Mid-arm circumference is a reliable method to estimate adiposity in preterm and term infants.

BACKGROUND: Premature birth is associated with increased adipose deposition after birth. Standard anthropometry (body weight, length, and head circumference) may not adequately assess fat deposition. Validated methods to assess adiposity are needed to optimize growth quality in preterm infants. The purpose of this study was to identify covariates of infant body fat. METHODS: Air displacement plethysmography (ADP), standard anthropometry, and body circumferences were measured at hospital discharge in preterm (n = 28; 31-35 wk postmenstrual age (PMA)) and term (n = 28; 38-41 wks PMA) infants. RESULTS: Body weight, length, and head circumference were lower for preterm infants (P < 0.05) at hospital discharge compared with that of term infants. Despite smaller body size and younger PMA, preterm infant percent body fat (%BF) by ADP was 12.33 ± 4.15% vs. 9.64 ± 4.01% in term infants (P = 0.01). Mid-arm circumference (MAC) is a covariate of %BF in both preterm and term infants (adjusted R(2) = 0.49; P < 0.001). In preterm infants alone, MAC accounted for 60.4% of the variability of percent body fat (%BF) by ADP (P < 0.01). CONCLUSIONS: Preterm infants have increased body fat deposition as they approach term-corrected age, and MAC is a reliable, low-cost measure for monitoring infant body fat deposition in preterm and term infants.

Heart rate variability during caregiving and sleep after massage therapy in preterm infants.

BACKGROUND: Preterm birth impairs the infant's stress response due to interruption of autonomic nervous system (ANS) development. Preterm infants demonstrate a prolonged and aberrant sympathetic response to stressors. ANS development may be promoted by massage therapy (MT), which has been shown to improve stress response in preterm infants. AIMS: The aim of this study was to compare preterm infant ANS function and stress response during sleep and caregiving epochs, as measured by heart rate variability (HRV), after two weeks of twice-daily MT. STUDY DESIGN: A subset of participants from a larger randomized, masked, controlled trial was used. SUBJECTS: Twenty-one infants (8 males and 13 females) from a larger study of 37 medically stable preterm infants were studied. The infants were receiving full volume enteral feedings with a mean post-menstrual age of 31.4 (MT) and 30.9 (control) weeks. OUTCOME MEASURES: Low to high frequency (LF:HF) ratio of HRV was the outcome of interest. RESULTS: There was a significant group×time×sex interaction effect (p<.05). Male control infants demonstrated a significant decline in LF:HF ratio from baseline to the second caregiving epoch, suggesting decreased mobilization of sympathetic nervous system response when exposed to stressors. Male MT infants demonstrated increased LF:HF ratio during caregiving and decreased LF:HF ratio during sleep epochs, suggesting improved ANS function, although this was not statistically significant. LF:HF ratio was similar in female MT and female control infants during caregiving and sleep. CONCLUSIONS: Control males had decreased HRV compared to MT males. There was no difference in HRV between MT and control females.

Mechanical-tactile stimulation (MTS) intervention in a neonatal stress model alters adult adipose tissue deposition and prevents hyperinsulinemia in male rats.

Preterm infants are exposed to numerous stressors during hospitalization and by term corrected gestational age they have lower body weight but a greater proportion of total body as well as abdominal visceral adipose tissue (VAT) accumulation. Greater abdominal VAT stores have a known association with metabolic syndrome. Mechanical-tactile stimulation (MTS) improves modulation of stress response in both humans and rodents. We hypothesize that MTS, administered during an established model of neonatal stress, would decrease stress-driven adiposity and prevent associated metabolic imbalances in adult rats. Neonatal stress, administered to rat pups from postnatal days 5 to P9, consisted of needle puncture and hypoxic/hyperoxic challenge during 60 min of maternal separation (STRESS; n=20). Mechanical-tactile stimulation (MTS; n=20) was administered to rat pups for 10 min during maternal separation in the stress protocol. Control animals received standard care (CTL; n=20). MRI measured adult (P120) abdominal total fat mass, subcutaneous (SAT) and visceral adipose tissue (VAT). Body weight and fasting serum adiponectin, leptin, glucose, insulin, and corticosterone were also measured. STRESS results in elevated VAT/SAT ratio compared to CTL but lower abdominal total fat mass and abdominal SAT. STRESS males experience hyperinsulinemia. Both STRESS and MTS had elevated leptin with lower adiponectin and corticosterone compared to CTL. In summary, neonatal stress promotes greater abdominal VAT accumulation and, in males, caused hyperinsulinemia and hypoadiponectinemia. Importantly, MTS normalized the VAT/SAT ratio and prevented hyperinsulinemia. We speculate that MTS ameliorates some of the negative metabolic consequences of early life perturbations due to neonatal stress exposure.

Massage improves growth quality by decreasing body fat deposition in male preterm infants.

OBJECTIVES: To assess the effect of massage on weight gain and body fat deposition in preterm infants. STUDY DESIGN: Preterm infants (29-32 weeks) were randomized to the massage group (n = 22, 12 girls, 10 boys) or the control group (n = 22, 12 girls, 10 boys). Treatment was masked with massage or control care administered twice-daily by licensed massage therapists (6 d/wk for 4 weeks). Body weight, length, Ponderal Index (PI), body circumferences, and skinfold thickness (triceps, mid-thigh, and subscapular [SSF]) were measured. Circulating insulin-like growth factor I, leptin, and adiponectin levels were determined by enzyme-linked immunosorbent assay. Daily dietary intake was collected. RESULTS: Energy and protein intake as well as increase in weight, length, and body circumferences were similar. Male infants in the massage group had smaller PI, triceps skinfold thickness, mid-thigh skinfold thickness, and SSF and increases over time compared with control male infants (P < .05). Female infants in the massage group had larger SSF increases than control female infants (P < .05). Circulating adiponectin increased over time in control group male infants (group × time × sex interaction, P < .01) and was correlated to PI (r = 0.39, P < .01). CONCLUSIONS: Twice-daily massage did not promote greater weight gain in preterm infants. Massage did, however, limit body fat deposition in male preterm infants. Massage decreased circulating adiponectin over time in male infants with higher adiponectin concentrations associated with increased body fat. These findings suggest that massage may improve body fat deposition and, in turn, growth quality of preterm infants in a sex-specific manner.

Intrauterine growth restriction decreases endochondral ossification and bone strength in female rats.

Intrauterine growth restriction (IUGR) modifications to postnatal skeletal growth may increase adult fracture, especially in females who have greater risk of osteoporosis. Little is known about the effect of IUGR on the patterns of postnatal endochondral ossification and bone development. Here for the first time we reveal bone formation, mineralization, and strength in IUGR female rats during early postnatal life and adulthood. Endochondral ossification rate of the hypertrophic zone (HZ) and hypertrophic cell length (HCL) at distal femur and proximal tibia, and primary ossification center (POC) of the whole femur and tibia were quantified at birth to day 21. Bone area (BA), bone mineral content (BMC), and bone density by dual-energy X-ray absorptiometry and bone strength determined from three-point bending were measured at days 21 and 120. IUGR femur and tibia HZ, HCL, and POC were significantly diminished at birth to day 21. IUGR decreased BA and BMC as well as femur/tibia diameter, length, stiffness, and peak load values at days 21 and 120. Our findings demonstrate a negative long-term effect of IUGR on bone size, mineral content, and strength in weanling and adult female rats. We speculate that IUGR decreases endochondral ossification responsiveness, and in turn, postnatal linear skeletal growth, mineralization, and strength in female rats.

Validity and reliability of perinatal biomarkers of adiposity after storage as dried blood spots on paper.

OBJECTIVE: To validate use of chip-based immunoaffinity capillary electrophoresis on dried blood spot samples (DBSS) to measure obesity-related hormones. METHODS: Chip-based immunoaffinity capillary electrophoresis was used to measure adiponectin, leptin and insulin in capillary serum and DBSS in pregnant women and infant heelstick at birth and six weeks. Concordance of measurements was determined with Pearson's correlation and Bland-Altman plots. RESULTS: We report high concordance between results obtained from serum and DBSS. CONCLUSIONS: Ease of sample collection and storage makes DBSS an optimal method for use in studies involving neonates and young children, as well as studies conducted in areas where freezer storage is not available.

Mechanical-tactile stimulation (MTS) during neonatal stress prevents hyperinsulinemia despite stress-induced adiposity in weanling rat pups.

Stress in early life negatively influences growth quality through perturbations in body composition including increased fat mass. At term (40 weeks) preterm infants have greater fat mass and abdominal visceral adipose tissue than term-born infants. Mechanical-tactile stimulation (MTS) attenuates the stress response in preterm infants and rodents. We tested the hypothesis that MTS, administered during an established model of neonatal stress, would decrease stress-driven adiposity and prevent associated metabolic imbalances in rat pups. Pups received one of three treatments from postnatal days 5 to P9: Neonatal Stress (Stress; n=20) = painful stimulus and hypoxic/hyperoxic challenge during 60 min of maternal separation; MTS (n=20) = neonatal stress+10 min of MTS; or Control (n=20). Body weight, DXA whole body fat mass (g), MRI subcutaneous and visceral adipose tissue, and fasting adiponectin, leptin, glucose, insulin, and corticosterone were measured at weaning (P21). Stress and MTS weight gain (g/d) were accelerated following neonatal stress with greater fat mass, abdominal subcutaneous adipose tissue, serum adiponectin, leptin, and fasting glucose at weaning (P21). Male Stress and MTS pups had greater visceral adipose tissue depot. Male and female Stress pups were hyperinsulinemic. In summary, neonatal stress compromised body composition by increasing fat mass and abdominal subcutaneous adipose tissue depot, and in males, visceral adipose tissue depot. Importantly, MTS prevented hyperinsulinemia despite of stress-induced adiposity. We conclude that MTS during neonatal stress has the potential to minimize metabolic consequences associated with stress-driven perturbations in fat mass and abdominal adipose depots.

Feasibility of community food item collection for the National Children's Study.

BACKGROUND: The National Children's Study proposes to investigate biological, chemical, physical, and psychosocial environmental exposures and their role on health outcomes in pregnant women and children. One specific area of concern is contaminant exposure through the ingestion of solid foods. National food contaminant databases may miss dietary exposures unique to specific communities and sources of food. OBJECTIVE: The purpose of this study was to evaluate the feasibility of community food item collection for the assessment of pesticide exposure in pregnant women and young children. METHODS: A prospective observational design was used to test the food collection protocol in mothers (n=45) of children aged 15-24 months in Salt Lake City, Utah. Foods for collection were based on: 1) frequency of different foods consumed by the target population as determined by the National Health and Nutrition Examination Survey data; 2) child food frequency questionnaire; and 3) likelihood of pesticide contamination in the foods. Assessment measures included: demographics, environmental health survey, quality assurance checklist, and participant evaluation form. RESULTS: An average of three food items were obtained from 44 households, yielding a collection rate of 97.8%. Overall, 100% of the food samples were rated as acceptable. Moreover, a vast majority of mothers reported that the study was not burdensome (95.5%) and that preparing the food sample was easy (93.2%). CONCLUSIONS: This study suggests that the community food item collection methodology shows promise as a low-burden approach for capturing dietary exposures on a household level, and appears to be a feasible tool for large population studies to assess dietary exposures unique to specific communities.

Uteroplacental insufficiency increases visceral adiposity and visceral adipose PPARgamma2 expression in male rat offspring prior to the onset of obesity.

Uteroplacental insufficiency (UPI) induced intrauterine growth restriction (IUGR) predisposes individuals to adult onset metabolic morbidities, including insulin resistance and cardiovascular disease. An underlying component of the development of these morbidities is adipose dysfunction; specifically a disproportionately abundant visceral adipose tissue. We hypothesize that IUGR will increase rats visceral adiposity and visceral expression of PPARgamma, a key regulator of adipogenesis. To test this hypothesis we employed a well described UPI induced IUGR rat model. Subcutaneous and visceral adipose levels were measured in adolescent control and IUGR rats using MRI. Expression of PPARgamma mRNA and protein, as well as PPARgamma target genes, was measured in neonatal, adolescent and adult rats. UPI induced IUGR increases the relative amount of visceral adipose tissue in male, but not female, adolescent rats in conjunction with an increase in PPARgamma2mRNA and protein in male visceral adipose. Importantly, these effects are seen prior to the onset of overt obesity. We conclude that increased PPARgamma2 expression in VAT of IUGR males is associated with increased visceral adiposity. We speculate that the increase in visceral adiposity may contribute to the metabolic morbidities experienced by this population.

Validity and reliability of a nutrition knowledge survey for assessment in elementary school children.

Limited surveys are available to assess the nutrition knowledge of children. The goals of this study were to test the validity and reliability of a computer nutrition knowledge survey for elementary school students and to evaluate the impact of the "Fit Kids 'r' Healthy Kids" nutrition intervention via the knowledge survey. During survey development, a sample (n=12) of health educators, elementary school teachers, and registered dietitians assessed the survey. The target population consisted of first- through fourth-grade students from Salt Lake City, UT, metropolitan area schools. Participants were divided into reliability (n=68), intervention (n=74), and control groups (n=59). The reliability group took the survey twice (2 weeks apart); the intervention and control groups also took the survey twice, but at pre- and post-intervention (4 weeks later). Only students from the intervention group participated in four weekly nutrition classes. Reliability was assessed by Pearson's correlation coefficients for knowledge scores. Results demonstrated appropriate content validity, as indicated by expert peer ratings. Test-retest reliability correlations were found to be significant for the overall survey (r=0.54; P<0.001) and for all subscales: food groups, healthful foods, and food functions (r=0.51, 0.65, and 0.49, respectively; P<0.001). Nutrition knowledge was assessed upon program completion with paired samples t tests. Students from the intervention group demonstrated improvement in nutrition knowledge (12.2+/-1.9 to 13.5+/-1.6; P<0.001), while scores for the control group remained unchanged. The difference in total scores from pre- to post-intervention between the two groups was significant (P<0.001). These results suggest that the computerized nutrition survey demonstrated content validity and test-retest reliability for first- through fourth-grade elementary school children. Also, the study results imply that the Fit Kids 'r' Healthy Kids intervention promoted gains in nutrition knowledge. Overall, the computer survey shows promise as an appealing medium for assessing nutrition knowledge in children.

Newborn adiposity measured by plethysmography is not predicted by late gestation two-dimensional ultrasound measures of fetal growth.

Noninvasive measures of fetal and neonatal body composition may provide early identification of children at risk for obesity. Air displacement plethysmography provides a safe, precise measure of adiposity and has recently been validated in infants. Therefore, we explored relationships between term newborn percent body fat (%BF) measured by air displacement plethysmography to 2-dimensional ultrasound (2-D US) biometric measures of fetal growth and maternal and umbilical cord endocrine activity. A total of 47 mother/infant pairs were studied. Fetal biometrics by 2-D US and maternal blood samples were collected during late gestation (35 wk postmenstrual age); infants were measured within 72 h of birth. Fetal biometrics included biparietal diameter, femur length, head circumference, abdominal circumference (AC), and estimated fetal weight (EFW). Serum insulin, insulin-like growth factor (IGF) 1, IGF binding protein-3, and leptin concentrations were measured in umbilical cord and maternal serum. The mean %BF determined by plethysmography was 10.9 +/- 4.8%. EFW and fetal AC had the largest correlations with newborn %BF (R(2) = 0.14 and 0.10, respectively; P < 0.05); however, stepwise linear regression modeling did not identify any fetal biometric parameters as a significant predictor of newborn %BF. Newborn mid-thigh circumference (MTC; cm) and ponderal index (PI; weight, kg/length, cm(3)) explained 21.8 and 14.4% of the variability in %BF, respectively, and gave the best stepwise linear regression model (%BF = 0.446 MTC + 0.347 PI -29.692; P < 0.001). We conclude that fetal growth biometrics determined by 2-D US do not provide a reliable assessment of %BF in term infants.

Do parents accurately perceive their child's weight status?

INTRODUCTION: Few studies have evaluated the accuracy of parental perceptions of their child's weight status. METHODS: A cross-sectional sample of children aged 5 to 12 years and their parents (n = 576 parent-child pairs) was enrolled from four schools. Child height and weight were measured. The parents classified their child on Likert scales ranging from "extremely overweight" to "extremely underweight." Parental perceptions were compared with their child's weight status according to body mass index (BMI) age-gender percentiles. Fisher-Halton-Freeman tests, chi(2), and logistic regression were used to compare demographic factors between parents who inaccurately estimated and those who accurately estimated child weight status. RESULTS: Misclassification occurred 25% of the time (95% confidence interval: 21.4-28.5). All parents of children with a BMI greater than or equal to the 95th percentile classified their child in a category other than "extremely overweight," and 75% of children with a BMI from the 85th to less than the 95th percentile were misclassified as "about right" or "underweight." Boys were more likely to be misclassified than were girls (29% vs 21%, P = .03). CONCLUSIONS: The majority of parents of obese and overweight children underestimate their child's weight status. Parents of boys are more likely to perceive their child's weight incorrectly.

Analysis of radiographic characteristics of anterolateral bowing of the leg before fracture in neurofibromatosis type 1.

BACKGROUND: Anterolateral leg bowing is associated with neurofibromatosis type 1 (NF1) frequently leading to fracture and nonunion of the tibia. The objective of the study was to characterize the radiographic findings of tibial dysplasia in NF1. METHODS: This study is a retrospective review of radiographs of tibial dysplasia obtained within 52 years, between 1950 and 2002, from the Shriners Hospitals for Children, Salt Lake City, and of peripheral quantitative computed tomographic images of 3 individuals with anterolateral bowing of the leg without fracture compared with age- and sex-matched controls. RESULTS: Individuals with NF1 with bowing of the leg have the appearance of thicker cortices with medullary narrowing on plain film radiographs. The peripheral quantitative computed tomographic images of individuals with NF1 with anterolateral bowing show an unusual configuration of the tibia. CONCLUSIONS: Anterolateral bowing of the leg in NF1 is associated with the appearance of thicker cortices with medullary narrowing rather than thinning of the long bone cortex on plain film radiographs as currently used as a qualifier in the sixth diagnostic criterion for the clinical diagnosis of NF1. Individuals with NF1 who have anterolateral bowing of the leg have differences in tibial geometry compared with age- and sex-matched controls. CLINICAL RELEVANCE: The characterization of the radiographic findings of long bone bowing in NF1 helps clarify the NF1 clinical diagnostic criteria.

Fitness of children with standard-risk acute lymphoblastic leukemia during maintenance therapy: response to a home-based exercise and nutrition program.

BACKGROUND: Altered nutrient intake and decreased exercise in response to cancer therapies and their side effects, particularly corticosteroids, may be key factors in the increased body weight and differences in physical fitness reported in survivors of childhood acute lymphoblastic leukemia (ALL). PURPOSE: To assess (1) the effect of a home-based nutrition and exercise intervention program on cardiovascular fitness, strength, and flexibility in children with ALL during maintenance therapy and (2) the feasibility of conducting and evaluating a home-based exercise and nutrition program in this patient population. DESIGN: Children ages 4 to 10 years with standard-risk ALL were randomized when starting maintenance therapy to a 12-month home-based exercise and nutrition program (n=6, 3 males/3 females) or control (n=7, 4 males/3 females) group. Assessment of anthropometrics, dietary intake, physical activity, and fitness was performed at baseline and 6 and 12 months of study. RESULTS: Although age, body size, and nutrient intakes were similar between both subject groups at 0, 6, and 12 months, exercise and nutrition program children had greater improvement in physical activity and cardiovascular fitness between 6 and 12 months than control children. CONCLUSIONS: These results suggest that a home-based exercise intervention during maintenance therapy encouraged greater physical activity and improved cardiovascular fitness in children with standard-risk ALL. Further investigation involving larger populations of children with ALL is warranted.

Tibial geometry in individuals with neurofibromatosis type 1 without anterolateral bowing of the lower leg using peripheral quantitative computed tomography.

INTRODUCTION: Lower leg bowing with tibial pseudarthrosis is associated with neurofibromatosis type 1 (NF1). The objective of the study is to determine if the geometry of the lower limb in individuals with neurofibromatosis type 1 (NF1) differs from controls, and to characterize the osseous components of the tibia in NF1. METHODS: Peripheral quantitative computed tomography (pQCT) of the lower limb was performed (90 individuals with NF1 without tibial and/or fibular dysplasia: 474 healthy individuals without NF1). Subjects were 4-18 years of age. Individuals with NF1 were compared to controls using an analysis-of-covariance with a fixed set of covariates (age, weight, height, Tanner stage, and gender). RESULTS: Using pQCT, NF1 individuals without bowing of the lower leg have smaller periosteal circumferences (p<0.0001), smaller cortical area (p<0.0001), and decreased tibial cortical and trabecular bone mineral content (BMC) (p<0.0001) compared to controls. DISCUSSION: Individuals with NF1 have a different geometry of the lower leg compared to healthy controls suggesting that NF1 haploinsufficiency impacts bone homeostasis although not resulting in overt anterolateral bowing of the lower leg.

Evaluation of the Gold Medal Schools program.

Utah's Gold Medal Schools program supports the adoption of school policies that provide opportunities for nutritious food choices and regular physical activity. The effectiveness of Gold Medal Schools was evaluated via anthropometric measurements and dietary and physical activity surveys. The study population included first-, third-, and fifth-grade elementary school students and parents from four schools in Tooele County, UT. Two schools implemented Gold Medal Schools (intervention) and two did not (comparison). Data were collected at baseline (June 2005) and 1 year (May 2006). Body mass index (calculated as kg/m(2)) z scores increased significantly in the comparison group (0.53+/-0.38; P<0.05), but not in the intervention group (0.21+/-0.47; P=0.484), from baseline to 1 year. Children in the Gold Medal Schools cohort reported drinking fewer soft drinks per day (excluding diet drinks) at 1 year (P=0.008) and walking or biking to school more often at baseline and 1 year (P<0.001) than non-Gold Medal Schools children. While children in both groups increased the days per week they walked or biked to school, a substantial improvement was observed for the non-Gold Medal Schools students only (P<0.001). Overall, this pilot study suggests that Gold Medal Schools positively impacted body mass index z scores and health behaviors among elementary-aged students.

IGF-1 and IGF-binding proteins and bone mass, geometry, and strength: relation to metabolic control in adolescent girls with type 1 diabetes.

Children and adolescents with poorly controlled type 1 diabetes mellitus (T1DM) are at risk for decreased bone mass. Growth hormone (GH) and its mediator, IGF-1, promote skeletal growth. Recent observations have suggested that children and adolescents with T1DM are at risk for decreased bone mineral acquisition. We examined the relationships between metabolic control, IGF-1 and its binding proteins (IGFBP-1, -3, -5), and bone mass in T1DM in adolescent girls 12-15 yr of age with T1DM (n = 11) and matched controls (n = 10). Subjects were admitted overnight and given a standardized diet. Periodic blood samples were obtained, and bone measurements were performed. Serum GH, IGFBP-1 and -5, glycosylated hemoglobin (HbA(1c)), glucose, and urine magnesium levels were higher and IGF-1 values were lower in T1DM compared with controls (p < 0.05). Whole body BMC/bone area (BA), femoral neck areal BMD (aBMD) and bone mineral apparent density (BMAD), and tibia cortical BMC were lower in T1DM (p < 0.05). Poor diabetes control predicted lower IGF-1 (r(2) = 0.21) and greater IGFBP-1 (r(2) = 0.39), IGFBP-5 (r(2) = 0.38), and bone-specific alkaline phosphatase (BALP; r(2) = 0.41, p < 0.05). Higher urine magnesium excretion predicted an overall shorter, lighter skeleton, and lower tibia cortical bone size, mineral, and density (r(2) = 0.44-0.75, p < 0.05). In the T1DM cohort, earlier age at diagnosis was predictive of lower IGF-1, higher urine magnesium excretion, and lighter, thinner cortical bone (r(2) >or=0.45, p < 0.01). We conclude that poor metabolic control alters the GH/IGF-1 axis, whereas greater urine magnesium excretion may reflect subtle changes in renal function and/or glucosuria leading to altered bone size and density in adolescent girls with T1DM.

Evidence of increased bone resorption in neurofibromatosis type 1 using urinary pyridinium crosslink analysis.

Although neurofibromatosis type 1 (NF1) is a neurocutaneous disorder, skeletal abnormalities such as long-bone dysplasia, scoliosis, sphenoid wing dysplasia, and osteopenia are observed. To investigate the role of bone resorption as a mechanism for the bony abnormalities, we selected urinary pyridinium crosslinks (collagen degradation products excreted in urine) as a measure of bone resorption in NF1. Bone resorption was evaluated by quantitative assessment of the urinary excretion of pyridinium crosslinks [pyridinoline (Pyd) and deoxypyridinoline (Dpd)]. Total (free plus peptide-bound) pyridinium crosslinks from the first morning urines from 59 NF1 children (ages 5-19) were extracted and analyzed (17 children with a localized skeletal dysplasia, and 42 without). The data were compared with a healthy reference population without NF1 (n = 99). Multivariate analyses, controlling for age showed statistically significant increases for Dpd (p < 0.001) and the Dpd/Pyd ratio (p < 0.001) in NF1 individuals with and without a skeletal dysplasia. NF1 children have an increase in the urinary excretion of pyridinium crosslinks, reflecting increased bone resorption. The effects of NF1 haploinsufficiency likely contribute to abnormal bone remodeling, either directly or indirectly by aberrant Ras signaling, potentially predisposing NF1 individuals to localized skeletal defects.

Peripheral quantitative computed tomography of the tibia: pediatric reference values.

Peripheral quantitative computed tomography (pQCT) has been used in a number of pediatric studies. Reference data for children are primarily limited to the radius. The purpose of this study was to establish normal reference ranges for pQCT measurements of the tibia for children. A cross-sectional sample of healthy, white, non-Hispanic children aged 5-18 years (n=416; 197 boys) was measured at the distal tibia metaphysis and diaphysis by pQCT to assess trabecular and cortical bone, respectively. Differences were determined between and within genders by height for bone geometry, density, and strength. Height-specific normal ranges were calculated, and gender-specific centile curves were generated. A positive, linear relationship was found between tibia cortical bone geometry and strength parameters and height (r2 >or=0.58, p<0.001), with mean values greater for boys than girls (p