Effects of DHEA and exercise on bone marrow fat in postmenopausal women

DHEA 和运动对绝经后妇女骨髓脂肪的影响

• 批准号: 10438681
• 负责人: Julio Carballido-Gamio
• 金额: $ 39.29万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10438681
• 关键词: Adrenal Glands; Aging; Ancillary Study; Androgens; Anterior; Bone Density; Bone Marrow; Chemicals; Clinical; Clinical Trials; Data; Elderly; Elements; Engineering; Estrogen Therapy; Estrogens; Exercise; Fatty acid glycerol esters; Financial Hardship; Finite Element Analysis; Fracture; Generations; Gonadal Steroid Hormones; Health Benefit; Hip region structure; Hormonal; Image; Image Analysis; Imaging Techniques; Laboratories; Lead; Linear Regressions; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Maps; Measures; Mechanics; Mediating; Menopause; Modeling; Monitor; Musculoskeletal; Neck; Older Population; Osteopenia; Osteoporosis; Parents; Persons; Pharmacology; Placebos; Population; Postmenopause; Procedures; Protons; Risk Assessment; Scanning; Societies; Spatial Distribution; Steroids; Techniques; Testosterone; Texture; Time; Tissues; Vertebral column; Water; Woman; X-Ray Computed Tomography; alternative treatment; arm; base; bone; bone loss; bone mass; bone quality; bone strength; cohort; cost; dehydroepiandrosterone; exercise training; fracture risk; imaging biomarker; improved; in vivo imaging; morphometry; novel strategies; older women; osteoporosis with pathological fracture; placebo group; primary outcome; prohormone; response; spine bone structure; treatment response

ABSTRACT The proportion of the U.S. population older than 65 years will increase from 12.7% in 2000 to 20.3% in 2050, and the number of fractures is expected to exceed 3 million by 2025 with associated costs in the order of $25.3 billion per year. DAMES is an ongoing clinical trial (NCT03227458) that aims to assess –for the first time– changes in areal bone mineral density (aBMD) and fat-free mass (FFM) in response to therapy with the adrenal steroid dehydroepiandrosterone (DHEA) alone and combined with bone-loading exercise (EX) in older women with bone loss. The hormonal and mechanical strategies proposed in DAMES represent a low-cost alternative treatment to improve bone quantity with a number of other health benefits not afforded by typical pharmacological approaches. However, bone strength –the main determinant of bone fracture– is a function of not only BMD and microstructure, but also of its microenvironment, including bone marrow fat (BMF). This in an ancillary study to the DAMES clinical trial. Here, we propose to leverage the well-characterized cohort of subjects, exercise training, clinical, laboratory and imaging data from DAMES, and add a small group of controls to its three existing arms (DHEA only, EX+Placebo, and EX+DHEA) to investigate the effects of DHEA therapy and EX on BMF in older women using advanced imaging, numerical engineering, and image analysis techniques. In particular, we aim to determine in the lumbar spine and hip of older women with low bone mass or moderate osteoporosis: 1) whether DHEA or EX leads to changes in BMF content; 2) whether BMF content is associated with bone strength at baseline, and whether changes in BMF content are associated with changes in bone strength, evaluating the impact of DHEA or EX on these associations; and 3) the spatial distribution of changes in BMF content in response to DHEA or EX. BMF will be measured with chemical shift– based water-fat separation magnetic resonance imaging, bone strength will be estimated with finite element modeling from quantitative computed tomography scans, and differences in the spatial distribution of BMF changes between groups will be assessed using voxel-based morphometry. Ultimately, we will leverage the DAMES clinical trial to unveil new information to improve our understanding of DHEA and EX on bone quantity and quality. The longitudinal assessments of bone quality in this ancillary proposal, with those of bone quantity in the parent study, in women who have already lost bone mass is unprecedented. Understanding how osteoporosis treatments –including exercise– act on BMF could lead to the generation of novel approaches for fracture risk assessment, procedures for therapy monitoring, and treatments for bone loss.

抽象的 65岁以上的美国人口比例将从2000年的12.7％增加到2050年的20.3％ 到2025年，骨折的数量预计将超过300万，相关费用为25.3美元。 每年十亿。 Dames是一项正在进行的临床试验（NCT03227458），旨在首次评估 - 响应于治疗的情况，面积骨矿物质密度（ABMD）和无脂肪质量（FFM）的变化 单独的肾上腺类固醇脱氢表甲酮（DHEA），并与较老的骨负荷运动（EX）结合 骨丢失的妇女。在坝中提出的马和机械策略代表低成本 替代治疗可改善骨骼数量，并获得许多其他健康益处 药理方法。但是，骨骼强度 - 骨折的主要确定 - 是 不仅是BMD和微观结构，还具有其微环境，包括骨髓脂肪（BMF）。这是 对DAMES临床试验的辅助研究。在这里，我们建议利用良好的人群 受试者，运动训练，临床，实验室和来自dames的成像数据，并添加一小组 控制其三个现有臂（仅DHEA，EX+安慰剂和Ex+DHEA）来研究DHEA的影响 使用高级成像，数值工程和图像分析的老年妇女的BMF治疗和EX 技术。特别是，我们旨在确定骨骼低的老年妇女的腰椎和臀部 或中度骨质疏松症：1）DHEA还是EX导致BMF含量的变化； 2）BMF内容是否 与基线时的骨骼强度有关，以及BMF含量的变化是否与 骨骼强度的变化，评估DHEA或EX对这些关联的影响； 3）空间 响应DHEA或EX的BMF含量变化的分布。 BMF将通过化学移位来测量 基于水脂的分离磁共振成像，将用有限元估计骨强度 从定量计算机断层扫描和BMF空间分布的差异进行建模 组之间的变化将使用基于体素的形态学评估。最终，我们将利用 DAMES临床试验以公布新信息，以提高我们对DHEA的理解和Ex骨骼数量 和质量。该辅助提案中骨质质量的纵向评估，骨骼数量的纵向评估 在父母的研究中，在已经失去骨骼质量的女性中是前所未有的。了解如何 骨质疏松症治疗（包括锻炼）对BMF的作用可能导致新的方法的新方法 断裂风险评估，治疗监测程序以及骨质流失的治疗方法。