Adipose tissue, estradiol levels, and bone health in obese men with metabolic syndrome

Abstract

Objective: Visceral adipose tissue (VAT) is associated with an increased risk of metabolic syndrome (MetS). Recent studies have suggested that VAT negatively affects bone. However, MetS has also been associated with higher estradiol (E 2 ) levels, which is bone protective. We therefore investigated the impact of VAT and E 2 levels on bone density, structural parameters, and strength estimates. Design: A cross-sectional study was conducted in 72 obese men with MetS to investigate the impact of VAT and E 2 levels on bone. Methods: Bone parameters were assessed by dual-energy X-ray absorptiometry (DXA), quantitative computed tomography (QCT), and high-resolution peripheral QCT (HRpQCT) at lumbar spine, proximal femur, radius, and tibia. VAT volume was measured by magnetic resonance imaging (MRI) and sexual hormones were measured in blood samples. Results: Men with high VAT had a lower bone density at the hip (P!0.05), lower cortical thickness, and higher buckling ratio at femoral neck (FN) (PZ0.008 and PZ0.02), compared with men with low VAT, despite a similar body weight and BMI. Generally, E 2 levels were low (median 43 pmol/l), and men with E 2 levels below median had reduced bone density at lumbar spine (PZ0.04), and impaired structural parameters at radius and tibia, compared with men with E 2 levels above median. At the hip, VAT volume and E 2 levels affected bone density independently and additively, and 50% of men with high VAT and low E 2 levels had osteopenia with significantly lower T-score at FN (PZ0.004). Conclusions: High VAT and low E 2 negatively affect bone in obese men with MetS. VAT and E 2 affect bone density at the hip independently and additively, revealing an unexpected high prevalence of osteopenia in middle-aged men with MetS.

The effects of visceral obesity and androgens on bone: trenbolone protects against loss of femoral bone mineral density and structural strength in viscerally obese and testosterone-deficient male rats

“…In our normal weight animals, the increase in VAT mass had harmful effects on BMD, bone geometry and bone strength (ultimate force) of the femurs from testosterone-deficient rats. Similar observations were recently reported in a cross-sectional study by Ornstrup et al [18] in femora of 72 obese middle-aged men. Although the mechanisms underpinning these changes are not described in the present study, our findings warrant further investigation into the potential roles of (1) VAT-induced systemic inflammation [7][8][9][10] and (2) ectopic deposition of fat [31] in bone remodelling, strength and fracture risk.…”

“…These discrepancies are likely due to the strong correlations between BMI and VAT in most populations [16,17], potentially impairing accurate statistical delineation due to co-linearity between each factor. In obese middle-aged men, increases in VAT are independently associated with harmful effects on BMD, bone geometry and femoral bone strength [18]. However, investigations which differentiate between the effects of subcutaneous and visceral adipose tissue on bone are critical to our understanding of the roles of these tissues in bone pathology.…”

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

“…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). The conflicting data suggest that insulin and IRS-1 play complex roles in bone metabolism.…”

Baseline estradiol concentration in community-dwelling Japanese American men is not associated with intra-abdominal fat accumulation over 10 years

“…These studies used various methods to assess adiposity, including clinical measures such as weight and waist-to-hip ratio and radiographic measures including dual-energy X-ray absorptiometry (DXA), magnetic resonance imaging (MRI), or computerized tomography (CT). Only four of these studies specifically examined the association between estradiol concentration and intra-abdominal fat, with one demonstrating a positive association and three finding no statistically significant association [7,9,12,18]. Additionally, most of these studies used radioimmunoassay (RIA) techniques to measure estradiol, which is less accurate than liquid chromatography—tandem mass spectrometry (LCMS) in quantifying the relatively low concentrations of circulating estradiol in men [20].…”