更高。 OI与年龄匹配的对照组相比，轻度OI儿童略高于重度OI儿童。我们的团队开发了一个 使用较大的OI皮质骨样本的方法。使用这项技术，发现OI骨干 与正常儿童骨相比，样本的材料强度降低。此外，我们的团队还拍摄了 使用微型计算机断层扫描（micro-CT）的骨微束。这允许检查皮质 骨质疏松成像分析提供了微观结构的细节，否则将是未知的。该数据 有助于我们了解骨强度和骨折风险。一种更详细的骨评估方法 强度是有限元分析（FEA），一种广泛用于工程中评估应力的计算工具 和菌株（即，内部局部载荷和变形）， 更简单的部分（元素）。使用患者特定的几何信息和OI的准确机械特性 有限元分析可以模拟长骨的行为并评估骨折风险。研究PI此前已 通过使用近似重建方法在股骨中产生弯曲，评估了OI中的股骨骨折风险 沿着估计的OI骨组织特性。这项工作还表明，随着骨折风险的增加， 弯曲以及OI严重性增加。然而，该模型无法验证，因为这需要了解 股骨断裂所需的精确力量大小和位置。开发OI骨的微观有限元模型 样本微型梁将提供OI骨强度建模的首次验证，并回答以下问题 微观结构、宏观结构、vBMD、临床数据和全骨强度之间的关系。