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

描述（由申请人提供）：骨质疏松症是美国主要的健康问题之一。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）和计算机断层摄影（CT）]也显示骨髓脂肪组织（BMAT）和骨矿物质密度（BMD）之间存在反比关系。目前还不清楚这种反向关系是否代表基质细胞从成骨细胞向脂肪细胞的优先分化，或者是随着年龄的增长，随着骨丢失和骨髓空间增加，脂肪的被动积累。更清楚地了解骨矿物质和骨髓脂肪之间的关系是通过增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的~1000名健康成年人都有全身MRI和DXA的数据，否则是非常昂贵的collect. The建议的目的是调查BMAT全身MRI和骨密度双能X射线吸收测定法（DXA）在一个受试者多样化的数据库之间的关系。以前使用MRS和CT方法的研究通常限于测量小体积中的BMAT，通常在单个骨内。单个骨腔或跨骨的BMAT均匀性的缺乏是使用MRS量化BMAT的研究报告BMAT与BMD之间的相关性低于我们的全身MRI方法的原因之一。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，允许研究多个松质骨的BMAT。这项拟议的研究将检查BMAT和BMD之间的关联是否存在差异，这些差异存在于已经达到或接近峰值骨量的年轻人和有潜在骨丢失的老年人中。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之间存在强负相关，则结果将支持较低BMD与基质细胞从成骨细胞向脂肪细胞的优先分化相关的假设。或者，如果BMAT和BMD之间的强负相关关系仅存在于可能有骨丢失的老年人中，而不存在于年轻人中，则脂肪的被动积累或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关系的潜在性别和种族差异。这些研究的结果将大大有助于理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。公共卫生相关性：将使用成像软件分析作为先前资助的身体组成研究的一部分收集的约1000个存档全身磁共振成像（MRI）扫描的大型数据库，以量化每个受试者扫描中的骨髓脂肪。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，将获得关于骨髓脂肪和骨矿物质之间是否存在竞争关系的重要证据，这将补充分子水平的研究。

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.