Imaging evidence: Is there competition between marrow fat and bone?

影像学证据：骨髓脂肪和骨骼之间是否存在竞争？

• 批准号: 7739303
• 负责人: WEI SHEN
• 金额: $ 24.23万
• 依托单位: ST. LUKE'S-ROOSEVELT INST FOR HLTH SCIS
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-02 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7739303
• 关键词: Adipocytes; Adipose tissue; Adult; Age; Aged, 80 and over; Aging; Applications Grants; Archives; Biological; Body Composition; Body fat; Bone Density; Bone Marrow; Bone Mineral Contents; Cell Lineage; Characteristics; Clinical; Complement; Complex; Computer software; Data; Data Set; Databases; Development; Elderly; Ethnic Origin; Ethnic group; Fatty acid glycerol esters; Functional disorder; Funding; Gender; Hand; Health; Human; Image; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Marrow; Measures; Menopause; Mesenchymal Stem Cells; Methods; Minerals; Molecular; Osteoblasts; Osteoporosis; Play; Prevention; Reporting; Role; Sampling; Scanning; Simulate; Spectrum Analysis; Stem cells; Stromal Cells; Testing; United States; Weight; Woman; X-Ray Computed Tomography; adipocyte differentiation; base; bone; bone loss; bone mass; drug development; ethnic difference; experience; human subject; imaging modality; men; osteogenic; public health relevance; treatment strategy; young adult

DESCRIPTION (provided by applicant): Osteoporosis is one of the leading health problems in the United States. Recent studies suggest that adipocytes in bone marrow and osteoblasts share the same precursor, mesenchymal stem cells (MSC). Human imaging studies [i.e., magnetic resonance spectroscopy (MRS), magnetic resonance imaging (MRI) and computed tomography (CT)] have also shown that there is an inverse relationship between bone marrow adipose tissue (BMAT) and bone mineral density (BMD). It is unknown whether this inverse relationship represents a preferential differentiation of stromal cells from osteoblasts to adipocytes, or a passive accumulation of fat as bone is lost and marrow space increases with aging. A clearer understanding of the relationship between bone mineral and marrow fat is a critical first step towards the development of prevention and treatment strategies for bone loss through enhancing the osteogenic differentiation of progenitor cells. This study pools a unique database of ~1000 healthy adults all of whom have both whole body MRI and DXA data which are otherwise very expensive to collect. The proposed aim is to investigate the relationship between BMAT by whole body MRI and BMD by dual-energy x-ray absorptiometry (DXA) in a subject-diverse database. Previous studies using MRS and CT methods are usually limited to measuring BMAT in a small volume usually within a single bone. Lack of BMAT homogeneity in the cavity of a single bone or across bones presents as one of the reasons why studies using MRS to quantify BMAT report a lower correlation between BMAT and BMD compared to our whole body MRI methods. Our proposed MRI methods overcome the sampling limitations of MRS or CT methods by possessing the unique ability to allow for the study of BMAT of multiple cancellous bones. The proposed study will examine whether there are differences between the association of BMAT and BMD in young adults who have achieved or are close to their peak bone mass and older adults with potential bone loss. If there is a strong inverse correlation between BMAT and BMD in both younger/peak bone mass subjects and older/potential bone loss subjects, the results would support the hypothesis that lower BMD is related to a preferential differentiation of stromal cells from osteoblasts to adipocytes. Alternatively, if a strong inverse relationship between BMAT and BMD exists only in older adults who potentially have bone loss but not in younger adults, either passive accumulation of fat or preferential differentiation of MSC from osteoblasts to adipocytes could explain the pathophysiology related to aging. Furthermore, this unique diverse large scale MRI and DXA database will allow us to first systematically investigate potential gender and ethnic differences in the relationship between bone and marrow fat. The findings from these studies will contribute significantly to understanding the interplay between marrow fat and bone and will complement and provide direction for ongoing molecular studies and drug development studies as clinical evidence. PUBLIC HEALTH RELEVANCE: A large database of approximately 1000 archived whole body magnetic resonance imaging (MRI) scans collected as part of previously funded body composition studies will be analyzed using imaging software to quantify bone marrow fat in each subject scan. By comparing the relationship between marrow fat and bone mineral in younger and older subjects, important evidence will be obtained on whether there is a competitive relationship between marrow fat and bone mineral which will complement molecular level studies.

描述(申请人提供)：骨质疏松症是美国的主要健康问题之一。最近的研究表明，骨髓中的脂肪细胞和成骨细胞具有相同的前体--间充质干细胞(MSC)。人体成像研究[即磁共振波谱(MRS)、磁共振成像(MRI)和计算机断层扫描(CT)]也表明，骨髓脂肪组织(BMAT)与骨密度(BMD)之间存在负相关关系。目前尚不清楚这种相反的关系是否代表了基质细胞从成骨细胞向脂肪细胞的优先分化，还是随着年龄的增长，随着骨骼的丢失和骨髓空间的增加，脂肪被动积累。更清楚地了解骨矿物质和骨髓脂肪之间的关系是通过加强祖细胞的成骨分化来预防和治疗骨丢失的关键的第一步。这项研究汇集了一个独特的数据库，其中包括大约1000名健康成年人，他们都有全身MRI和DXA数据，否则收集这些数据非常昂贵。本研究的目的是在一个不同受试者的数据库中，通过全身MRI和双能X线骨密度仪(DXA)来研究BMAT和BMD之间的关系。以前使用MRS和CT方法的研究通常局限于测量小体积的BMAT，通常是在单个骨骼内。BMAT在单个骨腔内或跨骨中缺乏均质性，这是使用MRS量化BMAT的研究报告与我们全身MRI方法相比BMAT和BMD相关性较低的原因之一。我们提出的MRI方法克服了MRS或CT方法的采样限制，具有独特的能力，可以研究多个松质骨的BMAT。这项拟议的研究将研究在达到或接近峰值骨量的年轻人和有潜在骨质丢失的老年人中，BMAT和BMD之间的相关性是否存在差异。如果在年轻/峰值骨量受试者和老年/潜在骨丢失受试者中，BMAT和BMD都存在强烈的负相关，结果将支持这样的假设，即较低的BMD与基质细胞从成骨细胞向脂肪细胞的优先分化有关。或者，如果BMAT和BMD之间存在强烈的负相关关系，只有可能有骨丢失的老年人，而不是年轻人，被动的脂肪积累或MSC从成骨细胞向脂肪细胞的优先分化可以解释与衰老相关的病理生理学。此外，这个独特的多样化的大规模MRI和DXA数据库将使我们能够首先系统地研究骨骼和骨髓脂肪之间的关系中潜在的性别和种族差异。这些研究的结果将有助于了解骨髓脂肪和骨之间的相互作用，并将补充和指导正在进行的分子研究和药物开发研究作为临床证据。与公共健康相关：作为先前资助的身体成分研究的一部分，收集了大约1000例存档的全身磁共振成像(MRI)扫描的大型数据库，将使用成像软件对每个受试者扫描中的骨髓脂肪进行量化分析。通过比较年轻和老年受试者骨髓脂肪和骨矿物质之间的关系，将为骨髓脂肪和骨矿物质之间是否存在竞争关系提供重要证据，这将补充分子水平的研究。