The Relationship of Fat Distribution and Insulin Resistance with Lumbar Spine Bone Mass in Women

Abstract

Bone marrow harbors a significant amount of body adipose tissue (BMAT). While BMAT might be a source of energy for bone modeling and remodeling, its increment can also represent impairment of osteoblast differentiation. The relationship between BMAT, bone mass and insulin sensitivity is only partially understood and seems to depend on the circumstances. The present study was designed to assess the association of BMAT with bone mineral density in the lumbar spine as well as with visceral adipose tissue, intrahepatic lipids, HOMA-IR, and serum levels of insulin and glucose. This cross-sectional clinical investigation included 31 non-diabetic women, but 11 had a pre-diabetes status. Dual X-ray energy absorptiometry was used to measure bone mineral density and magnetic resonance imaging was used to assess fat deposition in BMAT, visceral adipose tissue and liver. Our results suggest that in non-diabetic, there is an inverse relationship between bone mineral density in lumbar spine and BMAT and a trend persists after adjustment for weight, age, BMI and height. While there is a positive association between visceral adipose tissue and intrahepatic lipids with serum insulin levels, there is no association between BMAT and serum levels of insulin. Conversely, a positive relationship was observed between BMAT and serum glucose levels, whereas this association was not observed with other fat deposits. These relationships did not apply after adjustment for body weight, BMI, height and age. The present study shows that in a group of predominantly non-obese women the association between insulin resistance and BMAT is not an early event, as occurs with visceral adipose tissue and intrahepatic lipids. On the other hand, BMAT has a negative relationship with bone mineral density. Taken together, the results support the view that bone has a complex and non-linear relationship with energy metabolism.

Adipose, Bone, and Myeloma: Contributions from the Microenvironment

“…Therefore, deciphering the direction of cause and effect with MAT and bone loss is challenging as the relationship between BM adipocytes and bone cells remains elusive and becomes even more complex when assessed in the presence of myeloma cells. It is also clear that bone has a complicated, non-linear, genotype-dependent relationship with energy metabolism and MAT [19, 20]. Mice fed a high fat diet and humans with increased visceral adiposity also have an accompanying increase in MAT, providing a potential mechanism whereby obesity increases the risk for osteoporotic fractures due to increased MAT [21], although no bone changes were observed in this study, perhaps due to the short time course of observation.…”

“…It is important to note that MAT, and MAT responses to diet, drugs (e.g., rosiglitazone), cold exposure/thermoneutrality, unloading, and other environmental stimuli, have significant differences based on age, species, strain (eg. C57BL/6J vs C3H), sex and anatomical location [19, 21, 26, 30–32]. Moreover, many of the experiments characterizing MAT have not been done systematically across this spectrum of experimental conditions, and our understanding of human MAT is also relatively underdeveloped, in part due to the technical challenges of accessing and analyzing this tissue, and also due to previous omissions of this depot in research [33].…”

Insulin receptor substrate‐1 time‐dependently regulates bone formation by controlling collagen Iα2 expression via miR‐342

“…However, conflicting data have been reported for the influence of Irs‐1 on BMD for patients with T2DM that were both deficient in IRS‐1 expression and expressed insulin resistance. Several groups reported elevated BMD at the lumbar spine and femoral neck among postmenopausal women or men with metabolic syndrome and insulin resistance (25, 26). In contrast, many other studies have shown the opposite, significant reductions in lumbar spine BMD among women with metabolic syndrome and diabetic osteopathy in patients with T2DM and IRS‐1 deficiency (27, 28).…”

Diabetes and Bone Marrow Adiposity

“…There are limited data for those with pre-diabetes, but a study by de Paula et al suggested a potential correlation between dysglycemia and marrow fat [39•]. L3 vertebral fat content was measured by 1 H-MRS in 30 women, 11 of whom had pre-diabetes, with mean age of 47.8 years, BMI at 25.5 kg/m 2 , and A1c at 5.5 %.…”