VAT is an independent inverse determinant of bone density in obesity. This association may be mediated by adipokines and a chronic inflammatory state.

Background Anorexia nervosa (AN) is prevalent in adolescents and is associated with decreased bone mineral accrual at a time critical for optimizing bone mass. Low bone mineral density (BMD) in AN is a consequence of nutritional and hormonal alterations, including hypogonadism and low estradiol levels. Effective therapeutic strategies to improve BMD in adolescents with AN have not been identified. Specifically, high estrogen doses given as an oral contraceptive do not improve BMD. The impact of physiological estrogen doses that mimic puberty on BMD has not been examined. Subjects and Methods We enrolled 110 girls with AN and 40 normal-weight controls (C) 12–18y of similar maturity. Subjects were studied for 18 months. Mature AN [bone age (BA) ≥15 y; n=96] were randomized to transdermal 100mcg 17β-estradiol (with cyclic progesterone) or placebo for 18m. Immature AN (BA <15y; n=14) were randomized to incremental low dose oral ethinyl-estradiol (3.75mcg daily from 0–6m, 7.5mcg from 6–12m, 11.25mcg from 12–18m) to mimic pubertal estrogen increases, or placebo for the 18m duration. Results All BMD measures assessed by dual energy x-ray absorptiometry (DXA) were lower in AN than C. At baseline, AN randomized to estrogen (AN E+) did not differ from those randomized to placebo (AN E−) for age, maturity, height, BMI, amenorrhea duration and BMD parameters. Spine and hip BMD Z-scores increased over time in the AN E+ compared with AN E− group, even after controlling for baseline age and weight. Conclusion Physiological estradiol replacement increases spine and hip BMD in girls with AN.

In addition to low BMD, AA have impaired bone microarchitecture compared with EA and nonathletes. These are the first data to show abnormal bone microarchitecture in AA.

AN boys have low BMD at multiple sites associated with decreased bone turnover markers at a time when bone mass accrual is critical for attainment of peak bone mass.

A. Lower growth hormone and higher cortisol are associated with greater visceral adiposity, intramyocellular lipids, and insulin resistance in overweight girls. Am J Physiol Endocrinol Metab 295: E385-E392, 2008. First published June 10, 2008 doi:10.1152/ajpendo.00052.2008.-Although body composition, insulin sensitivity, and lipids are markedly altered in overweight adolescents, hormonal associations with these parameters have not been well characterized. Growth hormone (GH) deficiency and hypercortisolemia predispose to abdominal adiposity and insulin resistance, and GH secretion is decreased in obese adults. We hypothesized that low-peak GH on the GH-releasing hormone (GHRH)-arginine stimulation test and high cortisol in overweight adolescents would be associated with higher regional fat, insulin resistance, and lipids. We examined the following parameters in 15 overweight and 15 bone age-matched control 12-to 18-yr-old girls: 1) body composition using dual-energy X-ray absorptiometry and MR [visceral and subcutaneous adipose tissue at L4-L5 and soleus intramyocellular lipid ( 1 H-MR spectroscopy)], 2) peak GH on the GHRH-arginine stimulation test, 3) mean overnight GH and cortisol, 4) 24-h urinary free cortisol (UFC), 5) fasting lipids, and 6) an oral glucose tolerance test. Stepwise regression was the major tool employed to determine relationships between measured parameters. Log peak GH on the GHRH-arginine test was lower (P ϭ 0.03) and log UFC was higher (P ϭ 0.02) in overweight girls. Log mean cortisol (overnight sampling) was associated positively with subcutaneous adipose tissue and, with body mass index standard deviation score, accounted for 92% of its variability, whereas log peak GH and body mass index standard deviation score accounted for 88% of visceral adipose tissue variability and log peak GH for 34% of the intramyocellular lipid variability. Log mean cortisol was independently associated with log homeostasis model assessment of insulin resistance, LDL, and HDL and explained 49 -59% of the variability. Our data indicate that lower peak GH and higher UFC in overweight girls are associated with visceral adiposity, insulin resistance, and lipids. obesity; body composition; homeostasis model assessment of insulin resistance; lipids OBESITY IS A GLOBAL PROBLEM, and, according to recent estimates, 17% of US children and adolescents are overweight [body mass index (BMI) Ͼ95th percentile] and 16.5% are at risk for overweight (BMI between 85th and 95th percentiles) (11,19). Commensurate with the rising prevalence of overweight, the prevalence of type 2 diabetes is increasing, such that up to 30 -50% of all newly diagnosed children with diabetes are classified as having type 2 diabetes, in contrast to Ͻ5% before 1994 (13, 23). Although body composition and lipid profiles are markedly altered in overweight compared with normal-weight adolescents, associations of hormonal alterations with body composition and insulin sensitivity changes in overweight teenagers have not been well characterized.Disorders r...

Objective To (i) compare fracture prevalence in adolescent females with anorexia nervosa (AN) vs. normal-weight controls and (ii) examine whether reductions in areal bone mineral density (aBMD) predict fracture risk in females with AN. Methods 418 females (310 with active AN and 108 normal-weight controls) 12–22 years old were studied cross-sectionally. Lifetime fracture history was recorded by a physician during participant interviews. Body composition and aBMD measurements of the whole body, whole body less head, lumbar spine, and hip were assessed by dual-energy x-ray absorptiometry (DXA), and bone mineral apparent density (BMAD) was calculated for the lumbar spine. Results Participants with AN and normal-weight controls did not differ for chronological age, sexual maturity, or height. The lifetime prevalence of prior fracture was 59.8% higher in those with AN compared to controls (31.0 % versus 19.4 %, p = 0.02), and the fracture incidence rate peaked in our cohort after the diagnosis of AN. Lower aBMD and lumbar BMAD were not associated with a higher prevalence of fracture in the AN or control group on univariate or multivariate analyses. Compared to controls, fracture prevalence was significantly higher in the subgroup of girls with AN who had normal aBMD or only modest reductions of aBMD (Z-scores > −1 or −1.5). Discussion This is the first study to show that the risk of fracture during childhood and adolescence is significantly higher in patients with AN than in normal-weight controls. Fracture prevalence is increased in this cohort of subjects with AN even without significant reductions in aBMD.

Context:Adolescents with anorexia nervosa (AN) have low areal bone mineral density (aBMD) at both cortical and trabecular sites, and recent data show impaired trabecular microarchitecture independent of aBMD. However, data are lacking regarding both cortical microarchitecture and bone strength assessment by finite element analysis (FEA) in adolescents with AN. Because microarchitectural abnormalities and FEA may predict fracture risk independent of aBMD, these data are important to obtain. Objective: Our objective was to compare both cortical and trabecular bone microarchitecture and FEA estimates of bone strength in adolescent girls with AN vs normal-weight controls.Design, Setting, and Subjects: We conducted a cross-sectional study at a clinical research center that included 44 adolescent girls (21 with AN and 23 normal-weight controls) 14 to 22 years old. Main Outcome Measures:We evaluated 1) aBMD (dual-energy x-ray absorptiometry) at the distal radius, lumbar spine, and hip, 2) cortical and trabecular microarchitecture at the ultradistal radius (high-resolution peripheral quantitative computed tomography), and 3) FEA-derived estimates of failure load at the ultradistal radius.Results: aBMD was lower in girls with AN vs controls at the lumbar spine and hip but not at the distal radius. Girls with AN had lower total (P Ͻ .0001) and trabecular volumetric BMD (P ϭ .02) and higher cortical porosity (P ϭ .03) and trabecular separation (P ϭ .04). Despite comparable total crosssectional area, trabecular area was higher in girls with AN (P ϭ .04), and cortical area and thickness were lower (P ϭ .002 and .02, respectively). FEA-estimated failure load was lower in girls with AN (P ϭ .004), even after controlling for distal radius aBMD. Conclusions:Both cortical and trabecular microarchitecture are altered in adolescent girls with AN. FEA-estimated failure load is decreased, indicative of reduced bone strength. The finding of reduced cortical bone area in girls with AN is consistent with impaired cortical bone formation at the endosteum as a mechanism underlying these findings. (J Clin Endocrinol Metab 98:

Amenorrhea is common in young athletes and is associated with low fat mass. However, hormonal factors that link decreased fat mass with altered gonadotropin pulsatility and amenorrhea are unclear. Low levels of leptin (an adipokine) and increased ghrelin (an orexigenic hormone that increases as fat mass decreases) impact gonadotropin pulsatility. Studies have not examined luteinizing hormone (LH) secretory dynamics in relation to leptin or ghrelin secretory dynamics in adolescent and young adult athletes. We hypothesized that 1) young amenorrheic athletes (AA) would have lower LH and leptin and higher ghrelin secretion than eumenorrheic athletes (EA) and nonathletes and 2) higher ghrelin and lower leptin would be associated with lower LH secretion. This was a cross-sectional study. We examined ghrelin and leptin secretory patterns (over 8 h, from 11 PM to 7 AM) in relation to LH secretory patterns in AA, EA, and nonathletes aged 14-21 yr. Ghrelin and leptin were assessed every 20 min and LH every 10 min. Groups did not differ for age, bone age, or BMI. However, fat mass was lower in AA than in EA and nonathletes. AA had lower LH and higher ghrelin pulsatile secretion and AUC than nonathletes and lower leptin pulsatile secretion and AUC than EA and nonathletes. Percent body fat was associated positively with LH and leptin secretion and inversely with ghrelin. In a regression model, ghrelin and leptin secretory parameters were associated independently with LH secretory parameters. We conclude that higher ghrelin and lower leptin secretion in AA related to lower fat mass may contribute to altered LH pulsatility and amenorrhea.