N-terminal C-type natriuretic propeptide is associated with the endosteal apposition of bone in females with a persistent eating disorder.

BACKGROUND/AIM: Females with anorexia nervosa (AN) are often affected by osteoporosis. The study intends to investigate the association between serum levels of the N-terminal propeptide of the C-type natriuretic peptide (NT-proCNP) and bone development in anorexic females. SUBJECTS AND METHODS: In a catamnestic visit, 21 females, formerly treated for AN, were assessed for the presence of eating disorders and analyzed for bone parameters of the distal radius (4% site) with peripheral quantitative computed tomography (pQCT), for maximal isometric grip force (MIGF) and for NT-proCNP serum levels. RESULTS: The 9 females with a persistent eating disorder had lower height and weight than the recovered girls. NT-proCNP was correlated with the cortical area (r = 0.521), the endosteal circumference (CE, r = -0.468) and the ratio of MIGF to cross-sectional bone area (r = 0.434). CE explained 40% of the variance of NT-proCNP in females with persistent eating disorders, but was not associated with NT-proCNP in recovered girls (p = 0.691). The association between CE and NT-proCNP was not existent when the correlation was controlled for the duration of amenorrhea and the supplemented cumulative dose of ethinylestradiol (p = 0.275). CONCLUSION: NT-proCNP reflects metaphyseal inwaisting which is modified by estrogens and the pressure on the growth plate.

Do bone mineral density, bone geometry and the functional muscle-bone unit explain bone fractures in healthy children and adolescents?

BACKGROUND/AIMS: Because the increasing fracture incidence has not been understood, the present study compares variables of the muscle-bone interaction to examine the hypothesis that an impaired adaptation of bone strength to muscle forces explains this phenomenon. METHODS: The forearm of 220 individuals (mean age 11.1 ± 3.2 years; range 5.5-17.4 years) was analyzed by peripheral quantitative computed tomography. Bone mineral content (BMC), bone mineral density, periosteal circumference, cortical area, strength strain index (SSI) and muscle area (MA) were measured at the distal and proximal radius of the non-dominant forearm. Maximum isometric grip force was measured by a dynamometer. The fracture history was evaluated by a questionnaire after a period of 5 ± 1.7 years. RESULTS: During the observational period at least one fracture appeared in 78 children and adolescents (35.5%). Individuals with and without fractures were not different in age, height, weight, and body mass index. Variables of bone mineral density, bone geometry and muscle force were not different between both groups. BMC, MA and SSI were dependent on age and sex. CONCLUSION: Fracture risk in healthy children and adolescents is not sufficiently explained by volumetric bone mineral density, the skeletal phenotype and indices of the functional muscle-bone unit.

The relationship between body composition and the urinary excretion of deoxypyridinoline and galactosyl-hydroxylysine in children and adolescents.

The study intends to investigate the relationship of body composition (%fat, percent body fat; FM, fat mass; FFM, fat free mass; FA and MA cross-sectional fat and muscle area) to the urinary excretion of deoxypyridinoline (DPD) and galactosyl-hydroxylysine (Gal-Hyl). 231 healthy children and adolescents (age 5-19 years; 112 males) of the DONALD study were analyzed for FM and FFM by measuring 4 skinfold thicknesses, for DPD and Gal-Hyl in urine samples and for bone parameters, FA and MA at the forearm by peripheral quantitative computed tomography. In contrast to adrenarchal females, adrenarchal males with low %fat had low levels of DPD and Gal-Hyl. %fat was correlated with DPD in pre-adrenarchal males (r = 0.290) and females (r = 0.298). Cortical bone mineral density (BMDcort) was correlated with DPD (r = -0.351) in adrenarchal males. Controlled for BMDcort, FM was correlated with DPD in pre-adrenarchal males (r = 0.348), and FA was correlated with DPD in pre-adrenarchal females (r = 0.294). FFM was negatively correlated with Gal-Hyl in adrenarchal males (r = -0.436) and females (r = -0.338). Less than 40% of variance of excreted DPD and Gal-Hyl was explained by regression models based on parameters of body composition. The effect of body composition explains the minor part of variance of the urinary excretion of DPD and Gal-Hyl. The association of body composition to excreted DPD and Gal-Hyl was not explained by the effect of adipose tissue on bone formation and bone resorption.

High and low birth weight and its implication for growth and bone development in childhood and adolescence.

AIM: To investigate the relationship of birth weight (BW) to anthropometric measures, local body composition and bone development. POPULATION AND METHODS: 284 individuals (age 5-19 yr, 145 females) were recruited from the Dortmund Nutritional and Anthropometric Longitudinally Designed (DONALD) study. Parameters of bone development (cortical bone mineral density [BMDcort], endosteal circumference [CE]) and of local body composition (cross-sectional fat area [FA]) were analyzed by pQCT at the forearm. Parameters were transformed into SD scores to adjust for age or height. RESULTS: BW predicted weight-SDS (R = 0.221), height-SDS (R = 0.260) and FA-SDS (R = 0.150). Individuals with lower BW (< 10th percentile) had lower weight-SDS (p < 0.01), height-SDS (p < 0.01), BMDcort-SDS (p = 0.02) and higher CE-SDS (p = 0.05). BMDcort was correlated with BW (r = -0.319) and FA (r = -0.283) in pubertal females. CONCLUSION: BW is characterized by direct and indirect effects on growth, body composition and bone development.

The 'functional muscle-cartilage unit': a reasonable approach to describe a putative relationship between muscle force and longitudinal growth at the forearm in children and adolescents?

BACKGROUND: Several reports give evidence that the perichondral ossificiation of bone tubes (modeling) strongly depends on muscular forces in children and adolescents. The present analyses intend to investigate the hypothesis that muscular forces also partly determine enchondral ossification and, therefore, longitudinal growth of bone tubes. SUBJECTS AND METHODS: Analyses were based on a single cross-sectional investigation with peripheral quantitative computed tomography in 296 individuals (age 5-19 years) participating in the Dortmund Nutritional and Anthropometric Longitudinally Designed (DONALD) study. RESULTS: Forearm length (FL) was correlated with body height in gender-related subgroups of prepubertal and pubertal individuals (rs between 0.76 and 0.86). Cross-sectional muscle area (MA) increased faster than FL and faster than cross-sectional bone area (BA) close to the distal growth plate in puberty. Close to the growth plate, longitudinal growth was faster than perichondral ossification in females. The ratio MA/BA (surrogate of pressure on the distal growth plate) was correlated with FL in prepubertal boys (r = -0.249, p = 0.043) and pubertal individuals (r = 0.153, p = 0.051). CONCLUSIONS: Results support the hypothesis that longitudinal growth precedes modeling at the distal forearm. Confounding variables such as puberty may modify the relationship between muscle forces and longitudinal growth at the forearm in boys.

Subcutaneous fat and body fat mass have different effects on bone development at the forearm in children and adolescents.

The present study investigated whether subcutaneous fat differs in the impact on bone development from fat mass (FM). We analyzed 295 healthy children and adolescents (age 5-19 years, 139 males) for FM by measuring four skinfold thicknesses and for bone development and body composition at the forearm by peripheral quantitative computed tomography in a cross-sectional investigation. Relative cross-sectional fat area (FA) was a surrogate for relative subcutaneous FM at the forearm and was associated positively with percent fat in prepubertal individuals and pubertal females but negatively in pubertal males. Percent FM was associated with trabecular bone mineral density (BMDtrab) in prepubertal individuals (females r = 0.394, males r = 0.242) and pubertal individuals (females r = 0.215, males r = -0.275). Bone mineral count was correlated with percent FM in pubertal males (r = -0.287). FA was correlated with BMDtrab (r = 0.285) and with cortical bone mineral density (BMDcort, r = -0.296) in pubertal females. The ratio FA/ FM was negatively correlated with BMDcort (r = -0.299) in pubertal females. Pubertal females with relatively high subcutaneous fat area (high ratio FA/FM) were characterized by lower bone strength (P = 0.047). FM and the relative amount of subcutaneous fat have effects on bone formation and resorption that depend on gender and puberty. Especially in pubertal females, higher levels of subcutaneous fat may decrease bone strength due to increased cortical remodeling.

Local body composition is associated with gender differences of bone development at the forearm in puberty.

BACKGROUND/AIMS: The present analyses intend to clarify if gender and puberty modify the relationship between bone development (modeling and remodeling) and fat mass at the forearm. METHODS: Data were collected from participants (139 males, 157 females, age = 5-19 years) of the Dortmund Nutritional and Anthropometric Longitudinally Designed study in a cross-sectional investigation. The main outcome measures were total and trabecular bone mineral density (BMDtot and BMDtrab), strength strain index (SSI) and parameters associated with modeling (cortical area, CA; periosteal circumference, CP) and remodeling (cortical bone mineral density, BMDcort, endosteal circumference, CE) were analyzed in their relationship to cross-sectional fat (FA) and muscle area (MA) at the forearm. RESULTS: BMDtot was correlated with FA in pubertal males (r = -0.25). BMDtrab was contrarily predicted by FA in pubertal males and females (r = -0.28 vs. 0.31). FA was correlated with BMDcort (r = -0.32) and CE (r = 0.26) in pubertal females. MA was positively correlated with CA, CP and SSI. CONCLUSIONS: Modeling and bone strength were primarily predicted by MA. Markers of remodeling were positively correlated with FA in pubertal females, but not in prepubertal individuals and pubertal males. Therefore, gender and puberty modify the relationship between FA and bone development.

Results of a prospective pilot trial on mobility after whole body vibration in children and adolescents with osteogenesis imperfecta.

OBJECTIVE: To evaluate the effect of whole body vibration on the mobility of long-term immobilized children and adolescents with a severe form of osteogenesis imperfecta. Osteogenesis imperfecta is a hereditary primary bone disorder with a prevalence from 1 in 10000 to 1 in 20000 births. Most of these children are suffering from long-term immobilization after recurrent fractures. Due to the immobilization they are affected by loss of muscle (sarcopenia) and secondary loss of bone mass. SUBJECTS: Whole body vibration was applied to eight children and adolescents (osteogenesis imperfecta type 3, N=5; osteogenesis imperfecta type 4, N=3) over a period of six months. INTERVENTIONS AND RESULTS: Whole body vibration was applied by a vibrating platform (Galileo Systems) constructed on a tilting-table. Success of treatment was assessed by measuring alterations of the tilting-angle and evaluating the mobility (Brief Assessment of Motor Function). All individuals were characterized by improved muscle force documented by an increased tilting-angle (median = 35 degrees) or by an increase in ground reaction force (median at start=30.0 [N/kg] (14.48-134.21); median after six months = 146.0 [N/kg] (42.46-245.25). CONCLUSIONS: Whole body vibration may be a promising approach to improve mobility in children and adolescents severely affected with osteogenesis imperfecta.

Cross-sectional fat area at the forearm in children and adolescents.

BACKGROUND: Cross-sectional fat area (FA) and muscle area have been recently used to describe local body composition at the forearm in children and adolescents. The present analysis intends to characterize FA in a normal collective. METHODS: FA was measured by peripheral quantitative computed tomography in a study collective (DONALD study) of 296 children and adolescents. FA was analyzed in relation to fat mass (FM) measured by 4 skinfold thicknesses. RESULTS: FA was significantly correlated with FM (r = 0.8). FA was positively associated with height in prepubertal individuals and pubertal females, but negatively associated with height in pubertal males. Median and range of FA are displayed for different height ranges and pubertal stages in males and females to enable analyses of FA in subgroups. CONCLUSION: Because of the positive dependence of FA on height in prepubertal individuals and pubertal females, reference values of FA may be based on height. But reference values in pubertal males or in a mixed pubertal population should be rather based on pubertal stages than on height.

Predicting the growth response to growth hormone (GH) treatment in prepubertal and pubertal children with isolated GH deficiency--model validation in an observational setting (GeNeSIS).

AIM: Validation of a preexisting mathematical model for predicting height velocity in the first year of growth hormone (GH) treatment, using an independent cohort of pediatric patients with confirmed GH deficiency (GHD). DESIGN: 210 prepubertal and pubertal patients with isolated GHD were enrolled within the 'growth prediction module' of a prospective international postmarketing research program (GeNeSIS). METHODS: The patients were grouped as 'prepubertal', at 'start of puberty' and 'pubertal', and the performance of the model was validated by comparing predicted and observed height velocity (HV) in the first treatment year for each group. The operational characteristics of the model, when used as a screening method to predict poor and good growth response to GH, were calculated using the first year change in height standard deviation score as a cut-off for treatment response. RESULTS: Depending on pubertal stage, the growth prediction model explained 53-72% of the variability of the first year HV. The model fulfilled the statistical prerequisites to identify patients with poor and good responses to GH with sufficient reliability in individual patients. CONCLUSIONS: The growth prediction model was successfully validated in a large cohort of prepubertal and pubertal pediatric patients under field conditions.

Effect of pamidronate treatment on vertebral deformity in children with primary osteoporosis. A pilot study using radiographic morphometry.

OBJECTIVE: Bisphosphonates are effectively used in treatment for primary osteoporosis in children. In the present study, we quantitatively evaluated the effect of pamidronate treatment on lumbar vertebrae in children with primary osteoporosis using radiographic morphometry. METHODS: Paired lateral radiographs of the lumbar spine were obtained before and after pamidronate treatment in 5 children with primary osteoporosis. To characterize vertebral deformities, specific morphometrical ratios were calculated for vertebral bodies L1-L4. RESULTS: Significant reshape of lumbar vertebrae was observed: the concavity index (middle-anterior ratio) decreased from 55 to 36% (p = 0.006), and the anterior-posterior ratio (used as a surrogate of wedge deformity) decreased from 25 to 11% (p = 0.001). CONCLUSIONS: Pamidronate treatment significantly influences the restoration of vertebral fractures in children with primary osteoporosis. The present study demonstrates that radiographic morphometry is a suitable tool for quantitative assessment of the vertebral deformities in childhood.

Collagen markers deoxypyridinoline and hydroxylysine glycosides: pediatric reference data and use for growth prediction in growth hormone-deficient children.

BACKGROUND: In children and adolescents, markers of bone and collagen metabolism reflect the dynamics of skeletal growth and development. The aim of this study was to assess the relationship of the urinary collagen markers deoxypyridinoline (DPD) and hydroxylysine (Hyl) and its glycosides [galactosyl-Hyl (Gal-Hyl) and glucosyl-Gal-Hyl] with growth. METHODS: Urine samples from 240 apparently healthy children and adolescents (6-19 years; 124 girls) and from 51 prepubertal children with growth hormone (GH) deficiency (3-14 years; 14 girls) were analyzed. Urinary Hyl and its glycosides were quantified by HPLC, and DPD was assessed by chemiluminescence assay. Urinary concentrations of all markers were related to urinary creatinine. RESULTS: Multiple regression analysis revealed that only age and height velocity were independently associated with these markers in healthy children. In GH-deficient patients, the urinary excretion of both analytes after 4 weeks of GH therapy correlated significantly with the height increase during the first treatment year (r = 0.79 for Gal-Hyl; r = 0.70 for DPD; P <0.001 each). In a multivariate linear regression model using Gal-Hyl concentrations at 4 weeks, baseline concentrations of insulin-like growth factor 1 and height velocity after 3 months accounted for 80% of the variability in height gain during the first treatment year. A model using DPD concentrations at 4 weeks, in place of Gal-Hyl concentrations, as well as baseline concentrations of insulin-like growth factor 1 and height velocity after 3 months accounted for 83% of the variability. CONCLUSIONS: These urinary bone and collagen markers give some early indication of growth response, but the prediction of an individual marker is too imprecise to serve as a basis for clinical decisions. Markers of bone and collagen metabolism might be more useful as components of multivariate growth prediction models.