[Show abstract][Hide abstract] ABSTRACT: Overweight and obesity in childhood and adolescence are associated with reduced breast cancer risk, independent of adult body mass index (BMI). These associations may be mediated through breast density.
We prospectively examined associations of early life body fatness with adult breast density measured by MRI in 182 women in the Dietary Intervention Study in Children (DISC) who were ages 25-29 at follow-up. Height, weight, and other factors were measured at baseline (ages 8-10) and annual clinic visits through adolescence. We used linear mixed-effects models to quantify associations of percent breast density and dense and non-dense breast volume at ages 25-29 with quartiles of age-specific youth body mass index (BMI) Z-scores, adjusting for clinic, treatment group, current adult BMI, and other well-established risk factors for breast cancer and predictors of breast density.
We observed inverse associations between age-specific BMI Z-scores at all youth clinic visits and percent breast density, adjusting for current adult BMI and other covariates (all p values <0.01). Women whose baseline BMI Z-scores (at ages 8-10 years) were in the top quartile had significantly lower adult breast density, after adjusting for current adult BMI and other covariates [least squares mean (LSM): 23.4 %; 95 % confidence interval (CI): 18.0 %, 28.8 %] compared to those in the bottom quartile (LSM: 31.8 %; 95 % CI: 25.2 %, 38.4 %) (p trend <0.01). Significant inverse associations were also observed for absolute dense breast volume (all p values <0.01), whereas there were no clear associations with non-dense breast volume.
These results support the hypothesis that body fatness during childhood and adolescence may play an important role in premenopausal breast density, independent of current BMI, and further suggest direct or indirect influences on absolute dense breast volume.
NCT00458588 ; April 9, 2007.
Breast cancer research: BCR 12/2015; 17(1):95. DOI:10.1186/s13058-015-0601-4 · 5.88 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Obesity and its consequences, such as diabetes, are global health issues that burden about 171 × 10(6) adult individuals worldwide. Fat mass index (FMI, kg/m(2)), fat-free mass index (FFMI, kg/m(2)), and percent fat mass may be useful to evaluate under- and overnutrition and muscle development in a clinical or research environment. This proof-of-concept study tested whether frontal whole-body silhouettes could be used to accurately measure body composition parameters using active shape modeling (ASM) techniques.
Binary shape images (silhouettes) were generated from the skin outline of dual-energy x-ray absorptiometry (DXA) whole-body scans of 200 healthy children of ages from 6 to 16 yr. The silhouette shape variation from the average was described using an ASM, which computed principal components for unique modes of shape. Predictive models were derived from the modes for FMI, FFMI, and percent fat using stepwise linear regression. The models were compared to simple models using demographics alone [age, sex, height, weight, and body mass index z-scores (BMIZ)].
The authors found that 95% of the shape variation of the sampled population could be explained using 26 modes. In most cases, the body composition variables could be predicted similarly between demographics-only and shape-only models. However, the combination of shape with demographics improved all estimates of boys and girls compared to the demographics-only model. The best prediction models for FMI, FFMI, and percent fat agreed with the actual measures with R(2) adj. (the coefficient of determination adjusted for the number of parameters used in the model equation) values of 0.86, 0.95, and 0.75 for boys and 0.90, 0.89, and 0.69 for girls, respectively.
Whole-body silhouettes in children may be useful to derive estimates of body composition including FMI, FFMI, and percent fat. These results support the feasibility of measuring body composition variables from simple cameras such as those found in cell phones.
Medical Physics 08/2015; 42(8):4668. DOI:10.1118/1.4926557 · 3.01 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: INTRODUCTION: During adolescence the breasts undergo rapid growth and development under the influence of sex hormones. Although the hormonal etiology of breast cancer is hypothesized, it remains unknown whether adolescent sex hormones are associated with adult breast density, which is a strong risk factor for breast cancer.
METHODS: Percentage of dense breast volume (%DBV) was measured in 2006 by magnetic resonance imaging in 177 women aged 25–29 years who had participated in the Dietary Intervention Study in Children from 1988 to 1997. They had sex hormones and sex hormone-binding globulin (SHBG) measured in serum collected on one to five occasions between 8 and 17 years of age. Multivariable linear mixed-effect regression models were used to evaluate the associations of adolescent sex hormones and SHBG with %DBV.
RESULTS: Dehydroepiandrosterone sulfate (DHEAS) and SHBG measured in premenarche serum samples were significantly positively associated with %DBV (all Ptrend ≤0.03) but not when measured in postmenarche samples (all Ptrend ≥0.42). The multivariable geometric mean of %DBV across quartiles of premenarcheal DHEAS and SHBG increased from 16.7 to 22.1 % and from 14.1 to 24.3 %, respectively. Estrogens, progesterone, androstenedione, and testosterone in pre- or postmenarche serum samples were not associated with %DBV (all Ptrend ≥0.16).
CONCLUSIONS: Our results suggest that higher premenarcheal DHEAS and SHBG levels are associated with higher %DBV in young women. Whether this association translates into an increased risk of breast cancer later in life is currently unknown.
Breast Cancer Research 06/2015; 17(1):77. DOI:10.1186/s13058-015-0581-4 · 5.33 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We aimed to determine if adult bone mineral density (BMD) susceptibility loci were associated with pediatric bone mass and density, and if sex and pubertal stage influenced any association. We analyzed prospective areal BMD (aBMD) and bone mineral content (BMC) data from the Bone Mineral Density in Childhood Study (N = 603, European ancestry, 54% female). Linear mixed models were used to assess if 77 single nucleotide polymorphisms (SNPs) near known adult BMD susceptibility loci interacted with sex and pubertal stage to influence the aBMD/BMC; adjusting for age, BMI, physical activity, and dietary calcium. The strongest main association was observed between a SNP near C7orf58 and distal radius aBMD. However, this association had a significant sex•SNP interaction, revealing a significant association only in females (b = -0.32, P = 1.8 × 10(-6) ). Furthermore, the C12orf23 locus had significant interactions with both sex and pubertal stage, revealing associations in females during Tanner stage I for total hip aBMD (b = 0.24, P = 0.001) and femoral neck aBMD (b = 0.27, P = 3.0 × 10(-5) ). In contrast, the sex•SNP interactions for loci near LRP5 and WNT16 uncovered associations that were only in males for total body less head BMC (b = 0.22, P = 4.4 × 10(-4) ) and distal radius aBMD (b = 0.27, P = 0.001), respectively. Furthermore, the LRP5 locus interacted with both sex and pubertal stage, demonstrating associations that were exclusively in males during Tanner V for total hip aBMD (b = 0.29, P = 0.003). In total, significant sex•SNP interactions were found at 15 loci; pubertal stage•SNP interactions at 23 loci and 19 loci interacted with both sex and pubertal stage. In conclusion, variants originally associated with adult BMD influence bone mass in children of European ancestry, highlighting the fact that many of these loci operate early in life. However, the direction and magnitude of associations for a large number of SNPs only became evident when accounting for sex and maturation. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 03/2015; DOI:10.1002/jbmr.2508 · 6.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Elevated mammographic density is a breast cancer risk factor, which has a suggestive, but unproven, relationship with increased exposure to sex steroid hormones. We examined associations of serum estrogens and estrogen metabolites with area and novel volume mammographic density measures among 187 women, ages 40–65, undergoing diagnostic breast biopsies at an academic facility in Vermont. Serum parent estrogens, estrone and estradiol, and their 2-, 4-, and 16-hydroxylated metabolites were measured using liquid chromatography-tandem mass spectrometry. Area mammographic density was measured in the breast contralateral to the biopsy using thresholding software; volume mammographic density was quantified using a density phantom. Linear regression was used to estimate associations of estrogens with mammographic densities, adjusted for age and body mass index, and stratified by menopausal status and menstrual cycle phase. Weak, positive associations between estrogens, estrogen metabolites, and mammographic density were observed, primarily among postmenopausal women. Among premenopausal luteal phase women, the 16-pathway metabolite estriol was associated with percent area (p = 0.04) and volume (p = 0.05) mammographic densities and absolute area (p = 0.02) and volume (p = 0.05) densities. Among postmenopausal women, levels of total estrogens, the sum of parent estrogens, and 2-, 4- and 16-hydroxylation pathway metabolites were positively associated with area density measures (percent: p = 0.03, p = 0.04, p = 0.01, p = 0.02, p = 0.07; absolute: p = 0.02, p = 0.02, p = 0.01, p = 0.02, p = 0.03, respectively) but not volume density measures. Our data suggest that serum estrogen profiles are weak determinants of mammographic density and that analysis of different density metrics may provide complementary information about relationships of estrogen exposure to breast tissue composition.
[Show abstract][Hide abstract] ABSTRACT: A dietary assessment instrument designed for use in a nationally representative pediatric population was required to examine associations between calcium intake and bone mineral accrual in a large, multicenter study.
Journal of the American Academy of Nutrition and Dietetics 02/2015; 115(4). DOI:10.1016/j.jand.2014.12.016 · 2.44 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Mid-thigh cross-sectional muscle area (CSA), muscle attenuation, and greater trochanter soft tissue thickness have been shown to be independent risk factors of hip fracture. Our aim was to determine whether muscle and adipose tissue measures derived from DXA scans would have a similar risk association as those measured using other imaging methods. Using a case-cohort study design, we identified 169 incident hip fracture cases over an average of 13.5 years among participants from the Health ABC Study, a prospective study of 3,075 individuals initially aged 70-79. We modeled the thigh 3D geometry and compared DXA and CT measures. DXA-derived thigh CSA, muscle attenuation, and subcutaneous fat thickness were found to be highly correlated to their CT counterparts (Pearson's r = 0.82, 0.45, and 0.91, respectively; p < 0.05). The fracture risk of men and women were calculated separately. We found that decreased subcutaneous fat, CT thigh muscle attenuation, and appendicular lean mass by height squared (ALM/Ht2) were associated with fracture risk in men, hazard ratios (HR) equal 1.44 (1.02, 2.02), 1.40 (1.05, 1.85), and 0.58 (0.36, 0.91) respectively after adjusting for age, race, clinical site, BMI, chronic disease, hip BMD, self-reported health, alcohol use, smoking status, education, physical activity, cognitive function. In a similar model for women, only decreases in subcutaneous fat and DXA CSA were associated with hip fracture risk, HR equal 1.39 (1.07, 1.82) and 0.78 (0.62, 0.97) respectively. Men with a high ALM/Ht2 and low subcutaneous fat thickness had over 8 times higher risk for hip fracture compared to those with low ALM/Ht2 and high subcutaneous fat. In women, ALM/Ht2 did not improve the model when subcutaneous fat included. We conclude that the DXA-derived subcutaneous fat thickness is a strong marker for hip fracture risk in both men and women, and especially men with high ALM/Ht2. This article is protected by copyright. All rights reserved
Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 01/2015; DOI:10.1002/jbmr.2469 · 6.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Childhood and adolescence are critical periods of bone mineral content (BMC) accrual that may have long-term consequences for osteoporosis in adulthood. Adequate dietary calcium intake and weight-bearing physical activity are important for maximizing BMC accrual. However, the relative effects of physical activity and dietary calcium on BMC accrual throughout the continuum of pubertal development in childhood remains unclear. The purpose of this study was to determine the effects of self-reported dietary calcium intake and weight-bearing physical activity on bone mass accrual across the five stages of pubertal development in a large, diverse cohort of US children and adolescents. The Bone Mineral Density in Childhood study was a mixed longitudinal study with 7393 observations on 1743 subjects. Annually, we measured BMC by dual-energy X-ray absorptiometry (DXA), physical activity and calcium intake by questionnaire, and pubertal development (Tanner stage) by examination for up to 7 years. Mixed-effects regression models were used to assess physical activity and calcium intake effects on BMC accrual at each Tanner stage. We found that self-reported weight-bearing physical activity contributed to significantly greater BMC accrual in both sexes and racial subgroups (black and nonblack). In nonblack males, the magnitude of the activity effect on total body BMC accrual varied among Tanner stages after adjustment for calcium intake; the greatest difference between high- and low-Activity boys was in Tanner stage 3. Calcium intake had a significant effect on bone accrual only in nonblack girls. This effect was not significantly different among Tanner stages. Our findings do not support differential effects of physical activity or calcium intake on bone mass accrual according to maturational stage. The study demonstrated significant longitudinal effects of weight-bearing physical activity on bone mass accrual through all stages of pubertal development.
Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 01/2015; 30(1). DOI:10.1002/jbmr.2319 · 6.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Study Design. A descriptive study of the association between diffuse idiopathic skeletal hyperostosis (DISH) and kyphosis. Objective. To investigate the association of DISH with Cobb angle of kyphosis in a large cohort of older subjects from the Health Aging and Body Composition Study. Summary of Background Data. DISH and thoracic kyphosis are well-defined radiographical findings in spines of older individuals. Characteristics of DISH (ossifications between vertebral segments) reflect changes of spine anatomy and physiology that may be associated with Cobb angle of kyphosis. Methods. Using data from 1172 subjects aged 70 to 79 years, we measured DISH and Cobb angle of kyphosis from computed tomographic lateral scout scans. Characteristics of participants with and without DISH were assessed using the. 2 and t tests. Association between DISH and Cobb angle was analyzed using linear regression. Cobb angle and DISH relationship was assessed at different spine levels (thoracic and lumbar). Results. DISH was identified on computed tomographic scout scan in 152 subjects with 101 cases in only the thoracic spine and 51 in both thoracic and lumbar spine segments. The mean Cobb angle of kyphosis in the analytic sample was 31.3 degrees (standard deviation = 11.2). The presence of DISH was associated with a greater Cobb angle of 9.1 degrees and 95% confidence interval (95% CI) (5.6-12.6) among African Americans and a Cobb angle of 2.9 degrees and 95% CI (0.5-5.2) among Caucasians compared with those with no DISH. DISH in the thoracic spine alone was associated with a greater Cobb angle of 10.6 degrees and 95% CI (6.5-14.7) in African Americans and a Cobb angle of 3.8 degrees and 95% CI (1.0-6.5) in Caucasians compared with those with no DISH. Conclusion. DISH is associated with greater Cobb angle of kyphosis, especially when present in the thoracic spine alone. The association of DISH with Cobb angle is stronger within the African American population.
[Show abstract][Hide abstract] ABSTRACT: This study prospectively investigates associations between youth moderate-to-vigorous-intensity physical activity (MVPA) and body composition in young adult women using data from the Dietary Intervention Study in Children (DISC) and the DISC06 Follow-Up Study. MVPA was assessed by questionnaire on 5 occasions between the ages 8 and 18 years and at age 25-29 years in 215 DISC female participants. Using whole body dual-energy x-ray absorptiometry (DXA), overall adiposity and body fat distribution were assessed at age 25-29 years by percent body fat (%fat) and android-to-gynoid (A:G) fat ratio, respectively. Linear mixed effects models and generalized linear latent and mixed models were used to assess associations of youth MVPA with both outcomes. Young adult MVPA, adjusted for other young adult characteristics, was significantly inversely associated with young adult %fat (%fat decreased from 37.4% in the lowest MVPA quartile to 32.8% in the highest (p-trend=0.02)). Adjusted for youth and young adult characteristics including young adult MVPA, youth MVPA also was significantly inversely associated with young adult %fat (β=-0.40 per 10 MET-hrs/wk, p=0.02) . No significant associations between MVPA and A:G fat ratio were observed. Results suggest that youth and young adult MVPA are important independent predictors of adiposity in young women.
[Show abstract][Hide abstract] ABSTRACT: Background: Breast density is a strong risk factor for breast cancer and reflects epithelial and stromal content. Breast tissue is particularly sensitive to hormonal stimuli before it fully differentiates following the first full-term pregnancy. Few studies have examined associations between sex hormones and breast density among young women. Methods: We conducted a cross-sectional study among 180 women ages 25 to 29 years old who participated in the Dietary Intervention Study in Children 2006 Follow-up Study. Eighty-five percent of participants attended a clinic visit during their luteal phase of menstrual cycle. Magnetic resonance imaging measured the percentage of dense breast volume (%DBV), absolute dense breast volume (ADBV), and absolute nondense breast volume (ANDBV). Multiple-linear mixed-effect regression models were used to evaluate the association of sex hormones and sex hormone-binding globulin (SHBG) with % DBV, ADBV, and ANDBV. Results: Testosterone was significantly positively associated with % DBV and ADBV. The multivariable geometric mean of % DBV and ADBV across testosterone quartiles increased from 16.5% to 20.3% and from 68.6 to 82.3 cm(3), respectively (P-trend <= 0.03). There was no association of% DBV or ADBV with estrogens, progesterone, non-SHBG-bound testosterone, or SHBG (P-trend <= 0.27). Neither sex hormones nor SHBG was associated with ANDBV except progesterone; however, the progesterone result was nonsignificant in analysis restricted to women in the luteal phase. Conclusions: These findings suggest a modest positive association between testosterone and breast density in young women. Impact: Hormonal influences at critical periods may contribute to morphologic differences in the breast associated with breast cancer risk later in life. Cancer (C) 2014 AACR.
[Show abstract][Hide abstract] ABSTRACT: Summary New models describing anthropometrically adjusted normal values of bone mineral density and content in children have been created for the various measurement sites. The inclusion of multiple explanatory variables in the models provides the opportunity to calculate Z-scores that are adjusted with respect to the relevant anthropometric parameters. Introduction Previous descriptions of children’s bone mineral measurements by age have focused on segmenting diverse populations by race and sex without adjusting for anthropometric variables or have included the effects of a single anthropometric variable. Methods We applied multivariate semi-metric smoothing to the various pediatric bone-measurement sites using data from the Bone Mineral Density in Childhood Study to evaluate which of sex, race, age, height, weight, percent body fat, and sexual maturity explain variations in the population’s bone mineral values. By balancing high adjusted R 2 values with clinical needs, two models are examined. Results At the spine, whole body, whole body sub head, total hip, hip neck, and forearm sites, models were created using sex, race, age, height, and weight as well as an additional set of models containing these anthropometric variables and percent body fat. For bone mineral density, weight is more important than percent body fat, which is more important than height. For bone mineral content, the order varied by site with body fat being the weakest component. Including more anthropometrics in the model reduces the overlap of the critical groups, identified as those individuals with a Z-score below −2, from the standard sex, race, and age model. Conclusions If body fat is not available, the simpler model including height and weight should be used. The inclusion of multiple explanatory variables in the models provides the opportunity to calculate Z-scores that are adjusted with respect to the relevant anthropometric parameters.
Osteoporosis International 10/2014; 26(3). DOI:10.1007/s00198-014-2916-x · 4.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Breast density is an established predictor of breast cancer risk, and there is considerable interest in associations of modifiable lifestyle factors, such as diet, with breast density.
Journal of the American Academy of Nutrition and Dietetics 10/2014; 115(3). DOI:10.1016/j.jand.2014.08.015 · 2.44 Impact Factor