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

项目摘要 糖皮质激素诱导的骨质疏松症（GIO）是骨质疏松症最常见的继发性形式。 糖皮质激素使用者与非使用者相比，所有类型脆性骨折的风险都更高。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 骨质疏松症-双能X线吸收测定法（DXA）评估骨密度（BMD）和 FRAX -低估糖皮质激素使用者的骨折风险。因此，GIO诊断不足， 治疗。骨密度和GIO骨折风险之间缺乏相关性意味着糖皮质激素对GIO患者的骨密度和骨折风险有负面影响。 影响骨质量和骨强度的方式不被BMD捕获。最近，我们证明了 在临床3 T MRI扫描仪上对体内股骨近端微结构进行成像。我们已经证明， 微结构评估是可重现的，并提供了未捕获的骨质信息 DXA的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 微结构）和流变学（全国狼疮中心的大量糖皮质激素使用患者群体 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）增加 新的MRI测试的价值，超过DXA，灵敏地监测纵向，有害的变化，骨 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， 临床重要骨折部位和2）股骨近端微结构评估的价值，除此之外 用DXA/FRAX对GIO骨折组和对照组进行区分。实现 目的1，我们将招募40名狼疮患者新处方糖皮质激素和40名狼疮患者管理 无糖皮质激素（均为标准治疗）。我们假设在调整了区域BMD和 疾病严重程度，糖皮质激素使用者将显示12个月股骨颈皮质骨的有害变化 厚度、骨小梁厚度、分离度、数量、连通性和整个股骨刚度越大， 比对照组大。为了实现目标2，我们将分别招募138名长期（> 12个月）， 使用糖皮质激素的狼疮患者（除41例骨折外，97例无骨折）。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加微结构测量）用于预测骨折状态。我们假设 在DXA/FRAX中增加微结构测量将提高模型预测裂缝的准确性 与单独DXA/FRAX相比。该项目的成功实施将证明 检测目前需要骨质疏松治疗的隐匿性、神经脆弱的糖皮质激素使用者。通过 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GIO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 糖皮质激素导致的骨折

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.