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

摘要 美国65岁以上人口的比例将从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，相关成本约为25.3美元 每年10亿美元。DAMES是一项正在进行的临床试验(NCT03227458)，旨在首次评估- 面骨密度(ABMD)和脱脂体重(Ffm)的变化 肾上腺类固醇脱氢表雄酮(DHEA)单独和联合骨负荷运动(EX)治疗老年人 骨量减少的女性。在女性中提出的荷尔蒙和机械策略代表了一种低成本 替代疗法，以改善骨量，并提供许多其他健康益处 药理学方法。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，而且还有它的微环境，包括骨髓脂肪(BMF)。此入站 DAMES临床试验的辅助研究。在这里，我们建议利用具有良好特征的 受试者、运动训练、临床、实验室和来自女性的成像数据，并添加一小组 对其现有的三个分支(仅限DHEA、EX+安慰剂和EX+DHEA)进行对照，以调查DHEA的影响 应用先进的成像、数值工程和图像分析技术对老年女性的BMF进行治疗和EX 技巧。特别是，我们的目标是在腰椎和髋部确定骨量较低的老年女性。 或中度骨质疏松症：1)DHEA或EX是否导致BMF含量变化；2)BMF含量是否 与基线时的骨强度有关，以及BMF含量的变化是否与 骨强度的变化，评估DHEA或EX对这些关联的影响；以及3)空间 BMF含量变化对DHEA或EX的响应分布。BMF将用化学位移来测量- 基于水-脂分离的磁共振成像，骨强度将用有限元估计 定量计算机断层扫描的建模，以及BMF空间分布的差异 组之间的变化将使用基于体素的形态测量法进行评估。最终，我们将利用 DAMES临床试验将公布新信息，以提高我们对DHEA和EX关于骨量的了解 和质量。在这个辅助方案中，骨质量的纵向评估与骨量的评估 在父母的研究中，已经失去骨量的女性是史无前例的。了解如何 骨质疏松症的治疗-包括运动-对BMF的作用可能导致产生新的治疗方法 骨折风险评估、治疗监测程序和骨丢失治疗。

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.