Longitudinal changes in marrow fat, other fat depots and bone

描述（由申请人提供）：骨髓脂肪蓄积是影响骨密度和强度的动态过程的一部分。非侵入性地测量骨髓脂肪的能力极大地推进了该领域的临床研究。横截面研究已经确定了较高的骨髓脂肪和较低的骨密度（BMD）之间的关联，通过双能X线吸收测定法（DXA）和定量计算机断层扫描（QCT）测量。重要的是，以前的研究表明，骨髓脂肪与普遍的椎骨骨折有关，与BMD无关。这些横截面的结果是令人鼓舞的，但不能解决有关骨髓脂肪和骨连接的动态过程的关键问题。在这个节骨眼上，需要进行纵向研究来澄清骨髓脂肪是否预示着骨质流失，并确定骨髓脂肪的变化是否伴随着骨质的变化。还需要进行纵向研究来确定骨髓脂肪在减肥过程中的作用，骨髓脂肪是老年人骨质流失和骨折风险的重要危险因素。严格的热量限制会增加骨髓脂肪。需要进行研究以确定老年人体重减轻引起的骨质流失是否部分由骨髓脂肪增加介导。在骨髓脂肪和骨的研究中，重要的是要考虑其他脂肪库的潜在影响，包括全身脂肪、内脏脂肪和肌肉脂肪浸润，这些脂肪与骨密度和骨折相关，在一些研究中，与骨髓脂肪相关。另一个关键问题是确定在骨髓脂肪、骨和椎骨骨折的横截面研究中提出的性别差异是否在纵向研究中观察到，以及这些差异是否是由于性激素水平造成的。在女性中，较高的骨髓脂肪和较低的BMD之间的关联似乎更强。然而，在男性中，较高的骨髓脂肪和普遍的椎骨骨折之间的联系可能更强。为了满足对骨髓脂肪和骨骼纵向数据的需求，考虑到性激素水平，体重和其他脂肪库的变化，我们提出了一项在冰岛AGES雷克雅未克队列中的557名老年人中进行的研究，该研究将使用QCT和DXA测量脊柱和髋关节的骨骼变化，以及通过磁共振波谱（MRS）测量的脊椎骨髓脂肪变化，以及内脏和皮下腹部脂肪和大腿肌肉脂肪浸润（通过QCT测量）和全身软组织组成（通过DXA测量），在2-5年的时间内，在基线测量性激素水平和普遍的椎骨骨折。该项目将确定骨髓脂肪的变化是否与BMD的变化相关，独立于其他脂肪库的变化;骨髓脂肪的变化是否与体重减轻和骨质流失之间的任何关联有关;性激素水平是否改变骨髓脂肪和BMD之间的关系;以及较高的骨髓脂肪是否与男性和女性的椎骨骨折独立相关。这项研究有望大大推进我们对骨髓脂肪和骨之间动态关系的理解，这些进展可能转化为预防和治疗骨质疏松症的新的诊断和治疗方法。

DESCRIPTION (provided by applicant): Bone marrow fat accumulation is part of dynamic processes that affect bone density and strength. The ability to measure marrow fat non-invasively has greatly advanced clinical research in this area. Cross-sectional studies have identified associations between higher marrow fat and lower bone density (BMD) measured by dual x-ray absorptiometry (DXA) and quantitative computed tomography (QCT). Importantly, previous research shows that marrow fat is associated with prevalent vertebral fractures, independent of BMD. These cross- sectional results are encouraging but cannot address key questions regarding the dynamic processes connecting marrow fat and bone. At this juncture, longitudinal studies are needed to clarify whether marrow fat predicts bone loss and to determine if changes in marrow fat are accompanied by changes in bone. Longitudinal studies are also needed to determine the role of marrow fat during weight loss, an important risk factor for bone loss and fracture risk in older adults. Severe calorie restriction increases marrow fat. Research is needed to determine if bone loss caused by weight loss in older adults is mediated in part by increases in marrow fat. In studies of marrow fat and bone, it is important to account for the potential effects of other fat depots, including total body fat, visceral fat and fatty infiltration of muscle, that are associated with bone density and fracture and, in some studies, with marrow fat. Another crucial issue is to determine whether the gender differences suggested in cross-sectional studies of marrow fat, bone and vertebral fracture are observed in longitudinal studies and if these differences are due to sex hormone levels. Associations between higher marrow fat and lower BMD appear to be stronger in women. However, the association between higher marrow fat and prevalent vertebral fracture may be stronger in men. To address the need for longitudinal data on marrow fat and bone, taking into account sex hormone levels, changes in weight and in other fat depots, we propose a study among 557 older adults in the Iceland AGES Reykjavik cohort that will measure changes in bone at the spine and hip, using QCT and DXA, and changes in vertebral marrow fat, measured by magnetic resonance spectroscopy (MRS), as well as visceral and subcutaneous abdominal fat and thigh muscle fat infiltration (measured by QCT) and total body soft tissue composition (measured by DXA), over a period of 2-5 years, with sex hormone levels and prevalent vertebral fractures measured at baseline. This project will determine if changes in marrow fat are associated with changes in BMD, independent of changes in other fat depots; if changes in marrow fat account for any of the association between weight loss and bone loss; if sex hormone levels alter the relationship between marrow fat and BMD; and if higher marrow fat is independently associated with vertebral fractures in both men and women. This study promises to substantially advance our understanding of the dynamic relationship between marrow fat and bone, and these advances may translate into new diagnostic and therapeutic approaches for prevention and treatment of osteoporosis.