Peak Bone Mass and Patterns of Change in Total Bone Mineral Density and Bone Mineral Contents From Childhood Into Young Adulthood.

The literature has not reached a consensus on the age when peak bone mass is achieved. This study examines growth patterns of total bone mineral content (TBMC) and total bone mineral density (TBMD), peak bone mass, effect of concurrent anthropometry measures, and physical activity on growth patterns in a sample of 312 white males and 343 females aged 8-30 yr. We analyzed data from participants enrolled in Fels Longitudinal Study. Descriptive analysis was used to ascertain characteristics of participants and growth patterns of TBMC and TBMD. Mixed effects models were applied to predict ages at attainment of peak TBMC and TBMD and assess the effects of height, weight, body mass index (BMI), and habitual physical activity on the attainment. Significant differences between sexes were observed for measures of TBMC and TBMD, and differences varied with age. For females, predicted median ages at peak TBMC and TBMD attainments are 21.96 yr (interquartile range [IQR]: 21.81-22.21) and 22.31 yr (IQR: 21.95-22.59), respectively. For males, predicted median ages are 23.34 yr (IQR: 24.34-26.19) and 26.86 yr (IQR: 25.14-27.98) respectively. For females, height, weight, and BMI, but not physical activity, had significant influences on attainment of TBMC and TBMD (p<0.01). For males, weight and BMI, but not height and physical activity, exerted significant influence on attainment of TBMC and TBMD (p<0.01), and also modified correlations between age and peak TBMC and TBMD. Our results suggest that (1) for both sexes, trajectories of TBMC and TBMD follow a curvilinear pattern between ages 8 and 30 yr; (2) predicted ages at peak TBMC and TBMD are from early to late 20s for both white males and females, with females reaching their peaks significantly earlier than males; and (3) concurrent height, weight, and BMI, but not habitual physical activity, exert significant effects on trajectories of TBMC and TBMD.

Retarded tempo of physiological development in childhood delays the onset of the metabolic syndrome in adulthood.

Using serial data from the Fels Longitudinal Study, we investigated the effects of early and late attainment of the peak height velocity (PHV) in childhood on the timing of the appearance of the metabolic syndrome later in life. We aimed to show if early attainment of PHV engenders greater risks for chronic diseases in boys than in girls. Therefore, we defined those boys and girls in sex-specific quartiles of the study population that were slowest to attain PHV as having a slow tempo of development, and those in the growth that most rapidly attained PHV as having a rapid tempo of development. Boys who experienced an early onset of PHV tended to have a higher risk for the metabolic syndrome, dyslipidemia and impaired fasting glucose than those who had late onset of PHV. Girls who had an early onset of PHV tended to develop more abdominal obesity than females who had a late onset of PHV.

A confirmatory factor analysis of the metabolic syndrome in adolescents: an examination of sex and racial/ethnic differences.

OBJECTIVE: The metabolic syndrome (MetS) is a cluster of clinical indices that signals increased risk for cardiovascular disease and Type 2 diabetes. The diagnosis of MetS is typically based on cut-off points for various components, e.g. waist circumference and blood pressure. Because current MetS criteria result in racial/ethnic discrepancies, our goal was to use confirmatory factor analysis to delineate differential contributions to MetS by sub-group. RESEARCH DESIGN AND METHODS: Using 1999-2010 data from the National Health and Nutrition Examination Survey (NHANES), we performed a confirmatory factor analysis of a single MetS factor that allowed differential loadings across sex and race/ethnicity, resulting in a continuous MetS risk score that is sex and race/ethnicity-specific. RESULTS: Loadings to the MetS score differed by racial/ethnic and gender subgroup with respect to triglycerides and HDL-cholesterol. ROC-curve analysis revealed high area-under-the-curve concordance with MetS by traditional criteria (0.96), and with elevations in MetS-associated risk markers, including high-sensitivity C-reactive protein (0.71), uric acid (0.75) and fasting insulin (0.82). Using a cut off for this score derived from ROC-curve analysis, the MetS risk score exhibited increased sensitivity for predicting elevations in ≥2 of these risk markers as compared with traditional pediatric MetS criteria. CONCLUSIONS: The equations from this sex- and race/ethnicity-specific analysis provide a clinically-accessible and interpretable continuous measure of MetS that can be used to identify children at higher risk for developing adult diseases related to MetS, who could then be targeted for intervention. These equations also provide a powerful new outcome for use in childhood obesity and MetS research.

Secular trends in body composition for children and young adults: the Fels Longitudinal Study.

OBJECTIVES: To determine secular trends by birth decade in body mass index (BMI), waist circumference/height (W/Ht), percent body fat (PBF), and fat-free mass adjusted for height squared (FFM/Ht(2) ) in children and adolescents aged 8-18 years. METHODS: Serial data were analyzed from 628 boys and 591 girls aged 8-18 years who participated in the Fels Longitudinal Study. Subjects were stratified by birth decade from 1960 to 1999. Means and standard deviations were computed for all measurements by birth decade, age, and sex. A repeated-measures analysis of variance was used data to ascertain secular trends separately for boys and girls. RESULTS: Boys and girls born in the 1990s had significantly higher mean BMI, W/Ht, and PBF than did children born in previous decades. Mean FFM/Ht(2) was significantly smaller in boys born in the 1990s than boys of the same age born in earlier decades. No secular trend was noted in FFM/Ht(2) in girls by decade of birth. CONCLUSION: Our analysis of serial data collected over 4 decades confirms the secular trend in childhood BMI previously observed in successive cross-sectional studies. Our analysis discloses significant positive secular trends in W/Ht and PBF in both boys and girls and a significant negative secular trend in FFM/Ht(2) in boys over the last 4 decades of the 20th century. The secular changes presage increases in the prevalence of conditions associated with childhood and adolescent obesity-such as hypertension, glucose intolerance, and dyslipidemia-that may appear as early as the second decade of life.

Childhood waist growth curves and adult diabetes.

Our primary objectives are to empirically identify distinct childhood groups based on trajectories of waist circumference (WC) and waist circumference index measurements, and then to estimate associations between these groups and adult diabetes incidence, as well as other outcomes, including blood pressure, body size, body composition, and hemoglobin levels. Childhood WC and height measurements as well as various adult measurements are taken from participants in the Fels Longitudinal Study. Childhood groups are identified using group-based trajectory modeling. Associations between the resulting group probabilities and adult outcomes are examined using mixed models. Our results show that distinct childhood groups are identifiable for both waist size measurements, with growth curves exhibited by these groups becoming distinguishably separate at around 4 years of age. Higher probabilities for groups exhibiting the larger waist size for either measurement were estimated to have higher risks of developing diabetes in adulthood. Associations were also observed between group probabilities and systolic blood pressure, diastolic blood pressure, and various anthropomorphic measurements, with most associations consistently occurring in early adulthood. These findings expand upon the existing literature, showing that childhood trends in waist size, distinguishable at ages as early as 4 years, are associated with adult Type-2 diabetes.

Relationships between serial childhood adiposity measures and adult blood pressure: The Fels longitudinal study.

OBJECTIVES: Several studies have shown that causes of adult hypertension arise in childhood, and obesity may be a potential cause or at least a mitigating factor in this development. Body mass index is a well studied obesity metric, yet other potential adiposity measures such as percent body fat and waist circumference have been somewhat less considered. The purpose of this study is to determine associations between these alternative serial childhood adiposity measures and adulthood blood pressure. METHODS: Measurements from participants in the Fels Longitudinal Study were used to summarize childhood adiposity, represented by childhood measurements of percent body fat and height-adjusted waist circumference. These subjects also provided systolic and diastolic blood pressure as adults. Childhood adiposity levels were categorized as high or low as compared to the respective upper quartile, and associations with adult blood pressure were measured using Poisson regression to estimate the number of expected occurrences of elevated adiposity during childhood. Adult lifestyle covariates and adiposity were accounted for using multiple linear regression. RESULTS: Summary indices of the childhood adiposity measures were significantly associated with both adult blood pressure metrics in men and women, though some of these associations were altered or reduced in the presence of adult lifestyle characteristics and adult adiposity measures. CONCLUSIONS: Childhood measures of percent body fat and height-adjusted waist circumference have an effect on adult blood pressure, though the effect can be mitigated by adult lifestyles.

Prolonged juvenile States and delay of cardiovascular and metabolic risk factors: the Fels Longitudinal study.

OBJECTIVES: To ascertain the influence of such a prolonged juvenile state on delaying the onset of the metabolic syndrome, cardiovascular disease, and type 2 diabetes mellitus later in life. STUDY DESIGN: We define prolongation of a juvenile state as a retarded tempo of growth, determined by the timing of peak height velocity in each subject and relate the retarded tempo of growth to metabolic syndrome, cardiovascular disease, and type 2 diabetes mellitus later in life by use of serial data of 237 study participants (119 men and 118 women) enrolled in the Fels Longitudinal study. RESULTS: Children who matured early tended to have greater body mass index, waist circumference, and percent of body fat and were more likely to have adverse cardiovascular risk profiles than children who matured late. The differences in these risk factors between early and late maturers were significant for percent body fat, fasting plasma triglycerides, and fasting plasma insulin. CONCLUSIONS: The analyses disclosed a clear separation between early and late maturers in the appearance of these risk factors in young adulthood.

Patterns of change in cardiometabolic risk factors associated with the metabolic syndrome among children and adolescents: the Fels Longitudinal Study.

OBJECTIVES: To examine the patterns of change in cardiometabolic risk factors associated with the metabolic syndrome in children and adolescents between the ages of 8 to 19 years. STUDY DESIGN: Data of children and adolescents who participated in the Fels Longitudinal Study were analyzed. Body mass index, waist circumference, fasting insulin, fasting glucose, triglycerides, high-density lipoprotein cholesterol, systolic blood pressure, and diastolic blood pressure were assessed annually with a standardized protocol. RESULTS: The proportion of participants having at least 1 change between states of high and normal risk ranged from of 11.0% for body mass index to 30.4% for triglycerides. Youth in the high-risk category at baseline had a higher proportion having changed their status for all risk factors (all P < .05) except waist circumference compared with those in the normal-risk category. There were significant time effects for all risk factors (all P < .01) except fasting glucose and triglyceride levels in metric scores, but insignificant time effects for all risk factors in Z-scores in growth curve analyses. CONCLUSIONS: The cardiometabolic risk factors associated with the MetS were relatively stable among white children and adolescents in the normal risk category. Changes in status were common if the risk factor was elevated.

Additive utility of family history and waist circumference to body mass index in childhood for predicting metabolic syndrome in adulthood.

OBJECTIVE: To determine whether waist circumference (WC) and family history of disease increase the predictive utility of body mass index (BMI) for adult metabolic syndrome (MetS). STUDY DESIGN: A subsample of 161 men and women from the Fels Longitudinal Study with childhood and adulthood measures were analyzed. Using logistic regression, childhood BMI categories (50th, 75th, and 85th percentiles), WC categories (75th and 90th percentiles), and family history of type 2 diabetes mellitus or cardiovascular disease were modeled separately and in combinations to predict adult MetS. Predicted probabilities and c-statistics were compared across models. RESULTS: The addition of family history to BMI improved the predicted probability of adult MetS from 29% to 52% (Deltac-statistic = 0.13). The combination of WC and BMI was more predictive than BMI alone but did not outperform the combination of family history and BMI. In 3 of the 4 models with a combination of family history, WC, and BMI, the predicted probability of adult MetS did not exceed that from the combination of family history and BMI. CONCLUSIONS: Family history of type 2 diabetes or cardiovascular disease is a useful addition to BMI in childhood to predict the future risk of adult MetS.

Stability of the factor structure of the metabolic syndrome across pubertal development: confirmatory factor analyses of three alternative models.

OBJECTIVE: To test the fit and stability of 3 alternative models of the metabolic syndrome's factor structure across 3 developmental stages. STUDY DESIGN: With data from the Fels Longitudinal Study, confirmatory factor analyses tested 3 alternative models of the factor structure underlying relationships among 8 metabolic syndrome-associated risks. Models tested were a 1-factor model (A), a 4-factor model (B), and a second-order latent factor model (C). Developmental stages assessed were prepuberty (ages 8-10), puberty (ages 11-15), and postpuberty (ages 16-20). RESULTS: Convergence was achieved for all developmental stages for model A, but the fit was poor throughout (root mean square error of approximation > 0.1). Standardized factor loadings for waist circumference and body mass index were much stronger than those for fasting insulin at all 3 time points. Although prepuberty and postpuberty models converged for models B and C, each model had problems with Heywood cases. The puberty model did not converge for either model B or C. CONCLUSIONS: The hypothetical structures commonly used to support the metabolic syndrome concept do not provide adequate fit in a pediatric sample and may be variable by maturation stage. A components-based approach to cardiovascular risk reduction, with emphasis on obesity prevention and control, may be a more appropriate clinical strategy for children and youth than a syndromic approach.

Predictive ability of childhood metabolic components for adult metabolic syndrome and type 2 diabetes.

OBJECTIVE: To estimate sensitivity, specificity, and positive and negative predictive values of components of the metabolic syndrome (MetS) during childhood for MetS and type 2 diabetes (T2D) in adulthood. STUDY DESIGN: Data from 3 major studies-the Fels Longitudinal Study, the Muscatine Study, and the Princeton Follow-up Study-were combined to examine how thresholds of metabolic components during childhood determine adult MetS and T2D. Available metabolic components examined in the 1789 subjects included high-density lipoprotein, triglyceride levels, glucose, and percentiles for body mass index, waist circumference, triglycerides, and systolic and diastolic blood pressures. Sensitivity, specificity, and positive and negative predictive values for a refined set of component threshold values were examined individually and in combination. RESULTS: Sensitivity and positive predictive values remained low for adult MetS and T2D for individual components. However, specificity and negative predictive values were fairly high for MetS and exceptionally so for T2D. In combination, having 1 or more of the components showed the highest sensitivity over any individual component and high negative predictive value. Overall, specificity and negative predictive values remained high whether considering individual or combined components for T2D. CONCLUSIONS: Sensitivity and positive predictive values on the basis of childhood measures remained relatively low, but specificity and negative predictive values were consistently higher, especially for T2D. This indicates that these components, when examined during childhood, may provide a useful screening approach to identifying children not at risk so that further attention can be focused on those who may be in need of future intervention.

Childhood obesity predicts adult metabolic syndrome: the Fels Longitudinal Study.

OBJECTIVES: To determine the age of significant divergence in body mass index (BMI) and waist circumference in adults with and without the metabolic syndrome, and to provide age- and sex-specific childhood values that predict adult metabolic syndrome. STUDY DESIGN: Part 1 of this study is a retrospective cohort study of 92 men and 59 women (mean age, 51 years) who had metabolic syndrome and 154 randomly selected adults matched for age and sex who did not have the syndrome. Part 2 is a study of predictive accuracy in a validation sample of 743 participants. RESULTS: The first appearance of differences between adults with and without metabolic syndrome occurred at ages 8 and 13 for BMI and 6 and 13 for waist circumference in boys and girls, respectively. Odds ratios (ORs) for the metabolic syndrome at 30 years and older ranged from 1.4 to 1.9 across age groups in boys and from 0.8 to 2.8 across age groups in girls if BMI exceeded criterion values in childhood. The corresponding ORs for waist circumference ranged from 2.5 to 31.4 in boys and 1.7 to 2.5 in girls. These ORs increased with the number of examinations. CONCLUSIONS: Children with BMI and waist circumference values exceeding the established criterion values are at increased risk for the adult metabolic syndrome.

Quantitative genetics of cortical bone mass in healthy 10-year-old children from the Fels Longitudinal Study.

The genetic influences on bone mass likely change throughout the life span, but most genetic studies of bone mass regulation have focused on adults. There is, however, a growing awareness of the importance of genes influencing the acquisition of bone mass during childhood on lifelong bone health. The present investigation examines genetic influences on childhood bone mass by estimating the residual heritabilities of different measures of second metacarpal bone mass in a sample of 600 10-year-old participants from 144 families in the Fels Longitudinal Study. Bivariate quantitative genetic analyses were conducted to estimate genetic correlations between cortical bone mass measures, and measures of bone growth and development. Using a maximum likelihood-based variance components method for pedigree data, we found a residual heritability estimate of 0.71 for second metacarpal cortical index. Residual heritability estimates for individual measures of cortical bone (e.g., lateral cortical thickness, medial cortical thickness) ranged from 0.47 to 0.58, at this pre-pubertal childhood age. Low genetic correlations were found between cortical bone measures and both bone length and skeletal age. However, after Bonferonni adjustment for multiple testing, rho(G) was not significantly different from 0 for any of these pairs of traits. Results of this investigation provide evidence of significant genetic control over bone mass largely independent of maturation while bones are actively growing and before rapid accrual of bone that typically occurs during puberty.

Quantitative genetic analysis of cellular adhesion molecules: the Fels Longitudinal Study.

Circulating concentrations of inflammatory markers predict cardiovascular disease (CVD) risk and are closely associated with obesity. However, little is known concerning genetic influences on serum levels of inflammatory markers. In this study, we estimated the heritability (h2) of soluble cellular adhesion molecule (sCAM) concentrations and examined the correlational architecture between different sCAMs. The study population included 234 men and 270 women aged 18-76 years, belonging to 121 families participating in the Fels Longitudinal Study. Serum levels of soluble intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), E-selectin (sESEL-1) and P-selectin (sPSEL-1) were assayed using commercially available kits. A variance components-based maximum likelihood method was used to estimate the h2 of the different serum inflammatory markers while simultaneously adjusting for the effects of known CVD risk factors, such as age and smoking. Additionally, we used bivariate extensions of these methods to estimate genetic and random environmental correlations among sCAMs. Levels of sCAMs were significantly heritable: h2=0.24+/-0.10 for sICAM-1, h2=0.22+/-0.10 for sVCAM-1, h2=0.50+/-0.11 for sESEL-1, and h2=0.46+/-0.10 for sPSEL-1. In addition, a significant genetic correlation (rho(G)=0.63) was found between sICAM-1 and sVCAM-1 indicating some degree of shared genetic control. In the Fels Longitudinal Study, the levels of four sCAMs are significantly influenced by genetic effects, and sICAM-1 shares a common genetic background with sVCAM-1.

Effects of Curtailed Juvenile State on Cardiac Structure and Function in Adulthood: The Fels Longitudinal Study.

OBJECTIVE: Previous studies have shown associations between body mass index and cardiac structure in both childhood and adulthood. Using Fels Longitudinal Study measurements, we investigate the relationships between a curtailed juvenile state and both adult cardiac structure and function. METHODS: A linear mixed-effect repeated measure analysis of variance model is used to test if there is a relationship between juvenile state and each echocardiographic measurement. RESULTS: The curtailed juvenile state is significantly associated with adult left ventricular mass index for both males and females. It is also significantly associated with the interventricular septal wall thickness index and relative wall thickness index for females. In both cases, early juvenile states led to more abnormal structural estimates in adulthood than did late juvenile states. Among cardiac function measurements such as left ventricular ejection fraction and left ventricular shortening fraction, left ventricular ejection fraction is significantly associated with the juvenile state for females. CONCLUSION: The curtailed juvenile state at the childhood may have a long-term adverse effect on adult cardiac structure and function abnormalities.

Early menarche and the development of cardiovascular disease risk factors in adolescent girls: the Fels Longitudinal Study.

The purpose of this study was to evaluate the influence of menarcheal age on changes in insulin, glucose, lipids, and blood pressure during adolescence and to assess whether body composition modifies this relationship. We examined 391 girls, a subset of Fels Longitudinal Study female participants (8-21 yr of age). Self-reported menarcheal age was classified based on the National Health and Nutrition Examination Survey III distribution, in which early menarche was at the 25th percentile or less (11.9 yr). Age at menarche was examined in relation to measures of body composition [e.g. fat-free mass (FFM) and percent body fat (PBF)], insulin resistance, blood pressure, and lipid profile. The effects of menarcheal age and body composition on cardiovascular disease risk factor changes were analyzed with serial data mixed models. Median menarcheal age was 12.7 yr (range, 9.8-17.0 yr), with 91 girls (23%) classified as early menarche. Girls with early menarche had more deleterious changes in insulin, glucose, blood pressure, FFM, and PBF levels than girls with average or late menarche. Menarcheal age adversely affected cardiovascular disease risk factor changes independent of age and changes in FFM or PBF. Girls with early menarche exhibited elevated blood pressure and glucose intolerance compared with later maturing girls, independent of body composition.

Multivariate Granger Causality Analysis of Obesity Related Variables.

Obesity is a complex health outcome that is a combination of multiple health indicators. Here we attempt to explore the dependence network among multiple aspects of obesity. Two longitudinal cohort studies across multiple decades have been used. The concept of causality is defined similar to Granger causality among multiple time series, however, modified to accommodate multivariate time series as the nodes of the network. Our analysis reveals relatively central position of physical measurements and blood chemistry measures in the overall network across both genders. Also there are some patterns specific to only male or female population. The geometry of the causality network is expected to help in our strategy to control the increasing trend of obesity rate.

Fifty-year trends in serial body mass index during adolescence in girls: the Fels Longitudinal Study.

BACKGROUND: A decline in the age at menarche was recently reported for US girls. Although it is possible that this recent drop stems from the concurrent increase in childhood obesity, few longitudinal studies of growth and development have been undertaken to specifically address the temporal relation between growth, adiposity, and the age at menarche. OBJECTIVE: The objective was to simultaneously examine the effects of birth cohort (secular trend) and rate of maturation (age at menarche) on the timing and pattern of increases in body mass index (BMI) during adolescence in girls. DESIGN: We applied mixed-effects polynomial models to serial BMI data, spanning from 6 y before menarche to 6 y after menarche, obtained from 211 girls enrolled in the Fels Longitudinal Study. We examined the effects of birth cohort (defined as girls born 1929-1946, 1947-1964, and 1965-1983) and age at menarche (defined as < or =11.9 y, 12.0-13.1 y, and > or =13.2 y) on the magnitude and velocity of BMI during adolescence. RESULTS: BMI and BMI velocity in girls born after 1965 were significantly greater than those of girls of earlier birth cohorts, despite stability in the mean age at menarche. Although girls with early menarche tended to have significantly higher BMIs than did girls with average or later menarche, these differences did not emerge until after menarche. CONCLUSION: These data suggest that increases in relative weight are a consequence, rather than a determinant, of the age at menarche and that secular changes in BMI and in the mean age at menarche could be independent phenomena.

Development of bioelectrical impedance analysis prediction equations for body composition with the use of a multicomponent model for use in epidemiologic surveys.

BACKGROUND: Previous studies to develop and validate bioelectrical impedance analysis (BIA) equations to predict body composition were limited by small sample sizes, sex specificity, and reliance on reference methods that use a 2-component model. OBJECTIVE: This study was designed to develop sex-specific BIA equations to predict total body water (TBW) and fat-free mass (FFM) with the use of a multicomponent model for children and adults. DESIGN: Data from 5 centers were pooled to create a sample of 1474 whites and 355 blacks aged 12-94 y. TBW was measured by dilution, and FFM was estimated with a multicomponent model based on densitometry, isotope dilution, and dual-energy X-ray absorptiometry. RESULTS: The final race-combined TBW prediction equations included stature(2)/resistance and body weight (R(2) = 0.84 and 0.79 and root mean square errors of 3.8 and 2.6 L for males and females, respectively; CV: 8%) and tended to underpredict TBW in black males (2.0 L) and females (1.4 L) and to overpredict TBW in white males (0.5 L) and females (0.3 L). The race-combined FFM prediction equations contained the same independent variables (R(2) = 0.90 and 0.83 and root mean square errors of 3.9 and 2.9 kg for males and females, respectively; CV: approximately 6%) and tended to underpredict FFM in black males (2.1 kg) and females (1.6 kg) and to overpredict FFM in white males (0.4 kg) and females (0.3 kg). CONCLUSION: These equations have excellent precision and are recommended for use in epidemiologic studies to describe normal levels of body composition.

Heritability of calcaneal quantitative ultrasound measures in healthy adults from the Fels Longitudinal Study.

Quantitative ultrasound (QUS) measurements of bone have been reported to predict osteoporotic fracture risk in postmenopausal women and older men. Although many studies have examined the heritability of bone mineral density (BMD), few studies have estimated the heritability of calcaneal QUS phenotypes. In the present study, we examined the genetic regulation of calcaneal QUS parameters in individuals from nuclear and extended families. The study population includes 260 men and 295 women aged 18-91 years (mean+/-SD: 46+/-16 years) who belong to 111 pedigrees in the Fels Longitudinal Study. Three measures of calcaneal structure were collected from both the right and left heel using the Sahara bone sonometer. These measures included broadband ultrasound attenuation (BUA), speed of sound (SOS), and the quantitative ultrasound index (QUI). We used a variance components based maximum likelihood method to estimate the heritability of QUS parameters while simultaneously adjusting for covariate effects. Additionally, we used bivariate extensions of these methods to calculate additive genetic and random environmental correlations among QUS measures. All phenotypes demonstrated statistically significant heritabilities (P<0.0000001). Heritabilities in the right heel (h2+/-SE) were h2=0.59+/-0.10 for BUA, h2=0.73+/-0.09 for SOS, and h2=0.72+/-0.09 for QUI. Similarly, heritabilities for the left heel were h2=0.52+/-0.10, h2=0.75+/-0.10, and h2=0.70+/0.10, respectively. There was evidence for significant genetic and environmental correlations among these six QUS measures. Combinations of QUS measures in the right and left heel demonstrated genetic correlations of 0.94-0.99 and all were significantly different from one indicating at least a partially unique genetic architecture for each of these measures. This study demonstrates that QUS measures of the calcaneus among healthy men and women are heritable, and there are large shared additive genetic effects among all of the traits examined.