MRI of Proximal Femur Microarchitecture as a Biomarker of Bone Quality

描述(申请人提供)：这项研究的目标是使用一种新的磁共振成像(MRI)测试来确定股骨近端微结构的评估作为骨质量和髋部骨折风险的生物标记物是否具有附加价值。髋部或股骨近端骨折是最具破坏性的骨质疏松性骨折类型，影响30万美国人，每年造成120亿美元的医疗费用。迫切需要一种改进的方法来评估活体股骨近端的骨质量。在髋部骨折的女性中，54%的人被双能x射线骨密度仪误认为没有骨质疏松。尽管FRAX计算器、临床因素(如跌倒风险、静止)和髋关节宏观结构评估已被证明具有很高的价值，但检测有髋部骨折风险的受试者仍然是一个挑战。骨微结构是骨质疏松症疾病定义中包含的骨强度的关键决定因素，由于缺乏评估它的手段，在活体股骨近端从未进行过研究。我们取得了技术突破：使用新型26元接收探测器(提高信噪比)，我们在临床3T磁共振扫描仪上成功地在活体上成像了组成股骨近端微结构的单个小梁。我们现在将把这个工具应用到临床研究中。我们的具体目标(SA)是：1)确定绝经后未骨折妇女(n=100)股骨近端微结构如何随年龄变化。我们假设较高的年龄将与较低的股骨颈皮质厚度、骨小梁厚度、数量、连接性、板棒比以及较低的股骨近端整体刚度和极限强度相关。2)确定绝经后股骨颈骨折患者股骨近端微结构的紊乱情况(n=100)。我们假设骨折病例的股骨颈皮质厚度、骨小梁厚度、数量、连接性、板棒比以及股骨近端整体硬度和极限强度均低于SA1对照组。3)确定微结构的附加值，超越FRAX/已知的临床危险因素，对无髋部骨折和有髋部骨折的受试者进行分类。我们的主要假设是，在包含FRAX和临床危险因素的基线Logistic回归模型中加入微架构将提高骨折状态分类的模型准确性。我们的第二个假设是，微结构、FRAX和临床危险因素模型对骨折状态的分类比宏观结构、FRAX和临床危险因素模型更准确。如果成功，这项研究将：1)为髋部骨折的发病机制和预防方法提供新的见解；2)确定微架构评估是否可以检测目前逃脱检测的高危髋部骨折患者。如果在纵向研究中得到证实，这项MRI测试可以用作 其他研究/临床护理工具，以确定个人是否应该接受治疗，或是否适合临床试验登记。它也可以作为一种新颖的方法来监测不同干预措施对股骨近端微结构和强度的影响。

DESCRIPTION (provided by applicant): The goal of this study is to use a novel magnetic resonance imaging (MRI) test to determine if assessment of proximal femur microarchitecture has added value as a biomarker of bone quality and hip fracture risk. Hip or proximal femur fracture is the most devastating type of osteoporotic fracture, affecting 300,000 Americans and accounting for $12 billion in healthcare costs annually. There is a critical need for an improved method to assess proximal femur bone quality in vivo. 54% of women who suffer hip fractures are misclassified by dual- energy x-ray absorptiometry as not osteoporotic. And though the FRAX calculator, clinical factors (e.g. fall risk, immobility), and macrostructural hip assessment have proven highly valuable, the detection of subjects at risk for hip fracture remains a challenge. Bone microarchitecture, a key determinant of bone strength included in the disease definition of osteoporosis, has never been studied in the proximal femur in vivo because of a lack of means to assess it. We have achieved a technical breakthrough: using a novel 26 element receive detector (which boosts signal-to-noise ratio), we have successfully imaged individual trabeculae composing proximal femur microarchitecture on a clinical 3 T MRI scanner in vivo. We will now apply this tool in a clinical study. Our specific aims (SA) are to: 1) Determine how proximal femur microarchitecture changes with aging in post- menopausal women without fracture (n = 100). We hypothesize that higher age will correlate with lower femoral neck cortical thickness, trabecular thickness, number, connectivity, plate-to-rod ratio, and lower whole proximal femur stiffness and ultimate strength. 2) Determine how proximal femur microarchitecture is deranged in post-menopausal women with femoral neck fracture (n = 100). We hypothesize that fracture cases will demonstrate lower femoral neck cortical thickness, trabecular thickness, number, connectivity, plate-to-rod ratio, and lower whole proximal femur stiffness and ultimate strength compared to SA1 controls. 3) Determine the added value of microarchitecture, beyond FRAX/known clinical risk factors, for classifying subjects without and with hip fracture. Our main hypothesis is that adding microarchitecture to a baseline logistic regression model containing FRAX and clinical risk factors will improve model accuracy for classification of fracture status. Our secondary hypothesis is that a model of microarchitecture, FRAX, and clinical risk factors will be more accurate for classification of fracture status than a model of macrostructure, FRAX, and clinical risk factors. If successful, this study will: 1) provid new insight into the pathogenesis and means for prevention of hip fracture; and 2) determine whether microarchitectural assessment allows detection of high-risk hip fracture patients who currently escape detection. If validated in a longitudinal study, this MRI test could be used as an additional research/clinical care tool to determine whether an individual should or should not receive therapy, or be suitable for clinical trial enrollment. It could also be used as a novel too to monitor the effects of different interventions on proximal femur microarchitecture and strength.