MRI of Proximal Femur Bone Quality for Monitoring Short-Term Response to Osteoporosis Therapy

近端股骨骨质量 MRI 用于监测骨质疏松症治疗的短期反应

• 批准号: 10615628
• 负责人: Gregory Chang
• 金额: $ 49.42万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-05-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10615628
• 关键词: 3-Dimensional; Acceleration; Alendronate; Ankle; Biological Markers; Biopsy; Bone Density; Bone Diseases; Bone Tissue; Caring; Clinical; Clinical Trials; Deterioration; Diet; Discrimination; Disease; Distal; Drug Combinations; Dual-Energy X-Ray Absorptiometry; Early treatment; Epidemic; Exercise; Femur; Finite Element Analysis; Foundations; Fracture; Goals; Head; Hip Fractures; Hip region structure; Image; Incidence; Individual; Intervention; Ionizing radiation; Knowledge; Magnetic Resonance Imaging; Monitor; Multicenter Studies; Neck; Operative Surgical Procedures; Osteoporosis; Outcome; Peripheral; Pharmaceutical Preparations; Public Health; Radial; Regimen; Reproducibility; Resolution; Risk Reduction; Rod; Sample Size; Scanning; Signal Transduction; Site; Societies; Spinal Fractures; Surrogate Endpoint; Testing; Therapeutic; Thick; United States; United States Food and Drug Administration; Validation; Work; World Health Organization; Wrist; X-Ray Computed Tomography; active comparator; bone; bone fragility; bone imaging; bone mass; bone quality; bone strength; case control; cost; detector; digital; follow-up; fracture risk; fragility fracture; hip bone; imaging study; improved; in vivo; mechanical properties; mortality; novel therapeutics; osteoporosis with pathological fracture; placebo controlled trial; prevent; recruit; response; serial imaging; skeletal; standard of care; tibia; treatment response; trial comparing

Project Summary Osteoporosis, a disease of bone fragility predisposing an individual to fracture, is a major public health problem. Over two million osteoporotic fractures occur per year, resulting in greater than $17 billion in direct annual costs for fracture care. Hip fractures account for 70% of these costs as they have the most devastating clinical consequences; the mortality rate in the first year after hip fracture is as high as 24%. Osteoporosis is caused by reduced bone mass and deterioration in bone microarchitecture, which together weaken bone. Several bone-strengthening drugs are available to reduce fracture risk, and in placebo-controlled trials, these drugs have different efficacies for fracture risk reduction depending on the skeletal site. Unfortunately, it is unknown which drug or drug combination works best to reduce overall fracture risk and in particular fracture risk in the hip. This gap in knowledge exists because clinical trialists lack an endpoint in the hip that would permit superiority trials -- aimed at determining the best bone-strengthening drug or regimen -- to be performed with feasible costs, sample sizes, and follow-up times. Currently, fracture and bone mineral density (BMD) are the Food and Drug Administration (FDA)-approved endpoints used in clinical trials, but fractures have a low incidence and BMD changes very slowly. In addition, changes in BMD after therapy only reflect 4-52% of the variance in fracture risk reduction. As a result, tens of thousands of subjects are necessary to power head-to- head, active comparator trials aimed at demonstrating the superiority of one agent over another. Bone microarchitecture has not routinely been monitored in osteoporosis clinical trials, even though its deterioration is included in the World Health Organization disease definition of osteoporosis. We have recently demonstrated the feasibility of imaging hip microarchitecture in vivo using a clinical magnetic resonance imaging (MRI) scanner. We have shown that assessment of hip microarchitectural parameters (via digital and volumetric topological analysis) and strength (via finite element analysis) is reproducible and provides information about bone quality and fracture risk that is not captured by DXA. Unlike computed tomography (CT), MRI can image at a resolution high enough to depict bone microarchitecture and does not administer ionizing radiation, which is ideal for short-term serial imaging. And unlike prior microarchitectural imaging studies, which have been performed in the distal radius or distal tibia using either MRI or high-resolution peripheral quantitative computed tomography (HR-pQCT), we can now image bone microarchitecture in the hip, the most devastating fracture site. In this study, we now aim to demonstrate the value of the MRI test, beyond the value of DXA, for monitoring short-term therapy response in the hip. This work will lay the foundation for the use of hip microarchitecture and strength, in addition to hip BMD, as a biomarker of treatment response in multicenter studies and as a potential surrogate endpoint to reduce sample sizes and accelerate osteoporosis clinical trials. This will reduce the burden of osteoporotic fractures on society.

项目摘要 骨质疏松症是一种易使个体骨折的骨脆性疾病，是一种主要的公共卫生问题， 问题.每年发生超过200万例骨质疏松性骨折，导致超过170亿美元的直接经济损失。 每年的骨折护理费用。髋部骨折占这些费用的70%，因为它们具有最具破坏性的 临床后果;髋部骨折后第一年的死亡率高达24%。骨质疏松症是 由骨量减少和骨微结构恶化引起，它们共同削弱了骨骼。 有几种强化骨骼的药物可用于降低骨折风险，在安慰剂对照试验中，这些药物 药物对降低骨折风险的功效因骨骼部位而异。不幸的是 不知道哪种药物或药物组合最能降低整体骨折风险，特别是骨折风险。 臀部的风险。存在这种知识差距是因为临床试验者缺乏髋关节终点， 允许进行优效性试验--旨在确定最佳的骨强化药物或方案 具有可行的成本、样本量和随访时间。目前，骨折和骨矿物质密度（BMD）是 食品和药物管理局（FDA）批准的临床试验中使用的终点，但骨折具有低 发病率和BMD变化非常缓慢。此外，治疗后BMD的变化仅反映了4-52%的 骨折风险降低的差异。因此，需要数万名受试者来进行头对- 首项活性对照试验，旨在证明一种药物优于另一种药物。骨 在骨质疏松症临床试验中，尽管微结构的恶化， 被列入世界卫生组织对骨质疏松症的疾病定义。我们最近 证明了使用临床磁共振在体内对髋关节微结构进行成像的可行性 成像（MRI）扫描仪。我们已经表明，髋关节微结构参数的评估（通过数字和 体积拓扑分析）和强度（通过有限元分析）是可再现的，并提供 DXA无法捕获的有关骨质和骨折风险的信息。与计算机断层扫描不同 (CT)MRI可以以足够高的分辨率成像以描绘骨微结构，并且不施用 电离辐射，这是短期连续成像的理想选择。与先前的微结构成像不同 使用MRI或高分辨率在桡骨远端或胫骨远端进行的研究 外周定量计算机断层扫描（HR-pQCT），我们现在可以成像骨微结构在 髋关节，最具破坏性的骨折部位。在这项研究中，我们现在的目标是证明MRI测试的价值， 超过DXA的值，用于监测髋关节的短期治疗反应。这项工作将奠定 使用髋关节微结构和力量的基础，除了髋关节BMD，作为生物标志物 多中心研究中的治疗反应，并作为潜在的替代终点，以减少样本量， 加速骨质疏松症的临床试验。这将减轻艾滋病对社会造成的负担。