Comparison of metabolism of vitamins D2 and D3 in children with nutritional rickets

Abstract

Children with calcium-deficiency rickets may have increased vitamin D requirements and respond differently to vitamin D2 and vitamin D3. Our objective was to compare the metabolism of vitamins D2 and D3 in rachitic and control children. We administered an oral single dose of vitamin D2 or D3 of 1.25 mg to 49 Nigerian children—28 with active rickets and 21 healthy controls. The primary outcome measure was the incremental change in vitamin D metabolites. Baseline serum 25-hydroxyvitamin D [25(OH)D] concentrations ranged from 7 to 24 and 15 to 34 ng/mL in rachitic and control children, respectively (p < .001), whereas baseline 1,25-dihydroxyvitamin D [1,25(OH)2D] values (mean ± SD) were 224 ± 72 and 121 ± 34 pg/mL, respectively (p < .001), and baseline 24,25-dihydroxyvitamin D [24,25(OH)2D] values were 1.13 ± 0.59 and 4.03 ± 1.33 ng/mL, respectively (p < .001). The peak increment in 25(OH)D was on day 3 and was similar with vitamins D2 and D3 in children with rickets (29 ± 17 and 25 ± 11 ng/mL, respectively) and in control children (33 ± 13 and 31 ± 16 ng/mL, respectively). 1,25(OH)2D rose significantly (p < .001) and similarly (p = .18) on day 3 by 166 ± 80 and 209 ± 83 pg/mL after vitamin D2 and D3 administration, respectively, in children with rickets. By contrast, control children had no significant increase in 1,25(OH)2D (19 ± 28 and 16 ± 38 pg/mL after vitamin D2 and D3 administration, respectively). We conclude that in the short term, vitamins D2 and D3 similarly increase serum 25(OH)D concentrations in rachitic and healthy children. A marked increase in 1,25(OH)2D in response to vitamin D distinguishes children with putative dietary calcium-deficiency rickets from healthy children, consistent with increased vitamin D requirements in children with calcium-deficiency rickets. © 2010 American Society for Bone and Mineral Research.

Vitamin D treatment in calcium-deficiency rickets: a randomised controlled trial

“…Studies in adults indicate that intestinal calcium absorption is not significantly reduced until 25(OH)D concentrations are ≤10 nmol/L 12. Current evidence indicates that vitamin D requirements are greater when dietary calcium intakes are low 3 13. This is consistent with our findings in Nigerian children with calcium-deficiency rickets, who demonstrate a marked increase in 1,25(OH) 2 D in response to vitamin D administration 2 3.…”

CYP2R1Mutations Impair Generation of 25-hydroxyvitamin D and Cause an Atypical Form of Vitamin D Deficiency

“…The identity of the auxiliary 25-hydroxylase(s) is unknown. The increase in 1,25-dihydroxyvitamin D after oral administration of 50 000 IU of vitamin D 2 or D 3 in the L99P homozygous subjects was also consistent with functional vitamin D deficiency, characterized by induction of renal CYP27B1 by elevated PTH (25). Whether lower doses of vitamin D would raise the substrate concentration sufficiently to overcome the 25-hydroxylation deficit is unknown.…”

“…We confirmed rickets in all index cases and most siblings with rickets using a rickets radiographic score of greater than 1.5 on a 10-point severity scale (24). The control group consisted of 21 normal children between 19 and 59 months of age (mean Ϯ SD, 35.7 Ϯ 11.9 months) who had been previously characterized (25). We collected medical and demographic data from each subject, with particular emphasis on skeletal deformities consistent with rickets, and measured biochemical parameters of bone and mineral metabolism.…”

“…To assess the functional capacity of 25-hydroxylase in vivo, we administered 50 000 IU orally of vitamin D 2 (Pliva, Inc. East Hanover, NJ) or vitamin D 3 (Bio-Tech, Fayetteville, AR) on separate occasions at least three months apart to patients with CYP2R1 mutations, their unaffected first-degree relatives, and control subjects (25).…”

Vitamin D and its role in the management and prevention of lower respiratory tract infections in infants and young children

“…Few studies have assessed the pharmacokinetics of a bolus of vitamin D in young children. Thacher and colleagues [6] studied the change in serum 25(OH)D in groups of young Nigerian children following an oral bolus of 50,000 IU vitamin D2 or D3. Peak concentrations of 25(OH)D were found 3 days after bolus administration, which is longer than the time taken for resolution of the clinical features of severe pneumonia (median approximately 30 hours).…”