Translation of Hip Microarchitectural Assessment Technology to the Clinic to Diagnose Glucocorticoid-Induced Osteoporosis

项目摘要 糖皮质激素性骨质疏松症(GIO)是最常见的继发性骨质疏松症。 与不使用糖皮质激素的人相比，使用糖皮质激素的人患各种脆性骨折的风险更高。有效 存在可以降低GIO骨折风险的药物。然而，用于诊断的标准护理方法 骨质疏松--面骨密度(BMD)和骨密度的双能X射线吸收测量法(DXA) FRAX-低估了糖皮质激素使用者的骨折风险。因此，GIO被低估了，而且- 治疗过了。骨质疏松症患者骨密度与骨折风险之间缺乏相关性意味着糖皮质激素呈负相关 影响骨骼质量和强度的方式不会被BMD捕获。最近，我们论证了 在临床3T磁共振扫描仪上活体成像股骨近端微结构。我们已经证明了这样的 微结构评估是可重现的，并提供未捕获的有关骨质量的信息 由DXA提供。我们现在将利用独特的放射学资源(新的股骨近端成像测试 微体系结构)和风湿病(全国狼疮中心大量使用糖皮质激素的患者群体 以临床护理和研究著称)。在两个具体目标中，我们将确定：1)增加的 新型MRI测试Beyond DXA在灵敏监测骨骼纵向有害变化方面的价值 股骨近端的微结构和强度，是FRAX和A 临床上重要的骨折部位和2)股骨近端微结构评估的价值 DXA/FRAX用于区分有骨折的GIO患者和无骨折的对照组。要实现 目的1、我们将招募40名新开糖皮质激素的狼疮患者和40名管理的狼疮患者 不含糖皮质激素(两者均为标准护理)。我们假设，在调整了面积骨密度和 疾病严重程度，糖皮质激素使用者将在12个月内表现出股骨颈皮质的有害变化 厚度、骨小梁厚度、间距、数量、连通性和整个股骨的刚度较大 比对照组的大小。为了实现目标2，我们将单独招聘138名长期(&>12个月)， 狼疮患者应用糖皮质激素治疗(41例合并骨折，97例未合并骨折)。我们将建立多元的， Logistic回归模型预测骨折状态并比较不同模型的准确性(DXA， FRAX、DXA/FRAX加上微结构测量)用于预测骨折状态。我们假设 在DXA/FRAX中添加微架构措施将提高预测骨折的模型精度 与单独使用DXA/FRAX相比的状态。该项目的成功实施将证明 检测目前神秘的、骨骼脆弱的糖皮质激素使用者，他们需要骨质疏松症治疗。通过 提高临床医生精准诊断GIO能力，提高临床医生精准治疗能力 GIO或招募患者参加骨强化疗法的临床试验。这将减轻...的负担 糖皮质激素引起的社会骨折。

Project Summary Glucocorticoid-induced osteoporosis (GIO) is the most common secondary form of osteoporosis. Glucocorticoid users are at a higher risk for all types of fragility fractures compared to non-users. Effective medications exist that can reduce fracture risk in GIO. However, standard-of-care methods used to diagnose osteoporosis – dual-energy x-ray absorptiometry (DXA) estimation of areal bone mineral density (BMD) and FRAX – underestimate fracture risk in glucocorticoid users. As a result, GIO is under-diagnosed and under- treated. The lack of a relationship between BMD and fracture risk in GIO means that glucocorticoids negatively affect bone quality and strength in a way not captured by BMD. Recently, we demonstrated the feasibility of imaging proximal femur microarchitecture in vivo on a clinical 3T MRI scanner. We have shown that such microarchitectural assessment is reproducible and provides information about bone quality that is not captured by DXA. We will now leverage the unique resources of Radiology (novel imaging test of proximal femur microarchitecture) and Rheumatology (large glucocorticoid-using patient population at a lupus center nationally known for clinical care and research) at our institution. In two specific aims, we will determine: 1) the added value of the novel MRI test, beyond DXA, for sensitively monitoring longitudinal, detrimental changes in bone microarchitecture and strength in the proximal femur, a standard site of BMD assessment used in FRAX and a clinically important fracture site and 2) the value of proximal femur microarchitectural assessment, beyond that of DXA/FRAX, for the discrimination of GIO subjects with fracture from controls without fracture. To achieve Aim 1, we will recruit 40 lupus patients newly prescribed glucocorticoids and 40 lupus patients managed without glucocorticoids (both as standard-of-care). We hypothesize that after adjusting for areal BMD and disease severity, glucocorticoid users will demonstrate 12 month detrimental changes in femoral neck cortical thickness, trabecular thickness, separation, number, connectivity, and whole femur stiffness of greater magnitude than in controls. To achieve Aim 2, we will separately recruit 138 long-term (> 12 month), glucocorticoid using lupus patients (expect 41 with fracture, 97 without fracture). We will build multivariate, logistic regression models predictive of fracture status and compare the accuracy of different models (DXA, FRAX, DXA/FRAX plus microarchitectural measures) for prediction of fracture status. We hypothesize that the addition of microarchitectural measures to DXA/FRAX will improve model accuracy for prediction of fracture status compared to DXA/FRAX alone. Successful execution of this project will demonstrate the feasibility of detecting currently occult, skeletally fragile glucocorticoid users who are in need of osteoporosis therapy. By improving clinicians' ability to accurately diagnose GIO, we will improve clinicians' ability to accurately treat GIO or enroll patients in clinical trials for bone-strengthening therapies. This will reduce the burden of glucocorticoid-induced fractures on society.