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Intestinal magnesium (Mg) absorption was measured in six healthy children (control) and in four children treated for acute lymphoblastic leukemia with the single-isotope fecal recovery technique (SIFRT). The objective of this study was to determine Mg absorption in young children with acute lymphoblastic leukemia using stable isotope tracers. Fractional and absolute absorption levels determined by SIFRT were not significantly different between children with acute lymphoblastic leukemia (fractional absorption: 58.3 +/- 10.6% [mean +/- SEM], absolute absorption: 3.66 +/- 0.71 mg x kg(-1) x d(-1), [0.15 +/- 0.03 mmol x kg(-1) x d(-1)]) and control children (fractional absorption: 61.4 +/- 7.5%, absolute absorption: 5.69 +/- 0.85 mg x kg(-1) x d(-1), [0.23 +/- 0.03 mmol x kg(-1) x d(-1)]). Average Mg absorption in young children (aged 3--8 y) was 60.2 +/- 5.8%. This study describes the first application of the SIFRT to assess Mg absorption in young children and illustrates the feasibility of the SIFRT in this age group to obtain more accurate information on Mg absorption.

Extremely low birth weight infants who develop severe respiratory disease may have special nutrient requirements imposed by a combination of enhanced utilization of nutrients or the need for epithelial cell repair resulting from the disease process, as well as to support catch-up growth. Inositol, free fatty acids, vitamin E and vitamin A are proposed as nutrients for which infants at risk of chronic pulmonary insufficiency may have special requirements. Of these nutrients, only for vitamin A does suggestive evidence exist that high doses when given intramuscularly may reduce the incidence of death or chronic lung disease. Exogenous steroid therapy (dexamethasone), which is often used to improve pulmonary compliance in ventilated premature infants, may compromise vitamin A status and induce restricted somatic and bone mineral growth. Supplemental nutrition by means of enriched infant formulas has provided benefits in growth and bone mass accretion to infants recovering from bronchopulmonary dysplasia up to 3-mo corrected age. This growth advantage was not sustained over the subsequent 9 mo, suggesting that prolonged nutritional support is required until catch-up growth is complete. Further studies are required to delineate the needs for specific nutrients such as antioxidant vitamins and minerals or vitamin A that may play a role in preventing severe chronic lung disease in premature infants. As well, the role of supplemental nutrition (beyond the requirements of term infants) to support catch-up growth and maintenance during the critical stages of early development requires further investigation before evidence-based nutrient recommendations can be developed for this special population of infants.

Interactions between Ca(+2) and Zn(+2) at the intestinal brush border membrane occur via unclear mechanisms. We hypothesized that Zn(+2) and Ca(+2) are transported across the brush border membrane via a multidivalent metal channel. Using brush border membrane vesicles (BBMV) prepared from intestines of 8 sow-fed piglets, we sought to determine whether Ca(+2) competes with Zn(+2) for uptake. Extravesicular Zn(+2) was removed with ethylenediamine-tetraacetic acid. Time curves of Zn(+2) and Ca(+2) uptake by BBMV were conducted with increasing concentrations of Ca(+2) and Zn(+2), respectively. Saturation curves compared kinetic parameters of Zn(+2) uptake with and without Ca(+2). In addition, Zn(+2) uptake was measured in the presence of various classical Ca(+2) channel modulators. Over 20 min, a 0.4x concentration of Zn(+2) lowered Ca(+2) uptake by vesicles, whereas a 30x concentration of Ca(+2) was necessary to lower Zn(+2) uptake. These data suggest that Ca(+2) has lower affinity than Zn(+2) for a brush border membrane transport protein. Kinetic parameters showed higher K(m) values with 4 or 15 mM Ca(+2) but unchanged J(max), suggesting competitive inhibition. The Ca(+2) channel blocking agents, La(+3), Ba(+2), verapamil, and diltiazem, inhibited Zn(+2) uptake, whereas calcitriol, trans 1,2 cyclohexanediol, cis/trans 1,3 cyclohexanediol, and the L-type Ca(+2) channel agonist, Bay K8644, induced Zn(+2) uptake. These data were consistent with competition for a common transport mechanism on the brush border membrane, possibly a novel multimetal channel. Copyright 2001 Elsevier Science Inc.

The objectives of this study were 1) to determine whether a zenith in bone formation (indicated by circulating osteocalcin) existed at night in early life, and 2) to compare the effects of three different dexamethasone (DEX) treatment regimens on bone turnover, bone mineral content, and growth. Three DEX treatment regimens were tested in 8-d-old piglets (n = 8/group):1) low evening dose of DEX (0.5 mg/kg/d) as 70% in the morning and 30% in the evening for 10 d;2) tapering course of DEX (0.5, 0.3, and 0.2 mg/kg/d) as 50% in the morning and 50% in the evening for 14 d; and 3) constant dose of DEX (0.5 mg/kg/d) as 50% in the morning and 50% in the evening for 10 d. Oral water placebo groups were tested with the same time courses. At pretreatment, plasma osteocalcin was significantly higher (p < 0.05) at 0100 than at 0900 and 1700. At necropsy, measures for DEX groups were calculated as Z-scores using values from the placebo groups. The low evening DEX dose led to a significantly lower reduction in plasma osteocalcin compared with the tapered and constant dosing regimens (p < 0.05). The significant weight reduction in the DEX group occurred at d 9 in the low evening dose regimen but at d 7 in the constant dosing regimen, compared with the placebo group. Bone mineral content Z-score was reduced similarly in all DEX-treated groups across the three dosing regimens. We conclude that a plasma osteocalcin zenith at night exists in early life. A high DEX dose in the morning and low DEX dose in the evening may partially attenuate corticosteroid-induced suppression of bone formation and growth restriction.

The workshop entitled "Early Risk Determinants and Later Health Outcomes: Implications for Research Prioritization and the Food Supply," reported in this issue, was borne of a quest to consolidate current knowledge on the early determinants of maternal and child health outcomes related to obesity, cardiovascular disease risk, and neurodevelopment. The primary goal was to delineate the relative influence of genetics and environmental factors, particularly in relation to specific nutrients and food components, on determinants of risk within the developmental stages of pregnancy, infancy (0-12 mo), and early childhood up to 5 y of age. A panel of experts was charged with critiquing the evidence presented and with identifying research gaps and challenges for future research, such as when and how the food industry might translate knowledge of the determinants of disease into improvements in human health through food product development.

As the rate of survival of premature infants isincreasing, more attention is necessarily focused onimproving the quality of survival through optimalnutritional management. The nutritional needs of the premature infant are greater than at any othertime in the life cycle. The benefits of human milk forterm infants are well known. Emerging data suggest thathuman milk may especially benefit the premature infant. The human milk-fed premature infant mayexperience improved health (such as lower rates ofinfection and necrotizing enterocolitis),gastrointestinal function, and neurodevelopment. Thesefactors may outweigh the concerns about adequategrowth, nutrient accretion, and biochemical indices ofnutritional status attributed to the lower nutrientcontent of human milk compared with preterm formula.Some of the nutritional concerns may be met by theuse of multinutrient supplements during the time infantsreceive tube-feeding, generally the time prior toattaining complete oral feeding in-hospital. The available data suggest that the quality ofsurvival of premature infants can be improved, both inthe short-term and long-term, through the feeding ofhuman milk.

(1) To determine whether nutrient malabsorption or inadequate nutrient intake were involved in the cause of growth delay in patients with bronchopulmonary dysplasia, and (2) to determine whether a nutrient-enriched formula given to infants with bronchopulmonary dysplasia to 3 months corrected age improves the rate of growth with greater lean and bone mass accretion when compared with infants fed an isoenergetic standard infant formula.A blinded, nutrition intervention trial of 60 preterm infants with bronchopulmonary dysplasia (birth weight, 866 +/- 169 g, gestational age, 26 +/- 1.5 weeks) randomized to either nutrient-enriched formula or standard formula. Growth, body composition, and nutrient retention were compared between groups by Student's t tests and analysis of covariance.Infants fed the enriched formula had significantly greater nitrogen and mineral retention at 38 weeks' postmenstrual age, and only the infants fed enriched formula had zinc retention similar to the intrauterine accretion. At 3 months corrected age infants fed enriched formula attained greater length (P.05), greater radial bone mineral content (P.01), and greater lean mass (P.01). The male infants in the enriched formula group had greater whole body bone mineral content than did male infants in the standard formula group (P = .02).Greater linear growth and lean and bone mass in the enriched formula group suggests that infants with bronchopulmonary dysplasia attain faster "catch-up" growth when fed higher intakes of protein, calcium, phosphorus, and zinc than provided in standard proprietary formulas.

Dexamethasone (DEX) therapy improves pulmonary compliance in premature infants with chronic lung disease; however, normal growth and bone development are impaired. Because DEX may mediate its effects by altering the GH-IGF-I axis, we investigated whether adjunctive therapy with GH or GH + IGF-I during DEX therapy could attenuate these DEX-induced effects. Piglets were randomized to placebo, oral tapered DEX (0.5, 0.3, and 0.2 mg kg(-1) d(-1) over 14 d), DEX + GH (0.1 mg kg(-1) d(-1)) or DEX + GH + IGF-I (0.1 mg kg(-1) d(-1)). Final whole body weight and length were improved with GH or GH + IGF-I compared with the DEX alone group. Plasma GH and IGF-I were not influenced by DEX, but infusion of IGF-I resulted in higher (p0.05) plasma IGF-I compared with all other groups at d 15. DEX reduced (p0.05) circulating IGFBP-2 and IGFBP-3 and liver IGFBP-2 and IGFBP-4 mRNA expression compared with controls. Treatment with DEX alone resulted in lower (p0.05) plasma osteocalcin, urinary N-telopeptide, and whole body and femur bone mineral density compared with controls, whereas results with piglets receiving adjunctive GH or GH + IGF-I were similar to those of controls. Given adjunctively, GH alone appears to partially counter the abnormalities in growth and bone metabolism associated with DEX therapy; however, this improvement cannot be attributed to higher circulating IGF-I, because combined therapy did not further improve growth or bone homeostasis compared with DEX + GH treatment. Growth hormone therapy has the potential to stimulate growth in infants exposed to steroid treatment.

Tamoxifen (Tam) has been shown to inhibit dexamethasone (Dex)-mediated effects on bone formation in vitro. Our objective was to determine whether Tam would block Dex-induced osteopenia and growth inhibition in growing piglets. Four-day-old male Yorkshire piglets were adapted to a liquid formula diet (400 ml/kg x day) and randomized to one of four groups (n = 5/group): Dex (0.5 mg/kg x day), Tam (1 mg/kg x day), Dex plus Tam, or placebo control (vehicle only). Both drugs were administered by orogastric gavage twice daily for 12 days. At baseline and at the end of treatment, whole body bone mineral density (BMD) was determined by dual energy x-ray absorptiometry (Hologic QDR1000W). Plasma osteocalcin and PTH were measured on days 0 and 12, and urinary N-telopeptide was measured on day 12. Changes in axial length and daily weight were also measured. Delta whole body BMD was 29% lower (P0.05) in Dex alone treated piglets than in controls (0.033 vs. 0.047 g/cm2, respectively), whereas the maximum change in BMD in Dex plus Tam group (0.046 g/cm2) was similar to that in controls. Concurrent Tam administration reduced the Dex-induced deficit in weight gain by 56% (P0.05) and the deficit in axial length gain by 72% (P0.01). In Dex alone treated piglets, PTH was significantly elevated (7-fold), whereas osteocalcin and N-telopeptide were significantly reduced compared with control values. These effects were prevented by Tam. These data suggest that the suppression of growth and other changes in parameters of bone metabolism induced by glucocorticoids in vivo can be attenuated by Tam.

Background Symptomatic osteopenia is a common form of morbidity in children with acute lymphoblastic leukemia (ALL) before, during, and after treatment. A causal role for corticosteroids has been proposed, but other investigators have suggested that cranial irradiation is an important factor contributing to this disorder. Procedure. In this study of children with ALL, all of whom received steroids, skeletal morbidity was assessed radiographically by an observer who was blinded to the ages of the children, their risk categorization (and related treatment), and the timing of the assessments with respect to the administration of therapy. Discussion. Skeletal morbidity was most prevalent in older subjects who had been given cranial radiotherapy. However, there was no difference in the frequency of fractures in two groups of younger children (⩽9 years of age), one irradiated and the other not. Conclusions. It is likely that corticosteroid therapy plays an important part in the pathogenesis of this disorder. The role played by cranial irradiation is much less certain. Med. Pediatr. Oncol. 30:347–350, 1998. © 1998 Wiley-Liss, Inc.

In children with acute lymphoblastic leukemia (ALL), abnormalities in mineral homeostasis and bone mass were first reported by our group in the late 1980s. Prospective longitudinal cohort studies in 40 consecutive patients receiving treatment according to the Dana-Farber Cancer Institute (DFCI) protocol 87-001 and 16 children receiving DFCI protocol 91-001 afforded us the opportunity to explore various etiologies of the observed abnormalities in mineral and bone metabolism, specifically the leukemic disease process and chemotherapeutic drugs such as steroids and aminoglycoside antibiotics. At diagnosis of ALL, >70% of children had abnormally low plasma 1,25-dihydroxyvitamin D, 73% had low osteocalcin and 64% had hypercalciuria, indicating an effect of the leukemic process on vitamin D metabolism and bone turnover. During remission induction, treatment with high-dose steroid (prednisone or dexamethasone) resulted in further reduction in plasma osteocalcin and elevated parathyroid hormone levels. During 24 months of chemotherapy-maintained remission, reduction in bone mineral content (BMC), as measured by Z-scores, occurred in 64% of children, most severely affecting those >11 years of age. A reduction in BMC during the first 6 months had a positive predictive value of 64% for subsequent fracture. By the end of 2 years of therapy, fractures occurred in 39% of children and radiographic evidence of osteopenia was found in 83% of the entire study group. Investigations of the biochemical basis of the bone abnormalities revealed that by 6 months hypomagnesemia developed in 84% of children (of whom 52% were hypermagnesuric) and plasma 1,25-dihydroxyvitamin D remained abnormally low in 70%. Altered magnesium status was attributed to renal wastage of magnesium following cyclical prednisone therapy and treatment with aminoglycoside antibiotics such as amikacin for fever accompanying neutropenia. Dietary intake and absorption of magnesium were normal. In 10 children treated for hypomagnesemia with supplemental magnesium for up to 16–20 weeks, plasma magnesium normalized in only 50% of subjects. Int. J. Cancer Supplement 11:35–39, 1998. © 1998 Wiley-Liss, Inc.

Severely malnourished children afflicted by acute lymphoblastic leukemia (ALL), particularly in developing countries, have reduced tolerance to chemotherapy and a compromised prospect for survival. We investigated the prevalence and severity of alterations in growth and nutritional status in children with ALL from population-based referral areas in Canada. All children were treated with Dana-Farber Cancer Institute ALL Consortium protocols. First, the relative impact of cranial irradiation (CI) and chemotherapy on growth was studied in 116 children at diagnosis and at 6-month intervals during treatment. We observed a decline in height standard deviation (SD) score in the first year in all children, and a further decline in height SD score during the second year only in the children who received CI. Weight reduction occurred in the first year, but during the second year there was a disproportionate increase in weight compared with height, suggesting that children treated with ALL have a tendency toward obesity. Both chemotherapy and CI contribute to the altered growth observed in children treated for ALL. Second, intestinal functional integrity was assessed in 16 children during post-induction chemotherapy. Nutrient intake was adequate and there was minimal evidence of malabsorption: fat malabsorption occurred in only 1 child (after treatment-related pancreatitis), abnormal D-xylose absorption occurred in 2 children at 6 months of therapy (returning to normal 6 months later) and abnormal lactose absorption occurred in 4 children. Third, weight, height, whole body lean and fat mass measured by dual-energy X-ray absorptiometry and serum albumin were determined at diagnosis and at 6-month intervals throughout therapy in 19 children with ALL. Height SD scores decreased significantly during treatment. Serum albumin was abnormally low in 6/19 at diagnosis and 14/18 during intensive consolidation therapy. The mean change in the ratio of lean mass to total body weight showed a 5% reduction by 6 months of therapy. Body fat increased from a mean of 22% at diagnosis to 28% at completion of therapy. The majority of children treated for ALL thus have significant changes in nutritional status manifested by reductions in growth, alterations in lean and fat body mass and abnormally low serum proteins during intensive therapy.

Dual energy X-ray absorptiometry (DXA) is a recognized tool for measurement of body composition and provides benefits of low dose radiation, quick scan time and multiple measurement options. Challenges arise in scanning children, particularly with limb movement. We aimed to validate the use of surrogate limb substitutions compared with whole-body scans by DXA for measuring fat, lean and bone mass in children. DXA scans were obtained from 3-year-old children who had normal positioning and no limb movement (n=246) or movement of a single limb (n=55). By replacing the measurements of one scanned limb with those of the opposite limb, we obtained an estimate value that was compared with the original whole-body scan measures for fat, lean and bone mass, percent whole-body fat and total mass for scans without or with movement. Original normal scan analyses were highly correlated with estimates using substitution of the surrogate limb for all body compartments (R2=0.986–0.999, P

Background: We have previously shown that the majority of survivors treated for acute lymphoblastic leukemia (ALL) in childhood recovered their bone mineral density (BMD) despite disease effects and prolonged therapy with steroids and methotrexate. However, for a subset of patients who received higher total doses of methotrexate or prednisone, bone mass remained sub-optimal. This study’s objective was to determine whether altered bone turnover was reflected in profiles of bone biomarkers as a cause of their persistently reduced bone mass. Methods: Markers of bone metabolism were measured in 31 survivors of ALL with low BMD. The results were compared to 29 ALL survivors with normal BMD that were matched for gender, age and years since diagnosis. Blood samples obtained at the time of the scan by dual energy x-ray absorptiometry for BMD measure were assayed for 25-hydroxyvitamin D, parathyroid hormone (PTH), and serum CrossLaps. Results: No difference was found between survivors with low BMD and those with normal BMD for serum 25-OH Vitamin D, PTH or serum C-terminal telopeptide of type-1 collagen (CrossLaps). Vitamin D status was lower than accepted for normal bone health in 37% of subjects and 27% of controls. Conclusion: Survivors of childhood ALL as a whole recover normal BMD. Those that have low BMD after treatments do not have evidence of any permanent alterations in markers of bone turnover. Thus, survivors of childhood ALL who have low BMD likely do so for the same reasons as the general population, such as inadequate Vitamin D status.

The purpose of this study was to determine whether trabecular bone mineralization differed in adults with type 2 diabetes compared to adults without type 2 diabetes.Proximal femur specimens were obtained following a total hip replacement procedure from men and women ≥65 years of age with and without type 2 diabetes. A scanning electron microscope was used for quantitative backscattered electron imaging (qBEI) analysis of trabecular bone samples from the femoral neck. Gray scale images (pixel size=5.6 μm(2)) were uploaded to ImageJ software and gray level (GL) values were converted to calcium concentrations (weight [wt] % calcium [Ca]) using data obtained with energy dispersive X-ray spectrometry. The following bone mineralization density distribution (BMDD) outcomes were collected: the weighted mean bone calcium concentration (CaMEAN), the most frequently occurring bone calcium concentration (CaPEAK) and mineralization heterogeneity (CaWIDTH). Differences between groups were assessed using the Student's t-test for normally distributed data and Mann-Whitney U-test for non-normally distributed data. An alpha value of0.05 was considered significant.Thirty-five Caucasian participants were recruited (mean [standard deviation, SD] age, 75.5 [6.5]years): 14 adults with type 2 diabetes (years since type 2 diabetes diagnosis, 13.5 [7.4]years) and 21 adults without type 2 diabetes. In the adults with type 2 diabetes, bone CaMEAN was 4.9% greater (20.36 [0.98]wt.% Ca versus 19.40 [1.07]wt.% Ca, p=0.015) and CaWIDTH was 9.4% lower (median [interquartile range] 3.55 [2.99-4.12]wt.% Ca versus 3.95 [0.71]wt.% Ca, p0.001) compared to controls. There was no between-group difference in CaPEAK (21.12 [0.97]wt.% Ca for type 2 diabetes versus 20.44 [1.30]wt.% Ca for controls, p=0.121).The combination of elevated mean calcium concentration in bone and lower mineralization heterogeneity in adults with type 2 diabetes may have deleterious effects on the biomechanical properties of bone. These microscopic alterations in bone mineralization, which may be mediated by suppressed bone remodeling, further elucidate higher fracture risk in adults with type 2 diabetes.

Objective To examine the temporal and dose-related effects of glucocorticoids (GCs) on body mass index (BMI) in children with rheumatic diseases. Methods Children initiating GCs for a rheumatic disease (n = 130) were assessed every 3 months for 18 months. BMI, weight, and height Z score trajectories were described according to GC starting dosage in prednisone equivalents: high (≥1.0 mg/kg/day), low (

Optimal nutrition for infants in the first year of life is essential to attain normal trajectories of growth and development. Recommended nutrient intakes or dietary standards for infants less than 1 year of age most often adopt the quantity and quality of nutrients in human milk as the reference standard. The recommended intakes are usually intended for term-born, healthy, and normally growing infants who have a birth weight of more than 2500 g (and thus not small for gestational age). In this article, the nutrient recommendations outlined reflect recent reports of the Dietary Reference Intakes for USA and Canada as published by the Institute of Medicine.

We studied the effects of different CHO supplements on exercise metabolism (1 hr at 75% ) and performance (fatigue time at 85% ) in 8 male endurance athletes Four treatments were administered in a randomized, double-blind fashion: Trial A = 3-day pretest, postexercise supplementation (177 kcal [81% carbohydrate, 19% protein] consumed < 10 min after exercise) + 600 ml 8% glucose polymers/ fructose 1 hr pretesting + 600 ml 8% glucose polymers/glucose during testing; Trial B = placebo during 3-day pretest + remainder same as Trial A; Trial C = placebo at all time points; and Trial D = same as Trial B with 8% glucose 1 hr before the test as well as during the test. Time to fatigue at 85% (Í24%) and total CHO oxidation were greater for A versus C (p < .05). Plasma glucose concentration was higher for A and B versus C, while increases in plasma potassium concentration were attenuated for A versus C (both p < .05). None of the supplements had differential effects upon hematocrit, plasma sodium [Na+] and lactate, , or rating of perceived exertion during exercise. Three-day preexercise protein + carbohydrate supplements followed by 1-hr pre- and during-exercise mixed carbohydrate supplements increased time to fatigue and carbohydrate oxidation and attenuated rises in plasma [K+] com pared to placebo.

Calcium and vitamin D metabolism, bone mineralization, and growth were studied in piglets randomly assigned to 15 d of dexamethasone (0.5 mg.kg-1.d-1, orally) or placebo. Growth velocity was significantly reduced by dexamethasone treatment (P < 0.001). Pigs in the dexamethasone group demonstrated lower 45Ca absorption by in situ intestinal perfusion (P < 0.01). Plasma 25-hydroxycholecalciferol (calcidiol) and 1,25-dihydroxycholecalciferol (calcitriol) were lower (P < 0.05) and the urinary ratio of calcium to creatinine was higher (P < 0.05) after 15 d of dexamethasone compared with placebo. Differences between pre- and postosteocalcin (P < 0.01) and pyridinoline (P < 0.01) were higher and wholebody, lumbar, and femur bone mineral density were lower (P < 0.05) in dexamethasone-treated piglets. Dexamethasone-induced reductions in bone mineral mass likely result from reduced vitamin D status, reduced intestinal calcium absorption, elevated urinary calcium loss and direct effects of the steroid on bone. When dexamethasone is used in premature infants to improve lung function, negative effects on growth and bone metabolism could occur.

Ten trace elements that are nutritionally essential include: zinc, copper, selenium, chromium, manganese, molybdenum, cobalt, fluoride, iodine, and iron. This article briefly reviews the biochemistry of these trace elements, describes clinical deficiency states, and provides a rationale for recommended enteral and parenteral intakes for preterm infants.

BACKGROUND: The influence of multiple maternal and pregnancy characteristics on offspring cardiometabolic traits at birth is not well understood and was evaluated in this study. METHODS AND FINDINGS: The Family Atherosclerosis Monitoring In earLY life (FAMILY) Study prospectively evaluated 11 cardiometabolic traits in 901 babies born to 857 mothers. The influence of maternal age, health (pre-pregnancy weight, blood pressure, glycemic status, lipids), health behaviors (diet, activity, smoking) and pregnancy characteristics (gestational age at birth, gestational weight gain and placental-fetal ratio) were examined. Greater gestational age influenced multiple newborn cardiometabolic traits including cord blood lipids, glucose and insulin, body fat and blood pressure. In a subset of 442 singleton mother/infant pairs, principal component analysis grouped 11 newborn cardiometabolic traits into 5 components (anthropometry/insulin, 2 lipid components, blood pressure and glycemia), accounting for 74% of the variance of the 11 outcome variables. Determinants of these components, corrected for sex and gestational age, were examined. Baby anthropometry/insulin was independently predicted by higher maternal pre-pregnancy weight (standardized estimate 0.30) and gestational weight gain (0.30; both p

OBJECTIVE To examine the performance of current screening recommendations for detecting dysglycemia in children and adolescents with obesity. RESEARCH DESIGN AND METHODS In a cross-sectional study, an oral glucose tolerance test and demographic (age, sex, family history of diabetes, and ethnicity), clinical (BMI z score, waist circumference, and pubertal stage), and laboratory variables used in current pediatric screening criteria for type 2 diabetes mellitus were measured in 259 overweight or obese youth aged 5–17 years. Glycemic status was based on American Diabetes Association (ADA) thresholds. The performance (sensitivity and specificity) of current screening criteria and newly developed models to identify isolated IGT were compared. RESULTS Dysglycemia was present in 20.8% of the cohort. Of the 54 participants with dysglycemia, 68% had a normal fasting glucose and were identified with the 2-h glucose test. Current ADA criteria had low sensitivity (41.7% [95% CI 25.6–57.8]) and moderate specificity (69.5% [63.5–75.6]) to identify IGT. In receiver operating characteristic (ROC) analysis, the addition of hemoglobin A1c (HbA1c) or FPG did not improve the ROC area under the curve (AUC) (HbA1c: 0.64 vs. 0.63; P = 0.54; HbA1c + FPG: 0.66; P = 0.42), but adding triglyceride level did (AUC 0.72 vs. 0.63; P = 0.03). A simple model with fasting triglyceride level >1.17 mmol/L improved AUC compared with ADA screening criteria (0.68 vs. 0.57; P = 0.04). CONCLUSIONS The prevalence of IGT is high among obese children and youth. Current screening criteria have low sensitivity to detect isolated IGT. Although adding nonfasting laboratory values to history and physical measures does not improve diagnostic accuracy, adding fasting lipid profile improves predictive value.

Objective. To determine the frequency of incident vertebral fractures (IVF) 12 months after glucocorticoid (GC) initiation in children with rheumatic diseases and to identify children at higher risk. Methods. Children with rheumatic diseases initiating GC were enrolled in a prospective observational study. Annual spine radiographs were evaluated using the Genant semiquantitative method. Spine areal bone mineral density (aBMD) was measured every 6 months. Clinical features, including cumulative GC dose, back pain, disease and physical activity, calcium and vitamin D intake, and spine aBMD Z scores, were analyzed for association with IVF. Results. Seven (6%) of 118 children (95% confidence interval 2.9-11.7%) had IVF. Their diagnoses were: juvenile dermatomyositis (n = 2), systemic lupus erythematosus (n = 3), systemic vasculitis (n = 1), and mixed connective tissue disease (n = 1). One child was omitted from the analyses after 4 months because of osteoporosis treatment for symptomatic IVF. Children with IVF received on average 50% more GC than those without (P = 0.030), had a greater increase in body mass index (BMI) at 6 months (P = 0.010), and had greater decrements in spine aBMD Z scores in the first 6 months (P = 0.048). Four (67%) of 6 children with IVF and data to 12 months had spine aBMD Z scores less than-2.0 at 12 months compared to 16% of children without IVF (P = 0.011). Conclusion. The incidence of VF 12 months following GC initiation was 6%; most children were asymptomatic. Children with IVF received more GC, had greater increases in BMI, and had greater declines in spine aBMD Z scores in the first 6 months. © 2012, American College of Rheumatology.

Osteoporosis Canada's 2010 Clinical Practice Guidelines for the Diagnosis and Management of Osteoporosis in Canada focus on the clinical impact of fragility fractures, and on the assessment and management of women and men at high risk for fragility fracture. These guidelines now integrate a 10-year absolute fracture risk prediction into an overall management approach by using validated risk assessment tools. There currently is a large gap between optimal practices and those that are now being provided to Canadians with osteoporosis. These guidelines are part of a concerted effort to close this gap. Key changes from the 2002 guidelines of interest and relevance to radiologists are highlighted in this report.

Polybrominated diphenyl ethers (PBDEs), widely used as flame retardants in commercial products, have become ubiquitous environmental contaminants. Although adult human exposure to PBDEs is well documented, developmental exposure is less well characterized. The objectives of this study were to measure maternal and fetal exposure to nine PBDE congeners and to investigate potential associations with birth weight. PBDE congeners were quantified in maternal serum at 24-28 weeks of pregnancy, delivery, and umbilical cord serum (UCS) by gas chromatography-mass spectrometry (GC/MS/MS). Complete blood sample sets were obtained from 97 pregnant women (mean age 33.1±0.5 years). PBDE-28, -47 and -99 were quantified in all samples tested and PBDE-47 was the most abundant congener measured in both maternal (mid-pregnancy and delivery samples geometric mean=26.9 and 26.9, respectively) and UCS (GM=56.0 ng g(-1) lipid). The UCS concentration for all congeners with the exception of PBDE-153 was higher vs. maternal delivery samples (p

Premature infants receive high dietary zinc and often glucocorticoids as a treatment for chronic lung disease. A piglet model was developed to investigate intestinal zinc transport and distribution of tissue zinc in response to treatment with short-term (5 d) glucocorticoid therapy or a high zinc diet. Piglets (13–15 d old; n = 21) were randomly allocated to: 1) dexamethasone (DEX) therapy (1.5 mg/kg intramuscularly twice a day), 2) high zinc diet (15.3 mmol/kg), or 3) control group (0.3 mmol dietary zinc/kg and saline intramuscularly twice a day). Pig weight, formula intake, urine volume, and blood glucose were monitored. At necropsy, tissue samples were obtained to measure zinc in plasma and zinc and metallothionein in liver and small intestinal mucosa. Velocity of zinc uptake by intestinal brush border membrane vesicles was measured using 65Zn tracer. Maximum uptake rate and Km for zinc uptake by brush border membrane vesicles were significantly greater (p < 0.05) in DEX compared with control and high zinc groups. DEX-treated piglets had a significantly lower (p < 0.05) zinc efflux rate across brush border membrane vesicles compared with that of the control. The high zinc group had a higher liver (p < 0.05) and mucosal (p < 0.05) zinc content and higher liver metallothionein concentration (p < 0.001) compared with the control and DEX groups. Weight gain over 5 d was not different among groups. Daily blood glucose was higher (p < 0.05) in DEX versus control and high zinc groups. Short-term DEX treatment induced changes in mucosal uptake of zinc that are consistent with up-regulation of specific mucosal proteins, but this was not the case with metallothionein. These alterations in zinc metabolism may have consequences for zinc status in premature infants who receive glucocorticoids such as DEX and/or high zinc diets.

See related commentary by Kanis, page [1829][1] Since the publication of the Osteoporosis Canada guidelines in 2002, there has been a paradigm shift in the prevention and treatment of osteoporosis and fractures. [1][2],[2][3] The focus now is on preventing fragility fractures and their negative

The study objective was to validate a food frequency questionnaire (FFQ) to assess calcium, vitamin D and vitamin K intakes in overweight and obese postmenopausal community-dwelling women. The FFQ was validated against intakes derived from a 5-day diet record (5DDR) that also included assessment of supplement intake. Strong correlations between methods were observed for all nutrients (r = 0.63, 0.89, 0.54 for calcium, vitamin D and vitamin K, respectively) and cross-classification analyses demonstrated no major misclassification of participants into intake quartiles. Bland-Altman analysis showed that the FFQ overestimated intakes for calcium, by 576 mg/day (95% CI, −668 to 1,821 mg/day), for vitamin D by 75 IU/day (95% CI, −359 to 510 IU/day), and for vitamin K by 167 mcg/day (95% CI, −233 to 568 mcg/day). This pilot study showed promising validation evidence for the use of this FFQ, which focuses on calcium, vitamin D and vitamin K intakes in postmenopausal women, as a screening tool in clinical and research settings.

This randomized double-blind cross-over study assessed protein (PRO) requirements during the early stages of intensive bodybuilding training and determined whether supplemental PRO intake (PROIN) enhanced muscle mass/strength gains. Twelve men [22.4 +/- 2.4 (SD) yr] received an isoenergetic PRO (total PROIN 2.62 g.kg-1.day-1) or carbohydrate (CHO; total PROIN 1.35 g.kg-1.day-1) supplement for 1 mo each during intensive (1.5 h/day, 6 days/wk) weight training. On the basis of 3-day nitrogen balance (NBAL) measurements after 3.5 wk on each treatment (8.9 +/- 4.2 and -3.4 +/- 1.9 g N/day, respectively), the PROIN necessary for zero NBAL (requirement) was 1.4-1.5 g.kg-1.day-1. The recommended intake (requirement + 2 SD) was 1.6–1.7 g.kg-1.day-1. However, strength (voluntary and electrically evoked) and muscle mass [density, creatinine excretion, muscle area (computer axial tomography scan), and biceps N content] gains were not different between diet treatments. These data indicate that, during the early stages of intensive bodybuilding training, PRO needs are approximately 100% greater than current recommendations but that PROIN increases from 1.35 to 2.62 g.kg-1.day-1 do not enhance muscle mass/strength gains, at least during the 1st mo of training. Whether differential gains would occur with longer training remains to be determined.

The objectives of the study were to develop bone mineral density (BMD) reference norms and BMD Z-scores at various skeletal sites, to determine whether prior fracture and/or asthma were related to BMD, and to assess possible geographic variation of BMD among Canadian youth aged 16–24yr. Z-Scores were defined as the number of standard deviations from the mean BMD of a healthy population of the same age, race, and sex. Z-Scores were calculated using the reference sample defined as Canadian Caucasian participants without asthma or prior fracture. Reference standards were created for lumbar spine (L1–L4), femoral neck, total hip, and greater trochanter, by each year of age (16–24yr), and by sex. The Z-score norms were developed for groups noted earlier. Mean Z-scores between the asthma or fracture subgroups compared with the mean Z-scores in the reference sample were not different. There were minor differences in mean BMD across different Canadian geographic regions. This study provides age, sex, and skeletal site-specific Caucasian reference norms and formulae for the calculation of BMD Z-scores for Canadian youth aged 16–24yr. This information will be valuable to help to identify individuals with clinically meaningful low BMD.

There has been significant public debate about the susceptibility of research to biases of various kinds. The dialogue has extended to the peer-reviewed literature, scientific conferences, the mass media, government advisory bodies, and beyond. While biases can come from myriad sources, the overwhelming focus of the discussion, to date, has been on industry-funded science. Given the critical role that industry has played and will continue to play in the research process, the International Life Sciences Institute (ILSI) North America Working Group on Guiding Principles has, in this paper, set out proposed conflict-of-interest guidelines, regarding industry funding, for protecting the integrity and credibility of the scientific record, particularly with respect to health, nutrition, and food-safety science. Eight principles are enumerated, specifying ground rules for industry-sponsored research. The paper, which issues a challenge to the broader scientific community to address all bias issues, is only a first step; the document is intended to be dynamic, prompting ongoing discussion and refinement. The Guiding Principles are as follows. In the conduct of public/private research relationships, all relevant parties shall: 1) conduct or sponsor research that is factual, transparent, and designed objectively; according to accepted principles of scientific inquiry, the research design will generate an appropriately phrased hypothesis and the research will answer the appropriate questions, rather than favor a particular outcome; 2) require control of both study design and research itself to remain with scientific investigators; 3) not offer or accept remuneration geared to the outcome of a research project; 4) prior to the commencement of studies, ensure that there is a written agreement that the investigative team has the freedom and obligation to attempt to publish the findings within some specified time-frame; 5) require, in publications and conference presentations, full signed disclosure of all financial interests; 6) not participate in undisclosed paid authorship arrangements in industry-sponsored publications or presentations; 7) guarantee accessibility to all data and control of statistical analysis by investigators and appropriate auditors/reviewers; and 8) require that academic researchers, when they work in contract research organizations (CRO) or act as contract researchers, make clear statements of their affiliation; require that such researchers publish only under the auspices of the CRO.

Complex interactions among genetic, epigenetic, and environmental exposures, further modified by a child's postnatal environment, underlie the relationship among maternal health, fetal growth, and the development of cardiovascular disease (CVD) risk factors in the child and disease in the adult. Few available studies consider the genetic and environmental influences of the family, beyond maternal health. The purpose of this study is to examine the fetal and early childhood family-based determinants for the development of adiposity, CVD risk factors, and atherosclerosis in childhood.A cohort of 850 children and their families (mother, father, eldest sibling) are being recruited during pregnancy to a prospective longitudinal study to investigate the relative contribution of (a) prenatal and postnatal determinants and (b) individual and family (maternal/paternal) determinants for the development of adiposity and CVD risk factors at 3, 5, and 10 years of age and carotid intima media thickness at 10 years.The FAMILY study will advance understanding of the fetal and early childhood determinants for CVD development and will contribute to the design of primary prevention programs based on identification of the most important modifiable determinants for early childhood adiposity and CVD risk factor development.

Nutrient reference values have significant public health and policy implications. Given the importance of defining reliable nutrient reference values, there is a need for an explicit, objective, and transparent process to set these values. The Tufts Medical Center Evidence-based Practice Center assembled a group of nutrition experts from academic institutions and federal government agencies, led participants in discussions, conducted exercises in formulating questions and evidence review criteria that would be amenable to systematic reviews of the scientific literature, performed a literature search on the questions to identify potentially relevant publications, and identified challenges and limitations of applying this method to support the development of nutrient reference values using vitamin A as an example. The workgroup concluded that the systematic review approach could be productively used to inform the development of reference values. Challenges identified in this exercise include prioritizing and defining research questions when the volume of literature is large, relying on intermediate (surrogate) outcomes when few or no studies directly linking nutrient intake with clinical outcomes are available, and determining reliable nutrient biomarkers. Ultimately, an objective, unbiased systematic review of a defined question could be useful, not only in helping to set nutrient reference values, but also for increasing the transparency of the decision making process.

To test the efficacy of calcium glycerophosphate (CaGlyP) vs the conventional mineral salts, calcium gluconate plus KH2PO4 + K2HPO4 (CaGluc + P), in promoting mineral retention, 72-h mineral balance, biochemical status, net acid excretion, and growth were assessed in 16 low-birth-weight infants receiving total parenteral nutrition (TPN) containing approximately 1.5 mmol Ca and P.kg-1.d-1 for 5 d. Net retentions of calcium (1.2 +/- 0.2 vs 1.0 +/- 0.2 mmol.kg-1.d-1, means +/- SD) and phosphorus (1.1 +/- 0.3 vs 0.8 +/- 0.3 mmol.kg-1.d-1) from CaGluc + P vs CaGlyP, respectively, were similar, as were retentions of magnesium and sodium, urinary pH, and net acid excretion. Plasma ionized calcium, inorganic phosphorus, alkaline phosphatase, and osteocalcin were normal and not different between groups. CaGlyP is as effective as CaGluc + P in promoting mineral retention and normal mineral homeostasis. However, at intakes of less than or equal to 1.5 mmol Ca and P.kg-1.d-1 from either mineral salt, retention represented only 60% and 45%, respectively, of the predicted intrauterine accretion for calcium and phosphorus. Larger intakes permitted by the more-soluble CaGlyP may be desirable for infants receiving TPN.

Colostrum (d 2-4) and mature human milk samples (d 23-30) collected from eight mothers giving birth at 31 +/- 7 wk of gestation were analyzed for total sulfur, free inorganic sulfate and acid labile sulfoesters. The data presented are representative of complete 24-h expressions. Total sulfur was measured using a wet digestion procedure in which all forms of sulfur were converted to inorganic sulfate. The sulfate was quantified by a radiometric barium precipitation assay. Total sulfur showed no marked diurnal variation, but the mean concentration in 19 colostrum samples (10.2 +/- 4.2 mmol/L) was significantly higher than in 14 mature milk samples (4.3 +/- 0.8 mmol/L) (P less than 0.001). The range of predicted 24-h intakes of sulfur by infants fed colostrum (0.78-3.22 mmol/kg body weight) was slightly higher than those fed mature milk (0.54-1.06 mmol/kg), but it was not significantly different. The combined fractions of free inorganic sulfate and acid-labile sulfoester fractions contribute less than 5% to the total sulfur content of either colostrum or mature milk. However, the physiological significance of these milk components remains to be determined.

OBJECTIVE. In this cross-sectional observational study, we assessed both vitamins D and K status and bone health in pancreatic insufficient pediatric patients with cystic fibrosis from 3 Canadian cystic fibrosis centers. METHODS. Eighty-one patients who had cystic fibrosis and were clinically stable for at least 3 months were enrolled. At the time of the clinic visit, anthropometric variables, lung function, pubertal status, intake of calcium and vitamins D and K, and physical activity were assessed. Blood was taken for analysis of biochemical biomarkers of bone turnover and status of vitamins D and K, and a urine sample was obtained for calcium, creatinine, sodium, and deoxypyridoline analyses. Whole-body bone mineral content and lumbar spine (L1–L4) bone mineral density were measured. RESULTS. The children were relatively well nourished and had moderate to mild lung disease. Low bone mineral mass defined as a z score between −1.0 and −2.0, for gender and age was detected in 38% of the children for whole body and in 28% for lumbar spine. z score less than −2.0 was observed in 7 children for both bone measures. Suboptimal vitamin D status occurred in 95% of patients; suboptimal vitamin K status occurred in 82% of patients. Measures of plasma osteocalcin and carboxy-terminal propeptide type 1 procollagen and urinary deoxypyridoline compared with reference values for age, gender, and pubertal status reflected a state of suppressed bone formation and elevated bone resorption in a large proportion of the patients. CONCLUSIONS. Bone mass of the whole body and spine was lower than expected for chronological age in approximately one third of pediatric patients with cystic fibrosis irrespective of gender or age. This may be explained by the observation of low bone turnover for developmental stage as indicated by bone biomarkers. Suboptimal status of vitamins D and K may be key causative factors of the low bone status for age.

Perfluoroalkyl compounds (PFCs) are end-stage metabolic products from industrial flourochemicals used in the manufacture of plastics, textiles, and electronics that are widely distributed in the environment. The objective of the present study was to quantify exposure to perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA), perfluorodecanoic acid (PFDeA), perfluorohexane sulfonate (PFHxS), perfluoroheptanoic acid (PFHpA), and perfluorononanoic acid (PFNA) in serum samples collected from pregnant women and the umbilical cord at delivery. Pregnant women (n=101) presenting for second trimester ultrasound were recruited and PFC residue levels were quantified in maternal serum at 24-28 weeks of pregnancy, at delivery, and in umbilical cord blood (UCB; n=105) by liquid chromatography-mass spectrometry. Paired t-test and multiple regression analysis were performed to determine the relationship between the concentrations of each analyte at different sample collection time points. PFOA and PFOS were detectable in all serum samples analyzed including the UCB. PFOS serum levels (mean+/-S.D.) were significantly higher (p

Growth, bone, and body composition were studied at prepuberty in former very low birth weight (VLBW) infants who received dexamethasone (DEX) for bronchopulmonary dysplasia (BPD) compared with VLBW infants without DEX and term-born infants (TERM) to identify early life risk factors for later low bone mass. Children (56 girls/63 boys, 5-10 y) previously studied in neonatal life were recruited into three groups: VLBW + DEX, VLBW - DEX, and TERM children. Anthropometry and whole body bone, fat, and lean mass were measured. At prepuberty, the average height and weight for VLBW + DEX group were significantly lower than that for VLBW - DEX and TERM. Both VLBW groups had lower bone mass even adjusted for height and lean mass than TERM children and lower lean mass both total and adjusted for height. Z-scores for whole body bone mineral content below -1.5 occurred in 27.9% of VLBW + DEX children. The key factors for low bone mass were earlier gestational age and having BPD with DEX in neonatal life. In former VLBW infants, growth and bone mass attainment before puberty can be predicted from early life variables. VLBW + DEX children may be protected from overweight, but are at risk for short stature and low bone mass.