Effect of long-term growth hormone treatment on final height of children with Russell-Silver syndrome.

BACKGROUND: The aim of this study was to determine the beneficial effects of long-term growth hormone (GH) treatment on final height (FH) in 26 children with Russell-Silver syndrome (RSS). METHODS: Twenty-six patients (16 males) were diagnosed with RSS at a median age of 2.9 years according to clinical criteria. All patients were prepubertal at the commencement of treatment. They received treatment with biosynthetic human GH for 9.8 years (median) and all attained FH. RESULTS: The median height at the commencement of treatment was -2.7 SDS and increased to -1.3 SDS (p = 0.001). However, FH did not reach target height (-0.90 SDS, p = 0.003). Predictors of FH outcome were: the height at the start of treatment (r(2) = 0.419, p < 0.001) (inversely related) and the height gain at onset of puberty (r(2) = 0.257, p < 0.001) (positively related). The overall prediction model accounted for 67.6% of height gain. Sitting height improved gradually during GH treatment (-3.3 to -1.0 SDS, p = 0.012), as did weight (-3.3 to -1.3 SDS, p < 0.001) and BMI (-1.5 to -0.2 SDS, p < 0.001). CONCLUSIONS: A significant improvement of growth in RSS children has been shown after 10 years of GH treatment with a FH of -1.3 SDS. The shorter the patient at the start of treatment is, the greater the increment in FH. A significant response is also shown at the onset of puberty. GH treatment may also have a beneficial effect on the spinal length of RSS children.

Design and evaluation of a treatment programme for Spanish adolescents with overweight and obesity. The EVASYON Study.

BACKGROUND: The prevalence of overweight and obesity (OW/OB) among adolescents worldwide has increased since the 60 s. Spain has reached one of the highest OW/OB prevalence rates among adolescents from European countries. The aim of this methodological paper is to describe the design and evaluation in the EVASYON study (Development, implementation and evaluation of the efficacy of a therapeutic programme for adolescents with OW/OB: integral education on nutrition and physical activity). METHODS/DESIGN: The EVASYON was planned by a multidisciplinary team to treat OW/OB in Spanish adolescents. The EVASYON is a multi-centre study conducted in 5 hospitals in 5 Spanish cities (Granada, Madrid, Pamplona, Santander and Zaragoza) and two hundred and four OW/OB Spanish adolescents were recruited for this intervention. The treatment was implemented for approximately one-year follow-up. The adolescents were treated in groups of a maximum of 10 subjects; each group had 20 visits during the treatment period in two phases: intensive during the first 2 months (1st to 9th visits), and extensive during the last 11 months (10th to 20th visits). In order to assess the efficacy of the treatment, 8 dimensions were measured: diet; physical activity and fitness; eating behaviour; body composition; haematological profile; metabolic profile; minerals and vitamins; immuno-inflammatory markers. Moreover, genetic polymorphisms were also determined. DISCUSSION: The treatment programme developed in the EVASYON study was designed as a national pilot study to be implemented as an effective treatment for adolescents with OW/OB into the Spanish Health Care Service.

Interplay between weight loss and gut microbiota composition in overweight adolescents.

The aim of this study was to determine the influence of an obesity treatment program on the gut microbiota and body weight of overweight adolescents. Thirty-six adolescents (13-15 years), classified as overweight according to the International Obesity Task Force BMI criteria, were submitted to a calorie-restricted diet (10-40%) and increased physical activity (15-23 kcal/kg body weight/week) program over 10 weeks. Gut bacterial groups were analyzed by quantitative real-time PCR before and after the intervention. A group of subjects (n=23) experienced >4.0 kg weight loss and showed significant BMI (P=0.030) and BMI z-score (P=0.035) reductions after the intervention, while the other group (n=13) showed <2.0 kg weight loss. No significant differences in dietary intake were found between both groups. In the whole adolescent population, the intervention led to increased Bacteroides fragilis group (P=0.001) and Lactobacillus group (P=0.030) counts, and to decreased Clostridium coccoides group (P=0.028), Bifidobacterium longum (P=0.031), and Bifidobacterium adolescentis (P=0.044) counts. In the high weight-loss group, B. fragilis group and Lactobacillus group counts also increased (P=0.001 and P=0.007, respectively), whereas C. coccoides group and B. longum counts decreased (P=0.001 and P=0.044, respectively) after the intervention. Total bacteria, B. fragilis group and Clostridium leptum group, and Bifidobacterium catenulatum group counts were significantly higher (P<0.001-0.036) while levels of C. coccoides group, Lactobacillus group, Bifidobacterium, Bifidobacterium breve, and Bifidobacterium bifidum were significantly lower (P<0.001-0.008) in the high weight-loss group than in the low weight-loss group before and after the intervention. These findings indicate that calorie restriction and physical activity have an impact on gut microbiota composition related to body weight loss, which also seem to be influenced by the individual's microbiota.

Serum Amyloid A concentration is increased in obese children and adolescents.

OBJECTIVE: To compare the circulating concentrations of the acute-phase protein serum amyloid A (SAA) in lean, overweight, and obese children and adolescents and analyze the influence of body fat. STUDY DESIGN: A total of 63 children and adolescents (65% girls) with an average age of 12.1 +/- 2.7 years (range, 6 to 18 years) were included in the study. Each child was classified on the basis of age- and sex-specific body mass index (BMI) percentile as normal weight (BMI <85th percentile; n = 17), overweight (BMI >/=85th and <95th percentiles; n = 26), or obese (BMI >/=95th percentile; n = 20). Body fat was estimated by air-displacement plethysmography. RESULTS: Both overweight and obese children exhibited significantly increased circulating SAA concentrations (log SAA: lean, 0.66 +/- 0.20; overweight, 0.83 +/- 0.29; obese, 0.96 +/- 0.21; P = .002) compared with the lean children. Significant correlations were found between log SAA and body fat (r = 0.48; P < .0001). In multiple linear regression analysis, log C-reactive protein (CRP) (P = .014) and body fat (P = .031) emerged as significant predictors of log SAA. CONCLUSIONS: Plasma SAA concentrations are elevated in overweight and obese children, being strongly related to adiposity and log CRP. This finding suggests that increased body fat may contribute to the development of a low-grade chronic proinflammatory state at an early age, possibly contributing to the obesity-associated cardiovascular disease risk.

Association between obesity and insulin resistance with UCP2-UCP3 gene variants in Spanish children and adolescents.

A number of studies have yielded controversial results on the association between polymorphisms in UCP2 and UCP3 genes with obesity and its comorbidities. The discrepancy among studies might be partially explained by the lack of consideration of the effect of adjacent loci in the same haplotype and the exclusion of key lifestyle factors in the statistical analysis. In this study, we have assessed the association between three genetic variants of the UCP2-UCP3 gene cluster, the -866G/A (rs659366) and the 45bp insertion (in position 173247 of the AC019121) of the UCP2 gene, the -55C/T (rs1800849) polymorphism of the UCP3 gene and their estimated haplotypes with childhood obesity and insulin resistance. This research was designed as a case-control study and information about several environmental parameters such as leisure time physical activity and time spent watching television were included. The study sample consisted in 193 obese children and adolescents (cases) and 170 controls aged 6-18. We found that the individual polymorphisms were not associated with obesity, but the (-866G; rs659366)-(Del; 45bp)-(-55T; rs1800849) haplotype was significantly associated with obesity and its presence in the control group increased about nine times the insulin resistance risk. Thus, the (-866A; rs659366)-(Ins; 45bp)-(-55C; rs1800849) haplotype may protect against insulin resistance in the obese population group.

Bone mineral density and bone metabolism in children treated for bone sarcomas.

In adolescent bone sarcoma patients, bone mass acquisition is potentially compromised at a time in which it should be at a maximum. To evaluate the problem we measured bone mineral density (BMD) and serum markers of bone formation and resorption in a series of pediatric patients with bone tumors. BMD was measured by dual-energy x-ray absorptiometry, at clinical remission, for lumbar spine and the neck of the femur in 38 osteosarcoma and 25 Ewing's sarcoma patients. Mean age was 20.65 and 19.13 y respectively. Serum markers of bone metabolism were: OC, PICP, ICTP, 25-OH vit D and 1,25-(OH)(2) vit D, IGF-I, IGFBP-3 and intact PTH. Serum was sampled throughout anti-tumoral treatments and follow-up. We analyzed 85 samples from 59 osteosarcoma patients and 54 samples from 36 Ewing's sarcoma patients. Patients had decreased lumbar and femoral BMD. The decrease was more pronounced in pubertal patients compared with those who had completed pubertal development at the time of disease diagnosis. Multivariate analysis indicated that sex, age, weight and BMI were significant in lumbar BMD depletion. Weight and BMI were significant in femoral BMD depletion. Serum markers of bone formation (PICP and OC) and resorption (ICTP) were, throughout, lower than reference values. Significant alterations in other markers were also observed. Up to a third of osteosarcoma and Ewing's sarcoma patients in clinical remission had some degree of BMD deficit. The corresponding increased risk of pathologic bone fractures constitutes a reduction in future quality of life.

Fat mass by air-displacement plethysmography and impedance in obese/non-obese children and adolescents.

OBJECTIVE: To determine the level of agreement between measurements of body composition by air-displacement plethysmography (ADP) and bioelectrical impedance analysis (BIA) in obese/non-obese children and adolescents. METHODS: Fat mass (FM) and fat free mass (FFM) were measured by ADP using the BOD-POD system and foot-to-foot BIA in 187 children and adolescents (75 males and 112 females, aged 5 to 22 years). Obesity was defined as a percentage FM (determined by BOD-POD), as a percentage (%) higher than 25%-35%. Sixty-four subjects were obese and 123 non-obese. RESULTS: Lin's Concordance Coefficient (Rc) between estimates of FM (%) and FFM (kg) was 0.79 (95% CI: 0.73; 0.83) by BIA and 0.96 (95% CI: 0.95; 0.97) by ADP. For the group of patients as a whole, the mean difference (p < 0.001) between methods (the BIA measurement minus the ADP measurement) was -3.39 (95% CI: -4.13; -2.65) for FM (%) and 1.54 (95% CI: 1.10; 1.98) for FFM (kg) (p < 0.001). The limits of agreement were -13.70; 6.90 for FM (%) and 1.40; 7.60 for FFM (kg). In the obese group, the mean difference between methods was -5.01 (95% CI: -6.21; -3.81) for FM (%) and 2.58 (95% CI: 3.45; 1.71) for FFM (kg) (p < 0.001). In the non-obese group, these mean differences were 2.49 (95% CI: -3.41; -1.57) and 0.96 (95% CI: 1.43; 0.50), respectively (p < 0.001). CONCLUSIONS: Compared with ADP, foot-to-foot BIA overestimates FFM and underestimates FM in obese and non-obese children of either sex. ADP and BIA estimates of FFM and FM are highly correlated for both obese/non-obese children. However, the large limits of agreement suggest that these methods should not be used interchangeably.

Analysis of polymorphisms of the vitamin D receptor, estrogen receptor, and collagen Ialpha1 genes and their relationship with height in children with bone cancer.

PURPOSE: The authors' objectives were to compare height at diagnosis of children with bone tumors with that of Spanish reference children; to analyze the frequency of the genotypes for the polymorphisms of the vitamin D receptor (VDR), estrogen receptor (ER), and collagen Ialpha1 (COLIalpha1) genes in patients and in healthy controls; and to test the relationship between the genetic markers and height. PATIENTS AND METHODS: Height and weight at diagnosis were measured in 58 osteosarcoma and 36 Ewing sarcoma patients and compared with standards published for Spanish reference children according to sex and age. For the molecular analysis, genetic polymorphisms of the VDR (Fok I, Apa I, and TaqI), ER (Pvu II and XbaI), and COLIalpha1 (Msc I) genes were characterized in 72 osteosarcoma and 53 Ewing sarcomas and in a group of 143 healthy matched children. RESULTS: Osteosarcoma and Ewing sarcoma patients were significantly taller than Spanish reference children. Osteosarcoma patients showed a significantly higher frequency of the Ff genotype for the Fok I polymorphism (VDR gene) than the control group. The odds ratio for this genotype was 1.78, with an increased relative risk of 78% for heterozygous Ff carriers. Among Ewing sarcoma patients, this same genotype was significantly associated with lower height than homozygotes (FF or ff). CONCLUSIONS: Children with bone cancer are significantly taller than the reference population, which may be influenced by the genotype for the Fok I polymorphism of the VDR gene.

Reduced bone mineralization in adolescent survivors of malignant bone tumors: comparison of quantitative ultrasound and dual-energy x-ray absorptiometry.

PURPOSE: To assess bone mineralization in adolescents with bone tumors at remission using quantitative digital ultrasound (QUS) and dual-energy x-ray absorptiometry (DEXA), and to compare the bone mineralization values obtained by both methods. METHODS: Patients studied were 36 adolescents (21 boys, 15 girls) who had completed treatment of a bone tumor at the University Hospital of the University of Navarra (Pamplona, Spain). QUS was performed at the distal metaphysis of the proximal phalanxes of the last four fingers of the nondominant hand. A DBM Sonic 1200 Ultrasound densitometer was used. DEXA measurements were made at the lumbar spine (vertebrae L1-L4) using the Hologic QDR 4500 W device. Calcium and vitamin D daily intake and grade of physical activity were recorded. RESULTS: Mean age at bone mineralization determination was 19.11 years. Disease-free survival was 4.97 years. Decreased bone mineralization was observed by both methods. Bone mineralization absolute values measured by QUS and DEXA were significantly correlated. The sensitivity, specificity, diagnostic accuracy, and positive and negative predictive values of QUS for predicting osteopenia were 36.4%, 80.0%, 66.7%, 44.4%, and 74.1%, respectively. Daily vitamin D intake was below the recommended dietary allowances. CONCLUSIONS: Adolescents in remission from bone tumors have low bone mineralization determined by DEXA or QUS.