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.

摘要