MRI of Proximal Femur Microarchitecture as a Biomarker of Bone Quality

描述（由申请人提供）：本研究的目的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是否作为骨质量和髋部骨折风险的生物标志物具有附加价值。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，影响了30万美国人，每年的医疗费用高达120亿美元。目前迫切需要一种改进的方法来评估股骨近端骨质量。54%髋部骨折的女性被双能x线吸收仪错误地归类为非骨质疏松症。尽管FRAX计算器、临床因素（例如跌倒风险、不活动）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骨强度的关键决定因素，由于缺乏评估方法，从未在股骨近端进行过体内研究。我们已经取得了技术突破：使用一种新型的26元件接收检测器（提高信噪比），我们已经成功地在体内临床3t MRI扫描仪上对构成股骨近端微结构的单个小梁进行了成像。我们现在将把这个工具应用于临床研究。我们的具体目的（SA）是：1)确定绝经后无骨折妇女股骨近端微结构如何随年龄变化（n = 100）。我们假设较高的年龄与股骨颈较低的皮质厚度、小梁厚度、数量、连通性、板棒比以及股骨近端较低的整体刚度和最终强度有关。2)确定绝经后股骨颈骨折妇女股骨近端微结构紊乱程度（n = 100）。我们假设，与SA1对照组相比，骨折病例将表现出较低的股骨颈皮质厚度、小梁厚度、数量、连通性、钢板与棒比、较低的股骨近端刚度和极限强度。3)确定微结构在FRAX/已知临床危险因素之外的附加价值，用于对有无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逻辑回归模型中加入微结构将提高模型对骨折状态分类的准确性。我们的第二个假设是，微结构、FRAX和临床危险因素的模型比宏观结构、FRAX和临床危险因素的模型更准确地分类骨折状态。如果成功，本研究将：1)为髋部骨折的发病机制和预防手段提供新的见解；2)确定微结构评估是否可以发现目前无法发现的髋部骨折高危患者。如果在纵向研究中得到验证，该MRI测试可作为一种诊断方法

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.