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型磁共振成像（MRI）测试来确定股骨近端微结构评估是否具有作为骨质和髋部骨折风险生物标志物的附加价值。髋关节或股骨近端骨折是最具破坏性的骨折类型，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体内股骨近端骨质量。54%的髋部骨折妇女被双能X线吸收法误认为非骨质疏松。尽管FRAX计算器、临床因素（例如跌倒风险、不动性）和宏观结构髋关节评估已被证明具有很高的价值，但检测有髋关节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，因此从未在体内股骨近端进行过研究。我们取得了技术突破：使用新颖的26元件接收检测器（这提高了信噪比），我们已经成功地在临床3 T MRI扫描仪上对构成股骨近端微结构的个体骨小梁进行了体内成像。我们现在将在临床研究中应用该工具。我们的具体目标（SA）是：1）确定无骨折的绝经后妇女（n = 100）股骨近端微结构如何随年龄变化。我们假设年龄越大，股骨颈皮质厚度、骨小梁厚度、数量、连接性、板棒比越低，整个股骨近端刚度和极限强度越低。2)确定绝经后股骨颈骨折女性（n = 100）的股骨近端微结构是如何紊乱的。我们假设骨折病例与SA 1对照组相比，股骨颈皮质厚度、骨小梁厚度、数量、连接性、板棒比以及整个股骨近端刚度和极限强度较低。3)确定除FRAX/已知临床风险因素外的微结构的附加值，用于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，将微结构添加到包含FRAX和临床风险因素的基线逻辑回归模型中，将提高骨折状态分类的模型准确性。我们的次要假设是，微结构模型，FRAX，和临床危险因素将更准确的骨折状态的分类比宏观结构模型，FRAX，和临床危险因素。如果成功，这项研究将：1）提供新的见解的发病机制和手段，预防髋部骨折;和2）确定微结构评估是否允许检测高危髋部骨折患者目前逃避检测。如果在纵向研究中得到验证，该MRI测试可用作 额外的研究/临床护理工具，以确定个体是否应该接受治疗，或是否适合临床试验入组。它也可以作为一种新的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.