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Review
. 2014 May 14;2014(5):CD007298.
doi: 10.1002/14651858.CD007298.pub4.

Vitamin D supplementation for cystic fibrosis

Janet H Ferguson  1 , Anne B Chang
Affiliations
Review

Vitamin D supplementation for cystic fibrosis

Janet H Ferguson et al. Cochrane Database Syst Rev. .

Abstract

Background: Cystic fibrosis (CF) is a genetic disorder with multiorgan effects. In a subgroup with pancreatic insufficiency malabsorption of the fat soluble vitamins (A, D, E, K) may occur. Vitamin D is involved in calcium homeostasis and bone mineralisation and may have extraskeletal effects. This review examines the evidence for vitamin D supplementation in cystic fibrosis.

Objectives: To assess the effects of vitamin D supplementation on the frequency of vitamin D deficiency, respiratory outcomes and vitamin D toxicity in the cystic fibrosis population.

Search methods: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Date of the most recent search: 08 July 2013.

Selection criteria: Randomised and quasi-randomised controlled studies of vitamin D supplementation compared to placebo in the cystic fibrosis population regardless of exocrine pancreatic function.

Data collection and analysis: Both authors independently assessed the risk of bias of each included study and extracted outcome data (from published study information) for assessment of bone mineralization, growth and nutritional status, frequency of vitamin D deficiency, respiratory status, quality of life and adverse events.

Main results: Six studies (239 participants) are included, although only three studies provided data from 69 adults and children with cystic fibrosis for analysis. One study compared a single high dose of vitamin D (250,000 IU) to placebo at the time of hospital admission with a respiratory exacerbation in 30 pancreatic insufficient adults with cystic fibrosis. The second study compared supplemental 800 international units (IU) vitamin D and placebo for 12 months in 30 osteopenic pancreatic insufficient adults; both groups continued 900 IU vitamin D daily. The third study compared supplemental 1 g calcium alone, 1600 IU vitamin D alone, 1600 IU vitamin D and 1 g calcium and placebo in a double-blind randomised cross-over study; only nine children who completed both vitamin D and placebo groups after six-months supplementation and a three-month washout period are included; pancreatic sufficiency or disease status of participants are not defined. The studies are not directly comparable due to differences in supplementation, outcome reporting and possibly participant characteristics (e.g. severity of lung disease, growth and nutrition, pancreatic sufficiency).The only outcome for which we could combine data from more than two studies was 25-hydroxyvitamin D levels; patients receiving vitamin D supplementation had significantly higher levels, mean difference 7.24 ng/ml (95% confidence interval 5.01 to 9.46). However, ironically one study reported 1,25(OH)2D with levels significantly favouring the placebo group, mean difference -30.30 pmol/ml (95% confidence interval -59.89 to -0.71). Bone mineral density was measured in two studies; both described no significant change between groups. There were no adverse events in any study.The remaining three studies are published as abstracts only and did not provide data for analysis. These abstracts include: a report of pre-intervention data in a study comparing daily calcitriol (0.25 or 0.5 micrograms) with placebo in pancreatic insufficient children and young adults; an interim report of a double-blind randomised control study comparing 5000 IU vitamin D daily for 12 weeks during winter in 67 adult cystic fibrosis patients; and a comparison of the effect of three months of vitamin D supplementation (dose not specified) with placebo on bone mineral density in 42 children with cystic fibrosis and low bone mineral density.Risk of bias was highly variable between all studies. Only one study had a low risk of bias for the five main criteria (random sequence generation, allocation, blinding, attrition and reporting). The rest of the studies had unclear or high risks of bias. Two studies had a low risk of bias for blinding and another two studies for attrition bias. In the studies published as abstracts, assessment of the risks of bias was uncertain in many aspects.

Authors' conclusions: In patients receiving vitamin D supplementation, 25-hydroxyvitamin D levels are significantly higher. However, there is no evidence of clinical benefit or harm in the limited number of small-sized published studies. Adherence to relevant cystic fibrosis guidelines on vitamin D supplementation should be considered until further evidence is available.

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Conflict of interest statement

JF has attended paediatric diabetes and endocrinology conferences and workshops sponsored by Novo Nordisk and Medica Pacifica, for continuing medical education purposes. Neither herself nor Canterbury District Health Board have received payment for her attendance of these conferences.

AC declares receipt of a grant provided by GSK is unrelated to this topic.

Figures

1
1
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
2
2
Forest plot of comparison: 1 Vitamin D versus placebo, outcome: 1.2 Serum calcium (absolute final) [mmol/L].
3
3
Forest plot of comparison: 1 Vitamin D versus placebo, outcome: 1.3 25(OH)D [ng/ml].
4
4
Forest plot of comparison: 1 Vitamin D versus placebo, outcome: 1.5 PTH levels (absolute final) [pmol/L].
1.1
1.1. Analysis
Comparison 1 Vitamin D versus placebo, Outcome 1 Serum calcium change (mmol/L).
1.2
1.2. Analysis
Comparison 1 Vitamin D versus placebo, Outcome 2 Serum calcium (absolute final).
1.3
1.3. Analysis
Comparison 1 Vitamin D versus placebo, Outcome 3 25(OH)D.
1.4
1.4. Analysis
Comparison 1 Vitamin D versus placebo, Outcome 4 1,25(OH)2D (absolute final).
1.5
1.5. Analysis
Comparison 1 Vitamin D versus placebo, Outcome 5 PTH levels (absolute final).
1.6
1.6. Analysis
Comparison 1 Vitamin D versus placebo, Outcome 6 PTH levels (change from baseline).
2.1
2.1. Analysis
Comparison 2 Post‐hoc analysis: Vitamin D versus placebo, Outcome 1 Whole body bone mineral content change (g).
2.2
2.2. Analysis
Comparison 2 Post‐hoc analysis: Vitamin D versus placebo, Outcome 2 Lumbar spine z score.
2.3
2.3. Analysis
Comparison 2 Post‐hoc analysis: Vitamin D versus placebo, Outcome 3 Lumbar spine bone mineral density (% change).
2.4
2.4. Analysis
Comparison 2 Post‐hoc analysis: Vitamin D versus placebo, Outcome 4 Hip bone mineral density (% change).
2.5
2.5. Analysis
Comparison 2 Post‐hoc analysis: Vitamin D versus placebo, Outcome 5 Distal forearm bone mineral density (% change).
2.6
2.6. Analysis
Comparison 2 Post‐hoc analysis: Vitamin D versus placebo, Outcome 6 Hip bone mineral density (change).
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References

References to studies included in this review

Brown 2005 {published data only (unpublished sought but not used)}
    1. Brown SA, Aris RM, Leigh MW, Retsch‐Bogart GZ, Caminiti MJ, Jennings‐Grant T, et al. Baseline BMD status in children and young adults with CF: calcitriol intervention study [abstract]. Pediatric Pulmonology 2005;40 Suppl 28:354. [CFGD Register: CO20]
Deghan Manshadi 2012 {published data only}
    1. Deghan Manshadi S, Robert R, Brotherwood M, Tullis E, Stephenson A. A randomized placebo‐controlled trial of cholecalciferol for vitamin D deficiency in adults with cystic fibrosis [abstract]. Pediatric Pulmonology 2012;47 Suppl 35:412, Abstract no:515. [CFGD Register: GN228]
Grossmann 2012 {published data only}
    1. Grossmann RE, Zughaier S, Kumari M, Seydafkan S, Liu S, Lyles R, et al. Clinical responses to a novel vitamin D supplementation strategy in adult CF patients hospitalized for pulmonary exacerbations [abstract]. Pediatric Pulmonology 2011;46 Suppl 34:404, Abstract 526. [CFGD Register: GN217b]
    1. Grossmann RE, Zughaier SM, Kumari M, Seydafkan S, Lyles RH, Liu S, et al. Pilot study of vitamin D supplementation in adults with cystic fibrosis pulmonary exacerbation: A randomized, controlled trial. Dermato‐endocrinology 2012;4(2):191‐7. [CFGD Register: GN217d; ] - PMC - PubMed
    1. Grossmann RE, Zughaier SM, Liu S, Lyles RH, Tangpricha V. Impact of vitamin D supplementation on markers of inflammation in adults with cystic fibrosis hospitalized for a pulmonary exacerbation. European Journal of Clinical Nutrition 2012;66(9):1072‐4. [CFGD Register: GN217c] - PMC - PubMed
    1. Kumara M, Colman L, Grossmann R, Wolfenden LL, Tangpricha V. High dose vitamin D supplementation in cystic fibrosis patients hospitalised for respiratory exacerbation [abstract]. Pediatric Pulmonology 2009;44 Suppl 32:Abstract 549. [CFGD Register: GN217a]
Haworth 2004 {published data only}
    1. Haworth CS, Jones A, Selby PL, Adams JE, Mawer EB, Webb AK. Randomised, double blind, placebo controlled trial investigating the effect of calcium and vitamin D supplementation on bone mineral density and bone metabolism in adults with cystic fibrosis [abstract]. Pediatric Pulmonology 2001;32 Suppl 22:330‐1. [CFGD Register: CO18a] - PubMed
    1. Haworth CS, Jones AM, Adams JE, Selby PL, Webb AK. Randomised double blind placebo controlled trial investigating the effect of calcium and vitamin D supplementation on bone mineral density and bone metabolism in adult patients with cystic fibrosis. Journal of Cystic Fibrosis 2004;3(4):233‐6. [CFGD Register: CO18b] - PubMed
Hillman 2008 {published data only}
    1. Hillman LS, Cassidy JT, Popescu MF, Hewett JE, Kyger J, Robertson JD. Percent true calcium absorption, mineral metabolism, and bone mineralization in children with cystic fibrosis: effect of supplementation with vitamin D and calcium. Pediatric Pulmonology 2008;43(8):772‐80. [CFGD Register: CO21] - PubMed
    1. Popescu M, Morris J, Hillman L. Calcium and vitamin D supplementation in CF children [abstract]. Pediatric Pulmonology 1998;26 Suppl 17:359, Abstract no: 539.
Sciuca 2011 {published data only}
    1. Sciuca S, Turcu O. Correction of low bone mass density in patients with cystic fibrosis [abstract]. Journal of Cystic Fibrosis 2011;10 Suppl 1:S78, Abstract no: 308. [MEDLINE: ; CO46]

References to studies excluded from this review

Aris 2000 {published data only}
    1. Aris RM, Lester GE, Neuringer IP, Winders AW, Gott KK, Rea J, et al. Efficacy of pamidronate for osteoporosis in cystic fibrosis patients following lung transplantation [abstract]. Pediatric Pulmonology 1998;26(Suppl 17):365.
    1. Aris RM, Lester GE, Renner JB, Winders A, Denene Blackwood A, Lark RK, et al. Efficacy of pamidronate for osteoporosis in patients with cystic fibrosis following lung transplantation. American Journal of Respiratory and Critical Care Medicine 2000;162(3 part 1):941‐6. - PubMed
    1. Aris RM, Ontjes DA, Winders AW, Blackwood D, Lester GE. Effect of pamidronate on bone biomarkers in post‐transplant osteoporotic cystic fibrosis patients [abstract]. Pediatric Pulmonology 1998;26(Suppl 17):364‐5.
Gronowitz 2003 {published data only}
    1. Gronowitz E, Gilljam M, Hollsing A, Lindblad A, Larko O, Strandvik B. Ultraviolet B radiation improves serum levels of vitamin D in patients with cystic fibrosis (abstract). Pediatric Pulmonology 2003;36(Suppl 25):345. - PubMed
Homola 2010 {published data only}
    1. Homola L, Holcikova A, Mikolasek P, Pavelka J. Vitamin D supplementation in children with cystic fibrosis:sunshine, cholecalciferol and ergocalciferol [abstract]. Journal of Cystic Fibrosis 2011;10 Suppl 1:S76, Abstract no: 302. [CFGD Register: GN220; MEDLINE: ]
Khazai 2009 {published data only}
    1. Judd SE, Khazai N, Jeng L, Stecenko A, Wolfenden L, Tangpricha V. Evaluation of ergocalciferol, cholecalciferol or UVB light therapy to improve vitamin D status in cystic fibrosis: a prospective randomized study [abstract]. Pediatric Pulmonology 2008;43(Suppl 31):420.
    1. Khazai NB, Judd SE, Jeng L, Wolfenden LL, Stecenko A, Ziegler TR, Tangpricha V. Treatment and prevention of vitamin D insufficiency in cystic fibrosis patients: comparative efficacy of ergocalciferol, cholecalciferol, and UV light. Journal of Clinical Endocrinology and Metabolism 2009;94(6):2037‐43. [MEDLINE: ] - PMC - PubMed

Additional references

Aris 2005
    1. Aris RM, Merkel PA, Bachrach LK, Borowitz DS, Boyle MP, Elkin SL, et al. Consensus statement: Guide to bone health and disease in cystic fibrosis. Journal of Clinical Endocrinology and Metabolism 2005;90(3):1888‐96. - PubMed
Black 2005
    1. Black PN, Scragg R. Relationship between serum 25‐hydroxyvitamin d and pulmonary function in the third national health and nutrition examination survey. Chest 2005;128(6):3792‐8. - PubMed
Bonifant 2012
    1. Bonifant CM, Shevill E, Chang AB. Vitamin A supplementation for cystic fibrosis. Cochrane Database of Systematic Reviews 2012, Issue 8. [DOI: 10.1002/14651858.CD006751.pub3] - DOI - PubMed
Borowitz 2002
    1. Borowitz D, Baker RD, Stallings V. Consensus report on nutrition for pediatric patients with cystic fibrosis. Journal of Pediatric Gastroenterology and Nutrition 2002;35:246‐59. - PubMed
Brenckmann 2001
    1. Brenckmann C, Papaioannou A. Bisphosphonates for osteoporosis in people with cystic fibrosis. Cochrane Database of Systematic Reviews 2001, Issue 4. [DOI: 10.1002/14651858.CD002010] - DOI - PubMed
Cates 2003 [Computer program]
    1. Cates C. Visual Rx. Online NNT Calculator. http://www.nntonline.net/: Cates C, 2003.
Chesney 1989
    1. Chesney RW. Vitamin D: Can an Upper Limit be Defined?. Journal of Nutrition 1989;119(12 Suppl):1825‐8. - PubMed
Deeks 2011
    1. Deeks J, Higgins J, Altman D. Chapter 9 Analysing data and undertaking meta‐analysis. In: Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane‐handbook.org.
Dimitri 2007
    1. Dimitri P, Bishop N. Rickets. Paediatrics and Child Health 2007;17(7):279‐87.
Dodge 2006
    1. Dodge JA, Turck D. Cystic fibrosis: nutritional consequences and management. Best Practice & Research. Clinical Gastroenterology 2006;20(3):531‐46. - PubMed
Higgins 2003
    1. Higgins JPT, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta‐analyses. BMJ 2003;327(7414):557‐60. - PMC - PubMed
Higgins 2011
    1. Julian PT Higgins, Douglas G Altman and Jonathan AC Sterne on behalf of the Cochrane Statistical Methods Group and the Cochrane Bias Methods Group. Chapter 8: Assessing risk of bias in included studies. In: Higgins JPT, Green S (editors). Cochrane Handbook of Systematic Reviews of Interventions. Version 5.1.0 [updated March 2011]. Available from www.cochrane‐handbook.org. The Cochrane Collaboration, 2011.
Holick 2007
    1. Holick MF. Vitamin D deficiency. New England Journal of Medicine 2007;357(3):266‐81. - PubMed
Holick 2008
    1. Holick MF, Biancuzzo RM, Chen TC, Klein EK, Young A, Bibuld D, et al. Vitamin D2 is as effective as vitamin D3 in maintaining circulating concentrations of 25‐hydroxyvitamin D. Journal of Clinical Endocrinology and Metabolism 2007;Dec 18:[Epub ahead of print]. [DOI: 10.1210/jc.2007-2308] - DOI - PMC - PubMed
Jagannath 2013
    1. Jagannath VA, Fedorowicz Z, Thaker V, Chang AB. Vitamin K supplementation for cystic fibrosis. Cochrane Database of Systematic Reviews 2013, Issue 4. [DOI: 10.1002/14651858.CD008482.pub3] - DOI - PubMed
Joiner 2000
    1. Joiner TA, Foster C, Shape T. The many faces of vitamin D deficient rickets. Pediatrics in review 2000;21(9):296‐302. - PubMed
NIH 2007
    1. NIH. Office of Dietary Supplements. Dietary Supplement Fact Sheet: Vitamin D. http://ods.od.nih.gov/factsheets/vitamind.asp (accessed 31st October 2007).
Okebukola 2011
    1. Okebukola PO, Kansra S, McCabe H. Vitamin E supplementation in people with cystic fibrosis (Protocol). Cochrane Database of Systematic Reviews 2011, Issue 11. [DOI: 10.1002/14651858.CD009422] - DOI - PMC - PubMed
Popescu 1998
    1. Popescu M, Morris J, Hillman L. Calcium and vitamin D supplementation in CF children [abstract]. Pediatric Pulmonology 1998;26 Suppl 17:359.
RevMan 2012 [Computer program]
    1. The Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager (RevMan). Version 5.2. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2012.
Sethuraman 2006
    1. Sethuraman U. Vitamins. Pediatric Review 2006;27(2):44‐55. - PubMed
Sinaasappel 2002
    1. Sinaasappel M, Stern M, Littlewood J, Wolfe S, Steinkamp G, Heijerman HG, et al. Nutrition in patients with cystic fibrosis: a European Consensus. Journal of Cystic Fibrosis 2002;1:51‐75. - PubMed
Theodoratou 2014
    1. T heodoratou E, Tzoulaki I, Zgaga L, Ioannidis JP. Vitamin D and multiple health outcomes: umbrella review of systematic reviews and meta‐analyses of observational studies and randomised trials . BMJ 2014 ; 348 :g2035. - PMC - PubMed
UK CF Trust 2007
    1. The UK Cystic Fibrosis Trust Bone Mineralisation Working Group. Bone mineralisation in cystic fibrosis. Report of the UK Cystic Fibrosis Trust Bone Mineralisation Working Group. Cystic Fibrosis Trust, February 2007.
Wagener 2003
    1. Wagener JS, Headley AA. Cystic fibrosis: current trends in respiratory care. Respiratory Care 2003;48(3):234‐45. - PubMed
Wharton 2003
    1. Wharton B, Bishop N. Rickets. Lancet 2003;362(9393):1389‐400. - PubMed
World Health Organization 1994
    1. World Health Organization. Definition of osteoporosis. Assessment of Fracture Risk and Its Application to Screening for Postmenopausal Osteoporosis 1994:1‐129. - PubMed
Wright 2005
    1. Wright RJ. Make no bones about it: increasing epidemiologic evidence links vitamin D to pulmonary function and COPD. Chest 2005;128(6):3781‐3. - PubMed

References to other published versions of this review

Ferguson 2010
    1. Ferguson JH, Chang AB. Vitamin D supplementation for cystic fibrosis. Cochrane Database of Systematic Reviews 2010, Issue 6. [DOI: 10.1002/14651858.CD007298.pub2] - DOI
Ferguson 2012
    1. Ferguson JH, Chang AB. Vitamin D supplementation for cystic fibrosis. Cochrane Database of Systematic Reviews 2012, Issue 4. [DOI: 10.1002/14651858.CD007298.pub3] - DOI - PubMed

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