Failure of high-dose ergocalciferol to correct vitamin D deficiency in adults with cystic fibrosis

Abstract

Rationale: Treatment guidelines for vitamin D monitoring and supplementation in cystic fibrosis (CF) have recently been developed and published by a consensus committee, but have not been prospectively tested.

Objectives: To use these guidelines to determine the percentage of adults with CF requiring vitamin D repletion therapy and to evaluate the effectiveness of the currently recommended high-dose oral ergocalciferol repletion protocol.

Methods: Prospective study of clinical outcomes after therapy with the recommended vitamin D repletion algorithm.

Results: Of 134 adults with CF, 109 (81.3%) were found to have 25-hydroxyvitamin D (25-OHD) levels below the recommended 30 ng/ml. Sixty-six of these adults completed the recommended course of 400,000 IU of oral ergocalciferol over 2 months, and only five (8%) responded with correction of their serum 25-OHD to the goal of 30 ng/ml or greater (mean change, +0.3 ng/ml; from 18.8 to 19.1 ng/ml). In the 33 adults with CF who also completed the recommended second course of 800,000 IU of ergocalciferol over 2 months, none demonstrated correction of their deficiency (mean change, -1.2 ng/ml).

Conclusion: The results of this study demonstrate that a majority of adults with CF have serum 25-OHD levels below 30 ng/ml, and the currently recommended ergocalciferol repletion regimen often does not fully correct vitamin D deficiency and may need to be revised to include even higher dosing of ergocalciferol. Further work is needed to establish the ideal 25-OHD level for maximizing calcium absorption and bone health in CF.

Figure 1.

Screening and treatment protocol based on the Cystic Fibrosis Foundation's Bone Health Consensus Conference guidelines. 25-OHD = 25-hydroxyvitamin D.

Figure 2.

Serum 25-OHD levels in 134 adults with cystic fibrosis (CF). Mean 25-OHD was 21.5 ± 10.8 ng/ml; median, 20.3 ng/ml. Of the screened adults with CF, 81.3% (109/134) were below the recommended 25-OHD level of 30 ng/ml.

Figure 3.

Serum 25-OHD levels before and after treatment with recommended initial ergocalciferol course (50,000 IU/week orally for 8 weeks). Only individuals with screening 25-OHD levels below 30 ng/ml received therapy. Mean change with treatment, +0.3 ng/ml (18.8 to 19.1); p = 0.8.

Figure 4.

Serum 25-OHD levels before and after treatment with second ergocalciferol course (50,000 IU/twice weekly orally for 8 weeks). Only individuals failing to correct their serum 25-OHD level with initial ergocalciferol therapy received second course. Mean change with second treatment, −1.2 ng/ml (18.7 to 17.5); p = 0.3. Outlying point is more than 1.5× interquartile range below the 25th percentile.

Figure 5.

Change in serum 25-OHD levels by season after treatment with recommended initial ergocalciferol course (50,000 IU/week orally for 8 weeks). Season inclusion was based on date of follow-up serum level after completion of therapy. Individuals taking ergocalciferol during the late summer or early fall with follow-up levels during the fall had the largest increase in serum 25-OHD level (2.9 ± 7.3 ng/ml, n = 25, p = 0.02). Outlying points are more than 1.5 × interquartile range above the 75th percentile or below the 25th percentile.