The Impact of Whole Egg Consumption on Bone Accrual in Healthy Children: A Randomized Controlled Trial.

Dietary interventions designed to examine the role of nutrition on childhood bone accrual have often focused on the role of individual micronutrients (eg, calcium, vitamin D, and zinc) and macronutrients (eg, protein). The osteogenic benefits of whole foods, such as eggs, are not well understood despite eggs being a source of high-quality nutrients and bioactive compounds known to positively influence bone. A significant positive cross-sectional association between whole egg consumption and tibia cortical bone mass has recently been shown in young children; however, randomized controlled trials (RCTs) have not been conducted. This study is a double-blind RCT in male and female children ages 9-13 years of different ancestries, designed to determine if consuming food products with whole eggs (equivalent to 8-10 eggs/wk) versus foods with milk or gelatin (placebo) over a 9-month period will improve measures of bone strength. Total body less head (TBLH) and lumbar spine bone mineral content (BMC) and areal bone mineral density (aBMD) were assessed using dual-energy X-ray absorptiometry (DXA). DXA Z-scores were computed using published pediatric growth charts and were adjusted for height-for-age Z-score (HAZ). Mid-tibia cortical volumetric BMD, BMC, cortical area, total bone area, cortical thickness, and strength strain index were measured using peripheral quantitative computed tomography. Overall, there were no significant intervention effects for any bone outcomes. The increase in spine BMCHAZ Z-score in the egg group versus the gelatin group approached significance (p = 0.07). Significant time effects in TBLH aBMDHAZ Z-score occurred as all groups decreased over 9 months (p < 0.03). Most tibia cortical bone outcomes increased over time (all p < 0.02), but changes did not differ across intervention groups. Whole eggs provide important nutritional benefits for children, but the bone responses to consumption of 8-10 eggs/wk over a period of 9 months in children entering the early stages of puberty were small. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

The effects of 9 months of formulated whole-egg or milk powder food products as meal or snack replacements on executive function in preadolescents: A randomized, placebo-controlled trial.

BACKGROUND: Elevated brain choline is associated with better executive functions in preadolescents. Manipulating dietary choline prospectively in preadolescents using egg supplementation could improve executive functions via effects on brain cellular and neurotransmitter functions. OBJECTIVES: We tested the 9-month impacts of egg supplementation on executive functions. It was hypothesized that preadolescents who consumed meal or snack replacement products containing powder made from whole eggs would have the largest improvements in executive functions after 9 months compared to those consuming similar products with either added milk powder or gelatin as a placebo. METHODS: A randomized, parallel-group, double-blinded, placebo-controlled trial design was used. The executive functions of 122 preadolescents (58 females) aged 9-13 were analyzed before and after the 9-month intervention. The primary outcomes were 3 NIH Toolbox-Cognitive Battery measures of executive function: mental flexibility, working memory, and selective attention and inhibitory control. Participants were randomized to consume food products with either: 1) whole egg powder; 2) milk powder; or 3) gelatin as a placebo, all matched on macronutrient content and used as replacements for commonly consumed foods (i.e., waffles, pancakes, macaroni and cheese, ice cream, and brownies). Hypothesis testing used mixed-effects models that included physical activity and sleep scores as covariates. RESULTS: A statistically significant group × time interaction for selective attention and inhibitory control was found (P = 0.049) for the milk group. This interaction resulted from no change for the placebo group and an improvement in selective attention and inhibitory control performance for the milk group by a T-score of 5.8; the effect size (d) was 0.44 SD units. Other comparisons were statistically insignificant. CONCLUSIONS: Consumption of foods with added milk powder as a replacement for snacks or meals for 9 months improves selective attention and inhibitory control in preadolescents. Replacement of foods with added whole egg powder does not impact 9-month changes in preadolescent executive functions. This trial was registered at clinicaltrials.gov as NCT03739424.

Adherence to the Dietary Approaches to Stop Hypertension (DASH) diet is associated with low levels of insulin resistance among heart failure patients.

BACKGROUND AND AIMS: Heart failure (HF) patients are at risk of developing type 2 diabetes. This study examined the association between adherence to the Dietary Approaches to Stop Hypertension (DASH) diet and insulin resistance among U.S. adults with HF. METHODS AND RESULTS: Using data from National Health and Nutrition Examination Survey 1999-2016 cycles, we included 348 individuals aged 20+ years with HF and no history of diabetes. DASH diet adherence index quartile 1 indicated the lowest and quartile 4 indicated the highest adherence. The highest level of insulin resistance was defined by the upper tertile of the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). Associations between level of insulin resistance and DASH diet adherence and its linear trends were examined using logistic regressions. Trend analyses showed that participants in upper DASH diet adherence index quartiles were more likely older, female, non-Hispanic White, of normal weight, and had lower levels of fasting insulin than those in lower quartiles. Median values of HOMA-IR from lowest to highest DASH diet adherence index quartiles were 3.1 (interquartile range, 1.8-5.5), 2.9 (1.7-5.6), 2.1 (1.1-3.7), and 2.1 (1.3-3.5). Multivariable logistic analyses indicated that participants with the highest compared to the lowest DASH adherence showed 77.1% lower odds of having the highest level of insulin resistance (0.229, 95% confidence interval: 0.073-0.716; p = 0.017 for linear trend). CONCLUSION: Good adherence to the DASH diet was associated with lower insulin resistance among community-dwelling HF patients. Heart healthy dietary patterns likely protect HF patients from developing type 2 diabetes.

Prevalence and trends of type 2 diabetes mellitus and prediabetes among community-dwelling heart failure patients in the United States.

AIMS: This study estimated national prevalence and trends of diagnosed and undiagnosed type 2 diabetes mellitus (T2DM) and prediabetes among heart failure (HF) patients in the U.S. METHODS: This cross-sectional study included 527 participants aged 20+ years with a diagnosis of HF, using data from the National Health and Nutrition Examination Survey 2005-2016. We assessed prevalence estimates of diagnosed and undiagnosed T2DM and prediabetes stratified by age-standardized sociodemographic and health characteristics. Trends of T2DM and prediabetes prevalence were examined using logistic regressions. RESULTS: Prevalence rates of diagnosed and undiagnosed T2DM among HF patients were 34.7% (95% confidence interval (CI), 29.2-40.3%) and 12.8% (95% CI, 9.2-16.9%), respectively. Prediabetes affected 39.1% (95% CI, 33.6-44.9%) of HF patients. Prevalence estimates of diagnosed T2DM were significantly different between non-Hispanic White (20.1% [95% CI, 13.5-27.6%]) and Hispanic participants (52.1% [95% CI, 35.9-68.0%]) (P < 0.001). The prevalence of T2DM and prediabetes did not significantly change between 2005 and 2016. CONCLUSIONS: Prevalence rates of T2DM and prediabetes among community-dwelling HF patients in the U.S. remained high between 2005 and 2016. Prevention of and targeted intervention for T2DM among at-risk HF patients is needed, particularly among those of Hispanic origin.

Pentosidine Is Associated With Cortical Bone Geometry and Insulin Resistance in Otherwise Healthy Children.

Pentosidine is an advanced glycation end product (AGE) associated with fracture in adults with diabetes. AGE accumulation in bone collagen contributes to bone fragility but might also adversely influence bone turnover and, consequently, bone geometry. The relationships between AGEs and bone health have yet to be studied in children. Thus, the objective of this study was to assess relationships between pentosidine and cortical bone volumetric density, geometry, and estimated strength in children. Participants were otherwise healthy black and white boys and girls, ages 9 to 13 years, who were at sexual maturation stage 2 or 3 (N = 160). Tibia and radius cortical bone and muscle area (66% site) were assessed via pQCT. In fasting sera, insulin, glucose, and pentosidine were measured. The Quantitative Insulin Sensitivity Check Index (QUICKI), a measure of insulin sensitivity, was calculated. While controlling for race, sex, maturation, and height, pentosidine negatively correlated with QUICKI (P < 0.05). In unadjusted analyses, pentosidine was associated with lower radius and tibia cortical volumetric bone mineral density, bone mineral content (Ct.BMC), area (Ct.Ar), and thickness (Ct.Th); a larger radius endosteal circumference (Endo.Circ); and lower tibia polar strength strain index (all P < 0.05). While controlling for race, sex, maturation, height, and muscle area, pentosidine was negatively associated with tibia Ct.BMC, Ct.Ar, and Ct.Th but positively associated with Endo.Circ (all P < 0.05). Linear regression revealed a significant interaction between pentosidine and QUICKI in relation to tibia Ct.Th (pinteraction = 0.049), indicating that the negative relationship between pentosidine and Ct.Th was stronger in those with lower QUICKI (ie, greater insulin resistance). This is the first study to report evidence of a potentially adverse influence of AGEs on bone strength in otherwise healthy children. This relationship was strongest in children with the greatest insulin resistance, supporting further work in youth with chronic metabolic health conditions. © 2019 American Society for Bone and Mineral Research.

Serum 25-Hydroxyvitamin D and Intact Parathyroid Hormone Influence Muscle Outcomes in Children and Adolescents.

Increases in 25-hydroxyvitamin D concentrations are shown to improve strength in adults; however, data in pediatric populations are scant and equivocal. In this ancillary study of a larger-scale, multi-sited, double-blind, randomized, placebo-controlled vitamin D intervention in US children and adolescents, we examined the associations between changes in vitamin D metabolites and changes in muscle mass, strength, and composition after 12 weeks of vitamin D3 supplementation. Healthy male and female, black and white children and adolescents between the ages of 9 and 13 years from two US states (Georgia 34°N and Indiana 40°N) were enrolled in the study and randomly assigned to receive an oral vitamin D3 dose of 0, 400, 1000, 2000, or 4000 IU/d for 12 weeks between the winter months of 2009 to 2011 (N = 324). Analyses of covariance, partial correlations, and regression analyses of baseline and 12-week changes (post-baseline) in vitamin D metabolites (serum 25(OH)D, 1,25(OH)2 D, intact parathyroid hormone [iPTH]), and outcomes of muscle mass, strength, and composition (total body fat-free soft tissue [FFST], handgrip strength, forearm and calf muscle cross-sectional area [MCSA], muscle density, and intermuscular adipose tissue [IMAT]) were assessed. Serum 25(OH)D and 1,25(OH)2 D, but not iPTH, increased over time, as did fat mass, FFST, forearm and calf MCSA, forearm IMAT, and handgrip strength (p < 0.05). Vitamin D metabolites were not associated with muscle strength at baseline nor after the 12-week intervention. Changes in serum 25(OH)D correlated with decreases in forearm IMAT, whereas changes in serum iPTH predicted increases in forearm and calf MCSA and IMAT (p < 0.05). Overall, increases in 25(OH)D did not influence muscle mass or strength in vitamin D-sufficient children and adolescents; however, the role of iPTH on muscle composition in this population is unknown and warrants further investigation. © 2018 American Society for Bone and Mineral Research.

New Concepts in Vitamin D Requirements for Children and Adolescents: A Controversy Revisited.

North American and European authorities have identified thresholds up to 50 nmol/L serum 25-hydroxyvitamin D (25[OH]D) as optimal for pediatric vitamin D status. These recommendations are relative to skeletal endpoints, as vitamin D plays a pivotal role in bone mineral content (BMC) accretion. Suboptimal vitamin D consumption during youth may therefore hinder BMC acquisition, and contribute to an increased fracture risk. Though vitamin D requirements range between 400 and 800 IU/day, not all children achieve this. To encourage adequate vitamin D consumption, strategies such as supplementation, food labeling, and fortification, are currently being investigated. There is moderate support for the role of vitamin D supplementation on adolescent BMC accrual; however, factors such as age, maturation, population ancestry, and latitude, are not consistently accounted for across studies. Vitamin D is also linked with extraskeletal endpoints (e.g., muscle mass/function, adiposity, and metabolic health) in children, but the cross-sectional data do not necessarily align with results from experimental trials. Based on the evidence currently available, there is no need for a revision of the pediatric vitamin D recommendations at this time. Additional trials are required, however, to build upon the hypothesis-generating observational data, and to provide evidence for future vitamin D requirements across the globe.

A Twelve-Week Lifestyle Program to Improve Cardiometabolic, Behavioral, and Psychological Health in Hispanic Children and Adolescents.

OBJECTIVES: To examine the effectiveness of a 12-week lifestyle program on cardiometabolic, behavioral, and psychological outcomes among overweight Hispanic children and adolescents. DESIGN: A case series study with pre- and post-test analyses. Subjects/Settings/Location: A convenience sample of high-risk pediatric primary care patients (n = 22; 6 girls, 16 boys; M age = 11.73 ± 1.39 years) and their guardians in the Southeast United States. INTERVENTION: Twice per week 60 min (total of 24 h) of moderate-to-vigorous intensity boxing exercise training, 12 h of nutrition education for guardians, and a 30-min pediatrician appointment. OUTCOME MEASURES: Cardiometabolic (height [m], weight [kg], waist circumference [cm], body-mass index [BMI], BMI-z, BMI%, cholesterol [mg/dL], triglycerides [mg/dL], glucose [mg/dL], and low-density lipoprotein and high-density lipoprotein cholesterol [mg/dL]), behavioral (objective free time physical activity [PA] and sedentary time [min/day]), and psychological (self-determined exercise motivation) outcomes were measured/calculated, and paired-samples t-tests were conducted. RESULTS: A significant reduction was observed in waist circumference t(17) = -2.57, p = 0.020, d = 0.64; BMI% t(15) = -2.53, p = 0.023, d = 0.20; fasting glucose t(15) = -6.43, p < 0.001, d = 1.67; and amotivation (-) t(17) = -2.29, p = 0.036, d = 0.64; whereas a significant increase was identified in moderate t(10) = 4.01, p = 0.002, d = 1.23 and vigorous t(10) = 3.41, p = 0.007, d = 1.07 intensity PA; intrinsic motivation t(17) = 2.71, p = 0.015, d = 0.38; and introjected regulation t(17) = 2.74, p = 0.014, d = 0.64. CONCLUSIONS: A 12-week lifestyle program can be effective in improving selected health markers among overweight Hispanic children and adolescents. The positive changes in fasting glucose, BMI, and waist suggest that the participants are currently at lower risk for both type 2 diabetes and cardiovascular disease as a result of the Confidence, Ownership, Responsibility, and Exercise program.

Obese Versus Normal-Weight Late-Adolescent Females have Inferior Trabecular Bone Microarchitecture: A Pilot Case-Control Study.

Though still a topic of debate, the position that skeletal health is compromised with obesity has received support in the pediatric and adult literature. The limited data relating specifically to trabecular bone microarchitecture, however, have been relatively inconsistent. The aim of this pilot cross-sectional case-control study was to compare trabecular bone microarchitecture between obese (OB) and normal-weight (NW) late-adolescent females. A secondary aim was to compare diaphyseal cortical bone outcomes between these two groups. Twenty-four non-Hispanic white females, ages 18-19 years, were recruited into OB (n = 12) or NW (n = 12) groups based on pre-specified criteria for percent body fat (≥32 vs. <30, respectively), body mass index (>90th vs. 20th-79th, respectively), and waist circumference (≥90th vs. 25th-75th, respectively). Participants were also individually matched on age, height, and oral contraceptive use. Using magnetic resonance imaging, trabecular bone microarchitecture was assessed at the distal radius and proximal tibia metaphysis, and cortical bone architecture was assessed at the mid-radius and mid-tibia diaphysis. OB versus NW had lower apparent trabecular thickness (radius and tibia), higher apparent trabecular separation (radius), and lower apparent bone volume to total volume (radius; all P < 0.050). Some differences in radius and tibia trabecular bone microarchitecture were retained after adjusting for insulin resistance or age at menarche. Mid-radius and mid-tibia cortical bone volume and estimated strength were lower in the OB compared to NW after adjusting for fat-free soft tissue mass (all P < 0.050). These trabecular and cortical bone deficits might contribute to the increased fracture risk in obese youth.

Zinc Supplementation Does Not Alter Indicators of Insulin Secretion and Sensitivity in Black and White Female Adolescents.

Background: Zinc is a micronutrient involved in the production of, and peripheral sensitivity to, pancreatic ß cell-derived insulin. To our knowledge, the effect of zinc supplementation on insulin outcomes, and potential risk of diabetes, in otherwise healthy children in the United States has not been investigated.Objective: The objective of this study was to determine the influence of zinc supplementation on insulin outcomes in black and white girls in the early stages of adolescence. A secondary objective was to determine relations between baseline zinc concentrations and insulin outcomes.Methods: Healthy black and white girls aged 9-11 y were randomly assigned to daily supplementation of zinc (9 mg elemental Zn/d; n = 75; blacks: n = 35) or placebo (n = 72; blacks: n = 32) for 4 wk. Fasting serum insulin, glucose, and C-peptide were assessed at baseline and at 4 wk. C-peptide and glucose values were used to calculate the computer model-derived homeostatic model assessment of insulin resistance (HOMA2-IR). Changes in outcome measures were compared by using repeated-measures, mixed-model ANOVA.Results: Baseline plasma zinc was not correlated with C-peptide (r = -0.07), insulin (r = -0.06), or HOMA2-IR (r = -0.09) (all P > 0.05) after controlling for race and age. Treatment × time interactions for C-peptide and HOMA2-IR were not significant (both P > 0.05). Although the treatment × race × time interactions for C-peptide and HOMA2-IR were not significant (both P = 0.08), black girls who received the placebo experienced slight increases in C-peptide (15.7%) and HOMA2-IR (17.7%) (P = 0.06).Conclusions: Four weeks of zinc supplementation had no effect on insulin outcomes in healthy black and white early-adolescent girls, although C-peptide and HOMA2-IR tended to increase in black girls who received placebo. Additional trials that are appropriately powered should further explore the effect of zinc on markers of diabetes risk, and whether race affects this relation. This trial was registered at clinicaltrials.gov as NCT01892098.

Insulin Resistance and the IGF-I-Cortical Bone Relationship in Children Ages 9 to 13 Years.

IGF-I is a pivotal hormone in pediatric musculoskeletal development. Although recent data suggest that the role of IGF-I in total body lean mass and total body bone mass accrual may be compromised in children with insulin resistance, cortical bone geometric outcomes have not been studied in this context. Therefore, we explored the influence of insulin resistance on the relationship between IGF-I and cortical bone in children. A secondary aim was to examine the influence of insulin resistance on the lean mass-dependent relationship between IGF-I and cortical bone. Children were otherwise healthy, early adolescent black and white boys and girls (ages 9 to 13 years) and were classified as having high (n = 147) or normal (n = 168) insulin resistance based on the homeostasis model assessment of insulin resistance (HOMA-IR). Cortical bone at the tibia diaphysis (66% site) and total body fat-free soft tissue mass (FFST) were measured by peripheral quantitative computed tomography (pQCT) and dual-energy X-ray absorptiometry (DXA), respectively. IGF-I, insulin, and glucose were measured in fasting sera and HOMA-IR was calculated. Children with high HOMA-IR had greater unadjusted IGF-I (p < 0.001). HOMA-IR was a negative predictor of cortical bone mineral content, cortical bone area (Ct.Ar), and polar strength strain index (pSSI; all p ≤ 0.01) after adjusting for race, sex, age, maturation, fat mass, and FFST. IGF-I was a positive predictor of most musculoskeletal endpoints (all p < 0.05) after adjusting for race, sex, age, and maturation. However, these relationships were moderated by HOMA-IR (pInteraction < 0.05). FFST positively correlated with most cortical bone outcomes (all p < 0.05). Path analyses demonstrated a positive relationship between IGF-I and Ct.Ar via FFST in the total cohort (ßIndirect Effect = 0.321, p < 0.001). However, this relationship was moderated in the children with high (ßIndirect Effect = 0.200, p < 0.001) versus normal (ßIndirect Effect = 0.408, p < 0.001) HOMA-IR. These data implicate insulin resistance as a potential suppressor of IGF-I-dependent cortical bone development, though prospective studies are needed. © 2017 American Society for Bone and Mineral Research.

Associations among osteocalcin, leptin and metabolic health in children ages 9-13 years in the United States.

BACKGROUND: This study aimed to investigate the relationships among osteocalcin, leptin and metabolic health outcomes in children ages 9-13 years. METHODS: This was a cross-sectional analysis of baseline data from 161 boys and 157 girls (ages 9-13 years) who previously participated in a double-blinded randomized placebo controlled trial of vitamin D supplementation. Relationships among fasting serum total osteocalcin (tOC), undercarboxylated osteocalcin (ucOC), leptin, and metabolic health outcomes were analyzed. RESULTS: Approximately 52% of study participants were obese based on percent body fat cutoffs (>25% for boys and >32% for girls) and about 5% had fasting serum glucose within the prediabetic range (i.e. 100 to 125 mg/dL). Serum tOC was not correlated with leptin, glucose, insulin, HOMA-IR, or HOMA-ß after adjusting for percent body fat. However, serum ucOC negatively correlated with leptin (partial r = -0.16; p = 0.04) and glucose (partial r = -0.16; p = 0.04) after adjustment for percent body fat. Leptin was a positive predictor of insulin, glucose, HOMA-IR, and HOMA-ß after adjusting for age, sex and percent body fat (all p < 0.001). CONCLUSIONS: These data depict an inverse relationship between leptin and various metabolic health outcomes in children. However, the notion that tOC or ucOC link fat with energy metabolism in healthy children was not supported. CLINICAL TRIAL REGISTRATION NUMBER: NCT00931580.

Vitamin D Supplementation Does Not Impact Insulin Resistance in Black and White Children.

CONTEXT: Vitamin D supplementation trials with diabetes-related outcomes have been conducted almost exclusively in adults and provide equivocal findings. OBJECTIVE: The objective of this study was to determine the dose-response of vitamin D supplementation on fasting glucose, insulin, and a surrogate measure of insulin resistance in white and black children aged 9­13 years, who participated in the Georgia, Purdue, and Indiana University (or GAPI) trial: a 12-week multisite, randomized, triple-masked, dose-response, placebo-controlled vitamin D trial. DESIGN: Black and white children in the early stages of puberty (N = 323, 50% male, 51% black) were equally randomized to receive vitamin D3 (0, 400, 1000, 2000, or 4000 IU/day) for 12 weeks. Fasting serum 25-hydroxyvitamin D (25(OH)D), glucose and insulin were assessed at baseline and weeks 6 and 12. Homeostasis model assessment of insulin resistance was used as a surrogate measure of insulin resistance. Statistical analyses were conducted as intent-to-treat using a mixed effects model. RESULTS: Baseline serum 25(OH)D was inversely associated with insulin (r = −0.140, P = 0.017) and homeostasis model assessment of insulin resistance (r = −0.146, P = 0.012) after adjusting for race, sex, age, pubertal maturation, fat mass, and body mass index. Glucose, insulin, and insulin resistance increased (F > 5.79, P < .003) over the 12 weeks, despite vitamin D dose-dependent increases in serum 25(OH)D. CONCLUSIONS: Despite significant baseline inverse relationships between serum 25(OH)D and measures of insulin resistance, vitamin D supplementation had no impact on fasting glucose, insulin, or a surrogate measure of insulin resistance over 12 weeks in apparently healthy children.

Zinc Supplementation Increases Procollagen Type 1 Amino-Terminal Propeptide in Premenarcheal Girls: A Randomized Controlled Trial.

BACKGROUND: Data have shown that healthy children and adolescents have an inadequate intake of zinc, an essential nutrient for growth. It is unclear whether zinc supplementation can enhance bone health during this rapid period of growth and development. OBJECTIVE: The primary aim of this study was to determine the effect of zinc supplementation on biochemical markers of bone turnover and growth in girls entering the early stages of puberty. The secondary aim was to test moderation by race, body mass index (BMI) classification, and plasma zinc status at baseline. METHODS: One hundred forty seven girls aged 9-11 y (46% black) were randomly assigned to a daily oral zinc tablet (9 mg elemental zinc; n = 75) or an identical placebo (n = 72) for 4 wk. Fasting plasma zinc, procollagen type 1 amino-terminal propeptide (P1NP; a bone formation marker), carboxy-terminal telopeptide region of type 1 collagen (ICTP; a bone resorption marker), and insulin-like growth factor I (IGF-I) were assessed at baseline and post-test. Additional markers of bone formation (osteocalcin) and resorption (urinary pyridinoline and deoxypyridinoline) were also measured. RESULTS: Four weeks of zinc supplementation increased plasma zinc concentrations compared with placebo [mean change, 1.8 µmol/L (95% CI: 1.0, 2.6) compared with 0.2 µmol/L (95% CI: -0.3, 0.7); P < 0.01]. Zinc supplementation also increased serum P1NP concentrations compared with placebo [mean change, 23.8 µmol/L (95% CI: -14.9, 62.5) compared with -31.0 µmol/L (95% CI: -66.4, 4.2); P = 0.04). There was no effect from zinc supplementation on osteocalcin, ICTP, pyridinoline, deoxypyridinoline, or IGF-I. There was no moderation by race, BMI classification, or plasma zinc status at baseline. CONCLUSIONS: Our data suggest that 4 wk of zinc supplementation increases bone formation in premenarcheal girls. Further studies are needed to determine whether supplemental zinc can improve childhood bone strength. This trial was registered at clinicaltrials.gov as NCT01892098.

Zinc affects miR-548n, SMAD4, SMAD5 expression in HepG2 hepatocyte and HEp-2 lung cell lines.

MicroRNAs affect disease progression and nutrient status. miR-548n increased 57 % in Zn supplemented plasma from adolescent females (ages 9 to 13 years). The purpose of this study was to determine the effects of Zn concentration in cell culture on the expression of miR-548n, SMAD4 and SMAD5 in hepatocyte (HepG2) and lung epithelium (HEp-2) cell lines. Cells were incubated for 48 h in media containing 10 % Chelex 100-treated FBS (0 µM Zn), or with 15 or 50 µM Zn, before isolation of total RNA and cDNA. Expression of miR-548n, SMAD4 and SMAD5 was measured by qPCR. The ΔΔCT method was used to calculate the fold-change, and 15 µM expression levels were used as reference values. HepG2 miR-548n expression decreased 5-fold, and SMAD4 expression increased 4-fold in the absence of Zn, while HEp-2 miR-548n expression increased 10.5-fold, and SMAD5 expression increased 20-fold in the absence of Zn. HEp-2 miR-548n expression increased 23-fold, while SMAD4 expression decreased twofold, in 50 µM Zn-treated cells. However, SMAD4 and SMAD5 expression was not correlated. These data indicate that miR-548n expression is in part regulated by Zn in a cell-specific manner. SMAD4 and SMAD5 are genes in the TGF-ß/BMP signaling pathway, and SMAD5 is a putative target for miR-548n; Zn participates in regulating this pathway through controlling SMAD4 and SMAD5 expression. However, SMAD5 expression may be more sensitive to Zn than to miR-548n since SMAD5 expression was not inversely correlated with miR-548n expression.

Conflicting reports on vitamin D supplementation: Evidence from randomized controlled trials.

A significant number of children and adolescents worldwide have low serum 25(OH)D values relative to the 2010 Institute of Medicine criteria. Since approximately 90% of adult bone mineral content (BMC) is accrued by the end of adolescence, and approximately 40% of adult BMC accumulated during the 4 years surrounding peak BMC velocity, low circulating 25(OH)D during this time may attenuate gains in adolescent bone strength. Reduced bone mineralization and strength during pubertal growth tracks into adulthood and could lead to an increased risk of skeletal fractures. Observational studies examining the relationships between vitamin D and bone are conflicting and few randomized controlled trials (RCTs) have been conducted in children and adolescents. Four of these RCTs, however, provide moderate support for the role of vitamin D supplementation on BMC accrual in adolescent females with baseline serum concentrations <50 nmol/L. Though the daily vitamin D doses employed in these trials ranged from 200 to 3000 IU per day, it is not clear if a dose-response effect exists. Specific maturational stages were associated with optimal bone responses in each of these trials, but they were not consistent across studies. Furthermore, data on male children and among ethnicities other than white and Asian youth were limited in these studies and therefore reduce the generalizability of the findings. Finally, the evidence linking vitamin D supplementation to improved muscle gains and function, important variables to consider in bone health investigations during growth, might imply indirect effects of supplementation on bone. In conclusion, future RCTs are warranted that address the mechanisms by which vitamin D improves bone mineralization in adolescents, including trials that address the impact of vitamin D on muscle function.

Load-specific physical activity scores are related to tibia bone architecture.

Assessment of physical activity in clinical bone studies is essential. Two bone-specific physical activity scoring methods, the Bone Loading History Questionnaire (BLHQ) and Bone-Specific Physical Activity Questionnaire (BPAQ), have shown correlations with bone density and geometry, but not architecture. The purpose of this study was to determine relationships between physical activity scoring methods and bone architecture in non-Hispanic white adolescent females (N = 24; 18-19 years of age). Bone loading scores (BLHQ [hip and spine] and past BPAQ) and energy expenditure (7-day physical activity recall) were determined from respective questionnaires. Estimates of trabecular and cortical bone architecture at the nondominant radius and tibia were assessed via magnetic resonance imaging. Total body and regional areal bone mineral density (aBMD), as well as total body fat mass and fat-free soft tissue (FFST) mass were assessed via dual energy X-ray absorptiometry. Pearson's correlations and partial correlations adjusting for height, total body fat mass, and FFST were performed. Hip BLHQ scores were correlated with midtibia cortical volume (r = .43; p = .03). Adjusted hip and spine BLHQ scores were correlated with all midtibia cortical measures (r = .50-0.58; p < .05) and distal radius apparent trabecular number (r = .46-0.53; p < .05). BPAQ scores were correlated with all midtibia cortical (r = .41-0.51; p < .05) and most aBMD (r = .47-0.53; p < .05) measures. Energy expenditure was inversely associated with femoral neck aBMD only after statistical adjustment (r = .49, p < .05). These data show that greater load-specific physical activity scores, but not energy expenditure, are indicative of greater midtibia cortical bone quality, thus supporting the utility of these instruments in musculoskeletal research.

Weight gain in college females is not prevented by isoflavone-rich soy protein: a randomized controlled trial.

Human clinical trials targeted at preventing gains in body weight using soy protein and isoflavones are limited to adults and yield conflicting results. We hypothesized that daily intake of soy protein/isoflavones would attenuate gains in body weight to a greater extent than a casein-based control in 18 to 19 year-old females. To test this hypothesis, we conducted a randomized, double blind, placebo-controlled trial over 16 weeks to examine the effects of a soy protein/isoflavone-based meal replacement (experimental group) versus a casein-based meal replacement (control group) on body weight and body composition variables in female college freshmen (N = 120). Fat mass (FM), fat-free soft tissue mass (FFST), and percent body fat (%BF) were measured using dual energy X-ray absorptiometry (DXA; Delphi A). Repeated measures mixed models were used to determine the effects of treatment on anthropometric and body composition variables (body weight, waist circumference, FM, FFST, and %BF). No significant group×time interactions were observed, even when body mass index was controlled for in the analysis. Over 16 weeks, body weight, FM, FFST, and %BF significantly increased in both groups (P < .05). Our findings show that female college freshmen gained a significant amount of weight over the course of the 16-week study. Gains in body weight and FM were similar among participants assigned to the soy protein/isoflavone- and the casein-based meal replacements. Future research is warranted to determine the effects of soy protein/isoflavone- and casein-based meal replacements versus a non-intervention (i.e., non-protein based) control.

Adenovirus 36, adiposity, and bone strength in late-adolescent females.

Adenovirus 36 (Ad36) is the only adenovirus to date that has been linked with obesity in humans. Our previous studies in late-adolescent females suggest that excess weight in the form of fat mass is associated with lower cortical bone strength. The purpose of this study was to assess the relationship between Ad36-specific antibodies, adiposity, and bone strength in our sample of late-adolescent females. A cross-sectional study of 115 females aged 18 to 19 years was performed. Participants were classified according to adiposity by dual-energy X-ray absorptiometry (body fat percentage as normal-fat [ < 32% body fat; n = 93] or high-fat [ ≥ 32% body fat; n = 22]), and according to the presence of Ad36-specific neutralizing antibodies. Peripheral quantitative computed tomography measured bone parameters at the 4% (trabecular bone) and 20% (cortical bone) site, and muscle cross-sectional area (MCSA) at the 66% site, from the distal metaphyses of the radius and the tibia. Bone strength was determined from volumetric bone mineral density and bone geometry to calculate bone strength index (BSI; trabecular site) and polar strength-strain index (SSI; cortical site). After adjustment for MCSA and limb length, radial SSI was lower in Ad36+ versus Ad36- subjects from the high-fat group (p < 0.03), but not the normal-fat group. No significant differences were observed between groups in tibial SSI or BSI. These data support an association of adiposity and cortical bone strength at the radius with the presence of neutralizing antibodies to Ad36 in late-adolescent females.

Bone turnover is not influenced by serum 25-hydroxyvitamin D in pubertal healthy black and white children.

Low serum 25-hydroxyvitamin D [25 (OH) D] is common in healthy children particularly in blacks. However, serum 25 (OH) D concentrations for optimal bone turnover in children is unknown and few data exist that describe effects of increasing serum 25 (OH) D on bone turnover markers during puberty. The purpose of this study was to determine the relationships between serum 25 (OH) D and changes in serum 25 (OH) D and bone turnover in white and black pubertal adolescents. Bone turnover markers were measured in 318 healthy boys and girls from Georgia (34°N) and Indiana (40°N) who participated in a study of oral vitamin D(3) supplementation (0 to 4000 IU/d). Serum 25 (OH) D, osteocalcin, bone alkaline phosphatase, and urine N-telopeptide cross-links were measured at baseline and 12 weeks. Relationships among baseline 25 (OH) D and bone biomarkers, and between changes over 12 weeks were determined and tested for effects of race, sex, latitude, and baseline 25 (OH) D. Median 25 (OH) D was 27.6 ng/mL (n=318, range 10.1-46.0 ng/mL) at baseline and 34.5 ng/mL (n=302, range 9.7-95.1 ng/mL) at 12 weeks. Neither baseline nor change in 25 (OH) D over 12 weeks was associated with bone turnover. The lack of association was not affected by race, sex, latitude, or baseline serum 25 (OH) D. Serum 25 (OH) D in the range of 10-46 ng/mL appears to be sufficient for normal bone turnover in healthy black and white pubertal adolescents.