Bone Marrow Adiposity, Bone and Body Composition

骨髓肥胖、骨骼和身体成分

• 批准号: 7766336
• 负责人: Xiaojuan Li
• 金额: $ 55.42万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-01 至 2013-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7766336
• 关键词: Abdomen; Abdominal Mass; Address; Adipocytes; Adipose tissue; Affect; Age; Aging; Ancillary Study; Animals; Area; Body Composition; Body fat; Bone Density; Bone Marrow; Bone Resorption; Cell model; Clinical; Data; Elderly; Environment; Fatty acid glycerol esters; Filler; Fracture; Glucocorticoids; Hip region structure; Hormone replacement therapy; Human; Infiltration; Knowledge; Link; Magnetic Resonance Spectroscopy; Marrow; Measurement; Measures; Mesenchymal Stem Cells; Muscle; Neck; Obesity; Observational Study; Osteoblasts; Osteoclasts; Osteogenesis; Osteoporosis; Participant; Pathway interactions; Pharmaceutical Preparations; Predisposition; Prevalence; Principal Investigator; Process; Recording of previous events; Reporting; Research; Research Project Grants; Risk; Role; Scanning; Site; Spinal Fractures; Stem cells; Testing; Thigh structure; Translating; Vertebral Bone; Vertebral column; Visceral; Woman; X-Ray Computed Tomography; abdominal fat; aging gene; autocrine; base; bisphosphonate; bone; bone imaging; bone loss; bone preservation; bone turnover; cohort; cost; density; design; insight; meetings; novel strategies; novel therapeutic intervention; osteogenic; paracrine; prevent; public health relevance; spine bone structure; subcutaneous; substantia spongiosa

DESCRIPTION (provided by principal investigator): Marrow adiposity increases with age and osteoporosis. Although previously thought to function as a neutral filler in the marrow cavity, recent studies suggest that marrow fat accumulation is instead part of dynamic processes that also affect bone density and size. Animal and cell models suggest that marrow adiposity is linked to mesenchymal stem cell (MSC) allocation in the marrow. With aging, MSC allocation favors adipocytes over osteoblasts, leading to reduced bone formation with increased marrow fat. A better understanding of this process in humans could translate into new approaches to bone preservation, promoting MSC allocation towards osteoblasts. Marrow fat may also have direct effects on the bone marrow microenvironment. Similar to other fat depots, marrow fat secretes factors that could potentially affect bone turnover. With non-invasive measurements of marrow fat now possible using magnetic resonance spectroscopy (MRS), small studies have reported correlations between marrow fat and areal bone density by dual energy x-ray absorptiometry (DXA). Studies are needed to characterize associations between marrow fat and bone parameters available with computed tomography (CT), including cortical and trabecular bone density and bone size. In addition, studies are needed to determine if marrow fat is associated with the size of other fat depots to assess whether marrow fat is controlled through mechanisms that are similar or distinct from other fat depots. The effect of bone-active medications on marrow fat can provide additional insight. To address these research questions, we propose a study that will include MRS measurements of vertebral marrow adiposity combined with a full characterization of bone parameters and other fat depots in 300 participants in the Age Gene/Environment Susceptibility-Reykjavik Study (AGES-Reykjavik), a cohort of older adults. As an ancillary study, this research project can take advantage of the already planned CT measurements in AGES-Reykjavik, reducing project costs substantially. This project will determine whether marrow adiposity measured by MRS is associated with cortical and trabecular bone density and bone size at the spine, hip and femoral shaft measured by CT; with areal bone density of the hip and spine from DXA; and with bone turnover markers. Using DXA and CT measurements, the study will determine whether the size of total fat mass, abdominal visceral and subcutaneous fat depots, and the degree of fatty infiltration of muscle at mid-thigh correlate with marrow fat. The study will also evaluate the effect of glucocorticoids, hormone replacement therapy and bisphosphonates on marrow fat in a subset of women (N=45) selected from those who report current use and will assess the associations between marrow fat and fracture risk, including prevalent vertebral fractures and clinical fractures reported during the previous 12 years. This study promises to substantially advance our knowledge of the role of marrow fat in relation to bone and other fat depots, advances that may translate into new therapeutic approaches promoting the osteogenic potential of MSCs. PUBLIC HEALTH RELEVANCE: This study will determine if higher levels of fat in the bone marrow in older adults are associated with reduced bone density and size, and will assess the relationship between marrow fat and other types of body fat, including total and abdominal fat. A better understanding of the process underlying the accumulation of marrow fat with age and osteoporosis may provide new targets for treatments to prevent bone loss.

描述（由主要研究者提供）：骨髓肥胖随着年龄和骨质疏松症的增加而增加。虽然以前认为骨髓腔中的中性填充物，但最近的研究表明，骨髓脂肪积累是动态过程的一部分，也会影响骨密度和大小。动物和细胞模型表明，骨髓肥胖与骨髓间充质干细胞（MSC）的分配有关。随着年龄的增长，MSC的分配有利于脂肪细胞而不是成骨细胞，导致骨形成减少，骨髓脂肪增加。更好地理解人类的这一过程可以转化为骨保存的新方法，促进MSC向成骨细胞的分配。骨髓脂肪也可能对骨髓微环境有直接影响。与其他脂肪库类似，骨髓脂肪分泌可能影响骨转换的因子。随着使用磁共振波谱（MRS）对骨髓脂肪进行非侵入性测量成为可能，小型研究报告了双能X射线吸收法（DXA）骨髓脂肪和面积骨密度之间的相关性。需要进行研究以表征骨髓脂肪和计算机断层扫描（CT）可获得的骨参数之间的相关性，包括皮质骨和骨小梁密度以及骨大小。此外，需要进行研究以确定骨髓脂肪是否与其他脂肪库的大小相关，以评估骨髓脂肪是否通过与其他脂肪库相似或不同的机制进行控制。骨活性药物对骨髓脂肪的影响可以提供额外的见解。为了解决这些研究问题，我们提出了一项研究，将包括MRS测量脊椎骨髓肥胖结合骨参数和其他脂肪库的完整表征，在年龄基因/环境易感性雷克雅未克研究（AGES-Reykjavik），老年人队列的300名参与者。作为一项辅助研究，该研究项目可以利用AGES-Reykjavik已经计划的CT测量，大大降低项目成本。本项目将确定通过MRS测量的骨髓肥胖是否与通过CT测量的脊柱、髋关节和股骨干的皮质骨和骨小梁骨密度以及骨大小相关;与DXA测量的髋关节和脊柱的面骨密度相关;以及与骨转换标记物相关。使用DXA和CT测量，该研究将确定总脂肪量的大小、腹部内脏和皮下脂肪库以及大腿中部肌肉的脂肪浸润程度是否与骨髓脂肪相关。该研究还将评估糖皮质激素、激素替代疗法和双膦酸盐对从报告目前使用的女性中选择的一个子集（N=45）的骨髓脂肪的影响，并将评估骨髓脂肪与骨折风险之间的关联，包括在过去12年中报告的普遍椎骨骨折和临床骨折。这项研究有望大大提高我们对骨髓脂肪在骨和其他脂肪库中作用的认识，这些进展可能转化为促进MSC成骨潜力的新治疗方法。 公共卫生关系：这项研究将确定老年人骨髓中较高的脂肪水平是否与骨密度和骨大小降低有关，并将评估骨髓脂肪与其他类型的体脂（包括总脂肪和腹部脂肪）之间的关系。更好地了解骨髓脂肪随着年龄增长和骨质疏松症积累的过程可能为预防骨质流失的治疗提供新的靶点。