Vitamin D levels and vitamin D receptor gene polymorphisms in asthmatic children: a case-control study.

BACKGROUND: Vitamin D deficiency and single nucleotide polymorphisms (SNP) in the gene encoding vitamin D receptor (VDR) have been associated with asthma. OBJECTIVE: To compare 25-hydroxyvitamin D (25OHD) levels and the frequency of 3 SNPs in the VDR gene between asthmatic and healthy children. METHODS: In persistent asthmatic and healthy control children, the 25OHD levels were measured using radioimmunoassay and SNPs (FokI, ApaI, and TaqI) were analyzed by a PCR-RFLP assay. Relevant medical history was collected. RESULTS: About 75 asthmatic (median age: 9.1 years) and 227 healthy children (10.3 years) were studied. In the whole population, the proportion of sufficient, insufficient, and deficient levels of 25OHD were 14.9%, 44%, and 41.1%, respectively. 25OHD sufficiency status was similar in asthmatic and healthy children (p = 0.57). However, the proportion of 25OHD sufficient levels among asthmatics according to the Global Initiative for Asthma treatment steps 2, 3, and 4 was significantly different (8.6%, 16.6%, and 43.7%, respectively, p = 0.046). All patients on step 4 of the treatment (16/16) were heterozygous for the C allele (FokI VDR SNP). There was a lower presence of the C allele among asthmatics in step 2 (30/33), step 3 (16/24), and controls (45/50), p = 0.007, but this significance did not persist after logistic regression. No significant differences in ApaI and TaqI were found. CONCLUSIONS: We found a possible association of vitamin D sufficiency status and FokI C allele with higher requirement of therapy to reach asthma control, suggesting that it may be involved in treatment response. Variations in VDR might also play a role in the 25OHD levels.

Risedronate in children with osteogenesis imperfecta: a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Children with osteogenesis imperfecta are often treated with intravenous bisphosphonates. We aimed to assess the safety and efficacy of risedronate, an orally administered third-generation bisphosphonate, in children with the disease. METHODS: In this multicentre, randomised, parallel, double-blind, placebo-controlled trial, children aged 4-15 years with osteogenesis imperfecta and increased fracture risk were randomly assigned by telephone randomisation system in a 2:1 ratio to receive either daily risedronate (2·5 or 5 mg) or placebo for 1 year. Study treatment was masked from patients, investigators, and study centre personnel. Thereafter, all children received risedronate for 2 additional years in an open-label extension. The primary efficacy endpoint was percentage change in lumbar spine areal bone mineral density (BMD) at 1 year. The primary efficacy analysis was done by ANCOVA, with treatment, age group, and pooled centre as fixed effects, and baseline as covariate. Analyses were based on the intention-to-treat population, which included all patients who were randomly assigned and took at least one dose of assigned study treatment. The trial is registered with ClinicalTrials.gov, number NCT00106028. FINDINGS: Of 147 patients, 97 were randomly assigned to the risedronate group and 50 to the placebo group. Three patients from the risedronate group and one from the placebo group did not receive study treatment, leaving 94 and 49 in the intention-to-treat population, respectively. The mean increase in lumbar spine areal BMD after 1 year was 16·3% in the risedronate group and 7·6% in the placebo group (difference 8·7%, 95% CI 5·7-11·7; p<0·0001). After 1 year, clinical fractures had occurred in 29 (31%) of 94 patients in the risedronate group and 24 (49%) of 49 patients in the placebo group (p=0·0446). During years 2 and 3 (open-label phase), clinical fractures were reported in 46 (53%) of 87 patients in the group that had received risedronate since the start of the study, and 32 (65%) of 49 patients in the group that had been given placebo during the first year. Adverse event profiles were otherwise similar between the two groups, including frequencies of reported upper-gastrointestinal and selected musculoskeletal adverse events. INTERPRETATION: Oral risedronate increased areal BMD and reduced the risk of first and recurrent clinical fractures in children with osteogenesis imperfecta, and the drug was generally well tolerated. Risedronate should be regarded as a treatment option for children with osteogenesis imperfecta. FUNDING: Alliance for Better Bone Health (Warner Chilcott and Sanofi).

Parathyroid hormone-independent hypercalcemia in an infant with renal dysplasia: possible role of PTHrP.

BACKGROUND: Parathyroid hormone (PTH)-independent hypercalcemia in patients with chronic kidney failure is a rare and poor understood entity. CASE REPORT: We report the case of an infant with stage III chronic kidney failure secondary to multicystic dysplastic kidney disease, who presented at 3 months of life with severe hypercalcemia, suppressed PTH, and elevated PTH-related peptide. Malignancy was discarded, and the patient was treated twice with bisphosphonates with an initial partial response. During follow-up, the calcium levels descended. To date, he has maintained normal serum calcium level for 1 year after discharge. CONCLUSIONS: The presence of PTH-related peptide may play a role in hypercalcemia associated to multicystic dysplastic kidney disease possibly by the overproduction of this peptide in the kidney.

Glucocorticoids Decrease Longitudinal Bone Growth in Pediatric Kidney Transplant Recipients by Stimulating the FGF23/FGFR3 Signaling Pathway.

Renal transplantation (RTx) is an effective therapy to improve clinical outcomes in pediatric patients with terminal chronic kidney disease. However, chronic immunosuppression with glucocorticoids (GCs) reduces bone growth and BMD. The mechanisms causing GC-induced growth impairment have not been fully clarified. Fibroblast growth factor 23 (FGF23) is a peptide hormone that regulates phosphate homeostasis and bone growth. In pathological conditions, FGF23 excess or abnormal FGF receptors (FGFR) activity leads to bone growth impairment. Experimental data indicate that FGF23 expression is induced by chronic GC exposure. Therefore, we hypothesize that GCs impair bone growth by increasing FGF23 expression, which has direct effects on bone growth plate. In a post hoc analysis of a multicentric randomized clinical trial of prepubertal RTx children treated with early GC withdrawal or chronic GC treatment, we observed that GC withdrawal was associated with improvement in longitudinal growth and BMD, and lower plasma FGF23 levels as compared with a chronic GC group. In prepubertal rats, GC-induced bone growth retardation correlated with increased plasma FGF23 and bone FGF23 expression. Additionally, GC treatment decreased FGFR1 expression whereas it increased FGFR3 expression in mouse tibia explants. The GC-induced bone growth impairment in tibiae explants was prevented by blockade of FGF23 receptors using either a pan-FGFR antagonist (PD173074), a C-terminal FGF23 peptide (FGF23180-205) which blocks the binding of FGF23 to the FGFR-Klotho complex or a specific FGFR3 antagonist (P3). Finally, local administration of PD173074 into the tibia growth plate ameliorated cartilage growth impairment in GC-treated rats. These results show that GC treatment partially reduces longitudinal bone growth via upregulation of FGF23 and FGFR3 expression, thus suggesting that the FGF23/Klotho/FGFR3 axis at the growth plate could be a potential therapeutic target for the management of GC-induced growth impairment in children.

Bone mineral density in young Chilean patients with type 1 diabetes mellitus.

BACKGROUND: In this study, our aim was to analyze bone mineral density (BMD) in patients with type 1 diabetes mellitus (T1DM) and compare them with a healthy reference population; in addition, we aimed to observe the association between BMD and the following variables: age at onset, disease duration, metabolic control, pubertal stage, level of physical activity, clinical parameters and nutrient intake. METHODS: A total of 30 patients with T1DM were included in the study. BMD was determined using dual-energy X-ray densitometry (DXA). Participants with a z-score of values ≥-1 were accepted as normal; BMDs between -2 and -1 were defined as being in the low range of normality; ≤-2 were defined as having low BMD. The 25-hydroxy vitamin D level was classified as sufficient (30-100 ng/mL), insufficient (20-30 ng/mL), and deficient (<20 ng/mL). RESULTS: The percentages of patients with deficient and insufficient 25(OH) vitamin D levels were 50% and 45.8%, respectively. Lumbar spine (LS2-LS4) BMD, total body (TB) BMD and femoral neck (FN) BMD were found in the normal range for more than 80% of the subjects, with no significant differences due to gender. No strong correlations between clinical variables, biochemical parameters and nutrient intake were observed; however, a moderate positive correlation was found between serum calcium and LS2-LS4 BMD (p<0.05). Regression analysis showed that serum calcium, duration of diabetes and intake of sodium and protein are significant factors in determining LS2-LS4 BMD and TB BMD. CONCLUSIONS: Patients with T1DM had a normal mean BMD at all sites evaluated, except for two patients who had low BMD at the lumbar spine. More than 95% of patients had insufficient or deficient vitamin D levels. With respect to all the variables studied, serum calcium presented the highest significant correlation with LS2-LS4 BMD.

Determination of bisphenol A in canned fatty foods by coacervative microextraction, liquid chromatography and fluorimetry.

Decanoic acid reverse micelle-based coacervates were used to provide simple, rapid and almost solventless extraction of bisphenol A (BPA) from canned fatty foods. The procedure involved the extraction of 200-400 mg of homogenised food sample with an aqueous solution containing 20% THF and 200 mg of decanoic acid, conditions under which the coacervate (around 550 microl) formed in situ and instantaneously. The overall sample treatment took about 30 min and several samples could be simultaneously treated using conventional laboratory equipment. No clean-up or solvent evaporation were required before determination of BPA by liquid chromatography and fluorescence detection. Recoveries in samples were between 90 and 99%, with relative standard deviations in the range 2-7%. The limit of quantification ranged 29-15 ng g(-1) for 200-400 mg of sample, being far below the current specific migration limit (SML) set by the European Commission (600 ng g(-1)). The method was successfully applied to the determination of BPA in the solid content of canned fish (from 20 to 129 ng g(-1)) and meat (from undetected to 37 ng g(-1)).

Osteoporosis in children with severe congenital neutropenia: bone mineral density and treatment with bisphosphonates.

A high incidence of decreased bone mineral density (BMD) has been described in patients with severe congenital neutropenia (SCN). The objectives of the study are to describe changes in BMD in children with SCN treated with granulocyte colony-stimulating factor and evaluate the response to treatment with bisphosphonates in those who had osteoporosis. A prospective open-label study was performed evaluating BMD and metabolism in 9 Chilean patients with SCN, administrating bisphosphonates in those with osteoporosis. Follow-up ranged between 7 months and 3.5 years. Six out of 9 patients had reduced BMD on initial assessment: 3 had osteoporosis (z score <-2) and 3 had osteopenia (z score <-1). Four children presented vertebral fractures. Two presented osteopenia on follow-up without clinical symptoms. Five patients were treated with bisphosphonates, increasing their BMD z score (mean increase 1.2, range 0.27 to 2.62). z Score of hydroxyproline/creatinine ratios, which was elevated in 4 patients with osteoporosis, decreased during treatment (mean decrease 2.18, range 1.56 to 2.53). Four patients remodeled and reexpanded fractured vertebrae during treatment. No side effects of bisphosphonates were seen on follow-up. Osteoporosis is an important comorbidity in SCN patients probably due to increased bone resorption. Bisphosphonates seem to be an effective treatment for osteoporosis in these patients.

[Vitamin D deficiency in children with chronic diseases evaluated because of osteopenia]. / Deficiencia de vitamina D en niños con enfermedades crónicas evaluados por osteopenia.

BACKGROUND: Chronic diseases in children may determine limited sun exposure, use of drugs, and other risk factors of osteopenia. OBJECTIVE: To evaluate vitamin D deficiency and their risk factor, in children with chronic diseases with suspected osteopenia. METHODS: We measured bone mineral density, bone remodeling markers, calcium, phosphate, parathormone, and 25 hydroxyvitamin D levels, and wrist X-ray. RESULTS: We found 8 children of 25 with suspected osteopenia, with biochemical abnormalities suggestive of vitamin D deficiency. All children had low levels of 25 hydroxyvitamin D, 5 had reduced bone mineral density, 4 had hyperparathyroidism, 2 had hyperphosphatasemia, and 1 hypocalcemia and hypophosphatemia. None had rickets. DISCUSSION: Osteopenia in chronic sick children is due to multiple factors; however, vitamin D deficiency is a preventable disorder. We recommend that all children with a chronic disease with risk factors for vitamin D deficiency should be monitored with 25 hydroxyvitamin D serum levels.

Densitometría mineral ósea en pacientes pediátricos: interpretación de resultados e indicaciones / Indications and interpretation of results of pediatric bone densitometry

There is a growing interest in the evaluation of bone mass in children, to support the adequate management of several diseases in this age group. This interest was boosted by the improvement in bone mass measuring techniques and by the increase in the incidence of osteoporosis during childhood, due to the longer lifespan of children with congenital or acquired diseases. Other reason to measure bone mass is that an adequate bone accretion in children will prevent osteoporosis during adulthood. The extensive use of bone densitometry in children requires an adequate knowledge about its indications and interpretation. The morphology, size and constitution of the skeleton of child changes constantly, therefore densitometry results cannot be interpreted as those of a small adult. We review the advances in pediatric bone densitometry, specially its indications and the interpretation of results.

Encuesta endocrino-ginecológica de la adolescente / Endocrino-ginecologic survey in adolescent female

Se analizó una encuesta en adolescentes de colegios fiscales y particulares de la Quinta Región para determinar la cronología de algunos eventos de la pubertad y la magnitud de algunos problemas endocrino-ginecológicos. El estudio revela que el promedio de edad de aparición de la menarquia en nuestra región es similar a lo referido por autores de países desarrollados, siendo algo más precoz en adolescentes de colegios particulares. Dos tercios de las encuestadas presenta ciclos normales, aunque presentan dismenorrea moderada. Sólo una quinta parte de las encuestadas han consultado al ginecólogo, siendo este porcentaje mayor en adolescentes de colegios particulares. Los datos obtenidos sobre actividad sexual son poco confiables. Se requiere diseñar una metodología para conocer esta importante faceta de la conducta de la mujer adolescente