Vitamin D Deficiency Clinical Care Guidelines

These guidelines present recommendations on vitamin D screening, diagnosis, supplementation and treatment in children and adults with cystic fibrosis.

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Screening, Diagnosis, Management and Treatment of Vitamin D Deficiency in Individuals With Cystic Fibrosis: Executive Summary

Tangpricha V, Kelly A, Stephenson A, Maguiness K, Enders J, Robinson KA, Marshall BC, Borowitz D, for the Cystic Fibrosis Foundation Vitamin D Evidence-Based Review Committee. An Update on the Screening, Diagnosis, Management and Treatment of Vitamin D Deficiency in Individuals with Cystic Fibrosis: Evidence-Based Recommendations from the Cystic Fibrosis Foundation. J Clin Endocrinol Metab. 2012;97(4):1082-1093.

Vitamin D deficiency is common in individuals with cystic fibrosis due to impaired absorption of fat-soluble vitamins, decreased sunlight exposure, and suboptimal intake of vitamin D-containing foods and/or supplements. Vitamin D deficiency in CF has been associated with decreased bone mass in children, failure to achieve expected peak bone mass in young adults, and osteoporosis in mature adults, and it may impact other comorbidities common in CF.

These guidelines present evidence based recommendations on vitamin D screening, diagnosis, supplementation, and treatment in children and adults with CF. A summary of the vitamin D intakes and treatment recommendations can be found in Table 3 of the published manuscript.

Methodology

The guidelines multidisciplinary expert committee members developed and refined systematic review questions, and a systematic literature review was performed with the search terms “vitamin D” and “cystic fibrosis.” Recommendations were drafted, and anonymous voting was conducted for each consensus recommendation. Draft recommendations were reviewed by endorsing organizations, publicly posted for comment by all CF centers, and revised accordingly. Find additional information about the U.S. Preventive Services Task Force (USPSTF) grading definitions.

Recommendations

Assessment of Vitamin D Status and Target Treatment Goals

Recommendations Evaluation of the Evidence
1. The CF Foundation recommends that all individuals with CF have serum 25-hydroxyvitamin D measured to assess vitamin D status. Certainty: low
Consensus recommendation
2. The CF Foundation recommends that all individuals with CF maintain a serum 25-hydroxyvitamin D goal of at least 30 ng/ml (75 nmol/liter). Certainty: low
Consensus recommendation
3. The CF Foundation recommends that all individuals with CF and a serum 25-hydroxyvitamin D level of less than 30 ng/ml (75 nmol/liter) be assessed for adherence to the prescribed regimen. Certainty: low
Consensus recommendation
4. The CF Foundation recommends against the use of serum 1,25(OH)2D as the measurement to assess vitamin D status in all individuals with CF. Certainty: low
Consensus recommendation
5. The CF Foundation recommends against the routine measurement of parathyroid hormone (PTH), osteocalcin, alkaline phosphatase or other indirect markers to assess vitamin D status in all individuals with CF. Certainty: low
Consensus recommendation
6. The CF Foundation recommends that all individuals with CF have serum 25-hydroxyvitamin D measured annually, preferably at the end of winter. Certainty: low
Consensus recommendation
7. The CF Foundation is not able to make a recommendation for or against having all individuals with CF fast before the measurement of serum 25-hydroxyvitamin D. Certainty: low
Benefit: unknown
Grade: I
8. The CF Foundation recommends that all individuals with CF have serum 25-hydroxyvitamin D levels rechecked 3 months after the dose of vitamin D3 has been changed. Certainty: low
Consensus recommendation

Use of Vitamin D Compounds and Treatment Strategy

Recommendations Evaluation of the Evidence
9. The CF Foundation recommends that all individuals with CF be treated with vitamin D3 (cholecalciferol) to achieve and maintain serum 25-hydroxyvitamin D levels of at least 30 ng/ml (75 nmol/liter). Certainty: moderate 
Benefit: moderate 
Grade: B
10. The CF Foundation is not able to make a recommendation for or against the use of an oil vs. a powder-based formulation of vitamin D3 in all individuals with CF. Certainty: low
Consensus recommendationCertainty: low 
Benefit: unknown 
Grade: I
11. The CF Foundation recommends that all individuals with CF who are prescribed vitamin D3 (in addition to their CF-specific vitamins) take once-daily vitamin D3 therapy or its weekly equivalent to maintain serum 25-hydroxyvitamin D levels of at least 30 ng/ml (75 nmol/ liter).  Certainty: low
Consensus recommendation
12. The CF Foundation recommends that all individuals with CF with difficult to treat vitamin D deficiency be treated with calcitriol, doxercalciferol, or paricalcitol only in consultation with a specialist with expertise in vitamin D therapy.  Certainty: low
Consensus recommendation

Treatment of Infants

Recommendations Evaluation of the Evidence
13. The CF Foundation recommends that all individuals with CF, from birth to 12 months of age, be treated with an initial dose of 400-500 IU vitamin D3 per day. Certainty: low
Consensus recommendation
14. The CF Foundation recommends that all individuals with CF, from birth to 12 months of age, and a serum 25-hydroxyvitamin D level of less than 10 ng/ml (25 nmol/liter) be assessed for rickets and managed urgently in consultation with a specialist with expertise in vitamin D therapy. Certainty: low
Consensus recommendation
15. The CF Foundation recommends that all individuals with CF, from birth to 12 months of age, with a serum 25-hydroxyvitamin D level of at least 20 ng/ml (50 nmol/liter) but less than 30 ng/ml (75 nmol/liter), and with confirmed adherence to the prescribed regimen, have the dose of vitamin D3 increased to 800-1,000 IU per day. Certainty: low
Consensus recommendation
16. The CF Foundation recommends that all individuals with CF, from birth to 12 months of age, with a serum 25-hydroxyvitamin D level of less than 20 ng/ml (50 nmol/liter) or with a persistent serum 25-hydroxyvitamin D level of at least 20 ng/ml (50 nmol/liter) but less than 30 ng/ml (75 nmol/liter), and with confirmed adherence to the prescribed regimen, have the dose of vitamin D3 increased to a maximum of 2,000 IU per day. Certainty: low
Consensus recommendation
17. The CF Foundation recommends that all individuals with CF, from birth to 12 months of age, who are unable to achieve a serum 25-hydroxyvitamin D level of at least 30 ng/ml (75 nmol/liter) after treatment with 2,000 IU vitamin D3 per day, and with confirmed adherence to the prescribed regimen, be managed in consultation with a specialist with expertise in vitamin D therapy. Certainty: low
Consensus recommendation

Treatment of Children up to 10 Years of AgeTreatment of Children up to 10 Years of Age

Recommendations Evaluation of the Evidence
18. The CF Foundation recommends that all individuals with CF, age greater than 12 months to 10 yr, be treated with an initial dose of 800-1,000 IU vitamin D3 per day. Certainty: low 
Consensus recommendation
19. The CF Foundation recommends that all individuals with CF, age greater than 12 months to 10 yr, with a serum 25-hydroxyvitamin D level of at least 20 ng/ml (50 nmol/liter) but less than 30 ng/ml (75 nmol/liter), and with confirmed adherence to the prescribed regimen, have the dose of vitamin D3 increased to 1,600-3,000 IU per day. Certainty: low 
Consensus recommendationCertainty: low 
Consensus recommendation
20. The CF Foundation recommends that all individuals with CF, age greater than 12 months to 10 yr, with a serum 25-hydroxyvitamin D level of less than 20 ng/ml (50 nmol/liter) or with a persistent serum 25-hydroxyvitamin D level of at least 20 ng/ml (50 nmol/liter) but less than 30 ng/ml (75 nmol/liter), and with confirmed adherence to the prescribed regimen, have the dose of vitamin D3 increased to a maximum of 4,000 IU per day. Certainty: low 
Consensus recommendation
The CF Foundation recommends that all individuals with CF, age greater than 12 months to 10 yr, who are unable to achieve a serum 25-hydroxyvitamin D level of at least 30 ng/ml (75 nmol/liter) after treatment with 4,000 IU vitamin D3 per day, and with confirmed adherence to the prescribed regimen, be managed in consultation with a specialist with expertise in vitamin D therapy. Certainty: low 
Consensus recommendation

Treatment of Children Above 10 Years of Age and Adults

Recommendations Evaluation of the Evidence
22. The CF Foundation recommends that all individuals with CF, age greater than 12 months to 10 yr, be treated with an initial dose of 800-1,000 IU vitamin D3 per day. Certainty: low
Consensus recommendation
23. The CF Foundation recommends that all individuals with CF, age greater than 10 yr, with a serum 25-hydroxyvitamin D level of at least 20 ng/ml (50 nmol/liter) but less than 30 ng/ml (75 nmol/liter), and with confirmed adherence to the prescribed regimen, have the dose of vitamin D3 increased to 1,600-6,000 IU per day.  Certainty: low
Consensus recommendation
24. The CF Foundation recommends that all individuals with CF, age greater than 10 yr, with a serum 25-hydroxyvitamin D level less than 20 ng/ml (50 nmol/liter) or with a persistent serum 25-hydroxyvitamin D level of at least 20 ng/ml (50 nmol/liter) but less than 30 ng/ml (75 nmol/liter), and with confirmed adherence to the prescribed regimen, have the dose of vitamin D3 increased to a maximum of 10,000 IU per day.  Certainty: low
Consensus recommendation
25. The CF Foundation recommends that all individuals with CF, age greater than 10 yr, who are unable to achieve a serum 25-hydroxyvitamin D level of at least 30 ng/ml (75 nmol/liter) after treatment with 10,000 IU vitamin D3 per day, and with confirmed adherence to the prescribed regimen, be managed in consultation with a specialist with expertise in vitamin D therapy.  Certainty: low
Consensus recommendation

Use of UV lamps

Recommendations Evaluation of the Evidence
The CF Foundation is not able to recommend for or against the use of UV lamps in the management of vitamin D deficiency in all individuals with CF. Certainty: low
Benefit: Unknown
Grade: I

Further Reading

Relevant manuscripts published after the original guidelines are listed below. These manuscripts have not been reviewed or endorsed by the guidelines committee.

  1. Hermes WA, Alvarez JA, Lee MJ et al. A Prospective, Randomized, Double-Blind, Parallel-Group, Comparative Effectiveness Clinical Trial Comparing a Powder Vehicle Compound of Vitamin D with an Oil Vehicle Compound in Adults with Cystic Fibrosis. JPEN J Parenter Enteral Nutr. 2016 Feb 22. pii: 0148607116629673. [Epub ahead of print].
    Cholecalciferol was more efficiently absorbed in a powder than an oil vehicle in CF patients.
  2. Simoneau T, Sawicki GS, Milliren GS, et al. A Randomized Controlled Trial of Vitamin D Replacement Strategies in Pediatric CF Patients. J Cyst Fibros. 2016 Mar;15(2):234-4.
    Cholecalciferol 50,000IU once weekly was as effective as ergocalciferol 50,000IU twice weekly for 8 weeks in pediatric patients with CF and vitamin D deficiency.
  3. Grossman RE, Zughaier SM, Kumari M, et al. Pilot study of vitamin D supplementation in adults with cystic fibrosis pulmonary exacerbation: A randomized, controlled trial. Dermatoendocrinol. 2012 Apr 1; 4 (2): 191-7.
    A single, oral bolus of cholecalciferol 250,000 IU increased serum 25(OH)D concentrations and was associated with a trend toward improved clinical outcomes in CF subjects hospitalized for a pulmonary exacerbation.
  4. Lee MJ1, Kearns MD, Smith EM, et al. Free 25-Hydroxyvitamin D Concentrations in Cystic Fibrosis. Am J Med Sci. 2015 Nov;350(5):374-9.
    This study examined total, calculated and directly measured free 25(OH)D from a biobank of samples collected from patients with cystic fibrosis. The free 25(OH)D and total 25(OH)D concentrations were positively correlated.
  5. Vanstone MB, Egan ME, Zhang JH, et al.  Association between serum 25-hydroxyvitamin D level and pulmonary exacerbations in cystic fibrosis. Pediatr Pulmonol. 2015 May;50(5):441-6.
    The annual number of pulmonary exacerbations in pediatric patients with CF was significantly associated with lower 25(OH)D levels and female gender.
  6. Ferguson JH1, Chang AB. Vitamin D supplementation for cystic fibrosis. Cochrane Database Syst Rev. 2014 May 14;(5):CD007298.
  7. McCauley LA, Thomas W, Laguna TA, et al. Vitamin D deficiency is associated with pulmonary exacerbations in children with cystic fibrosis. Ann Am Thorac Soc. 2014 Feb;11(2):198-204.
    Higher 25(OH)D levels in children with CF were associated with lower rates of pulmonary exacerbations and, in children, higher FEV1.

This executive summary was prepared by:

Melissa Putman MD, MSc (Harvard University) and Vin Tangpricha, MD, PhD (Emory University)

The guidelines were published in April 2012, they were reviewed in April 2019 and it was determined that no update is needed at this time.

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