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

将髋关节微结构评估技术应用于临床诊断糖皮质激素引起的骨质疏松症

• 批准号: 9759776
• 负责人: Gregory Chang
• 金额: $ 51.98万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-12 至 2021-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9759776
• 关键词: Address; Adult; Affect; Age; Biopsy; Bone Density; Classification; Clinic; Clinical; Clinical Research; Clinical Trials; Detection; Deterioration; Diagnosis; Diagnostic Procedure; Discrimination; Disease; Distal; Dose; Dual-Energy X-Ray Absorptiometry; Elements; Enrollment; Femur; Finite Element Analysis; Fracture; Glucocorticoids; Goals; Hip Fractures; Hip region structure; Image; Individual; Institution; Logistic Regressions; Lupus; Magnetic Resonance Imaging; Measures; Methods; Modeling; Monitor; Morbidity - disease rate; Neck; Osteoporosis; Patients; Peripheral; Pharmaceutical Preparations; Physicians; Radial; Radiology Specialty; Recommendation; Reproducibility; Research; Research Design; Resolution; Resources; Rheumatology; Risk; Risk Factors; Scanning; Severities; Severity of illness; Site; Societies; Steroids; Technology; Technology Assessment; Testing; Thick; Translations; Vision; World Health Organization; X-Ray Computed Tomography; accurate diagnosis; base; bone; bone imaging; bone quality; bone strength; clinical care; clinical research site; cohort; fracture risk; fragility fracture; high risk; improved; in vivo; mortality; negative affect; novel; patient population; predictive modeling; recruit; skeletal; standard of care; tibia; tool; translational study

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.

项目概要 糖皮质激素引起的骨质疏松症（GIO）是最常见的继发性骨质疏松症。 与非使用者相比，糖皮质激素使用者发生各种类型脆性骨折的风险更高。有效的 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 骨质疏松症 – 双能 X 射线吸收测定法 (DXA) 估算面积骨矿物质密度 (BMD) 和 FRAX – 低估糖皮质激素使用者的骨折风险。因此，GIO 的诊断和诊断不足 治疗。 BMD 与 GIO 骨折风险之间缺乏相关性，这意味着糖皮质激素对 GIO 患者有负面影响 以 BMD 未捕获的方式影响骨骼质量和强度。最近，我们论证了以下方案的可行性： 在临床 3T MRI 扫描仪上对近端股骨微结构进行体内成像。我们已经证明，这样的 微结构评估是可重复的，并提供未捕获的有关骨质量的信息 通过 DXA。我们现在将利用放射学的独特资源（股骨近端的新型成像测试 微架构）和风湿病学（全国狼疮中心大量使用糖皮质激素的患者群体 我们机构以临床护理和研究而闻名）。在两个具体目标中，我们将确定：1）添加的 超越 DXA 的新型 MRI 测试对于灵敏监测骨骼纵向有害变化的价值 股骨近端的微结构和强度，这是 FRAX 中使用的 BMD 评估的标准部位， 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，用于区分骨折的 GIO 受试者与未骨折的对照组。达到 目标 1，我们将招募 40 名新开糖皮质激素的狼疮患者和 40 名接受管理的狼疮患者 不含糖皮质激素（两者均作为护理标准）。我们假设调整面积 BMD 后 根据疾病的严重程度，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、小梁厚度、分离、数量、连接性和整个股骨刚度 幅度大于对照。为了实现目标2，我们将单独招募138名长期（> 12个月）， 使用糖皮质激素的狼疮患者（预计 41 名骨折患者，97 名无骨折患者）。我们将建立多元、 预测骨折状态的逻辑回归模型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 中添加微结构测量将提高断裂预测的模型准确性 与单独 DXA/FRAX 相比的状态。该项目的成功实施将证明该项目的可行性 检测当前需要骨质疏松症治疗的隐秘、骨骼脆弱的糖皮质激素使用者。经过 提高临床医生准确诊断GIO的能力，我们将提高临床医生准确治疗的能力 GIO 或招募患者参加骨强化疗法的临床试验。这将减轻负担 糖皮质激素引起的社会骨折。