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: 10225870
• 负责人: Julio Carballido-Gamio
• 金额: $ 40.69万
• 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/10225870
• 关键词: Adrenal Glands; Aging; Ancillary Study; Androgens; Anterior; Biological; 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; 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

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 美国65岁以上人口比例将从2000年的12.7%增加到2050年的20.3%， 预计到 2025 年，骨折数量将超过 300 万，相关费用约为 25.3 美元 DAMES 是一项正在进行的临床试验 (NCT03227458)，旨在首次评估 - 面骨矿物质密度 (aBMD) 和去脂体重 (FFM) 因治疗而变化 老年人单独使用肾上腺类固醇脱氢表雄酮 (DHEA) 并结合骨负荷运动 (EX) DAMES 提出的激素和机械策略代表了一种低成本的方法。 改善骨量的替代疗法，具有典型疗法无法提供的许多其他健康益处 然而，骨强度（骨折的主要决定因素）是以下因素的函数： 不仅是骨密度和微观结构，还有它的微环境，包括骨髓脂肪（BMF）。 这是 DAMES 临床试验的一项辅助研究，我们建议利用特征明确的队列。 来自 DAMES 的受试者、运动训练、临床、实验室和影像数据，并添加一小组 对其现有的三个组（仅 DHEA、EX+安慰剂和 EX+DHEA）进行控制，以研究 DHEA 的效果 使用先进成像、数值工程和图像分析对老年女性进行 BMF 治疗和 EX 特别是，我们的目标是确定骨量低的老年女性的腰椎和臀部。 或中度骨质疏松：1）DHEA或EX是否会导致BMF含量变化；2）BMF含量是否变化； 与基线时的骨强度相关，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； BMF 含量随 DHEA 或 EX 变化的分布将通过化学位移来测量。 基于水脂分离磁共振成像，利用有限元估计骨强度 定量计算机断层扫描建模以及 BMF 空间分布的差异 最终，我们将利用基于体素的形态测量来评估组之间的变化。 DAMES 临床试验揭示新信息，以提高我们对 DHEA 和 EX 对骨量影响的了解 本辅助提案中对骨质量和骨量的纵向评估。 在家长研究中，对于已经失去骨量的女性来说，这是前所未有的了解。 骨质疏松症治疗（包括运动）对 BMF 的作用可能会产生新的治疗方法 骨折风险评估、治疗监测程序以及骨质流失治疗。