Gonadal steroids and body composition, strength, and sexual function in men.

BACKGROUND: Current approaches to diagnosing testosterone deficiency do not consider the physiological consequences of various testosterone levels or whether deficiencies of testosterone, estradiol, or both account for clinical manifestations. METHODS: We provided 198 healthy men 20 to 50 years of age with goserelin acetate (to suppress endogenous testosterone and estradiol) and randomly assigned them to receive a placebo gel or 1.25 g, 2.5 g, 5 g, or 10 g of testosterone gel daily for 16 weeks. Another 202 healthy men received goserelin acetate, placebo gel or testosterone gel, and anastrozole (to suppress the conversion of testosterone to estradiol). Changes in the percentage of body fat and in lean mass were the primary outcomes. Subcutaneous- and intraabdominal-fat areas, thigh-muscle area and strength, and sexual function were also assessed. RESULTS: The percentage of body fat increased in groups receiving placebo or 1.25 g or 2.5 g of testosterone daily without anastrozole (mean testosterone level, 44±13 ng per deciliter, 191±78 ng per deciliter, and 337±173 ng per deciliter, respectively). Lean mass and thigh-muscle area decreased in men receiving placebo and in those receiving 1.25 g of testosterone daily without anastrozole. Leg-press strength fell only with placebo administration. In general, sexual desire declined as the testosterone dose was reduced. CONCLUSIONS: The amount of testosterone required to maintain lean mass, fat mass, strength, and sexual function varied widely in men. Androgen deficiency accounted for decreases in lean mass, muscle size, and strength; estrogen deficiency primarily accounted for increases in body fat; and both contributed to the decline in sexual function. Our findings support changes in the approach to evaluation and management of hypogonadism in men. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT00114114.).

Using cone-beam CT as a low-dose 3D imaging technique for the extremities: initial experience in 50 subjects.

PURPOSE: To prospectively evaluate a dedicated extremity cone-beam CT (CBCT) scanner in cases with and without orthopedic hardware by (1) comparing its imaging duration and image quality to those of radiography and multidetector CT (MDCT) and (2) comparing its radiation dose to that of MDCT. MATERIALS AND METHODS: Written informed consent was obtained for all subjects for this IRB-approved, HIPAA-compliant study. Fifty subjects with (1) fracture of small bones, (2) suspected intraarticular fracture, (3) fracture at the site of complex anatomy, or (4) a surgical site difficult to assess with radiography alone were recruited and scanned on an extremity CBCT scanner prior to FDA approval. Same-day radiographs were performed in all subjects. Some subjects also underwent MDCT within 1 month of CBCT. Imaging duration and image quality were compared between CBCT and radiographs. Imaging duration, effective radiation dose, and image quality were compared between CBCT and MDCT. RESULTS: Fifty-one CBCT scans were performed in 50 subjects. Average imaging duration was shorter for CBCT than radiographs (4.5 min vs. 6.6 min, P = 0.001, n = 51) and MDCT (7.6 min vs. 10.9 min, P = 0.01, n = 7). Average estimated effective radiation dose was less for CBCT than MDCT (0.04 mSv vs. 0.13 mSv, P = .02, n = 7). CBCT images yielded more diagnostic information than radiographs in 23/51 cases and more diagnostic information than MDCT in 1/7 cases, although radiographs were superior for detecting hardware complications. CONCLUSION: CBCT performs high-resolution imaging of the extremities using less imaging time than radiographs and MDCT and lower radiation dose than MDCT.

Lower leg muscle involvement in Duchenne muscular dystrophy: an MR imaging and spectroscopy study.

OBJECTIVE: To describe the involvement of lower leg muscles in boys with Duchenne muscular dystrophy (DMD) by using MR imaging (MRI) and spectroscopy (MRS) correlated to indices of functional status. SUBJECTS AND METHODS: Nine boys with DMD (mean age, 11 years) and eight healthy age- and BMI-matched boys (mean age, 13 years) prospectively underwent lower leg MRI, 1H-MRS of tibialis anterior (TA) and soleus (SOL) for lipid fraction measures, and 31P-MRS for pH and high-energy phosphate measures. DMD subjects were evaluated using the Vignos lower extremity functional rating, and tests including 6 min walk test (6MWT) and 10 m walk. RESULTS: DMD subjects had highest fatty infiltration scores in peroneal muscles, followed by medial gastrocnemius and soleus. Compared to controls, DMD boys showed higher intramuscular fat (P = 0.04), lipid fractions of TA and SOL (P = 0.02 and 0.003, respectively), pH of anterior compartment (P = 0.0003), and lower phosphocreatine/inorganic phosphorus ratio of posterior compartment (P = 0.02). The Vignos rating correlated with TA (r = 0.79, P = 0.01) and SOL (r = 0.71, P = 0.03) lipid fractions. The 6MWT correlated with fatty infiltration scores of SOL (r = -0.76, P = 0.046), medial (r = -0.80, P = 0.03) and lateral (r = -0.84, P = 0.02) gastrocnemius, intramuscular fat (r = -0.80, P = 0.03), and SOL lipid fraction (r = -0.89, P = 0.007). Time to walk 10 m correlated with anterior compartment pH (r = 0.78, P = 0.04). CONCLUSION: Lower leg muscles of boys with DMD show a distinct involvement pattern and increased adiposity that correlates with functional status. Lower leg MRI and 1H-MRS studies may help to noninvasively demonstrate the severity of muscle involvement.

Modular MR-compatible lower leg exercise device for whole-body scanners.

PURPOSE: To develop a modular MR-compatible lower leg exercise device for muscle testing using a clinical 3 T MR scanner. MATERIALS AND METHODS: An exercise device to provide isotonic resistance to plantar- or dorsiflexion was constructed from nonferrous materials and designed for easy setup and use in a clinical environment. Validation tests were performed during dynamic MR acquisitions. For this purpose, the device was tested on the posterior lower leg musculature of five subjects during 3 min of exercise at 30% of maximum voluntary plantarflexion during 31-phosphorus MR spectroscopy ((31)P-MRS). Measures of muscle phosphocreatine (PCr), inorganic phosphate (Pi), and pH were obtained before, during, and after the exercise protocol. RESULTS: At the end of exercise regimen, muscle PCr showed a 28% decrease from resting levels (to 21.8 ± 3.9 from 30.4 ± 3.0 mM) and the average PCr recovery rate was 35.3 ± 8.3 s. Muscle Pi concentrations increased 123% (to 14.6 ± 4.7 from 6.5 ± 3.3 mM) and pH decreased 1.5% (to 7.06 ± 0.14 from 7.17 ± 0.07) from resting levels. CONCLUSION: The described MR-compatible lower leg exercise was an effective tool for data acquisition during dynamic MR acquisitions of the calf muscles. The modular design allows for adaptation to other whole-body MR scanners and incorporation of custom-built mechanical or electronic interfaces and can be used for any MR protocol requiring dynamic evaluation of calf muscles.

Comparison of 3.0 T proton magnetic resonance spectroscopy short and long echo-time measures of intramyocellular lipids in obese and normal-weight women.

PURPOSE: To compare correlations of intramyocellular lipids (IMCL) measured by short and long echo-time proton magnetic resonance spectroscopy (1H-MRS) with indices of body composition and insulin resistance in obese and normal-weight women. MATERIALS AND METHODS: We quantified IMCL of tibialis anterior (TA) and soleus (SOL) muscles in 52 premenopausal women (37 obese and 15 normal weight) using single-voxel 1H-MRS PRESS at 3.0 T with short (30 msec) and long (144 msec) echo times. Statistical analyses were performed to determine correlations of IMCL with body composition as determined by computed tomography (CT) and insulin resistance indices and to compare correlation coefficients from short and long echo-time data. Signal-to-noise ratio (SNR), linewidth, and coefficients of variation (CV) of short and long echo-time spectra were calculated. RESULTS: Short and long echo-time IMCL from TA and SOL significantly correlated with body mass index (BMI) and abdominal fat depots (r = 0.32 to 0.70, P = <0.05), liver density (r = -0.39 to -0.50, P < 0.05), and glucose area under the curve as a measure of insulin resistance (r = 0.47 to 0.49, P < 0.05). There was no significant difference between correlation coefficients of short and long echo-time spectra (P > 0.5). Short echo-time IMCL in both muscles showed significantly higher SNR (P < 0.0001) and lower CVs when compared to long echo-time acquisitions. Linewidth measures were not significantly different between groups. CONCLUSION: IMCL quantification using short and long echo-time 1H-MRS at 3.0 T is useful to detect differences in muscle lipid content in obese and normal-weight subjects. In addition, IMCL correlates with body composition and markers of insulin resistance in this population with no significant difference in correlations between short and long echo-times. Short echo-time IMCL quantification of TA and SOL muscles at 3.0 T was superior to long echo-time due to better SNR and better reproducibility.

Breath-hold 1H-magnetic resonance spectroscopy for intrahepatic lipid quantification at 3 Tesla.

OBJECTIVE: To compare breath-hold 1H-magnetic resonance spectroscopy (1H-MRS) with respiratory-gated 1H-MRS and computed tomography (CT) for quantification of hepatic lipid content. METHODS: Twenty-three premenopausal women underwent breath-hold point-resolved single-voxel 1H-MRS of the liver followed by respiratory-gated 1H-MRS at 3 Tesla and CT slice through the liver. Interscan variability for 1H-MRS was assessed in 6 volunteers. Pearson correlation coefficients, Bland-Altman 95% limit of agreement, and concordance correlation coefficients were calculated. RESULTS: There was a strong correlation between breath-hold and respiratory-gated 1H-MRS (r = 0.94, P < 0.0001; concordance correlation coefficient, 0.75). Using Bland-Altman analysis, all but 2 data points were within the limits of agreement. Both 1H-MRS techniques had low interscan variability. There was an inverse correlation of both 1H-MRS techniques with CT attenuation values of the liver. CONCLUSIONS: Breath-hold 1H-MRS is a reliable method to measure hepatic lipid content at 3 Tesla. Breath-hold 1H-MRS of the liver provides data that closely correlates with that obtained from longer-duration respiratory-gated technique.

Ischiofemoral impingement syndrome: an entity with hip pain and abnormalities of the quadratus femoris muscle.

OBJECTIVE: The purpose of this study was to describe the MRI findings of an entity in which patients present with hip pain, abnormal MR signal intensity of the quadratus femoris muscle, and narrowing of the ischiofemoral space. MATERIALS AND METHODS: We reviewed MR images of 12 hips in nine patients with hip pain and abnormal MR signal intensity of the quadratus femoris muscle. Using axial MR images, two musculoskeletal radiologists measured the ischiofemoral and quadratus femoris spaces. We also examined changes to muscles and tendons for the presence of edema and tears. Data were compared with 11 hips in 10 control subjects. Statistical analyses determined interobserver variability and differences between groups. RESULTS: Subjects with an abnormal quadratus femoris muscle were all women 30-71 years old (mean age, 53 years) and had significantly narrower ischiofemoral spaces when compared with control subjects (13 +/- 5 vs 23 +/- 8 mm, respectively; p = 0.002). The quadratus femoris space was significantly narrower in affected subjects (7 +/- 3 vs 12 +/- 4 mm; p = 0.002). Abnormalities of the quadratus femoris muscle included edema (100%), partial tear (33%), and fatty infiltration (8%). The hamstring tendons of affected subjects showed evidence of edema (50%) and partial tears (25%). CONCLUSION: Ischiofemoral impingement may represent a cause of hip pain and should be considered in cases with MR signal abnormality of quadratus femoris muscle.

MRI of metatarsal head subchondral fractures in patients with forefoot pain.

OBJECTIVE: The purpose of our study was to determine the MRI features of metatarsal head subchondral fractures in symptomatic adults. MATERIALS AND METHODS: A retrospective review of foot MRI procedures was performed to detect cases of metatarsal head subchondral fractures over a 6-year period. MR images of selected cases were analyzed by two reviewers for the presence of subchondral fracture, marrow edema-like pattern, metatarsal head flattening, and subchondral sclerosis. Patients with a history of foot surgery, infection, or inflammatory arthritis were excluded. Assessment for coexisting osseous and soft-tissue abnormalities was also performed. RESULTS: Subchondral fractures of the metatarsal heads were seen in 14 patients. All patients were women. The metatarsal head most commonly affected was the second (71%, 10/14) and the dorsal third of the metatarsal articular surface was involved in 79% (11/14). MRI findings of subchondral fracture of the metatarsal head with severe marrow edema-like pattern were seen in 71% (10/14), suggesting early stage changes. Metatarsal head collapse with subchondral sclerosis and mild or absent marrow edema-like pattern were seen in 29% (4/14) indicating late-stage changes. Concurrent abnormalities included three patients (21%) with metatarsal shaft fractures and one patient (7%) with an interdigital neuroma. One subject was treated surgically. CONCLUSION: Subchondral fractures of the metatarsal heads can be detected on MR examinations of adults with forefoot pain. A subchondral fracture with associated marrow edema-like pattern is the most common presentation and likely reflects early stages of metatarsal head infraction.

Intramyocellular lipid quantification: comparison between 3.0- and 1.5-T (1)H-MRS.

OBJECTIVE: This study aimed to prospectively compare measurement precision of calf intramyocellular lipid (IMCL) quantification at 3.0 and 1.5 T using (1)H magnetic resonance spectroscopy ((1)H-MRS). MATERIALS AND METHODS: We examined the soleus and tibialis anterior (TA) muscles of 15 male adults [21-48 years of age, body mass index (BMI)=21.9-38.0 kg/m(2)]. Each subject underwent 3.0- and 1.5-T single-voxel, short-echo-time, point-resolved (1)H-MRS both at baseline and at 31-day follow-up. The IMCL methylene peak (1.3 ppm) was scaled to unsuppressed water peak (4.7 ppm) using the LCModel routine. Full width at half maximum (FWHM) and signal-to-noise ratios (SNRs) of unsuppressed water peak were measured using jMRUI software. Measurement precision was tested by comparing interexamination coefficients of variation (CV) between different field strengths using Wilcoxon matched pairs signed rank test in all subjects. Overweight subjects (BMI>25 kg/m(2)) were analyzed separately to examine the benefits of 3.0-T acquisitions in subjects with increased adiposity. RESULTS: No significant difference between 3.0 and 1.5 T was noted in CVs for IMCL of soleus (P=.5). CVs of TA were significantly higher at 3.0 T (P=.02). SNR was significantly increased at 3.0 T for soleus (64%, P<.001) and TA (62%, P<.001) but was lower than the expected improvement of 100%. FWHM at 3.0 T was significantly increased for soleus (19%, P<.001) and TA (7%, P<.01). Separate analysis of overweight subjects showed no significant difference between 3.0- and 1.5-T CVs for IMCL of soleus (P=.8) and TA (P=.4). CONCLUSION: Using current technology, (1)H-MRS for IMCL at 3.0 T did not improve measurement precision, as compared with 1.5 T.

Increased intramyocellular lipid accumulation in HIV-infected women with fat redistribution.

The human immunodeficiency virus (HIV)-lipodystrophy syndrome is associated with fat redistribution and metabolic abnormalities, including insulin resistance. Increased intramyocellular lipid (IMCL) concentrations are thought to contribute to insulin resistance, being linked to metabolic and body composition variables. We examined 46 women: HIV infected with fat redistribution (n = 25), and age- and body mass index-matched HIV-negative controls (n = 21). IMCL was measured by 1H-magnetic resonance spectroscopy, and body composition was assessed with computed tomography, dual-energy X-ray absorptiometry (DEXA), and magnetic resonance imaging. Plasma lipid profile and markers of glucose homeostasis were obtained. IMCL was significantly increased in tibialis anterior [135.0 +/- 11.5 vs. 85.1 +/- 13.2 institutional units (IU); P = 0.007] and soleus [643.7 +/- 61.0 vs. 443.6 +/- 47.2 IU, P = 0.017] of HIV-infected subjects compared with controls. Among HIV-infected subjects, calf subcutaneous fat area (17.8 +/- 2.3 vs. 35.0 +/- 2.5 cm2, P < 0.0001) and extremity fat by DEXA (11.8 +/- 1.1 vs. 15.6 +/- 1.2 kg, P = 0.024) were reduced, whereas visceral abdominal fat (125.2 +/- 11.3 vs. 74.4 +/- 12.3 cm2, P = 0.004), triglycerides (131.1 +/- 11.0 vs. 66.3 +/- 12.3 mg/dl, P = 0.0003), and fasting insulin (10.8 +/- 0.9 vs. 7.0 +/- 0.9 microIU/ml, P = 0.004) were increased compared with control subjects. Triglycerides (r = 0.39, P = 0.05) and extremity fat as percentage of whole body fat by DEXA (r = -0.51, P = 0.01) correlated significantly with IMCL in the HIV but not the control group. Extremity fat (beta = -633.53, P = 0.03) remained significantly associated with IMCL among HIV-infected patients, controlling for visceral abdominal fat, abdominal subcutaneous fat, and antiretroviral medications in a regression model. These data demonstrate increased IMCL in HIV-infected women with a mixed lipodystrophy pattern, being most significantly associated with reduced extremity fat. Further studies are necessary to determine the relationship between extremity fat loss and increased IMCL in HIV-infected women.

Simulated increases in body fat and errors in bone mineral density measurements by DXA and QCT.

Major alterations in body composition, such as with obesity and weight loss, have complex effects on the measurement of bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA). The effects of altered body fat on quantitative computed tomography (QCT) measurements are unknown. We scanned a spine phantom by DXA and QCT before and after surrounding with sequential fat layers (up to 12 kg). In addition, we measured lumbar spine and proximal femur BMD by DXA and trabecular spine BMD by QCT in 13 adult volunteers before and after a simulated 7.5 kg increase in body fat. With the spine phantom, DXA BMD increased linearly with sequential fat layering at the normal (p < 0.01) and osteopenic (p < 0.01) levels, but QCT BMD did not change significantly. In humans, fat layering significantly reduced DXA spine BMD values (mean ± SD: -2.2 ± 3.7%, p = 0.05) and increased the variability of measurements. In contrast, fat layering increased QCT spine BMD in humans (mean ± SD: 1.5 ± 2.5%, p = 0.05). Fat layering did not change mean DXA BMD of the femoral neck or total hip in humans significantly, but measurements became less precise. Associations between baseline and fat-simulation scans were stronger for QCT of the spine (r(2)= 0.97) than for DXA of the spine (r(2)= 0.87), total hip (r(2) = 0.80), or femoral neck (r(2)= 0.75). Bland-Altman plots revealed that fat-associated errors were greater for DXA spine and hip BMD than for QCT trabecular spine BMD. Fat layering introduces error and decreases the reproducibility of DXA spine and hip BMD measurements in human volunteers. Although overlying fat also affects QCT BMD measurements, the error is smaller and more uniform than with DXA BMD. Caution must be used when interpreting BMD changes in humans whose body composition is changing.

Determinants of bone microarchitecture and mechanical properties in obese men.

CONTEXT: Recent studies have suggested that obesity in men is associated with increased fracture risk. Obesity in men is also associated with dysregulation of the GH/IGF-I and gonadal steroid axes, important regulators of bone homeostasis. OBJECTIVE: The aim of the study was to investigate body composition and endocrine determinants of bone microarchitecture and mechanical properties in obese men. DESIGN AND SETTING: We conducted a cross-sectional study at a clinical research center. PARTICIPANTS: Thirty-five obese men (mean age, 33.8 ± 6.4 yr; mean body mass index, 36.5 ± 5.8 kg/m(2)) participated in the study. OUTCOME MEASURES: Distal radius microarchitecture and mechanical properties were measured by three-dimensional high-resolution peripheral quantitative computed tomography and microfinite element analysis; body composition by computed tomography; bone marrow fat by proton magnetic resonance spectroscopy; total and free estradiol and testosterone; IGF-I; peak glucagon-stimulated GH; 25-hydroxyvitamin D. RESULTS: Men with high visceral adipose tissue (VAT) had impaired mechanical properties compared to men with low VAT (P < 0.05), despite comparable body mass index. VAT was inversely associated and thigh muscle was positively associated with mechanical properties (P < 0.05). Bone marrow fat was inversely associated with cortical parameters (P ≤ 0.02). Free estradiol was positively associated with total density (P = 0.05). Free testosterone was positively associated with trabecular thickness and inversely with trabecular number (P ≤ 0.05). Peak stimulated GH was positively associated with trabecular thickness, as was IGF-I with cortical area (P ≤ 0.04). CONCLUSION: VAT and bone marrow fat are negative predictors and muscle mass is a positive predictor of microarchitecture and mechanical properties in obese men. Testosterone, estradiol, and GH are positive determinants of trabecular microarchitecture, and IGF-I is a positive determinant of cortical microarchitecture. This supports the notion that VAT is detrimental to bone and that decreased GH and testosterone, characteristic of male obesity, may exert deleterious effects on microarchitecture, whereas higher estradiol may be protective.

Marrow fat and preadipocyte factor-1 levels decrease with recovery in women with anorexia nervosa.

Women with anorexia nervosa (AN) have elevated marrow fat mass despite low visceral and subcutaneous fat depots, which is inversely associated with bone mineral density (BMD). Whether marrow fat mass remains persistently elevated or decreases with recovery from AN is currently unknown. In this study, we investigated changes in marrow fat in women who have recovered from AN (AN-R). We also studied the relationship between preadipocyte factor (Pref)-1-a member of the EGF-like family of proteins and regulator of adipocyte and osteoblast differentiation-and fat depots and BMD in AN-R compared with women with AN and healthy controls (HC). We studied 29 women: 14 with active or recovered AN (30.7 + 2.2 years [mean ± SEM]) and 15 normal-weight controls (27.8 ± 1.2 years). We measured marrow adipose tissue (MAT) of the L4 vertebra and femur by (1) H-magnetic resonance spectroscopy; BMD of the spine, hip, and total body by DXA; and serum Pref-1 and leptin levels. We found that MAT of the L4 vertebra was significantly lower in AN-R compared with AN (p = 0.03) and was comparable to levels in HC. Pref-1 levels were also significantly lower in AN-R compared with AN (p = 0.02) and comparable to levels in healthy controls. Although Pref-1 was positively associated with MAT of the L4 vertebra in AN (R = 0.94; p = 0.002), we found that it was inversely associated with MAT of the L4 vertebra in HC (R = -0.71; p = 0.004). Therefore, we have shown that MAT and Pref-1 levels decrease with recovery from AN. Our data suggest that Pref-1 may have differential effects in states of nutritional deprivation compared with nutritional sufficiency.

Effects of GH in women with abdominal adiposity: a 6-month randomized, double-blind, placebo-controlled trial.

OBJECTIVE: Abdominal adiposity is associated with increased cardiovascular risk and decreased GH secretion. The objective of our study was to determine the effects of GH on body composition and cardiovascular risk markers in abdominally obese women. MATERIALS AND METHODS: In this randomized, double-blind, placebo-controlled study, 79 obese premenopausal women received GH vs placebo for 6 months. Primary endpoints were i) total abdominal (total abdominal adipose tissue, TAT) fat by computed tomography (CT) (body composition) and ii) high-sensitivity C-reactive protein (hsCRP) (cardiovascular risk marker). Body composition was assessed by CT, dual-energy X-ray absorptiometry, and proton MR spectroscopy. Serum cardiovascular risk markers, carotid intima-media thickness, and endothelial function were measured. RESULTS: Mean 6-month GH dose was 1.7±0.1 mg/day, resulting in a mean IGF1 SDS increase from -1.7±0.08 to -0.1±0.3 in the GH group. GH administration decreased TAT and hsCRP compared with placebo. In addition, it increased thigh muscle mass and lean body mass and decreased subcutaneous abdominal and trunk fat, tissue plasminogen activator, apoB, and apoB/low-density lipoprotein compared with placebo. Visceral adipose tissue (VAT) decreased and intramyocellular lipid increased within the GH group. Six-month change in IGF1 levels was negatively associated with 6-month decrease in TAT and VAT. One subject had a 2 h glucose >200 mg/ml at 3 months; four subjects, three of whom were randomized to GH, had 2 h glucose levels >200 mg/ml at the end of the study. CONCLUSION: GH administration in abdominally obese premenopausal women exerts beneficial effects on body composition and cardiovascular risk markers but is associated with a decrease in glucose tolerance in a minority of women.

Relationship between sleep apnea, fat distribution, and insulin resistance in obese children.

BACKGROUND: Obstructive sleep apnea (OSA) is associated with obesity, inflammation, and insulin resistance. The role of fat distribution in OSA pathogenesis has not been established in children. The objective of the study is to examine the relationship between fat distribution, OSA, and insulin resistance in an unselected population of obese children. METHODS: All obese (BMI > 95th percentile) children (ages 5-18 y) seen at a pediatric obesity clinic were invited to participate. Subjects underwent polysomnography, and were tested for dyslipidemia, inflammation, and insulin resistance measured by the homeostasis model assessment (HOMA). In a subset of subjects, magnetic resonance (MRI) imaging was used to determine the abdominal visceral and subcutaneous adipose tissue areas and magnetic resonance spectroscopy (MRS) spectroscopy was used to intramyocellular lipids in leg muscles. MEASUREMENTS AND MAIN RESULTS: 31 obese subjects enrolled and completed polysomnography and serum testing, and 19 subjects underwent MRI/MRS. The mean age was 12.6 ± 3.0 y and the mean body mass index (BMI) was 39.5 ± 11.2 kg/m(2). Forty-eight percent had OSA (mean apnea hypopnea index [AHI] 6.26 ± 6.77 events/h) Subjects with OSA had significantly increased BMI, log HOMA, triglycerides, and leptin compared to those without OSA. In regression analysis, only BMI z-score was associated with log HOMA. In the subset of patients with imaging data, visceral fat area was strongly predictive of AHI (p = 0.003, r(2) = 0.556). BMI z-score, gender, and age were not predictive. CONCLUSIONS: Visceral fat distribution is independently predictive of OSA severity in obese children.

Vertebral bone marrow fat is positively associated with visceral fat and inversely associated with IGF-1 in obese women.

Recent studies have demonstrated an important physiologic link between bone and fat. Bone and fat cells arise from the same mesenchymal precursor cell within bone marrow, capable of differentiation into adipocytes or osteoblasts. Increased BMI appears to protect against osteoporosis. However, recent studies have suggested detrimental effects of visceral fat on bone health. Increased visceral fat may also be associated with decreased growth hormone (GH) and insulin-like growth factor 1 (IGF-1) levels which are important for maintenance of bone homeostasis. The purpose of our study was to assess the relationship between vertebral bone marrow fat and trabecular bone mineral density (BMD), abdominal fat depots, GH and IGF-1 in premenopausal women with obesity. We studied 47 premenopausal women of various BMI (range: 18-41 kg/m², mean 30 ± 7 kg/m²) who underwent vertebral bone marrow fat measurement with proton magnetic resonance spectroscopy (1H-MRS), body composition, and trabecular BMD measurement with computed tomography (CT), and GH and IGF-1 levels. Women with high visceral fat had higher bone marrow fat than women with low visceral fat. There was a positive correlation between bone marrow fat and visceral fat, independent of BMD. There was an inverse association between vertebral bone marrow fat and trabecular BMD. Vertebral bone marrow fat was also inversely associated with IGF-1, independent of visceral fat. Our study showed that vertebral bone marrow fat is positively associated with visceral fat and inversely associated with IGF-1 and BMD. This suggests that the detrimental effect of visceral fat on bone health may be mediated in part by IGF-1 as an important regulator of the fat and bone lineage.

Adiponectin is inversely associated with intramyocellular and intrahepatic lipids in obese premenopausal women.

Adiponectin, an adipokine secreted by adipocytes, exerts beneficial effects on glucose and lipid metabolism and has been found to improve insulin resistance by decreasing triglyceride content in muscle and liver in obese mice. Adiponectin is found in several isoforms and the high-molecular weight (HMW) form has been linked most strongly to the insulin-sensitizing effects. Fat content in skeletal muscle (intramyocellular lipids, IMCL) and liver (intrahepatic lipids, IHL) can be quantified noninvasively using proton magnetic resonance spectroscopy ((1)H-MRS). The purpose of our study was to assess the relationship between HMW adiponectin and measures of glucose homeostasis, IMCL and IHL, and to determine predictors of adiponectin levels. We studied 66 premenopausal women (mean BMI 31.0 ± 6.6 kg/m(2)) who underwent (1)H-MRS of calf muscles and liver for IMCL and IHL, computed tomography (CT) of the abdomen for abdominal fat depots, dual-energy X-ray absorptiometry (DXA) for fat and lean mass assessments, HMW and total adiponectin, fasting lipid profile and an oral glucose tolerance test (homeostasis model assessment of insulin resistance (HOMA(IR)), glucose and insulin area under the curve). There were strong inverse associations between HMW adiponectin and measures of insulin resistance, IMCL and IHL, independent of visceral adipose tissue (VAT) and total body fat. IHL was the strongest predictor of adiponectin and adiponectin was a predictor of HOMA(IR). Our study showed that in premenopausal obese women HMW adiponectin is inversely associated with IMCL and IHL content. This suggests that adiponectin exerts positive effects on insulin sensitivity in obesity by decreasing intracellular triglyceride content in skeletal muscle and liver; it is also possible that our results reflect effects of insulin on adiponectin.

Determinants of bone mineral density in obese premenopausal women.

Despite being a risk factor for cardiovascular disease and diabetes mellitus, obesity has been thought to protect against osteoporosis. However, recent studies have demonstrated a differential impact of specific fat compartments on bone mineral density (BMD) with visceral adipose tissue (VAT) having potential detrimental effects on BMD. Visceral obesity is also associated with dysregulation of the GH/IGF-1 axis, an important regulator of bone homeostasis. The purpose of our study was to evaluate the differential effects of abdominal fat depots and muscle, vitamin D, and hormonal determinants, including insulin-like growth factor-1 (IGF-1), testosterone, and estradiol, on trabecular BMD of the lumbar spine. We studied 68 healthy obese premenopausal women (mean BMI, 36.7±4.2 kg/m(2)). Quantitative computed tomography (QCT) was used to assess body composition and lumbar trabecular BMD. There was an inverse association between BMD and VAT, independent of age and BMI (p=0.003). IGF-1 correlated positively with BMD and negatively with VAT and, in stepwise multivariate regression modeling, was the strongest predictor of BMD and procollagen type 1 amino-terminal propeptide (P1NP). Thigh muscle cross sectional area (CSA) and thigh muscle density were also associated with BMD (p<0.05), but 25-hydroxyvitamin D [25(OH)D], testosterone, free testosterone, and estradiol levels were not. 25(OH)D was associated inversely with BMI, total, and subcutaneous abdominal adipose tissue (p<0.05). These findings support the hypothesis that VAT exerts detrimental effects, whereas muscle mass exerts positive effects on BMD in premenopausal obese women. Moreover, our findings suggest that IGF-1 may be a mediator of the deleterious effects of VAT on bone health through effects on bone formation.

Comparison of DXA and CT in the assessment of body composition in premenopausal women with obesity and anorexia nervosa.

Accurate methods for assessing body composition in subjects with obesity and anorexia nervosa (AN) are important for determination of metabolic and cardiovascular risk factors and to monitor therapeutic interventions. The purpose of our study was to assess the accuracy of dual-energy X-ray absorptiometry (DXA) for measuring abdominal and thigh fat, and thigh muscle mass in premenopausal women with obesity, AN, and normal weight compared to computed tomography (CT). In addition, we wanted to assess the impact of hydration on DXA-derived measures of body composition by using bioelectrical impedance analysis (BIA). We studied a total of 91 premenopausal women (34 obese, 39 with AN, and 18 lean controls). Our results demonstrate strong correlations between DXA- and CT-derived body composition measurements in AN, obese, and lean controls (r = 0.77-0.95, P < 0.0001). After controlling for total body water (TBW), the correlation coefficients were comparable. DXA trunk fat correlated with CT visceral fat (r = 0.51-0.70, P < 0.0001). DXA underestimated trunk and thigh fat and overestimated thigh muscle mass and this error increased with increasing weight. Our study showed that DXA is a useful method for assessing body composition in premenopausal women within the phenotypic spectrum ranging from obesity to AN. However, it is important to recognize that DXA may not accurately assess body composition in markedly obese women. The level of hydration does not significantly affect most DXA body composition measurements, with the exceptions of thigh fat.

Increased bone marrow fat in anorexia nervosa.

CONTEXT: Although women with anorexia nervosa (AN) have severe depletion of body fat, a paradoxical increase in bone marrow fat has been described. Recent data suggest that marrow fat measured by 1H-magnetic resonance spectroscopy (MRS) in combination with bone mineral density (BMD) may be more valuable than either parameter alone in detecting bone weakness. OBJECTIVE: The objective of the study was to investigate the effect of AN on accumulation of marrow fat in spine and femur using 1H-MRS and the relationship between marrow fat, BMD, and body composition in subjects with AN and normal-weight controls. DESIGN: This was a cross-sectional study. SETTING: The study was conducted at a referral center. PATIENTS: Patients included 10 women with AN (29.8 +/- 7.6 yr) and 10 normal-weight age-matched women (29.2 +/- 5.2 yr). INTERVENTIONS: There were no interventions. MAIN OUTCOMES MEASURE: Marrow fat content of the fourth lumbar vertebra and femur measured by 1H-MRS. BMD of spine and hip measured by dual-energy x-ray absorptiometry. RESULTS: Subjects with AN had higher marrow fat at the fourth lumbar vertebra and femur compared with controls (P = 0.004-0.01). There was an inverse correlation between marrow fat of L4 and femur and BMD of the spine and hip (r = -0.56 to -0.71, P = 0.01-0.0002) and body mass index and sc adipose tissue of the thigh (r = -0.49 to -0.71, P = 0.03-0.0007). There was an inverse correlation between femur marrow fat and sc and total abdominal adipose tissue (r = -0.53 to -0.67, P = 0.003-0.03). CONCLUSION: Women with AN have greater lumbar and femoral marrow fat than controls, and marrow fat correlates inversely with BMD. This paradoxical increase in marrow fat at a time when sc and visceral fat are markedly reduced raises important questions about functional consequences of this process.