Hope A. Weiler

Percent Body Fat and Bone Mass in Healthy Canadian Females 10 to 19 Years of Age

The primary aim of the investigation was to assess the relationship between whole-body fat expressed as a percentage of body weight with whole-body bone mineral content relative to age and anthropometry. Sixty females between 10 and 19 years of age were recruited to this cross-sectional study, which included measurements of weight and height and whole-body fat and bone mineral content using dual-energy X-ray absorptiometry. To assess bone mineral content, data were expressed as a weight or standard deviation scores using age and bone area. Relationships between outcome variables were determined using multiple correlation analysis followed by multiple linear regression with age, weight, height, and fat as predictor variables for outcomes of bone mineral content and density. Correlation analysis indicated that whole-body fat expressed as a percent was significantly related to weight (p < 0.01), but was not related to age or bone mineral content or density unless bone mineral content was corrected to age or bone area using standard deviation scores. In addition, body fat was associated with bone area for age and height (p < 0.01). However, multiple linear regression yielded opposite results. When included in regression, body fat had a negative impact on bone mineral content (p = 0.003), mineral content corrected to bone area (p = 0.02), and bone density (p = 0.003), while age, weight, and height had positive impacts on these outcome measurements. The data suggest that for younger children, the relative influence of percent body fat will be greater and could be linked with suboptimal attainment of peak bone mass. The females in this study appeared to be within reference limits for percent body fat. However, greater amounts of body fat relative to weight could be a marker for lifestyles that do not support attainment of optimal peak bone mass.

Vitamin D deficiency and whole-body and femur bone mass relative to weight in healthy newborns

Background: Vitamin D is required for normal bone growth and mineralization. We sought to determine whether vitamin D deficiency at birth is associated with bone mineral content (BMC) of Canadian infants. Methods: We measured plasma 25-hydroxyvitamin D [25(OH)D] as an indicator of vitamin D status in 50 healthy mothers and their newborn term infants. In the infants, anthropometry and lumbar, femur and whole-body BMC were measured within 15 days of delivery. Mothers completed a 24-hour recall and 3-day food and supplement record. We categorized the vitamin D status of mothers and infants as deficient or adequate and then compared infant bone mass in these groups using nonpaired t tests. Maternal and infant variables known to be related to bone mass were tested for their relation to BMC using backward stepwise regression analysis. Results: Twenty-three (46%) of the mothers and 18 (36%) of the infants had a plasma 25(OH)D concentration consistent with deficiency. Infants who were vitamin D deficient were larger at birth and follow-up. Absolute lumbar spine, femur and whole-body BMC were not different between infants with adequate vitamin D and those who were deficient, despite larger body size in the latter group. In the regression analysis, higher whole-body BMC was associated with greater gestational age and weight at birth as well as higher infant plasma 25(OH)D. Conclusion: A high rate of vitamin D deficiency was observed among women and their newborn infants. Among infants, vitamin D deficiency was associated with greater weight and length but lower bone mass relative to body weight. Whether a return to normal vitamin D status, achieved through supplements or fortified infant formula, can reset the trajectory for acquisition of BMC requires investigation.

Effect of Different Dosages of Oral Vitamin D Supplementation on Vitamin D Status in Healthy, Breastfed Infants: A Randomized Trial

IMPORTANCE Vitamin D supplementation in infancy is required to support healthy bone mineral accretion. A supplement of 400 IU of vitamin D per day is thought to support plasma 25-hydroxyvitamin D (25[OH]D) concentrations between 40 and 50 nmol/L; some advocate 75 to 150 nmol/L for bone health. OBJECTIVE To investigate the efficacy of different dosages of vitamin D in supporting 25(OH)D concentrations in infants. DESIGN, SETTING, AND PARTICIPANTS Double-blind randomized clinical trial conducted among 132 one-month-old healthy, term, breastfed infants from Montréal, Québec, Canada, between March 2007 and August 2010. Infants were followed up for 11 months ending August 2011 (74% completed study). INTERVENTION Participants were randomly assigned to receive oral cholecalciferol (vitamin D3) supplements of 400 IU/d (n=39), 800 IU/d (n=39), 1200 IU/d (n=38), or 1600 IU/d (n=16). MAIN OUTCOMES AND MEASURES The primary outcome was a plasma 25(OH)D concentration of 75 nmol/L or greater in 97.5% of infants at 3 months. Secondary outcomes included 25(OH)D concentrations of 75 nmol/L or greater in 97.5% of infants at 6, 9, and 12 months; 25(OH)D concentrations of 50 nmol/L or greater across all times; growth; and whole body and regional bone mineral content. Data were analyzed by intention to treat using available data, logistic regression, and mixed-model analysis of variance. RESULTS By 3 months, 55% (95% CI, 38%-72%) of infants in the 400-IU/d group achieved a 25(OH)D concentration of 75 nmol/L or greater vs 81%(95% CI, 65%-91%) in the 800-IU/d group, 92% (95% CI, 77%-98%) in the 1200-IU/d group, and 100% in the 1600-IU/d group. This concentration was not sustained in 97.5% of infants at 12 months in any of the groups. The 1600-IU/d dosage was discontinued prematurely because of elevated plasma 25(OH)D concentrations. All dosages established 25(OH)D concentrations of 50 nmol/L or greater in 97% (95% CI, 94%-100%) of infants at 3 months and sustained this in 98% (95% CI, 94%-100%) to 12 months. Growth and bone mineral content did not differ by dosage. CONCLUSIONS AND RELEVANCE Among healthy, term, breastfed infants, only a vitamin D supplement dosage of 1600 IU/d (but not dosages of 400, 800, or 1200 IU/d) increased plasma 25(OH)D concentration to 75 nmol/L or greater in 97.5% of infants at 3 months. However, this dosage increased 25(OH)D concentrations to levels that have been associated with hypercalcemia. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00381914.

Long chain polyunsaturated fatty acids : selected mechanisms of action on bone

Evidence presented over the past 20 years has shown that long-chain polyunsaturated fatty acids (LCPUFAs), especially the n-3 fatty acids such as eicospentaenoic acid (EPA) and docosahexaenoic acid (DHA) are beneficial for bone health. Some studies in humans indicate that LCPUFAs can increase bone formation, affect peak bone mass in adolescents and reduce bone loss as measured using bone mineral densitometry. The cellular mechanisms of action of the LCPUFAs, however, are complex and involve modulation of fatty acid metabolites such as prostaglandins, resolvins and protectins, several signalling pathways, cytokines and growth factors. LCPUFAs affect receptor activator of nuclear factor κβ (RANK), a receptor found on the osteoclast, the cell causing bone resorption, which controls osteoclast formation. Lipoxygenase (LOX) generated lipid mediators (resolvins, lipoxins, protectins and docosanoids) have both anti-inflammatory and pro-resolving activities. Both resolvins and lipoxins inhibit inflammation-induced bone resorption. Arachidonic acid significantly upregulates inducible NO synthase (iNOS) mRNA expression in human osteoblast-like cells, thereby possibly enhancing osteoclastic activity. The protective effect of EPA on osteoblastogenesis could be mediated by the biphasic cross-talk between PGE(2) and NO production involving COX-2 and iNOS pathways. Other mediators of osteoblast maturation include PPARα ligands such as linoleic acid and possibly DHA in association with bone morphogenic proteins. Since DHA is a weaker ligand for PPARγ, more uncommitted mesenchymal stem cells are thought to differentiate into osteoblasts rather than adipocytes. This review addresses selected cellular mechanisms that may explain the beneficial effects of the LCPUFAs on bone.

Improvement in the Accuracy of Dual Energy X-ray Absorptiometry for Whole Body and Regional Analysis of Body Composition: Validation Using Piglets and Methodologic Considerations in Infants

Previously, we conducted dual energy x-ray absorptiometry (DXA) (Hologic QDR-1000/W) scans and carcass analysis of piglets to evaluate the Pediatric Whole Body software (PedWB) (V5.35) for use in infants. A software upgrade designed for infant whole body (InfWB) (V5.56) led to a reassessment of DXA by: 1) reanalysis of the original scans using InfWB software and 2) comparison of InfWB-estimates of bone mineral content (BMC) and lean and fat mass with chemical analysis. Other assessments included 1) methods of regional analysis and 2) artifacts and the Infant Table Pad in the scan field. The mean coefficients of variation for InfWB whole body measures in small piglets(n = 10, weight 1575 ± 73 g) and large piglets (n = 10, weight 5894 ± 208 g) were less than 2.6% except for fat mass which was higher (8.0% versus 6.3% and 6.6% versus 3.5%, respectively) compared with PedWB. In large piglets InfWB produced good estimates of BMC, lean and fat masses. In small piglets, fat mass by InfWB was correlated with chemical analysis, but not by PedWB. There was improvement in the estimation of BMC with InfWB, from 27 ± 2.2 g to 32 ± 2.3 g(carcass ash = 38 ± 3.3 g). Femur BMC analysis by InfWB was precise and was accurate when compared with chemical analysis. Artifacts in the DXA scan field (diapers and blankets) resulted in an increase of the DXA-estimated fat and lean masses. The Infant Table Pad increased the estimate of fat mass in a small piglet by 50%, thus further study is required before it is used routinely. Improvements of the DXA technology have resulted in a more accurate tool, if scanning procedures are carefully implemented.

Food Insecurity and Nutrition Transition Combine to Affect Nutrient Intakes in Canadian Arctic Communities

Food insecurity and the nutrition transition have been noted in arctic communities. We therefore evaluated biomarkers of nutritional status and nutrient intakes by traditional food (TF) and food security status among Inuit in Canada. A cross-sectional health survey of Inuit (≥18 y) in 36 arctic communities was conducted in 2007-2008. Food security was assessed by 24-h dietary recalls using USDA questionnaires and nutrient intakes. Biomarkers included serum 25-hydroxy vitamin D [25(OH)D], hemoglobin, serum ferritin, and erythrocyte RBC fatty acids (FA). Analyses were stratified by past-day TF consumption (yes vs. no) and food security status (secure vs. insecure). Food insecurity was prevalent (62.6%) and associated with higher RBC trans-FA and lower hemoglobin levels and serum ferritin, whereas TF consumption was associated with higher serum 25(OH)D, (n-3) FA, and serum ferritin (P ≤ 0.05). In men, food insecurity was associated with lower intake of energy and energy-adjusted fiber, vitamin C, iron, zinc, and magnesium. In women, food insecurity was associated with a higher intake of carbohydrates and lower intake of fiber, dietary folate equivalent, vitamin C, iron, magnesium, calcium, and vitamin D. For both sexes, when TF was consumed, there was a higher intake of protein, protein-related micronutrients, and vitamins A and C and a lower intake of carbohydrates, saturated fat, and fiber and a lower sodium:potassium ratio (P ≤ 0.05). Nutrition transition and food insecurity are associated with a multifaceted shift in nutrient status and intakes with implications for increased risk of diet-sensitive chronic diseases.

Efficacy of food fortification on serum 25-hydroxyvitamin D concentrations: systematic review

BACKGROUND Many residents of the United States and Canada depend on dietary sources of vitamin D to help maintain vitamin D status. Because few natural food sources contain vitamin D, fortified foods may be required. OBJECTIVE We aimed to determine the effects of vitamin D-fortified foods on serum 25-hydroxyvitamin D [25(OH)D] concentrations. DESIGN We searched MEDLINE (1966 to June Week 3 2006), Embase, CINAHL, AMED, Biological Abstracts, and the Cochrane Central Register of Controlled Trials for randomized controlled trials (RCTs) comparing vitamin D-fortified foods with a control and reporting serum 25(OH)D concentrations. Two reviewers independently determined study eligibility, assessed trial quality, and extracted relevant data. Disagreements were resolved by consensus. Meta-analyses of absolute mean change in 25(OH)D were conducted by using a random-effects model, with evaluation of heterogeneity. RESULTS Nine RCTs (n = 889 subjects) were included, of which 8 consistently showed a significant beneficial effect of food fortification on 25(OH)D concentrations. Although 7 RCTs (n = 585 subjects) potentially were meta-analyzable, we were unable to combine the overall results because of significant heterogeneity. The individual treatment effects ranged from 14.5 (95% CIs: 10.6, 18.4) nmol/L to 34.5 (17.64, 51.36) nmol/L (3.4-25 microg vitamin D/d). Subgroup analyses showed a reduction in heterogeneity and significant treatment effect when 4 trials that used milk as the fortified food source were combined. CONCLUSION Most trials were small in size and inadequately reported allocation concealment, but results showed that vitamin D-fortified foods improved vitamin D status in adults.

Cohort Profile: The Maternal-Infant Research on Environmental Chemicals Research Platform

BACKGROUND The Maternal-Infant Research on Environmental Chemicals (MIREC) Study was established to obtain Canadian biomonitoring data for pregnant women and their infants, and to examine potential adverse health effects of prenatal exposure to priority environmental chemicals on pregnancy and infant health. METHODS Women were recruited during the first trimester from 10 sites across Canada and were followed through delivery. Questionnaires were administered during pregnancy and post-delivery to collect information on demographics, occupation, life style, medical history, environmental exposures and diet. Information on the pregnancy and the infant was abstracted from medical charts. Maternal blood, urine, hair and breast milk, as well as cord blood and infant meconium, were collected and analysed for an extensive list of environmental biomarkers and nutrients. Additional biospecimens were stored in the studys Biobank. The MIREC Research Platform encompasses the main cohort study, the Biobank and follow-up studies. RESULTS Of the 8716 women approached at early prenatal clinics, 5108 were eligible and 2001 agreed to participate (39%). MIREC participants tended to smoke less (5.9% vs. 10.5%), be older (mean 32.2 vs. 29.4 years) and have a higher education (62.3% vs. 35.1% with a university degree) than women giving birth in Canada. CONCLUSIONS The MIREC Study, while smaller in number of participants than several of the international cohort studies, has one of the most comprehensive datasets on prenatal exposure to multiple environmental chemicals. The biomonitoring data and biological specimen bank will make this research platform a significant resource for examining potential adverse health effects of prenatal exposure to environmental chemicals.

Dietary supplementation of arachidonic acid is associated with higher whole body weight and bone mineral density in growing pigs.

Essential fatty acids are fundamental to normal growth and development, but North American formulas do not contain arachidonic (AA) and docosahexaenoic acid (DHA). The main objective of the present study was to determine whether addition of AA and DHA to formula elevates growth and bone mineralization in piglets. A secondary objective was to establish whether liver fatty acid composition is related to that of bone. Twelve 10-d-old male piglets were randomized to receive either a standard formula with an n-6:n-3 fatty acid ratio of 4.9:1.0 or the same formula made with an equal amount of fat but containing AA (0.5% wt/wt total fat) and DHA (0.1% wt/wt total fat) for 14 d. Piglets in the supplemented group had significantly (p < 0.05) higher weight and greater bone mineral density of the whole body, lumbar spine, and femur. No differences were observed in whole body length, calcium absorption, or biochemical markers of bone metabolism. Feeding AA resulted in lower linoleic acid (p < 0.05) and higher (p < 0.05) AA in liver total lipid (% wt/wt) and bone FFA (% wt/wt) but no change to DHA. Liver AA (% wt/wt total lipid) was positively related (p < 0.05) to growth, free AA (% wt/wt) in bone, bone mineral content, bone mineral density, and urinary prostaglandin E2 but negatively related (p < 0.05) to free linoleic acid in bone. Inverse relationships were observed when liver linoleic acid was substituted for liver AA as the independent variable. These data indicate that feeding AA is associated with elevated weight and higher whole body and regional bone mineral density.

Growth and bone mineralization of young adults weighing less than 1500 g at birth

BACKGROUND Preterm infants are at risk for suboptimal growth and bone mineralization compared to infants born at term but long-term outcomes into early adulthood are unclear. AIMS To determine (1) if growth and nutrition in the first year of life significantly predict the outcomes measured at adulthood and (2) whole body and regional bone mineral content (BMC) of young adults who were born preterm and weighing <1500 g. STUDY DESIGN AND SUBJECTS In this descriptive follow-up study, subjects were born preterm and weighing <1500 g (n=25, 17.2+/-1.2 years of age) and originally participated in a 1-year follow-up study of infant growth or subjects born at term (n=25, 17.3+/-1.4 years of age). OUTCOME MEASURES In the preterm group, relationships of growth and nutrition in the first year of life with adult anthropometry and BMC were identified using correlation and regression analysis. Birth groups were compared for measurements of anthropometry and whole body and regional BMC obtained at adulthood using t-tests. RESULTS After correcting for the effects of bone area using regression, rate of weight gain had a positive relationship and days to regain birth weight a negative relationship to adult BMC. Young adults, born preterm, were significantly shorter with lower whole body BMC than of those born at term, but BMC was appropriate for size. CONCLUSIONS Growth early in life predicts subsequent attainment of growth and bone mass. Premature birth results in lower attainment of height achieved by young adult age but bone mass is appropriate for body size.