calcitriol and Cystic-Fibrosis

Vitamin D toxicity is associated with accidental overdoses due to manufacturing or intake errors and its secondary hypercalcemia can result in severe morbidity. Although patients with cystic fibrosis are potentially at increased risk for this intoxication as prescription of vitamin D preparations is a common practice in this population, the frequency of such events is currently unknown. We performed a retrospective analysis of all the files of cystic fibrosis patients followed at the Cliniques universitaires Saint-Luc over a 10-year period, recording 25(OH)- and 1,25(OH)

Topics: Adolescent; Adult; Cohort Studies; Cystic Fibrosis; Drug Overdose; Female; Humans; Male; Medication Errors; Retrospective Studies; Vitamin D; Young Adult

There is current interest in vitamin D as a potential anti-inflammatory treatment for chronic inflammatory lung disease, including cystic fibrosis (CF). Vitamin D transcriptionally up-regulates the anti-inflammatory gene DUSP1, which partly controls production of the inflammatory chemokine IL-8. IL-8 is overabundant in CF airways, potentially due to hyperinflammatory responses of CF macrophages. We tested the ability of vitamin D metabolites to down-regulate IL-8 production in CF macrophages.. CF and healthy monocyte-derived macrophages (MDM) were treated with two vitamin D metabolites, 25-hydroxyvitamin D3 (25OHD3 ) and 1,25-dihydroxyvitamin D3 (1,25(OH)2 D3 ), or paricalcitol, synthetic analogue of 1,25(OH)2 D3 . 25OHD3 was tested at doses of 25-150 nM, whereas 1,25(OH)2 D3 and paricalcitol at doses of up to 100 nM. IL-8 was stimulated by bacterial virulence factors. As potential anti-inflammatory mechanism of vitamin D metabolites, we assessed up-regulation of DUSP1.. MDM from patients with CF and some healthy donors showed excessive production of stimulated IL-8, highlighting their hyperinflammatory phenotype. Vitamin D metabolites down-regulated stimulated IL-8 only in those hyperinflammatory MDM, and only when used at high doses (>100 nM for 25OHD3 , or >1 nM for 1,25(OH)2 D3 and paricalcitol). The magnitude of IL-8 down-regulation by vitamin D metabolites or paricalcitol was moderate (∼30% vs. >70% by low-dose dexamethasone). Transcriptional up-regulation of DUSP1 by vitamin D metabolites was seen in all tested MDM, regardless of IL-8 down-regulation.. Vitamin D metabolites and their analogues moderately down-regulate IL-8 in hyperinflammatory macrophages, including those from CF. This down-regulation appears to go through DUSP1-independent mechanisms.

Topics: 25-Hydroxyvitamin D3 1-alpha-Hydroxylase; Adult; Calcifediol; Cells, Cultured; Cystic Fibrosis; Down-Regulation; Dual Specificity Phosphatase 1; Ergocalciferols; Gene Expression Regulation; Humans; Interleukin-8; Macrophages; Receptors, Calcitriol; Up-Regulation; Vitamin D; Vitamin D3 24-Hydroxylase; Young Adult

To determine whether osteopenia is evident in prepubertal children with cystic fibrosis (CF) and, if so, whether it is caused by a deficiency in bone formation or increased bone resorption.. With the use of a prospective case control study design, we investigated 11 prepubertal children with CF between the ages of 8 and 12 years old and a non-CF control group matched by weight and sex. Bone density at the radius, ulnar, trochanter, femoral neck, and lumbar spine, biochemical markers of bone metabolism, calcium, vitamin D metabolites, and intact parathyroid hormone were measured in all subjects. Comparisons between the 2 groups were performed with Wilcoxon matched pairs and Fisher exact tests.. Intake of total calories, calcium, phosphorus, and vitamin D was significantly greater in the CF group than in the control group. Serum 25(OH)vitamin D levels were significantly lower in the CF group: median 22 ng/mL for the CF group and 39 ng/mL for the control group (P =.02). 1,25(OH)(2) vitamin D levels were borderline or low in 7 subjects in the CF group and 2 members of the control group (P =.08, Fisher exact test). Intact parathyroid hormone levels were higher than the upper limit of normal in 4 subjects of the CF group and 1 member of the control group. Despite these biochemical abnormalities, we found no evidence of bone mineral deficiency in the CF group.. Prepubertal children with CF do not have bone mineral deficit compared with a weight- and sex-matched control group; however, their lower vitamin D levels may portend problems with bone mineralization during adolescence and adulthood.

Topics: Bone Density; Bone Resorption; Calcium; Case-Control Studies; Child; Cystic Fibrosis; Diet Records; Female; Humans; Male; Parathyroid Hormone; Phosphorus; Prospective Studies; Vitamin D

Serum levels of the important hormone 1,25-dihydroxyvitamin D (1,25-diOHD, calcitriol) have not been extensively evaluated in patients with cystic fibrosis (CF) during the critical period of skeletal growth and development. This study was a cross-sectional, observational assessment of 25-hydroxyvitamin D (25-OHD, calcidiol) and 1,25-diOHD levels in 54 patients with CF. The patients' ages ranged from 4.9 years to 19.5 years (mean, 11.0 years). Levels were correlated with pulmonary function tests, chest x-ray scores, height and weight Z scores, skinfold percentiles, CF genotype, serum chemistries, and use of a vitamin supplement. Levels were compared with those in more than 160 other pediatric patients living in the same region, and all assays were done in the same laboratory. Despite low-normal levels of the 25-OHD precursor, there was a high prevalence of low (18%) and marginal (18%) levels of 1,25-diOHD. None of the various parameters examined correlated with either 25-OHD or 1,25-diOHD levels. The cause, clinical significance, and treatment of low levels of this important hormone in children with CF warrant further study.

Topics: Adolescent; Adult; Body Height; Body Weight; Child; Cross-Sectional Studies; Cystic Fibrosis; Food, Fortified; Genotype; Humans; Lung; Radiography; Respiratory Function Tests; Skinfold Thickness; Vitamin D