Determination of Pediatric Osteogenesis Imperfecta Bone Material Properties

项目摘要/摘要 成骨不全(OI)是儿童最常见的遗传性骨脆性疾病，也是最常见的 通常由影响I型胶原产生的基因突变引起，I型胶原是 骨头。OI在儿科整形外科中心很常见，因为受影响的人经常需要整形外科护理 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 对评估OI骨折现有和新的预防和治疗的有效性至关重要。临床 如果有一种更客观、更定量的方法来评估一块骨头的话，决策可以建立在更坚实的基础上 承受载荷的能力。本项目的目标是开发一种OI骨微型有限元模型 BEAMS和一个根据临床骨密度数据预测强度的模型。到目前为止，可用的数据非常少 描述OI中的骨材料特性。我们团队完成的第一个OI骨的特征研究使用了 纳米压痕用于测量小活检或外科标本中微观结构尺度的弹性模量值 Oi的骨头。在该范围内，发现患有严重骨质疏松症的儿童骨组织弹性模数较高 OI与年龄匹配的对照组相比，轻度OI儿童与重度OI儿童的OI略高。我们的团队开发了一种 方法使用较大的OI皮质骨标本。利用这项技术，人们发现OI骨干 与正常的儿科骨相比，标本的材料强度降低。此外，我们团队还拍摄了 使用微型计算机断层扫描(Micro-CT)的骨微梁。这允许对大脑皮质进行检查 骨质疏松。成像分析提供了原本未知的微观结构细节。此数据 有助于我们了解骨骼强度和骨折风险。一种更详细的骨骼评估方法 强度是有限元分析(FEA)，是一种在工程中广泛使用的计算工具，用于评估应力 以及复杂结构内的应变(即内部局部载荷和变形)， 较简单的部件(元素)。使用患者特定的几何信息和准确的OI机械特性 对于骨骼，有限元分析可以模拟长骨的行为并评估骨折风险。研究PI之前已经 用近似重建方法评估OI患者股骨弯曲的骨折风险 以及估计的OI骨组织特性。这项研究还显示，骨折风险随着 鞠躬以及增加OI的严重程度。然而，这个模型不能被验证，因为这需要知道 股骨骨折所需的确切力量大小和位置。OI骨的微观有限元模型的建立 试件微梁将提供OI骨强度建模的第一次验证，并回答以下问题 显微结构、宏观结构、vBMD、临床数据与整体骨强度的关系。

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.