Bone disease in chronic childhood cholestasis. I. vitamin D absorption and metabolism†

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Abstract
Metabolic bone disease is common in children and adults with chronic cholestasis. We evaluated baseline vitamin D (vitamin D2 and D3), 25-OH vitamin D2 and D3, 1,25(OH)2 vitamin D, vitamin D-binding protein, bone mineral content and dietary mineral content in six children (mean age: 12.1 years) with cholestasis since infancy. Absorption of 25-OH vitamin D3 and vitamin D2 was evaluated by measuring serial serum concentrations after a test dose. Bone mineral content was reduced by >2 S.D. in five of six subjects compared to age-specific controls; none had radiographic evidence of rickets but all had osteopenia. Dietary Ca and P content in the subjects was comparable to the recommended daily allowance for age-specific children. Baseline serum vitamin D2 concentrations were undetectable in all but one cholestatic subject despite oral supplementation with 2,500 to 50,000 IU per day vitamin D2. Baseline serum 25-OH vitamin D was 33.2 ± 6.0 ng per ml (mean ± S.E.) and comparable to our laboratory norms (15 to 50 ng per ml). Serum 1,25(OH)2 vitamin D and “free” 1,25(OH)2 vitamin D were both significantly (p2 was found in cholestatic children (0.8 ng ± 0.5 ng per ml and 18.0 ± 14.3 ng hr per ml, respectively) compared to controls (59.5 ± 10.0 ng per ml and 1,780 ± 253 ng hr per ml, respectively). The peak change and area under the absorption curve for 25-OH vitamin D3 from baseline after 10 μg per kg 25-OH vitamin D3 was significantly reduced (both p<0.05) in cholestatic children (60.2 ± 13.8 ng per ml and 751.5 ± 189.9 ng hr per ml, respectively) compared to controls (151.6 ± 30.7 ng per ml and 2,021 ± 472 ng hr per ml, respectively). We conclude that despite severe vitamin D malabsorption, normal serum 25-OH vitamin D concentrations in cholestatic children most likely result from sunlight-stimulated endogenous vitamin D synthesis. Use of oral 25-OH vitamin D should be considered in cholestatic children because its absorption is less impaired than vitamin D.
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