Bone Marrow Adiposity, Bone and Body Composition

描述(由首席研究员提供)：骨髓肥胖症随着年龄和骨质疏松而增加。尽管之前被认为是骨髓腔中的中性填充物，但最近的研究表明，骨髓脂肪堆积是动态过程的一部分，也影响骨密度和大小。动物和细胞模型表明，骨髓肥胖症与骨髓间充质干细胞(MSC)的分配有关。随着年龄的增长，MSC的分配更倾向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。更好地了解人类的这一过程可以转化为骨保存的新方法，促进MSC分配给成骨细胞。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，骨髓脂肪会分泌可能影响骨骼周转的因子。随着使用磁共振波谱(MRS)对骨髓脂肪的非侵入性测量成为可能，通过双能X射线吸收法(DXA)进行的小型研究报告了骨髓脂肪与面骨密度之间的相关性。需要进行研究，以确定骨髓脂肪和计算机断层扫描(CT)提供的骨参数之间的关系，包括皮质骨和松质骨密度以及骨大小。此外，还需要研究来确定骨髓脂肪是否与其他脂肪库的大小有关，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来控制。骨活性药物对骨髓脂肪的影响可以提供额外的洞察力。为了解决这些研究问题，我们提出了一项研究，包括对年龄基因/环境易感性-雷克雅未克研究(AGEs-Reykjavik)的300名参与者进行MRS测量，并对骨骼参数和其他脂肪库进行全面表征，该研究是一项老年人队列研究。作为一项辅助研究，该研究项目可以利用AGES-雷克雅未克地区已经规划的CT测量，大幅降低项目成本。该项目将确定MRS测量的骨髓肥胖症是否与CT测量的脊柱、髋部和股骨干的皮质和松质骨密度及骨大小有关；是否与DXA测量的髋部和脊柱的面骨密度有关；是否与骨转换标志有关。通过DXA和CT测量，这项研究将确定总脂肪团的大小、腹部内脏和皮下脂肪储备以及大腿中部肌肉的脂肪渗透程度是否与骨髓脂肪相关。这项研究还将评估糖皮质激素、激素替代疗法和双膦酸盐对一组女性(N=45)骨髓脂肪的影响，这些女性是从报告当前使用情况的患者中挑选出来的，并将评估骨髓脂肪与骨折风险之间的关系，包括过去12年中报告的常见脊椎骨折和临床骨折。这项研究有望大大提高我们对骨髓脂肪与骨和其他脂肪库相关的作用的了解，这些进展可能会转化为促进MSCs成骨潜力的新治疗方法。 公共卫生相关性：这项研究将确定老年人骨髓中较高水平的脂肪是否与骨密度和骨大小减少有关，并将评估骨髓脂肪与其他类型的体脂之间的关系，包括总脂肪和腹部脂肪。更好地了解骨髓脂肪随年龄增加和骨质疏松的潜在过程，可能会为预防骨质丢失的治疗提供新的靶点。

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.