Waist to hip ratio and trunk to extremity fat (DXA) are better surrogates for IMCL and for visceral fat respectively than for subcutaneous fat in adolescent girls

<p>Abstract</p> <p>Background</p> <p>Increased visceral adipose tissue (VAT) and intramyocellular lipids (IMCL) are associated with increased metabolic risk. Clinical and DXA body composition measures that are associated with VAT are generally even more strongly associated with subcutaneous adipose tissue (SAT) reflecting general adiposity, and thus are not specific for VAT. Measures more strongly associated with VAT than SAT (thus more specific for VAT), and predictors of IMCL have not been reported.</p> <p>Subjects/Methods</p> <p>We studied 30 girls 12-18 years; 15 obese, 15 normal-weight. The following were assessed: (1) anthropometric measures: waist circumference at the umbilicus and iliac crest (WC-UC and WC-IC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), (2) DXA measures: total fat, percent body fat (PBF), percent trunk fat (PTF), trunk-to-extremity fat ratio (TEFR), (3) MRI and 1H-MRS: VAT and SAT (L4-L5), soleus-IMCL.</p> <p>Results</p> <p><b><it>Group as a whole: </it></b>WC, trunk fat and PBF were more strongly associated with SAT than VAT; none were specific for VAT. In contrast, PTF and TEFR were more significantly associated with VAT (r = 0.83 and 0.81 respectively, p <0.0001 for both) than SAT (r = 0.77 and 0.75, p < 0.0001 for both). Strongest associations of S-IMCL were with WHR (r = 0.66, p = 0.0004). <b><it>Subgroup analysis: </it></b>In obese girls, WHR and WHtR were more strongly correlated with VAT (r = 0.62 and 0.82, p = 0.04 and 0.001) than SAT (r = 0.41 and 0.73, p not significant and 0.007), and for DXA measures, PTF and TEFR were more significantly associated with VAT (r = 0.70 and 0.72, p = 0.007 and 0.006) than SAT (r = 0.52 and 0.53, p = 0.07 and 0.06). In controls, PTF and TEFR were more strongly correlated with VAT (r = 0.79, p = 0.0004 for both) than SAT (r = 0.71 and 0.72, p = 0.003 for both). WHR was associated with IMCL in obese girls (r = 0.78, p = 0.008), but not controls.</p> <p>Conclusion</p> <p>Overall, WHR (anthropometry), and PTF and TEFR (DXA) are good surrogates for IMCL and for visceral fat respectively in adolescent girls.</p

The effects of anorexia nervosa on bone metabolism in female adolescents

Osteopenia is a frequent, often persistent, complication of anorexia nervosa (AN) in adolescent girls and occurs during a critical time in bone development. Little is known about bone metabolism in this patient population. Therefore, we measured bone density (BMD) and body composition by dual energy x-ray absorptiometry, nutritional status, bone turnover, calcium, and hormonal status in 19 adolescent girls with AN (mean +/- SEM, 16.0+/-0.4 yr) and 19 bone age-matched controls. The mean duration of AN was 19+/-5 months. Spinal (L1-L4) osteopenia was common in AN. Lumbar anterioposterior BMD was more than 1 SD below the mean in 42% of patients, and lateral spine BMD was more than 1 SD below in 63% of patients compared with controls. Lean body mass significantly predicted lumbar bone mineral content (r = 0.75; P \u3c 0.0001) in controls only. In AN, duration of illness was the most significant predictor of spinal BMD (lumbar: r = -0.44; P = 0.06; lateral: r = -0.59; P = 0.008). AN adolescents with mature BA (15 yr and greater) were hypogonadal [estradiol, 16.2+/-1.9 vs. 23.3+/-1.6 pg/mL (P = 0.01); free testosterone, 0.70+/-0.17 vs. 1.36+/-0.14 pg/mL (P = 0.01)] although dehydroepiandrosterone sulfate and urinary free cortisol levels did not differ. Leptin levels were reduced in AN (2.9+/-2.1 vs. 16.5+/-1.8 ng/mL; P \u3c 0.0001). Insulin-like growth factor I (IGF-I) was reduced in AN to 50% of control levels (219+/-41 vs. 511+/-35 ng/mL; P \u3c 0.0001) and correlated with all measures of nutritional status, particularly leptin (r = 0.80; P \u3c 0.0001). Surrogate markers of bone formation, serum osteocalcin (OC) and bone-specific alkaline phosphatase (BSAP), were significantly (P = 0.02) reduced in AN vs. controls (OC, 39.1+/-6.4 vs. 59.2+/-5.2 ng/mL; BSAP, 27.9+/-4.0 vs. 40.6+/-3.4 U/L). The majority of the variation in bone formation in AN was due to IGF-I levels (OC: r2 = 0.72; P = 0.002; BSAP: r2 = 0.53; P = 0.01) in stepwise regression analyses. Bone resorption was comparable in patients and controls. These data demonstrate that bone formation is reduced and uncoupled to bone resorption in mature adolescents with AN in association with low bone density. Lean body mass was a significant predictor of BMD in controls, but not AN patients. The major correlate of bone formation in AN was the nutritionally dependent bone trophic factor, IGF-I. Reduced IGF-I during the critical period of bone mineral accumulation may be an important factor in the development of osteopenia in adolescents with AN

Abnormal bone mineral accrual in adolescent girls with anorexia nervosa

Anorexia nervosa (AN) is increasingly common in adolescent girls and occurs at a time of peak bone mass formation. Osteopenia is common in adolescent girls with AN, and in a cross-sectional study, we have reported low bone formation markers in such girls. To determine the impact of chronic undernutrition on bone mineral accrual in contrast to healthy controls, we prospectively measured bone mineral density (BMD) and body composition by dual energy x-ray absorptiometry, bone metabolism markers, and nutritional and hormonal status at baseline, 6 months, and 12 months in 19 adolescent girls with AN (mean +/- SEM, 15.4 +/- 0.4 yr) and 19 controls of comparable chronological and skeletal age. Overall, nutritional status in subjects with AN improved (mean percentage increase in body mass index from baseline, 9.2 +/- 1.9% and 15.2 +/- 2.6% at 6 and 12 months, respectively), with 11 subjects having recovered weight at 12 months. However, lumbar BMD at 12 months (AN, 0.88 +/- 0.02 g/cm(2), vs. control, 0.98 +/- 0.03 g/cm(2); P = 0.008) remained significantly reduced in AN compared with controls, even in recovered subjects. This was due to significant increases in lumbar BMD in controls vs. no change in AN subjects over the year (0.003 +/- 0.001 g/cm(2).month vs. 0.000 +/- 0.001 g/cm(2).month, respectively; P = 0.04). The most significant determinant of change in lumbar BMD at 12 months was change in lean body mass in both AN (r = 0.62; P = 0.008) and control (r = 0.80; P = 0.0006) groups. There were significant increases in surrogate markers of bone turnover in subjects with AN compared with controls as assessed by osteocalcin (AN, 0.9 +/- 0.4 micro g/liter.month, vs. control, -1.1 +/- 0.4 micro g/liter.month; P = 0.0007), bone-specific alkaline phosphatase (AN, 0.6 +/- 0.5 U/liter.month, vs. control, -1.5 +/- 0.4 U/liter.month; P = 0.002), deoxypyridinoline [AN, 0.1 +/- 0.1 nmol/mmol creatinine (cr).month, vs. control, -0.4 +/- 0.1 nmol/mmol cr.month; P = 0.005], and N-telopeptide (AN, 4 +/- 4 nmol BCE/mmol cr/month, vs. control, -9 +/- 4 nmol BCE/mmol cr/month; P = 0.01). Changes in IGF-I levels over the year were highly correlated with changes in bone turnover over the same period in AN (osteocalcin, r = 0.77; P = 0.001; deoxypyridinoline, r = 0.66; P = 0.01). A rise in N-telopeptide over the year was correlated with an increase in all bone mineral measures, including lumbar bone mineral content (r = 0.58; P = 0.03) and BMD (r = 0.53; P = 0.05) and total bone mineral content (r = 0.69; P = 0.006) and BMD (r = 0.69; P = 0.006) in the AN group. Therefore, despite recovery over 1 yr, poor bone mineral accrual persists in adolescent girls with AN in contrast to rapid bone accrual in healthy girls. Normalization of bone turnover markers occurs in association with nutritional recovery and an increase in the nutritionally dependent bone trophic factor IGF-I. A rise in bone turnover markers may be an early indicator of increase in BMD in recovering girls with AN

Impact of Sex and Menopausal Status on Episodic Memory Circuitry in Early Midlife

Cognitive neuroscience of aging studies traditionally target participants age 65 and older. However, epidemiological surveys show that many women report increased forgetfulness earlier in the aging process, as they transition to menopause. In this population-based fMRI study, we stepped back by over a decade to characterize the changes in memory circuitry that occur in early midlife, as a function of sex and women's reproductive stage. Participants (N = 200; age range, 45–55) performed a verbal encoding task during fMRI scanning. Reproductive histories and serologic evaluations were used to determine menopausal status. Results revealed a pronounced impact of reproductive stage on task-evoked hippocampal responses, despite minimal difference in chronological age. Next, we examined the impact of sex and reproductive stage on functional connectivity across task-related brain regions. Postmenopausal women showed enhanced bilateral hippocampal connectivity relative to premenopausal and perimenopausal women. Across women, lower 17β-estradiol concentrations were related to more pronounced alterations in hippocampal connectivity and poorer performance on a subsequent memory retrieval task, strongly implicating sex steroids in the regulation of this circuitry. Finally, subgroup analyses revealed that high-performing postmenopausal women (relative to low and middle performers) exhibited a pattern of brain activity akin to premenopausal women. Together, these findings underscore the importance of considering reproductive stage, not simply chronological age, to identify neuronal and cognitive changes that unfold in the middle decades of life. In keeping with preclinical studies, these human findings suggest that the decline in ovarian estradiol production during menopause plays a significant role in shaping memory circuitry

Serum osteoprotegerin in adolescent girls with anorexia nervosa

Low bone mineral density (BMD) in adolescents with anorexia nervosa (AN) is associated with a low bone turnover state. Osteoprotegerin (OPG), a cytokine that acts as a decoy receptor for receptor activator of nuclear factor-kappaB ligand, decreases bone resorption by inhibiting differentiation of osteoclast precursors and activation of mature osteoclasts, and by stimulating osteoclast apoptosis. We compared OPG levels in 43 adolescent girls with AN with 38 controls and examined bone density, bone turnover, and hormonal parameters. Girls with AN had lower fat mass, lean body mass, lumbar BMD z-scores, and lumbar bone mineral apparent density than controls. OPG levels were higher in girls with AN than in controls (44.5 +/- 22.5 pg/ml vs. 34.5 +/- 12.7 pg/ml, P = 0.02). Osteocalcin, deoxypyridinoline, estradiol, free testosterone, IGF-I, and leptin were lower in AN than in healthy adolescents. OPG values correlated negatively with body mass index (r = -0.27, P = 0.02), percent fat mass (r = -0.35, P = 0.0002), leptin (r = -0.28, P = 0.02), lumbar BMD z-scores (r = -0.25, P = 0.03), and lumbar bone mineral apparent density (r = -0.26, P = 0.03). In conclusion, adolescent girls with AN have higher serum OPG values than controls. OPG values correlate negatively with markers of nutritional status and lumbar bone density z-scores and may be a compensatory response to the bone loss seen in this population

The impact of movement behaviors on bone health in elderly with adequate nutritional status: compositional data analysis depending on the frailty status

The aim of this study was to determine the relationship between bone mass (BM) and physical activity (PA) and sedentary behavior (SB) according to frailty status and sex using compositional data analysis. We analyzed 871 older people with an adequate nutritional status. Fried criteria were used to classify by frailty status. Time spent in SB, light intensity PA (LPA) and moderate-to-vigorous intensity PA (MVPA) was assessed from accelerometry for 7 days. BM was determined by dual-energy X-ray absorptiometry (DXA). The combined effect of PA and SB was significantly associated with BM in robust men and women (p ≤ 0.05). In relation to the other behaviors, SB was negatively associated with BM in robust men while BM was positively associated with SB and negatively with LPA and MVPA in robust women. Moreover, LPA also was positively associated with arm BM (p ≤ 0.01). Finally, in pre-frail women, BM was positively associated with MVPA. In our sample, to decrease SB could be a good strategy to improve BM in robust men. In contrast, in pre-frail women, MVPA may be an important factor to consider regarding bone health

A consensus on the diagnosis and treatment of acromegaly complications

In March 2011, the Acromegaly Consensus Group met to revise and update the guidelines on the diagnosis and treatment of acromegaly complications. The meeting was sponsored by the Pituitary Society and the European Neuroendocrinology Association and included experts skilled in the management of acromegaly. Complications considered included cardiovascular, endocrine and metabolic, sleep apnea, bone diseases, and mortality. Outcomes in selected, related clinical conditions were also considered, and included pregnancy, familial acromegaly and invasive macroadenomas. The need for a new disease staging model was considered, and design of such a tool was proposed

Red and White Blood Cell Counts Are Associated With Bone Marrow Adipose Tissue, Bone Mineral Density, and Bone Microarchitecture in Premenopausal Women

Bone marrow adipose tissue (BMAT) resides within the bone marrow microenvironment where its function remains poorly understood. BMAT is elevated in anorexia nervosa, a disease model of chronic starvation, despite depletion of other fat depots. In addition to BMAT, the marrow microenvironment also consists of osteoblast and hematopoietic progenitors. BMAT is inversely associated with bone mineral density (BMD) in multiple populations including women with anorexia nervosa, and regulates hematopoiesis in animal models. We hypothesized that BMAT would be associated with circulating populations of hematopoietic cells (red and white blood cells) in humans and performed a post hoc analysis of two studies—a cross‐sectional study and a longitudinal study—to investigate this hypothesis. We studied 89 premenopausal women cross‐sectionally (median age [interquartile range], 27 [24.5, 31.7] years), including 35 with anorexia nervosa. We investigated associations between red blood cell (RBC) and white blood cell (WBC) counts and BMAT assessed by 1H‐magnetic resonance spectroscopy, BMD assessed by DXA, and bone microarchitecture assessed by HR‐pQCT. In addition, we analyzed longitudinal data in six premenopausal women with anorexia nervosa treated with transdermal estrogen for 6 months and measured changes in BMAT and blood cell counts during treatment. Cross‐sectionally, BMAT was inversely associated with WBC and RBC counts. In contrast, BMD and parameters of bone microarchitecture were positively associated with WBC and RBC. In women with anorexia nervosa treated with transdermal estrogen for 6 months, decreases in BMAT were significantly associated with increases in both RBC and hematocrit (rho = −0.83, p = 0.04 for both). In conclusion, we show that BMAT is inversely associated with WBC and RBC in premenopausal women, and there is a potential association between longitudinal changes in BMAT and changes in RBC. These associations warrant further study and may provide further insight into the role and function of this understudied adipose depot. © 2020 American Society for Bone and Mineral Research.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155991/1/jbmr3986.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155991/2/jbmr3986_am.pd