Longitudinal patterns of abdominal visceral and subcutaneous adipose tissue, total body composition, and anthropometric measures in postmenopausal women: Results from the Women's Health Initiative.

BACKGROUND: Abdominal adiposity, including visceral and subcutaneous abdominal adipose tissue (VAT and SAT), is recognized as a strong risk factor for cardiometabolic disease, cancer, and mortality. OBJECTIVE: The primary aim of this analysis is to describe longitudinal patterns of change in abdominal adipose tissue in postmenopausal women, overall and stratified by age, race/ethnicity, and years since menopause. METHODS: The data are from six years of follow up on 10,184 postmenopausal women (7828 non-Hispanic White women, 1423 non-Hispanic Black women, and 703 Hispanic women) who participated in the Women's Health Initiative (WHI). The WHI is a large prospective cohort study of postmenopausal women across the United States. All participants in this analysis had DXA scans in the 1990s as part of the WHI protocol. Hologic APEX software was used to re-analyze archived DXA scans and obtain measures of abdominal adipose tissue. Analyses examined differences in abdominal adipose tissue, overall adiposity, and anthropometric variables. RESULTS: There were important differences in VAT and SAT by age and race/ethnicity. In women <60 years, VAT increased over the follow-up period, while in women ≥70 years, VAT decreased. Non-Hispanic Black women had the highest levels of SAT. Hispanic women had the highest VAT levels. Women more than ten years since menopause had less SAT and more VAT than women less than ten years since menopause, resulting in a higher VAT/SAT ratio. There was a moderate to strong correlation between measures of abdominal adipose tissue and anthropometric measurements of body size. Still, there were substantial differences in the quantity of VAT and SAT within BMI and waist circumference categories. CONCLUSIONS: These results demonstrate differences in VAT and SAT according to age, race/ethnicity, time since menopause, and compared to standard measures of body composition in a large and diverse cohort of postmenopausal women.

MRI Based Validation of Abdominal Adipose Tissue Measurements From DXA in Postmenopausal Women.

INTRODUCTION: Visceral adipose tissue (VAT) is a hypothesized driver of chronic disease. Dual-energy X-ray absorptiometry (DXA) potentially offers a lower cost and more available alternative compared to gold-standard magnetic resonance imaging (MRI) for quantification of abdominal fat sub-compartments, VAT and subcutaneous adipose tissue (SAT). We sought to validate VAT and SAT area (cm2) from historical DXA scans against MRI. METHODOLOGY: Participants (n = 69) from the Women's Health Initiative (WHI) completed a 3 T MRI scan and a whole body DXA scan (Hologic QDR2000 or QDR4500; 2004-2005). A subset of 43 participants were scanned on both DXA devices. DXA-derived VAT and SAT at the 4th lumbar vertebrae (5 cm wide) were analyzed using APEX software (v4.0, Hologic, Inc., Marlborough, MA). MRI VAT and SAT areas for the corresponding DXA region of interest were quantified using sliceOmatic software (v5.0, Tomovision, Magog, Canada). Pearson correlations between MRI and DXA-derived VAT and SAT were computed, and a Bland-Altman analysis was performed. RESULTS: Participants were primarily non-Hispanic white (86%) with a mean age of 70.51 ± 5.79 years and a mean BMI of 27.33 ± 5.40 kg/m2. Correlations between MRI and DXA measured VAT and SAT were 0.90 and 0.92, respectively (p ≤ 0.001). Bland-Altman plots showed that DXA-VAT slightly overestimated VAT on the QDR4500 (-3.31 cm2); this bias was greater in the smaller subset measured on the older DXA model (QDR2000; -30.71 cm2). The overestimation of DXA-SAT was large (-85.16 to -118.66 cm2), but differences were relatively uniform for the QDR4500. CONCLUSIONS: New software applied to historic Hologic DXA scans provide estimates of VAT and SAT that are well-correlated with criterion MRI among postmenopausal women.

Rationale and design of a type 2 diabetes prevention intervention for at-risk mothers and children at a Federally Qualified Healthcare Center: EPIC El Rio Families Study Protocol.

BACKGROUND: Exposure to gestational diabetes mellitus (GDM) is associated with increased risk for type 2 diabetes (T2DM) in mothers, and poor cardiovascular health among offspring. Identifying effective methods to mitigate T2DM risk has the potential to improve health outcomes for mothers with a history of GDM and their children. The goal of the EPIC El Rio Families Study is to implement and evaluate the effects of a 13-week behavioral lifestyle intervention on T2DM risk factors in at-risk mothers and their 8- to 12-year-old children. We describe herein the rationale for our specific approach, the adaption of the DPP-based curriculum for delivery to patients of a Federally Qualified Health Center (FQHC), and the study design and methodology. METHODS: The effects of the intervention on reduction in excess body weight (primary outcome), hemoglobin A1c, blood pressure, and changes in lifestyle behaviors associated with weight trajectory and T2DM risk in mother-child dyads will be evaluated during a 13-week, group randomized trial wherein 60 mothers and their children will be recruited to the intervention or wait-listed control conditions at one of two FQHC locations. Intervention participants (n = 30) will begin the group program immediately, whereas the wait-listed controls (n = 30) will receive a booklet describing self-guided strategies for behavior change. Associated program delivery costs, acceptability of the program to participants and FQHC staff, and potential for long-term sustainability will also be evaluated. DISCUSSION: Successful completion in our aims will produce a scalable program with high potential for replication and dissemination, and estimated intervention effects to inform T2DM prevention efforts on families who use the FQHC system. The results from this study will be critical in developing a T2DM prevention model that can be implemented and scaled across FQHCs serving populations disproportionately burdened by T2DM. TRIAL REGISTRATION: ClinicalTrials.gov NCT03781102 ; Date of registration: 19 December 2018.

Effect of cardiometabolic risk factors on the relationship between adiposity and bone mass in girls.

BACKGROUND/OBJECTIVE: Childhood obesity has been separately associated with cardiometabolic risk factors (CMRs) and increased risk of fracture. However, both augmented and compromised bone mass have been reported among overweight/obese children. Metabolic dysfunction, often co-existing with obesity, may explain the discrepancy in previous studies. The aim of this study was to examine whether the relationship between adiposity and dual-energy X-ray absorptiometry (DXA) derived bone mass differed in young girls with and without CMR(s). SUBJECTS/METHODS: Whole-body bone and body composition measures by DXA and measures of CMR (fasting glucose, high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), systolic and diastolic blood pressure, waist circumference (WC)) were obtained from 307, 9- to 12-year-old girls. Girls with 1 or ≥ 2 CMR(s) were considered to be at risk (vs. no CMR). Multiple linear regression was used to test the relationship of total fat mass with total body bone mineral content (BMC) after controlling for height, lean mass, CMR risk, and other potential confounders. RESULTS: There was a significant interaction between CMR risk and total body fat mass. When girls were stratified by CMR group, all groups had a significant positive relationship between fat mass and BMC (p < 0.05), however, girls with ≥ 2 CMRs had a lower BMC for a given level of body fat. Total body fat was not significantly related to bone mineral density (p > 0.05). CONCLUSION: Fat mass has a positive relationship with BMC even after controlling for lean mass. However, the positive relationship of fat mass with BMC may be attenuated if multiple CMRs are present.

Validation of Peripheral Quantitative Computed Tomography-Derived Thigh Adipose Tissue Subcompartments in Young Girls Using a 3 T MRI Scanner.

The ability to assess skeletal muscle adipose tissue is important given the negative clinical implications associated with greater fat infiltration of the muscle. Computed tomography and magnetic resonance imaging (MRI) are highly accurate for measuring appendicular soft tissue and muscle composition, but have limitations. Peripheral quantitative computed tomography (pQCT) is an alternative that investigators find valuable because of its low radiation, fast scan time, and comparatively lower costs. The present investigation sought to assess the accuracy of pQCT-derived estimates of total, subcutaneous, skeletal muscle, intermuscular, and calculated intramuscular adipose tissue areas, and muscle density in the midthigh of young girls using the gold standard, 3 T MRI, as the criterion. Cross-sectional data were analyzed for 26 healthy girls aged 9-12 years. Midthigh soft tissue composition was assessed by both pQCT and 3 T MRI. Mean tissue area for corresponding adipose compartments by pQCT and MRI was compared using t tests, regression analysis, and Bland-Altman plots. Muscle density was regressed on MRI skeletal muscle adipose tissue, intermuscular adipose tissue, and intramuscular adipose tissue, each expressed as a percentage of total muscle area. Correlations were high between MRI and pQCT for total adipose tissue (r2 = 0.98), subcutaneous adipose tissue (r2 = 0.95), skeletal muscle adipose tissue (r2 = 0.83), and intermuscular adipose tissue (r2 = 0.82), and pQCT muscle density correlated well with both MRI skeletal muscle adipose tissue (r2 = 0.70) and MRI intermuscular adipose tissue (r2 = 0.70). There was a slight, but statistically significant underestimation by pQCT for total and subcutaneous adipose tissue, whereas no significant difference was observed for skeletal muscle adipose tissue. Both pQCT-estimated intramuscular adipose tissue and muscle density were weakly correlated with MRI-intramuscular adipose tissue. We conclude that pQCT is a valid measurement technique for estimating all adipose subcompartments, except for intramuscular adipose tissue, for the midthigh region in young/adolescent girls.

Relationship between fat distribution and cardiometabolic risk in Hispanic girls.

OBJECTIVE: In adults, certain body fat depots have greater impact on cardiometabolic risk than total adiposity. Whether similar relationships exist in children is uncertain. The aim of this study was to examine the relationships among dual x-ray absorptiometry (DXA) measures of body fat distribution and total body adiposity with cardiometabolic risk factors in Hispanic girls. METHODS: Measures of total percent body fat, percent of total fat within the android, gynoid, leg, and trunk regions, and cardiometabolic biomarkers (insulin, glucose, homeostatic model assessment of insulin resistance (HOMA-IR), triglycerides (TG), low and high lipoprotein cholesterol (LDL-C, HDL-C)) were obtained from 232 Hispanic girls (age 10.7 ±1.1 years). Regression models for each metabolic parameter were run against adiposity measures. Partial correlations of the adiposity measures were used to compare associations between adiposity measures and the cardiometabolic risk factors, controlling for somatic maturation. RESULTS: Total and regional adiposity were significantly related with cardiometabolic risk factors (P < 0.05) except fasting glucose. The partial correlations of total and regional adiposity measures with each cardiometabolic biomarker were similar. More variance was explained for insulin and the HOMA-IR (33%-43%) than other risk factors. Partial correlations for the percentage of total fat in the gynoid and leg regions with insulin, HOMA-IR, TG, and LDL-C were negative, and positive with HDL-C. CONCLUSION: Measures of total and regional fat perform similarly in predicting cardiometabolic risk in Hispanic girls. A higher proportion of fat distributed in the gynoid or leg region is associated with lower cardiometabolic risk.

Comparison of direct measures of adiposity with indirect measures for assessing cardiometabolic risk factors in preadolescent girls.

BACKGROUND: Childhood overweight and obesity remains high, contributing to cardiometabolic risk factors at younger ages. It is unclear which measures of adiposity serve as the best proxies for identifying children at metabolic risk. This study assessed whether DXA-derived direct measures of adiposity are more strongly related to cardiometabolic risk factors in children than indirect measures. METHODS: Anthropometric and DXA measures of adiposity and a comprehensive assessment of cardiometabolic risk factors were obtained in 288, 9-12 year old girls, most being of Hispanic ethnicity. Multiple regression models for each metabolic parameter were run against each adiposity measure while controlling for maturation and ethnicity. In addition, regression models including both indirect and direct measures were developed to assess whether using direct measures of adiposity could provide a better prediction of the cardiometabolic risk factors beyond that of using indirect measures alone. RESULTS: Measures of adiposity were significantly correlated with cardiometabolic risk factors (p < 0.05) except fasting glucose. After adjusting for maturation and ethnicity, indirect measures of adiposity accounted for 29-34% in HOMA-IR, 10-13% in TG, 14-17% in HDL-C, and 5-8% in LDL-C while direct measures accounted for 29-34% in HOMA-IR, 10-12% in TG, 13-16% in HDL-C, and 5-6% in LDL-C. The addition of direct measures of adiposity to indirect measures added significantly to the variance explained for HOMA-IR (p = 0.04). CONCLUSION: Anthropometric measures may perform as well as the more precise direct DXA-derived measures of adiposity for assessing most CVD risk factors in preadolescent girls. The use of DXA-derived adiposity measures together with indirect measures may be advantageous for predicting insulin resistance risk. TRIAL REGISTRATION: NCT02654262 . Retrospectively registered 11 January 2016.

Resistance Training Effects on Metabolic Function Among Youth: A Systematic Review.

PURPOSE: This systematic review evaluates the relationship between resistance training and metabolic function in youth. METHODS: PubMed, Embase, Cochrane Library, Web of Science, CINAHL, and ClinicalTrials. gov were searched for articles that (1): studied children (2); included resistance training (3); were randomized interventions; and (4) reported markers of metabolic function. The selected studies were analyzed using the Cochrane Risk-of-Bias Tool. RESULTS: Thirteen articles met inclusion criteria. Mean age ranged from 12.2 to 16.9 years, but most were limited to high school (n = 11) and overweight/obese (n = 12). Sample sizes (n = 22-304), session duration (40-60min), and intervention length (8-52 wks) varied. Exercise frequency was typically 2-3 d/wk. Resistance training was metabolically beneficial compared with control or resistance plus aerobic training in 5 studies overall and 3 out of the 4 studies with the fewest threats to bias (p ≤ .05); each was accompanied by beneficial changes in body composition, but only one study adjusted for change in body composition. CONCLUSIONS: Limited evidence suggests that resistance training may positively affect metabolic parameters in youth. Well-controlled resistance training interventions of varying doses are needed to definitively determine whether resistance training can mitigate metabolic dysfunction in youth and whether training benefits on metabolic parameters are independent of body composition changes.

Standardizing evaluation of pQCT image quality in the presence of subject movement: qualitative versus quantitative assessment.

Peripheral quantitative computed tomography (pQCT) is an essential tool for assessing bone parameters of the limbs, but subject movement and its impact on image quality remains a challenge to manage. The current approach to determine image viability is by visual inspection, but pQCT lacks a quantitative evaluation. Therefore, the aims of this study were to (1) examine the reliability of a qualitative visual inspection scale and (2) establish a quantitative motion assessment methodology. Scans were performed on 506 healthy girls (9-13 years) at diaphyseal regions of the femur and tibia. Scans were rated for movement independently by three technicians using a linear, nominal scale. Quantitatively, a ratio of movement to limb size (%Move) provided a measure of movement artifact. A repeat-scan subsample (n = 46) was examined to determine %Move's impact on bone parameters. Agreement between measurers was strong (intraclass correlation coefficient = 0.732 for tibia, 0.812 for femur), but greater variability was observed in scans rated 3 or 4, the delineation between repeat and no repeat. The quantitative approach found ≥95% of subjects had %Move <25 %. Comparison of initial and repeat scans by groups above and below 25% initial movement showed significant differences in the >25 % grouping. A pQCT visual inspection scale can be a reliable metric of image quality, but technicians may periodically mischaracterize subject motion. The presented quantitative methodology yields more consistent movement assessment and could unify procedure across laboratories. Data suggest a delineation of 25% movement for determining whether a diaphyseal scan is viable or requires repeat.

Adding a Brief Continuous Glucose Monitoring Intervention to the National Diabetes Prevention Program: A Multimethod Feasibility Study.

The National Diabetes Prevention Program (DPP) promotes lifestyle changes to prevent diabetes. However, only one-third of DPP participants achieve weight loss goals, and changes in diet are limited. Continuous glucose monitoring (CGM) has shown potential to raise awareness about the effects of diet and activity on glucose among people with diabetes, yet the feasibility of including CGM in behavioral interventions for people with prediabetes has not been explored. This study assessed the feasibility of adding a brief CGM intervention to the Arizona Cooperative Extension National DPP. Extension DPP participants were invited to participate in a single CGM-based education session and subsequent 10-day CGM wear period, during which participants reflected on diet and physical activity behaviors occurring prior to and after hyperglycemic events. Following the intervention, participants completed a CGM acceptability survey and participated in a focus group reflecting on facilitators and barriers to CGM use and its utility as a behavior change tool. A priori feasibility benchmarks included opt-in participation rates ≥ 50%, education session attendance ≥ 80%, acceptability scores ≥ 80%, and greater advantages than disadvantages of CGM emerging from focus groups, as analyzed using the Key Point Summary (KPS) method. Thirty-five DPP members were invited to participate; 27 (77%) consented, and 24 of 27 (89%) attended the brief CGM education session. Median survey scores indicated high acceptability of CGM (median = 5, range = 1-5), with nearly all (n = 23/24, 96%) participants believing that CGM should be offered as part of the DPP. In focus groups, participants described how CGM helped them make behavior changes to improve their glucose (e.g., reduced portion sizes, increased activity around eating events, and meditation). In conclusion, adding a single CGM-based education session and 10-day CGM wear to the DPP was feasible and acceptable. Future research will establish the efficacy of adding CGM to the DPP on participant health outcomes and behaviors.

DXA-derived abdominal fat free mass to predict MRI skeletal muscle mass in postmenopausal women.

Dual-energy X-ray absorptiometry (DXA) is more available than gold-standard magnetic resonance imaging (MRI), but DXA ability to estimate abdominal skeletal muscle mass (SMM) is unknown. DXA-derived abdominal fat-free mass (FFM; Hologic QDR2000 or QDR4500w) was correlated with single-slice MRI SMM at L4 (N = 69; r QDR2000=0.71, QDR4500w=0.69; p<.0001). Linear regression to predict SMM, including DXA FFM, BMI, and age, resulted in an R-squared of 0.72 and 0.65 for QDR2000 and QDR4500. Bland-Altman limits of agreement were ±21g and ±31g for 2-3 standard deviations from the mean difference. DXA predicted abdominal SSM is a moderate proxy for MRI abdominal SMM.

Association of ß-glucuronidase activity with menopausal status, ethnicity, adiposity, and inflammation in women.

OBJECTIVES: Many dietary polyphenols with potential health-promoting benefits undergo hepatic conjugation and circulate as inactive glucuronides that can be cleaved by ß-glucuronidase to reform the bioactive aglycone. Although indirect evidence suggests estrogen may induce ß-glucuronidase, little is known about ß-glucuronidase regulation across women's reproductive lifespan. Correlates of serum ß-glucuronidase activity in healthy premenopausal versus postmenopausal women were therefore examined. METHODS: ß-Glucuronidase activity and C-reactive protein (CRP) were assayed in stored serum from the Women's Breast and Bone Density Study, and dual-energy x-ray absorptiometry and anthropometry assessed body composition. Participants were premenopausal (n = 133) or postmenopausal (n = 89), and Hispanic (37%) or non-Hispanic White (63%). Multivariate linear regression models tested associations between ß-glucuronidase and menopausal status, ethnicity, CRP, and body composition metrics, overall and stratified by menopausal status. RESULTS: Postmenopausal (vs premenopausal) women were older (60.4 ± 3.7 vs 44.8 ± 2.4 y) with a lower Hispanic ethnicity prevalence (27% vs 44%), and higher serum ß-glucuronidase activity (1.5 ± 0.8 vs 1.3 ± 0.5 U/L) and CRP (4.2 ± 4.4 vs 3.3 ± 4.7 mg/L). Adjusting for confounders, ß-glucuronidase was positively associated with Hispanic ethnicity, CRP, body mass index, and total fat mass (all, P < 0.01), but not menopausal status nor lean mass. Central adiposity measures were also positively associated with ß-glucuronidase with the same covariates. CONCLUSIONS: ß-Glucuronidase enzyme activity, upon which polyphenol health-related benefits may depend, is not associated with menopausal status. Future studies are required to determine clinical significance and mechanisms driving ß-glucuronidase associations with ethnicity, inflammation, and adiposity in women.

Visceral adipose tissue and cardiometabolic risk factors in young Hispanic and non-Hispanic girls.

Background: Risk factors for cardiometabolic diseases (e.g., type 2 diabetes, cardiovascular disease) can begin developing in childhood. Elevated body mass index (BMI) is associated with greater likelihood of developing such diseases; however, this relationship varies by race and ethnicity. Notably, Hispanics tend to have high rates of obesity and are disproportionately affected by type 2 diabetes. We aimed to determine if visceral adiposes tissue (VAT) is associated with cardiometabolic risk factors (i.e., triglycerides, cholesterol, insulin resistance, C-reactive protein, and blood pressure), independent of BMI percentile, in a sample of primarily Hispanic adolescent girls. Methods and results: A total of 337 girls (73% Hispanic) took part in the cross-sectional study. Hispanic girls generally had greater BMI percentile, VAT, and cardiometabolic risk factors compared to non-Hispanic girls. Multiple linear regression was used to assess the relationships between Dual-energy X-ray Absorptiometry (DXA)-derived VAT and cardiometabolic outcomes, controlling for BMI percentile (<85th percentile or ≥85th percentile), age, ethnicity (Hispanic/non-Hispanic), and Tanner stage. Significant interactions between VAT and BMI percentile were identified for almost all cardiometabolic outcomes. Upon stratification, the association between VAT and cardiometabolic outcomes was strongest in girls ≥85th BMI percentile, as compared to girls <85th percentile. However, VAT was only significantly associated with higher triglycerides (girls ≥85th percentile) and higher insulin resistance (both BMI percentiles) after stratification. Conclusion: VAT was associated with increased triglycerides and insulin resistance in girls with overweight or obesity. These findings warrant further investigation between VAT and cardiometabolic health in Hispanic adolescents who tend to accumulate more adipose tissue during adolescence.

Influence of Changes in Soft Tissue Composition on Changes in Bone Strength in Peripubertal Girls: The STAR Longitudinal Study.

Obesity and osteoporosis remain two major public health concerns. Soft tissue composition and bone are interrelated; however, it is still not well understood how changes in adiposity during adolescence affect bone development. The aim of this study was to assess how changes in DXA-derived total body lean mass (TBLM) and total body fat mass (TBFM) associate with 2-year changes in bone outcomes at the 20% femur, 66% tibia, 66% radius, and 4% tibia, as measured by pQCT, during the years surrounding the onset of menarche in a cohort of 9- to 12-year-old (baseline) adolescent girls (70% Hispanic). From baseline to 2-year follow-up, girls showed statistically significant increases in all bone outcomes, except radial endosteal circumference. In separate linear regression models, change in TBLM and change in TBFM were both positively associated with 2-year changes in bone outcomes at all measured bone sites, after controlling for relevant covariates. However, when change in TBLM and change in TBFM were included in the same model, change in TBLM was the predominant predictor of bone outcomes, explaining 4% to 14% of the variance in bone strength outcomes. Change in TBFM remained a positive predictor of tibia polar strength strain index (SSIp) (2% variance explained). A significant interaction between change in TBFM and menarcheal status was identified at the radius for SSIp and indicated that greater gains in TBFM were beneficial for SSIp in girls that were premenarcheal at baseline but detrimental for girls who were postmenarcheal at baseline. The overall findings suggest that changes in TBLM during the peripubertal years have a greater influence on bone outcomes than changes in TBFM. While gains in TBFM might benefit the weight bearing 66% tibia, greater gains in TBFM may be detrimental to bone development at the non-weight bearing 66% radius after the onset of menarche. © 2020 American Society for Bone and Mineral Research (ASBMR).

Relationship of cardiometabolic risk biomarkers with DXA and pQCT bone health outcomes in young girls.

BACKGROUND: Excess weight exerts the positive effect of mechanical loading on bone during development whereas obesity-related metabolic dysfunction may have a detrimental impact. In adults, the presence of metabolic syndrome and type 2 diabetes has been associated with compromised bone density, quality, and strength, and an increased incidence of fractures. The few studies that have investigated the role of cardio-metabolic disease risk biomarkers (CMR) on bone strength in children have given conflicting results. The aim of this study was to assess the combined and independent relationships of cardio-metabolic biomarkers with total body and regional bone parameters in young girls. METHODS: In 306, 9-12 year old girls, measures of whole body fat and lean mass, areal bone mineral density (aBMD), bone mineral content (BMC), and bone area (BA) were obtained by dual-energy x-ray absorptiometry (DXA). Bone mineral density (vBMD), geometry, and strength of metaphyseal and diaphyseal regions of the femur and tibia and a diaphyseal region of the radius were measured using peripheral quantitative computed tomography (pQCT). Fasting serum measures of CMRs included, fasting glucose, insulin, homeostatic model assessment for insulin resistance (HOMA-IR), high-density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triglyceride (TG), systolic and diastolic blood pressure (SBP and DBP), and C-reactive protein (CRP). Multiple linear regression was used to assess the independent associations of a single CMR with total body and peripheral measures of bone strength after controlling for the other CMRs, plus total body soft tissue, and other relevant covariates. Also, a standardized total CMR composite score, calculated by standardizing to z-scores and then summing z-scores of each CMR biomarker, was regressed with total body and regional bone measures to assess the relationship of a cluster of risk factors with bone health. RESULTS: Total CMR composite score had inverse associations (p < 0.001) with DXA total BMC and BA. Inverse associations (p < 0.05) of CMR risk score with pQCT regional bone measures occurred with total and trabecular BA at the 4% tibia. Of the individual CMRs, HOMA-IR and CRP were significant predictors of total body bone measures by DXA accounting for ~1-5% of the variance in BMC, BA, and/or aBMD. HOMA-IR was the main predictor of regional pQCT bone outcomes, accounting for the most variance in trabecular vBMD (2.6%) and BSI (3.8%) at the 4% tibia. Most markers of dyslipidemia (TG, HDL-C, LDL-C) and hypertension (SBP, DBP) were not associated (p > 0.05) with any total body or regional bone outcomes with the exception of the inverse relationship of LDL-C with total and trabecular BA and the positive relationship of DBP with cortical vBMD at the radius. CONCLUSION: Of the obesity-related metabolic impairments, insulin resistance and chronic inflammation may compromise whole body bone development in young girls. In particular, trabecular bone, such as that found at the metaphysis of long bones, may be more susceptible to the detrimental effects associated with obesity-related metabolic dysfunction.

Relative contributions of lean and fat mass to bone strength in young Hispanic and non-Hispanic girls.

BACKGROUND: With the high prevalence of childhood obesity, especially among Hispanic children, understanding how body weight and its components of lean and fat mass affect bone development is important, given that the amount of bone mineral accrued during childhood can determine osteoporosis risk later in life. The aim of this study was to assess the independent contributions of lean and fat mass on volumetric bone mineral density (vBMD), geometry, and strength in both weight-bearing and non-weight-bearing bones of Hispanic and non-Hispanic girls. METHODS: Bone vBMD, geometry, and strength were assessed at the 20% distal femur, the 4% and 66% distal tibia, and the 66% distal radius of the non-dominant limb of 326, 9- to 12-year-old girls using peripheral quantitative computed tomography (pQCT). Total body lean and fat mass were measured by dual-energy x-ray absorptiometry (DXA). Multiple linear regression was used to assess the independent relationships of fat and lean mass with pQCT bone measures while adjusting for relevant confounders. Potential interactions between ethnicity and both fat and lean mass were also tested. RESULTS: Lean mass was a significant positive contributor to all bone outcomes (p < 0.05) with the exception of vBMD at diaphyseal sites. Fat mass was a significant contributor to bone strength at weight bearing sites, but did not significantly contribute to bone strength at the non-weight bearing radius and was negatively associated with radius cortical content and thickness. Bone measures did not significantly differ between Hispanic and non-Hispanic girls, although there was a significant interaction between ethnicity and fat mass with total bone area at the femur (p = 0.02) and 66% tibia (p = 0.005) as well as bone strength at the femur (p = 0.03). CONCLUSION: Lean mass is the main determinant of bone strength for appendicular skeletal sites. Fat mass contributes to bone strength in the weight-bearing skeleton but does not add to bone strength in non-weight-bearing locations and may potentially be detrimental. Bone vBMD, geometry, and strength did not differ between Hispanic and non-Hispanic girls; fat mass may be a stronger contributor to bone strength in weight-bearing bones of Hispanic girls compared to non-Hispanic.

Effects of exercise training and hormone replacement therapy on lean and fat mass in postmenopausal women.

BACKGROUND: Menopause is associated with decreases in lean mass and increases in fat mass. Serum hormone levels and hormone replacement therapy (HRT) may modify the effects of exercise training on body composition in postmenopausal women. METHODS: We assessed the changes in total body and regional lean soft tissue and fat mass (using dual-energy x-ray absorptiometry) in 94 sedentary postmenopausal women, aged 40-65 years, after 12 months of resistance and weight-bearing aerobic exercise training. Women currently on oral HRT (n = 39) and not on HRT (n = 55) were randomized within groups to exercise and no exercise, resulting in four groups: exercise + HRT (n = 20), HRT (n = 22), exercise (n = 24), and control (n = 28). Fasting blood samples were measured for resting serum total levels of estrone, estradiol, cortisol, androstenedione, growth hormone, and insulin-like growth factor 1 at baseline and 12 months. RESULTS: We found significant effects of exercise on increases in total body, arm, and leg lean soft tissue mass, and decreases in leg fat mass and percentage of body fat. There were no interaction effects of exercise and HRT on the changes in muscle strength and body composition. No significant changes in total hormone levels were found after 12 months. CONCLUSIONS: Exercise training resulted in significant beneficial changes in lean soft tissue and fat mass in early postmenopausal women. These changes in body composition were neither influenced by prolonged HRT use nor accompanied by changes in total levels of the hormones determined in this study.

Resistance training in postmenopausal women with and without hormone therapy.

PURPOSE: The main purpose of this study was to analyze the impact of a 1-yr resistance-training program on body composition and muscle strength in postmenopausal women, and to describe the impact of hormone replacement therapy (HRT) on body composition changes, with and without exercise. Secondarily, we wanted to study dose-response relationships between measures of program compliance and changes in primary outcomes. METHODS: Subjects were postmenopausal women (40-66 yr) randomly assigned to an exercise (EX) group (N = 117) and a nonexercise group (N = 116). The EX group participated in a 1 yr trainer-supervised resistance-training program, 60-75 min.d-1, 3 d.wk-1. Lean soft tissue (LST) and fat tissue (FT) changes were measured by dual-energy x-ray absorptiometry and strength by one-repetition maximum testing. RESULTS: Significant (P < 0.001) gains in LST were observed for women who exercised, regardless of HRT status, whereas women who did not exercise lost LST (P < 0.05) if they were not taking HRT, and gained LST (P = 0.08) if they were on HRT. The only significant FT losses were observed for women who exercised while on HRT (P < 0.05). Strength increases were observed at all sites (P < 0.001). Total weight lifted by subjects in their training sessions was a significant predictor of changes in LST (P < 0.001) and strength (P < 0.01). CONCLUSIONS: Resistance and weight-bearing exercise significantly changed total and regional body composition in postmenopausal women by increasing LST in all women and decreasing FT in women on HRT. Hormone therapy showed no independent effects on body composition, but it protected nonexercising women from losses in LST. The lean and muscle strength changes observed were partially dependent on the volume of training, as expressed by attendance and total weight lifted in 1 yr of training.

Effects of physical activity and muscle quality on bone development in girls.

INTRODUCTION: Poor muscle quality and sedentary behavior are risk factors for metabolic dysfunction in children and adolescents. However, because longitudinal data are scarce, relatively little is known about how changes in muscle quality and physical activity influence bone development. PURPOSE: In a 2-yr longitudinal study, we examined the effects of physical activity and changes in muscle quality on bone parameters in young girls. METHODS: The sample included 248 healthy girls age 9-12 yr at baseline. Peripheral quantitative computed tomography was used to measure calf and thigh muscle density, an indicator of skeletal muscle fat content or muscle quality, as well as bone parameters at diaphyseal and metaphyseal sites of the femur and tibia. Physical activity was assessed using a validated questionnaire specific for youth. RESULTS: After controlling for covariates in multiple regression models, increased calf muscle density was independently associated with greater gains in cortical (ß = 0.13, P < 0.01) and trabecular (ß = 0.25, P < 0.001) volumetric bone mineral density and the bone strength index (ß = 0.25, P < 0.001) of the tibia. Importantly, these relationships were generalized, as similar changes were present at the femur. Associations between physical activity and changes in bone parameters were weaker than those observed for muscle density. Nevertheless, physical activity was significantly (all P < 0.05) associated with greater gains in trabecular volumetric bone mineral density and the bone strength index of the distal femur. CONCLUSIONS: These findings suggest that poor muscle quality may put girls at risk for suboptimal bone development. Physical activity is associated with more optimal gains in weight-bearing bone density and strength in girls, but to a lesser extent than changes in muscle quality.

Longitudinal relationships between whole body and central adiposity on weight-bearing bone geometry, density, and bone strength: a pQCT study in young girls.

UNLABELLED: Longitudinal relationships between adiposity (total body and central) and bone development were assessed in young girls. Total body and android fat masses were positively associated with bone strength and density parameters of the femur and tibia. These results suggest adiposity may have site-specific stimulating effects on the developing bone. INTRODUCTION: Childhood obesity may impair bone development, but the relationships between adiposity and bone remain unclear. Failure to account for fat pattern may explain the conflicting results. PURPOSE: Longitudinal associations of total body fat mass (TBFM) and android fat mass (AFM) with 2-year changes in weight-bearing bone parameters were examined in 260 girls aged 8-13 years at baseline. Peripheral quantitative computed tomography was used to measure bone strength index (BSI, square milligrams per quartic millimeter), strength-strain index (SSI, cubic millimeters), and volumetric bone mineral density (vBMD, milligrams per cubic centimeter) at distal metaphyseal and diaphyseal regions of the femur and tibia. TBFM and AFM were assessed by dual-energy x-ray absorptiometry. RESULTS: Baseline TBFM and AFM were positively associated with the change in femur BSI (r = 0.20, r = 0.17, respectively) and femur trabecular vBMD (r = 0.19, r = 0.19, respectively). Similarly, positive associations were found between TBFM and change in tibia BSI and SSI (r = 0.16, r = 0.15, respectively), and femur total and trabecular vBMD (r = 0.12, r = 0.14, respectively). Analysis of covariance showed that girls in the middle thirds of AFM had significantly lower femur trabecular vBMD and significantly higher tibia cortical vBMD than girls in the highest thirds of AFM. All results were significant at p < 0.05. CONCLUSIONS: Whereas baseline levels of TBFM and AFM are positive predictors of bone strength and density at the femur and tibia, higher levels of AFM above a certain level may impair cortical vBMD growth at weight-bearing sites. Future studies in obese children will be needed to test this possibility.