Bone marrow composition, diabetes, and fracture risk: More bad news for saturated fat

Abstract

I n this month's issue, Patsch and colleagues(1) offer ample food for thought for anyone interested in marrow adipocytes, the enigmatic endosteal fat cells whose developmental origins, function, and impact on bone mass are currently subjects of active investigation.(2) Marrow fat is often associated with low bone mass, as in anorexia nervosa, aging, and osteoporosis, but is also present in normal bone in complex age-, sex-, and sitespecific patterns. (3)(4)(5) Although marrow adipocytes were historically assumed to be neutral, quiescent space fillers,recent studies have demonstrated that marrow adipose tissue has a role in systemic energy metabolism (7,8) and that bone marrow fat mass and bone mass are inversely correlated even within normal subjects. (9,10) Marrow fat is now understood as a metabolically active depot that can be mobilized in starvation and that exerts potential beneficial as well as deleterious effects on skeletal and overall metabolism. However, many questions remain about exactly how marrow fat might increase fracture risk, and how this risk varies with age, sex, and comorbidities. Patsch and colleagues (1) tackle two key outstanding questions about marrow fat: whether the composition of marrow fat, as opposed to the quantity, is related to fracture risk; and whether there is an interaction between marrow fat, diabetes, and skeletal fragility. To address these questions, the authors measured vertebral bone marrow adiposity via magnetic resonance imaging (MRI), areal bone mineral density (aBMD) by dualenergy X-ray absorptiometry (DXA), and volumetric BMD (vBMD) by quantitative computed tomography (QCT) in the lumbar spine (L 1 -L 3 ) in postmenopausal women with and without prior fracture history and with or without type 2 diabetes. Marrow fat quantification included both the total lipid and the proportions of saturated, unsaturated, and residual lipid, differentiated by the presence or absence of double bonds. Overall, the results corroborate patterns seen in previous studies: aBMD at the hip and spine was highest in women with type 2 diabetes but no fracture, and lowest in nondiabetic women with prior fracture, whereas vBMD of the spine was lower in women with fracture versus women without fracture, both within controls and within diabetics. Interestingly, there were no differences in total marrow fat content among groups, regardless of diabetes or fracture status, in contrast to at least one recent study that found higher vertebral marrow fat in subjects with prevalent vertebral fractures.(11) However, both diabetes and fracture history were correlated with differences in marrow fat composition. As shown in Table 2 in Patsch and colleagues, (1) the degree of unsaturation was lower in individuals with both diabetes and fractures (DMFx) compared to controls without fracture (Co) and diabetics without fracture (DM), and the degree of saturation was higher in DM and DMFx versus Co. In other words, people with diabetes had more saturated marrow fat, and people with diabetes and history of fractu...

Oleate Abrogates Palmitate-Induced Lipotoxicity and Proinflammatory Response in Human Bone Marrow-Derived Mesenchymal Stem Cells and Osteoblastic Cells

“…On the whole, these data demonstrate the complexity of the relationship between exogenous lipid intake, MAT and bone health. Of note, the concept that the FA profile as well as the amount of marrow adipocytes may be relevant for skeletal preservation is emerging (59,60). Recent experimental data suggest that FA and lipotoxicity could play a role in the initiation and/or evolution of metabolic bone diseases such as osteoporosis.…”

Marrow Fat and Bone: Review of Clinical Findings

“…The composition as well as the quantity of marrow fat may be relevant for skeletal health ( 47 ). The relative amounts of saturated and unsaturated lipids in marrow fat can be measured non-invasively with MR spectroscopy, allowing exploration of this aspect of marrow fat composition.…”

Effects of voluntary running exercise on bone histology in type 2 diabetic rats

“…The increased fracture risk in diabetes may be due to increasing bone fragility caused by diabetes or an increased incidence of falling, which is related to diabetic complications [ 22 ]. Several studies have suggested that bone fragility in diabetes is caused by adiposity, insulin resistance, fatty acid composition, and hormones [ 23 – 24 ]. Marrow fat may negatively affect bone fragility in diabetes.…”