To determine if bone mineral content (BMC) and density (BMD) of infants and children with parenteral nutrition (PN)-dependent intestinal failure (IF) is lower than healthy controls, and investigate potential causes of lower BMC and BMD.
We performed a cross-sectional study comparing infants and children with PN-dependent IF with duos of age, sex, and race matched controls. Lumbar spine BMC and BMD were measured by dual energy x-ray absorptiometry, and serum cytokines, aluminum, IGF-1, insulin-like growth factor-binding protein (IGF-BP)-3, parathyroid hormone, 25(OH) vitamin D, and 1,25(OH)2 vitamin D were measured. Generalized estimating equation models accounting for matching were used for comparisons.
BMC was 15% and BMD was 12% lower in IF participants than controls (p≤0.004). Group differences were attenuated to 3% and 7% and were not statistically significant (p=0.40 and p=0.07) when adjusted for length and weight; length- and weight-for-age were lower in IF than control participants (12.5% vs. 63%; 29.5% vs. 54%, p≤0.03). IF participants had higher serum aluminum (23 vs. 7 mcg/L, p<0.0001), IGF-1 (97 vs. 64 ng/mL, p=0.04), and 25(OH) vitamin D concentrations (40 vs. 30 ng/mL, p=0.0005), and lower IGF-BP3 (1418 vs. 1812 ng/mL, p<0.0001) and parathyroid hormone concentrations (51 vs. 98 pg/mL, p=0.0002) than controls. There was no difference in serum cytokine concentrations (p≥0.09).
Growth retardation is a significant problem for PN-dependent IF patients. Additional investigation is needed to elucidate the cause and its impact on bone mass and density, especially the role of IGF-1 resistance and aluminum toxicity.
pediatric; growth; bone mineral density; parenteral nutrition; DXA
Here we determined if vitamin D deficiency is more common in children with chronic kidney disease compared to healthy children. In addition we sought to identify disease-specific risk factors for this deficiency as well as its metabolic consequences. We found that nearly half of 182 patients (ages 5 to 21) with kidney disease (stages 2 to 5) and a third of age-matched 276 healthy children were 25-hydroxyvitamin D deficient (less than 20 ng/ml). The risk of deficiency was significantly greater in advanced disease. Focal segmental glomerulosclerosis and low albumin were significantly associated with lower 25-hydroxyvitamin D which, in turn, was associated with significantly higher intact parathyroid hormone levels. We found that 25-hydroxyvitamin D levels were positively associated with 1,25-dihydroxyvitamin D, the relationship being greatest in advanced disease (significant interaction), and inversely related to those of inflammatory markers C-reactive protein and IL-6. The association with C-reactive protein persisted when adjusted for the severity of kidney disease. Thus, lower 25-hydroxyvitamin D may contribute to hyperparathyroidism, inflammation and lower 1,25-dihydroxyvitamin D in children and adolescents, especially those with advanced kidney disease.
This prospective study evaluated changes in DXA whole body bone mineral content (WB-BMC) and spine areal bone mineral density (spine-BMD), and tibia quantitative CT (QCT) trabecular and cortical volumetric BMD and cortical area in 56 children over 12 months following renal transplantation. At transplant, spine-BMD Z-scores were greater in younger recipients (<13 years), vs. 898 reference participants (p<0.001). In multivariate models, greater decreases in spine-BMD Z-scores were associated with greater glucocorticoid dose (p<0.001) and declines in parathyroid hormone levels (p=0.008). Changes in DXA spine-BMD and QCT trabecular BMD were correlated (R=0.47, p<0.01). At 12 months, spine-BMD Z-scores remained elevated in younger recipients, but did not differ in older recipients (≥13) and reference participants. Baseline WB-BMC Z-scores were significantly lower than reference participants (p=0.02). Greater glucocorticoid doses were associated with declines in WB-BMC Z-scores (p<0.001) while greater linear growth was associated with gains in WB-BMC Z-scores (p=0.01). Changes in WB-BMC Z-scores were associated with changes in tibia cortical area Z-scores (R=0.52, p<0.001), but not changes in cortical BMD Z-scores. Despite resolution of muscle deficits, WBBMC Z-scores at 12 months remained significantly reduced. These data suggest spine and whole body DXA provide insight into trabecular and cortical outcomes following pediatric renal transplantation.
Bone mineral density; nutrition; renal transplantation; pediatric
When estimating dietary intake across multiple countries, the lack of a single comprehensive dietary database may lead researchers to modify one database to analyze intakes for all participants. This approach may yield results different from those using the country-specific database and introduce measurement error. We examined whether nutrient intakes of Australians calculated with a modified US database would be similar to those calculated with an Australian database. We analyzed 3-day food records of 68 Australian adults using the US-based Nutrition Data System for Research, modified to reflect food items consumed in Australia. Modification entailed identifying a substitute food whose energy and macronutrient content were within 10% of the Australian food or by adding a new food to the database. Paired Wilcoxon signed rank tests were used to compare differences in nutrient intakes estimated by both databases, and Pearson and intraclass correlation coefficients measured degree of association and agreement between intake estimates for individuals. Median intakes of energy, carbohydrate, protein, and fiber differed by <5% at the group level. Larger discrepancies were seen for fat (11%; P<0.0001) and most micronutrients. Despite strong correlations, nutrient intakes differed by >10% for an appreciable percentage of participants (35% for energy to 69% for total fat). Adding country-specific food items to an existing database resulted in similar overall macronutrient intake estimates but was insufficient for estimating individual intakes. When analyzing nutrient intakes in multinational studies, greater standardization and modification of databases may be required to more accurately estimate intake of individuals.
Food composition; Nutrient database; International; Harmonization
Vitamin D-binding protein (DBP) and catabolism have not been examined in childhood chronic kidney disease (CKD).
Serum vitamin D [25(OH)D, 1,25(OH)2D, 24,25(OH)2D], DBP, intact parathyroid hormone (iPTH), and fibroblast growth factor-23 (FGF23) concentrations were measured in 148 participants with CKD stages 2–5D secondary to congenital anomalies of the kidney/urinary tract (CAKUT), glomerulonephritis (GN), or focal segmental glomerulosclerosis (FSGS). Free and bioavailable 25(OH)D were calculated using total 25(OH)D, albumin and DBP.
All vitamin D metabolites were lower with more advanced CKD (p<0.001) and glomerular diagnoses (p≤0.002). Among non-dialysis participants, DBP was lower in FSGS vs. other diagnoses (FSGS-dialysis interaction p=0.02). Winter season, older age, FSGS and GN, and higher FGF23 were independently associated with lower free and bioavailable 25(OH)D. Black race was associated with lower total 25(OH)D and DBP, but not free or bioavailable 25(OH)D. 24,25(OH)2D was the vitamin D metabolite most strongly associated with iPTH. Lower 25(OH)D, black race, greater CKD severity, and higher iPTH were independently associated with lower 24,25(OH)2D, while higher FGF23 and GN were associated with greater 24,25(OH)2D.
Children with CKD exhibit altered catabolism and concentrations of DBP and free and bioavailable 25(OH)D, and there is an important impact of their underlying disease.
Vitamin D catabolism; vitamin D-binding protein; glomerular disease; chronic kidney disease; pediatric
Establishing and maintaining healthy physical activity (PA) levels is important throughout life. The purpose of this study was to determine the extent of PA tracking between ages 3 and 7 y. Objective measures of PA (RT3, triaxial accelerometer) were collected every 4 mo from ages 3 to 7; data from 234 children with PA measures available during each year of age were analyzed. Mean PA (total, moderate/vigorous(MV), and inactivity(IA)) was calculated for each year of age and adjusted for wear time. Correlations with age 3 PA were moderate at age 4 (r=0.42–0.45) but declined by age 7 (r=0.19–0.25). After classification into sex-specific tertiles of PA at age 3, boys in the High age 3 MVPA tertile maintained significantly higher PA at all subsequent ages, while girls in the High age 3 MVPA tertile were not significantly higher at age 6 and 7. Boys and girls in the High age 3 IA tertile had significantly higher IA at multiple subsequent years of age (P<0.05 at ages 5 and 6). In conclusion, boys who were relatively more active at age 3 remained more active for several subsequent years. These findings highlight early childhood differences in physical activity patterns between boys and girls.
The impact of pediatric chronic kidney disease (CKD) on acquisition of volumetric bone mineral density (BMD) and cortical dimensions is lacking. To address this issue we obtained tibia quantitative computed tomography scans from 103 patients age 5-21 years with CKD (26 on dialysis) at baseline and 12 months later. Gender, ethnicity, tibia length and/or age-specific Z-scores were generated for trabecular and cortical BMD, cortical area, periosteal and endosteal circumference, and muscle area based on over 700 reference subjects. Muscle area, cortical area, and periosteal and endosteal Z-scores were significantly lower at baseline compared to the reference cohort. Cortical BMD, cortical area and periosteal Z-scores all exhibited a significant further decrease over 12 months. Higher parathyroid hormone levels were associated with significantly greater increases in trabecular BMD and decreases in cortical BMD in younger patients (significant interaction terms for trabecular BMD and cortical BMD). The estimated GFR was not associated with changes in BMD Z-scores independent of parathyroid hormone. Changes in muscle and cortical area were significantly and positively associated in control subjects but not in CKD patients. Thus, children and adolescents with CKD have progressive cortical bone deficits related to secondary hyperparathyroidism and potential impairment of the functional muscle-bone unit. Interventions are needed to enhance bone accrual in childhood-onset CKD.
Osteoporosis is primarily evident in postmenopausal women, but its roots are traceable to periods of growth, including during adolescence. Depression, anxiety, and smoking are associated with lower bone mineral density (BMD) in adults. These associations have not been studied longitudinally across adolescence when more than 50% of bone accrual occurs.
To determine the impact of depressive and anxiety symptoms, smoking, and alcohol use on bone accrual in girls 11–19 years, 262 healthy girls were enrolled in age cohorts of 11, 13, 15, and 17 years. Using a cross-sequential design, girls were seen for 3 annual visits. Outcome measures included total body bone mineral content (TB BMC) and BMD of the total hip and lumbar spine using dual energy x-ray absorptiometry. Depressive and anxiety symptoms and smoking and alcohol use were by self-report.
Higher-frequency smoking was associated with a lower rate of lumbar spine and total hip BMD accrual from age 11–19. Higher depressive symptoms were associated with lower lumbar spine BMD across all ages. There was no effect of depressive symptoms on TB BMC, and there was no effect of alcohol intake on any bone outcome.
Adolescent smokers are at higher risk for less than optimal bone accrual. Even in the absence of diagnosable depression, depressive symptoms may influence adolescent bone accrual. These findings have import for prevention of later osteoporosis and fractures.
bone accrual; depression; smoking; adolescent; substance use
Little is known about factors that affect bone mass and density of infants and toddlers and the means to assess their bone health owing to challenges in studying this population. The objectives of this study were to describe age, sex, race, growth and human milk feeding effects on bone mineral content (BMC) and areal density (aBMD) of the lumbar spine, and determine precision of BMC and aBMD measurements. We conducted a cross sectional study of 307 healthy participants (63 black), ages 1 to 36 months. BMC and aBMD of the lumbar spine were measured by dual energy x-ray absorptiometry. Duplicate scans were obtained on 76 participants for precision determination. Age specific Z-scores for aBMD, weight and length (BMDZ, WAZ, LAZ) were calculated. Information on human milk feeding duration was ascertained by questionnaire. Between ages 1 and 36 mo, lumbar spine BMC increased about 5-fold and aBMD increased 2-fold (p<0.0001). BMC was greater (5.8%) in males than in females (p=0.001), but there was no difference in aBMD (p=0.37). There was no difference in BMC or aBMD between whites and blacks (p≥0.16). WAZ and LAZ were positively associated with BMDZ (r=0.34 and 0.24, p<0.001). Duration of human milk feeding was negatively associated with BMDZ in infants <12 months of age (r=−0.42, p<0.001). Precision of BMC and aBMD measurements was good, 2.20% and 1.84%, respectively. Dramatic increases in BMC and aBMD of the lumbar spine occur in the first 36 months of life. We provide age-specific values for aBMD of healthy infants and toddlers that can be used to evaluate bone deficits. Future studies are needed to identify the age when sex and race differences in aBMD occur, and how best to account for delayed or accelerated growth in the context of bone health assessment of infants and toddlers.
Dual-energy x-ray absorptiometry; infants; children; bone mineral content; bone density
To examine risk factors for fracture in a racially diverse cohort of healthy children in the United States.
A total of 1,470 healthy children, ages 6–17 years, underwent yearly evaluations of height, weight, body mass index, skeletal age, sexual maturation, calcium intake, physical activity levels, and dual-energy x-ray absorptiometry (DXA) bone and fat measurements for up to 6 years. Fracture information was obtained at each annual visit, and risk factors for fracture were examined using the time-dependent Cox proportional hazards model.
The overall fracture incidence was 0.034 fractures per person-year with 212 children reporting a total of 257 fractures. Being white (hazard ratio [HR]=2.1), male (HR=1.8), and having skeletal age of 10–14 years (HR=2.2) were the strongest risk factors for fracture (all P≤0.001). Increased sports participation (HR=1.4), lower body fat percentage (HR=0.97), and previous fracture in white females (HR=2.1) were also significant risk factors (all P≤0.04). Overall, fracture risk decreased with higher DXA Z-scores, except in white males who had increased fracture risk with higher DXA Z-scores (HR=1.7, P<0.001).
Boys and girls of European descent had double the fracture risk of children from other backgrounds, suggesting that the genetic predisposition to fractures seen in elderly adults also manifests in children.
bone mass; bone density; pediatric fracture; teenagers; adolescents; race; ethnicity
Many (56%) US children aged 3–5 years are in center-based childcare and are not obtaining recommended levels of physical activity. In order to determine what child-care teachers/providers perceived as benefits and barriers to children’s physical activity in child-care centers, we conducted nine focus groups and 13 one-on-one interviews with 49 child-care teachers/providers in Cincinnati, OH. Participants noted physical and socio-emotional benefits of physical activity particular to preschoolers (e.g. gross motor skill development, self-confidence after mastery of new skills and improved mood, attention and napping after exercise) but also noted several barriers including their own personal attitudes (e.g. low self-efficacy) and preferences to avoid the outdoors (e.g. don’t like hot/cold weather, getting dirty, chaos of playground). Because individual teachers determine daily schedules and ultimately make the decision whether to take the children outdoors, they serve as gatekeepers to the playground. Participants discussed a spectrum of roles on the playground, from facilitator to chaperone to physical activity inhibitor. These findings suggest that children could have very different gross motor experiences even within the same facility (with presumably the same environment and policies), based on the beliefs, creativity and level of engagement of their teacher.
BACKGROUND AND OBJECTIVES:
Three-fourths of US preschool-age children are in child care centers. Children are primarily sedentary in these settings, and are not meeting recommended levels of physical activity. Our objective was to identify potential barriers to children’s physical activity in child care centers.
Nine focus groups with 49 child care providers (55% African American) were assembled from 34 centers (inner-city, suburban, Head Start, and Montessori) in Cincinnati, Ohio. Three coders independently analyzed verbatim transcripts for themes. Data analysis and interpretation of findings were verified through triangulation of methods.
We identified 3 main barriers to children’s physical activity in child care: (1) injury concerns, (2) financial, and (3) a focus on “academics.” Stricter licensing codes intended to reduce children's injuries on playgrounds rendered playgrounds less physically challenging and interesting. In addition, some parents concerned about potential injury, requested staff to restrict playground participation for their children. Small operating margins of most child care centers limited their ability to install abundant playground equipment. Child care providers felt pressure from state mandates and parents to focus on academics at the expense of gross motor play. Because children spend long hours in care and many lack a safe place to play near their home, these barriers may limit children's only opportunity to engage in physical activity.
Societal priorities for young children—safety and school readiness—may be hindering children’s physical development. In designing environments that optimally promote children’s health and development, child advocates should think holistically about potential unintended consequences of policies.
child care; physical activity; health promotion; health policy
Chronic kidney disease (CKD) is associated with increased fracture risk and skeletal deformities. The impact of CKD on volumetric bone mineral density (BMD) and cortical dimensions during growth is unknown. Tibia quantitative computed tomography scans were obtained in 156 children with CKD [69 stage 2–3, 51 stage 4–5, and 36 stage 5D (dialysis)] and 831 healthy participants, ages 5–21 years. Sex-, race-, and age- or tibia length-specific Z-scores were generated for trabecular BMD (TrabBMD), cortical BMD (CortBMD), cortical area (CortArea) and endosteal circumference (EndoC). Greater CKD severity was associated with higher TrabBMD-Z in younger participants (p < 0.001), compared with healthy children; this association was attenuated in older participants (interaction p < 0.001). Mean CortArea-Z was lower (p < 0.01) in CKD 4–5 [−0.49 (95% C.I. −0.80, −0.18)] and 5D [−0.49 (−0.83, −0.15)], compared with healthy children. Among CKD participants, parathyroid hormone (PTH) levels were positively associated with TrabBMD-Z (p < 0.01), and this association was significantly attenuated in older participants (interaction p < 0.05). Higher levels of PTH and biomarkers of bone formation (bone-specific alkaline phosphatase) and resorption (β-CTX) were associated with lower CortBMD-Z and CortArea-Z, and greater EndoC-Z (r = 0.18–0.36; all p ≤ 0.02). CortBMD-Z was significantly lower in CKD participants with PTH levels above vs. below the upper limit of the KDOQI CKD stage-specific target range: −0.46 ± 1.29 vs. 0.12 ± 1.14, p < 0.01. In summary, childhood CKD and secondary hyperparathyroidism were associated with significant reductions in cortical area and CortBMD, and greater TrabBMD in younger children. Future studies are needed to establish the fracture implications of these alterations and to determine if cortical and trabecular abnormalities are reversible.
pediatrics; bone quantitative computed tomography; parathyroid hormone; chronic kidney disease
To examine the variability of physical activity environments and outdoor play-policies in child-care centers, and to determine if they are associated with center demographic characteristics
Telephone survey—the Early Learning Environments Physical Activity and Nutrition Telephone Survey (ELEPhANTS)
Child-care centers in Hamilton County (Cincinnati area), Ohio, 2008–9.
Directors of all 185 licensed full-time child-care centers in Hamilton County.
Descriptive measures of center playground and indoor physical activity environments, and weather-related outdoor-play policies.
162 (88%) centers responded. Most (93%) centers reported an on-site playground, but only half reported their playgrounds as large, at least 1/3rd covered in shade, or having a variety of portable play equipment. Only half reported having a dedicated indoor gross-motor room where children could be active during inclement weather. Only 20% of centers allowed children to go outside in temperatures below 32°F, and 43% of centers reported allowing children outdoors during light rain. A higher percent of children receiving tuition-assistance was associated with lower quality physical activity facilities and stricter weather-related practices. National accreditation was associated with more physical-activity promoting practices.
We found considerable variability in the indoor and outdoor playground offerings among child-care centers, even within a single county of Ohio. Per center policy and limited inside options, children’s active opportunities are curtailed due to sub-freezing temperatures or light rain. Policy change and parent/teacher education may be needed to ensure children achieve ample opportunity for daily physical activity.
To evaluate bone loss in adolescents after Roux-en-Y gastric bypass surgery and to determine the extent to which bone loss was related to weight loss. We hypothesized that adolescents would lose bone mass after surgery and that it would be associated with weight loss.
PATIENTS AND METHODS:
We conducted a retrospective case review of 61 adolescents after bariatric surgery. Whole-body bone mineral content (BMC) and density (BMD) were measured by dual-energy radiograph absorptiometry, and age- and gender-specific BMD z scores were calculated. Measurements were obtained when possible before surgery and then every 3 to months after surgery for up to 2 years. Data were analyzed by using a mixed-models approach, and regression models were adjusted for age, gender, and height.
Whole-body BMC, BMD z score, and weight decreased significantly over time after surgery (P < .0001 for all). In the first 2 years after surgery, predicted values on the basis of regression modeling for BMC decreased by 7.4%, and BMD z score decreased from 1.5 to 0.1. During the first 12 months after surgery, change in weight was correlated with change in BMC (r = 0.31; P = .02). Weight loss accounted for 14% of the decrease in BMC in the first year after surgery.
Bariatric surgery is associated with significant bone loss in adolescents. Although the predicted bone density was appropriate for age 2 years after surgery, longer follow-up is warranted to determine whether bone mass continues to change or stabilizes.
bone density; bariatric surgery; obesity; weight loss; adolescents
Children with autism spectrum disorder (ASD) are reported to have decreased bone cortical thickness (BCT). Vitamin D plays an important physiological role in bone growth and development, so deficiency of vitamin D could contribute to decreased BCT. The goal of this study was to compare plasma 25(OH)D concentration in three groups of Caucasian males age 4 to 8 years old: (1) ASD and an unrestricted diet (n=40), (2) ASD and a casein-free diet (n=9), and (3) unaffected controls (n=40). No significant group differences were observed (p=0.4). However, a total of 54 (61%) of the children in the entire cohort had a plasma 25(OH)D concentration of less than 20ng/mL, similar to findings of low 25(OH)D concentrations in population-based studies. Children with ASD should be monitored for vitamin D deficiency.
To examine the relation between baseline fat mass and gain in bone area and bone mass in preschoolers studied prospectively for 4 y, with a focus on the role of physical activity and TV viewing.
Children were part of a longitudinal study in which measures of fat, lean and bone mass, height, weight, activity, and diet were taken every 4 months from ages 3 to 7 y. Activity was measured by accelerometer, and TV viewing by parent checklist. We included 214 children with total body dual energy x-ray absorptiometry (Hologic 4500A) scans at ages 3.5 and 7 y.
Higher baseline fat mass was associated with smaller increases in bone area and bone mass over the next 3.5 y (p<0.001). More TV viewing was related to smaller gains in bone area and bone mass accounting for race, sex, and height. Activity by accelerometer was not associated with bone gains.
Adiposity and TV viewing are related to less bone accrual in preschoolers.
bone mineral; preschool; fat mass; sedentary; obesity; outdoor play
Three-quarters of 3-6 year-old children in the U.S. spend time in childcare; many spend most of their waking hours in these settings. Daily physical activity offers numerous health benefits, but activity levels vary widely across centers. This study was undertaken to explore reasons why physical activity levels may vary. The purpose of this paper is to summarize an unexpected finding that child-care providers cited was a key barrier to children's physical activity.
Nine focus groups with 49 child-care providers (55% black) from 34 centers (including inner-city, suburban, Head Start and Montessori) were conducted in Cincinnati, OH. Three independent raters analyzed verbatim transcripts for themes. Several techniques were used to increase credibility of findings, including interviews with 13 caregivers.
Two major themes about clothing were: 1) children's clothing was a barrier to children's physical activity in child-care, and 2) clothing choices were a significant source of conflict between parents and child-care providers. Inappropriate clothing items included: no coat/hat/gloves in the wintertime, flip flops or sandals, dress/expensive clothes, jewelry, and clothes that were either too loose or too tight. Child-care providers explained that unless there were enough extra coats at the center, a single child without a coat could prevent the entire class from going outside. Caregivers suggested several reasons why parents may dress their child inappropriately, including forgetfulness, a rushed morning routine, limited income to buy clothes, a child's preference for a favorite item, and parents not understanding the importance of outdoor play. Several child-care providers favored specific policies prohibiting inappropriate clothing, as many reported limited success with verbal or written reminders to bring appropriate clothing.
Inappropriate clothing may be an important barrier to children's physical activity in child-care settings, particularly if the clothing of a few children preclude physical activity for the remaining children. Center directors and policy makers should consider devising clear and specific policies for the types of clothing that will be permitted in these settings so that children's active play opportunities are not curtailed. To enhance compliance, parents may need education about the importance and benefits of active play for children's development.
Variation in blood lead concentration is caused by a complex interaction of environmental, social, nutritional, and genetic factors. We evaluated the association between blood lead concentration and a vitamin D receptor (VDR) gene polymorphism. Environmental samples and blood were analyzed for lead, nutritional and behavioral factors were assessed, and VDR -Fok1 genotype was determined in 245 children. We found a significant interaction between floor dust lead and genotype on blood lead concentration. For every 1 microg/ft(2) increase in floor dust, children with VDR -FF genotype had a 1.1% increase in blood lead [95% confidence interval (CI), 0.69-1.5], VDR -Ff, 0.53% increase (95% CI, 0.1-0.92), and VDR -ff, 3.8% increase (95% CI, 1.2-6.3); however, at floor dust levels < 10 microg/ft(2), children with VDR -ff had the lowest blood lead concentrations. These data suggest that VDR -Fok1 is an effect modifier of the relationship of floor dust lead exposure and blood lead concentration.