Treatment of vitamin D deficiency in CF Several forms of vitamin D supplementation have been used in an attempt to improve calcium homeostasis and normalize serum vitamin D levels in CF including cholecalciferol (animal form), ergocalciferol (plant form), and calcitriol (active 1,25-dihydroxyvitamin D). Which form of vitamin D and how much is needed to normalize serum levels most effectively in CF is unknown. Hanly et al assessed the response to 800 IU daily of cholecalciferol for a minimum of 4 weeks in twenty adolescents and young adults with CF. Serum levels of 25OHD increased although several subjects remained below the normal range despite supplementation.16 In the only published randomized placebo-controlled trial, Haworth et al studied 30 adults with CF and showed that calcium and cholecalciferol supplementation reduced the rate of bone turnover and bone loss although this did not reach statistical significance. Interestingly however, serum 25OHD levels were unchanged despite an additional 800 IU of cholecalciferol daily for 12 months.24 Pilot work recently published on our CF population shows that additional cholecalciferol can successfully increased serum 25OHD levels.25 This study was a retrospective review and a randomized clinical trial is needed to confirm these results. With ergocalciferol, Lark et al found absorption to be significantly lower and highly variable in adults with CF compared to controls.26 Furthermore, these patients demonstrated poor conversion of ergocalciferol to 25OHD raising the possibility of impaired hydroxylation by the hepatic enzyme, 25-hydroxylase. In 2005, Boyle et al showed that even with high-dose ergocalciferol (50-100,000 IU weekly), serum levels did not correct vitamin D deficiency to the target level of 75 nmol/L in subjects with CF.18 Some studies have shown that cholecalciferol is more efficacious than ergocalciferol in correcting vitamin D deficiency in the non-CF population.27;28 Possible mechanisms for this differential response to supplemental vitamin D include differences in affinity of vitamin D-binding protein for the two calciferols or increased affinity for the hepatic 25-hydroxylase for cholecalciferol. Finally, one study published showed short-term use of calcitriol, (1,25 dihydroxyvitamin D) increased calcium absorption in CF but serum 25OHD levels remained unchanged.29