Abstract
The features of cystic fibrosis (CF) include chronic infection and inflammation of the lungs and malabsorption due to pancreatic insufficiency. In people with CF, the many factors contributing to vitamin D deficiency include reduced sun exposure, pancreatic insufficiency, reduced levels of vitamin D binding protein, reduced fat stores, liver disease, accelerated enterohepatic excretion and influence of CF transmembrane conductance regulator (CFTR). The clinical impact of vitamin D deficiency on bone metabolism is known; however, its effects beyond the skeletal system is less recognized. The evidence for routine vitamin D supplementation and management in the presence of vitamin D deficiency are discussed.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Ratjen F, Doring G. Cystic fibrosis. Lancet. 2003;361(9358):681–9.
Rowe SM, Miller S, Sorscher EJ. Cystic fibrosis. N Engl J Med. 2005;352(19):1992–2001.
Shead EF, Haworth CS, Condliffe AM, McKeon DJ, Scott MA, Compston JE. Cystic fibrosis transmembrane conductance regulator (CFTR) is expressed in human bone. Thorax. 2007;62(7):650–1.
Laohapitakworn S, Thongbunchoo J, Nakkrasae LI, Krishnamra N, Charoenphandhu N. Parathyroid hormone (PTH) rapidly enhances CFTR-mediated HCOFormula secretion in intestinal epithelium-like Caco-2 monolayer: a novel ion regulatory action of PTH. Am J Physiol Cell Physiol. 2011;301(1):C137–49.
Yim S, Dhawan P, Ragunath C, Christakos S, Diamond G. Induction of cathelicidin in normal and CF bronchial epithelial cells by 1,25-dihydroxyvitamin D(3). J Cyst Fibros. 2007;6(6):403–10.
Xystrakis E, Kusumakar S, Boswell S, et al. Reversing the defective induction of IL-10-secreting regulatory T cells in glucocorticoid-resistant asthma patients. J Clin Invest. 2006;116(1):146–55.
Kreindler JL, Steele C, Nguyen N, et al. Vitamin D3 attenuates Th2 responses to Aspergillus fumigatus mounted by CD4+ T cells from cystic fibrosis patients with allergic bronchopulmonary aspergillosis. J Clin Invest. 2010;120(9):3242–54.
Pincikova T, Nilsson K, Moen IE, et al. Inverse relation between vitamin d and serum total immunoglobulin g in the Scandinavian cystic fibrosis nutritional study. Eur J Clin Nutr. 2011;65(1):102–9.
West NE, Lechtzin N, Merlo CA, et al. Appropriate goal level for 25-hydroxyvitamin D in cystic fibrosis. Chest. 2011;140(2):469–74.
Haworth CS, Selby PL, Horrocks AW, Mawer EB, Adams JE, Webb AK. A prospective study of change in bone mineral density over one year in adults with cystic fibrosis. Thorax. 2002;57(8):719–23.
Donovan Jr DS, Papadopoulos A, Staron RB, et al. Bone mass and vitamin D deficiency in adults with advanced cystic fibrosis lung disease. Am J Respir Crit Care Med. 1998;157(6 Pt 1):1892–9.
Elkin SL, Fairney A, Burnett S, et al. Vertebral deformities and low bone mineral density in adults with cystic fibrosis: a cross-sectional study. Osteoporos Int. 2001;12(5):366–72.
Boyle MP, Noschese ML, Watts SL, Davis ME, Stenner SE, Lechtzin N. Failure of high-dose ergocalciferol to correct vitamin D deficiency in adults with cystic fibrosis. Am J Respir Crit Care Med. 2005;172(2):212–7.
Rossini M, Del Marco A, Dal Santo F, et al. Prevalence and correlates of vertebral fractures in adults with cystic fibrosis. Bone. 2004;35(3):771–6.
Flohr F, Lutz A, App EM, Matthys H, Reincke M. Bone mineral density and quantitative ultrasound in adults with cystic fibrosis. Eur J Endocrinol. 2002;146(4):531–6.
Buntain HM, Greer RM, Schluter PJ, et al. Bone mineral density in Australian children, adolescents and adults with cystic fibrosis: a controlled cross sectional study. Thorax. 2004;59(2):149–55.
Stephenson A, Brotherwood M, Robert R, Atenafu E, Corey M, Tullis E. Cholecalciferol significantly increases 25-hydroxyvitamin D concentrations in adults with cystic fibrosis. Am J Clin Nutr. 2007;85(5):1307–11.
Gronowitz E, Garemo M, Lindblad A, Mellstrom D, Strandvik B. Decreased bone mineral density in normal-growing patients with cystic fibrosis. Acta Paediatr. 2003;92(6):688–93.
Wolfenden LL, Judd SE, Shah R, Sanyal R, Ziegler TR, Tangpricha V. Vitamin D and bone health in adults with cystic fibrosis. Clin Endocrinol. 2008;69(3):374–81.
Conway SP, Morton AM, Oldroyd B, et al. Osteoporosis and osteopenia in adults and adolescents with cystic fibrosis: prevalence and associated factors. Thorax. 2000;55(9):798–804.
Bhudhikanok GS, Wang MC, Marcus R, Harkins A, Moss RB, Bachrach LK. Bone acquisition and loss in children and adults with cystic fibrosis: a longitudinal study. J Pediatr. 1998;133(1):18–27.
Ujhelyi R, Treszl A, Vasarhelyi B, et al. Bone mineral density and bone acquisition in children and young adults with cystic fibrosis: a follow-up study. J Pediatr Gastroenterol Nutr. 2004;38(4):401–6.
Rovner AJ, Stallings VA, Schall JI, Leonard MB, Zemel BS. Vitamin D insufficiency in children, adolescents, and young adults with cystic fibrosis despite routine oral supplementation. Am J Clin Nutr. 2007;86(6):1694–9.
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. Pediatr Pulmonol. 2008;43(8):772–80.
Chavasse RJ, Francis J, Balfour-Lynn I, Rosenthal M, Bush A. Serum vitamin D levels in children with cystic fibrosis. Pediatr Pulmonol. 2004;38(2):119–22.
Conway SP, Oldroyd B, Brownlee KG, Wolfe SP, Truscott JG. A cross-sectional study of bone mineral density in children and adolescents attending a cystic fibrosis centre. J Cyst Fibros. 2008;7(6):469–76.
Fewtrell MS, Benden C, Williams JE, et al. Undercarboxylated osteocalcin and bone mass in 8–12 year old children with cystic fibrosis. J Cyst Fibros. 2008;7(4):307–12.
Grey V, Atkinson S, Drury D, et al. Prevalence of low bone mass and deficiencies of vitamins D and K in pediatric patients with cystic fibrosis from 3 Canadian centers. Pediatrics. 2008;122(5):1014–20.
Nicolaidou P, Stavrinadis I, Loukou I, et al. The effect of vitamin K supplementation on biochemical markers of bone formation in children and adolescents with cystic fibrosis. Eur J Pediatr. 2006;165(8):540–5.
Hall WB, Sparks AA, Aris RM. Vitamin D deficiency in cystic fibrosis. Int J Endocrinol. 2010;2010:218691.
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. J Cyst Fibros. 2004;3(4):233–6.
Brown SA, Ontjes DA, Lester GE, et al. Short-term calcitriol administration improves calcium homeostasis in adults with cystic fibrosis. Osteoporos Int. 2003;14(5):442–9.
Khazai NB, Judd SE, Jeng L, et al. Treatment and prevention of vitamin D insufficiency in cystic fibrosis patients: comparative efficacy of ergocalciferol, cholecalciferol, and UV light. J Clin Endocrinol Metabol. 2009;94(6):2037–43.
Green D, Carson K, Leonard A, et al. Current treatment recommendations for correcting vitamin D deficiency in pediatric patients with cystic fibrosis are inadequate. J Pediatr. 2008;153(4):554–9.
Gronowitz E, Larko O, Gilljam M, et al. Ultraviolet B radiation improves serum levels of vitamin D in patients with cystic fibrosis. Acta Paediatr. 2005;94(5):547–52.
Buntain HM, Schluter PJ, Bell SC, et al. Controlled longitudinal study of bone mass accrual in children and adolescents with cystic fibrosis. Thorax. 2006;61(2):146–54.
Paccou J, Zeboulon N, Combescure C, Gossec L, Cortet B. The prevalence of osteoporosis, osteopenia, and fractures among adults with cystic fibrosis: a systematic literature review with meta-analysis. Calcif Tissue Int. 2010;86(1):1–7.
Gore AP, Kwon SH, Stenbit AE. A roadmap to the brittle bones of cystic fibrosis. J Osteoporos. 2010;2011:926045.
Haworth CS. Impact of cystic fibrosis on bone health. Curr Opin Pulm Med. 2010;16(6):616–22.
Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357(3):266–81.
Aris RM, Merkel PA, Bachrach LK, et al. Guide to bone health and disease in cystic fibrosis. J Clin Endocrinol Metab. 2005;90(3):1888–96.
Dong Y, Pollock N, Stallmann-Jorgensen IS, et al. Low 25-hydroxyvitamin D levels in adolescents: race, season, adiposity, physical activity, and fitness. Pediatrics. 2010;125(6):1104–11.
King SJ, Topliss DJ, Kotsimbos T, et al. Reduced bone density in cystic fibrosis: DeltaF508 mutation is an independent risk factor. Eur Respir J. 2005;25(1):54–61.
Gronowitz E, Mellstrom D, Strandvik B. Normal annual increase of bone mineral density during two years in patients with cystic fibrosis. Pediatrics. 2004;114(2):435–42.
Koch C, Cuppens H, Rainisio M, et al. European Epidemiologic Registry of Cystic Fibrosis (ERCF): comparison of major disease manifestations between patients with different classes of mutations. Pediatr Pulmonol. 2001;31(1):1–12.
Greer RM, Buntain HM, Potter JM, et al. Abnormalities of the PTH-vitamin D axis and bone turnover markers in children, adolescents and adults with cystic fibrosis: comparison with healthy controls. Osteoporos Int. 2003;14(5):404–11.
Aris RM, Ontjes DA, Buell HE, et al. Abnormal bone turnover in cystic fibrosis adults. Osteoporos Int. 2002;13(2):151–7.
Bhudhikanok GS, Lim J, Marcus R, Harkins A, Moss RB, Bachrach LK. Correlates of osteopenia in patients with cystic fibrosis. Pediatrics. 1996;97(1):103–11.
Haworth CS, Selby PL, Webb ME, et al. Low bone mineral density in adults with cystic fibrosis. Thorax. 1999;54(11):961–7.
Ionescu AA, Nixon LS, Evans WD, et al. Bone density, body composition, and inflammatory status in cystic fibrosis. Am J Respir Crit Care Med. 2000;162(3 Pt 1):789–94.
Mortensen LA, Chan GM, Alder SC, Marshall BC. Bone mineral status in prepubertal children with cystic fibrosis. J Pediatr. 2000;136(5):648–52.
Sood M, Hambleton G, Super M, Fraser WD, Adams JE, Mughal MZ. Bone status in cystic fibrosis. Arch Dis Child. 2001;84(6):516–20.
Malabanan A, Veronikis IE, Holick MF. Redefining vitamin D insufficiency. Lancet. 1998;351(9105):805–6.
Nixon PA, Orenstein DM, Kelsey SF. Habitual physical activity in children and adolescents with cystic fibrosis. Med Sci Sports Exerc. 2001;33(1):30–5.
Selvadurai HC, Blimkie CJ, Cooper PJ, Mellis CM, Van Asperen PP. Gender differences in habitual activity in children with cystic fibrosis. Arch Dis Child. 2004;89(10):928–33.
Lark RK, Lester GE, Ontjes DA, et al. Diminished and erratic absorption of ergocalciferol in adult cystic fibrosis patients. Am J Clin Nutr. 2001;73(3):602–6.
Dorlochter L, Aksnes L, Fluge G. Faecal elastase-1 and fat-soluble vitamin profiles in patients with cystic fibrosis in Western Norway. Eur J Nutr. 2002;41(4):148–52.
Coppenhaver D, Kueppers F, Schidlow D, et al. Serum concentrations of vitamin D-binding protein (group-specific component) in cystic fibrosis. Hum Genet. 1981;57(4):399–403.
Debray D, Kelly D, Houwen R, Strandvik B, Colombo C. Best practice guidance for the diagnosis and management of cystic fibrosis-associated liver disease. J Cyst Fibros. 2011;10 Suppl 2:S29–36.
Grey AB, Ames RW, Matthews RD, Reid IR. Bone mineral density and body composition in adult patients with cystic fibrosis. Thorax. 1993;48(6):589–93 [see comments].
Leifke E, Friemert M, Heilmann M, et al. Sex steroids and body composition in men with cystic fibrosis. Eur J Endocrinol. 2003;148(5):551–7.
Haslam RH, Borovnicar DJ, Stroud DB, Strauss BJ, Bines JE. Correlates of prepubertal bone mineral density in cystic fibrosis. Arch Dis Child. 2001;85(2):166–71.
Henderson RC, Madsen CD. Bone density in children and adolescents with cystic fibrosis. J Pediatr. 1996;128(1):28–34.
Henderson RC, Madsen CD. Bone mineral content and body composition in children and young adults with cystic fibrosis. Pediatr Pulmonol. 1999;27(2):80–4.
Elkin SL, Vedi S, Bord S, Garrahan NJ, Hodson ME, Compston JE. Histomorphometric analysis of bone biopsies from the iliac crest of adults with cystic fibrosis. Am J Respir Crit Care Med. 2002;166(11):1470–4.
Haworth CS, Freemont AJ, Webb AK, et al. Hip fracture and bone histomorphometry in a young adult with cystic fibrosis. Eur Respir J. 1999;14(2):478–9.
Haworth CS, Webb AK, Egan JJ, et al. Bone histomorphometry in adult patients with cystic fibrosis. Chest. 2000;118(2):434–9.
Bachrach LK. Acquisition of optimal bone mass in childhood and adolescence. Trends Endocrinol Metab. 2001;12(1):22–8.
Davies JH, Evans BA, Gregory JW. Bone mass acquisition in healthy children. Arch Dis Child. 2005;90(4):373–8.
Aris RM, Lester GE, Dingman S, Ontjes DA. Altered calcium homeostasis in adults with cystic fibrosis. Osteoporos Int. 1999;10(2):102–8.
Schulze KJ, O’Brien KO, Germain-Lee EL, Booth SL, Leonard A, Rosenstein BJ. Calcium kinetics are altered in clinically stable girls with cystic fibrosis. J Clin Endocrinol Metab. 2004;89(7):3385–91.
Schulze KJ, O’Brien KO, Germain-Lee EL, Baer DJ, Leonard AL, Rosenstein BJ. Endogenous fecal losses of calcium compromise calcium balance in pancreatic-insufficient girls with cystic fibrosis. J Pediatr. 2003;143(6):765–71.
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.
Ferguson JH, Chang AB. Vitamin D supplementation for cystic fibrosis. Cochrane Database Syst Rev. 2009;4:CD007298.
Sermet-Gaudelus I, Bianchi ML, Garabedian M, et al. European cystic fibrosis bone mineralisation guidelines. J Cyst Fibros. 2011;10 Suppl 2:S16–23.
Group TUcftbmw. Bone mineralisation in cystic fibrosis. London: Cystic Fibrosis Trust; 2007.
Robberecht E, Vandewalle S, Wehlou C, Kaufman JM, De Schepper J. Sunlight is an important determinant of vitamin D serum concentrations in cystic fibrosis. Eur J Clin Nutr. 2011;65(5):574–9.
Samanek AJ, Croager EJ, Gies P, et al. Estimates of beneficial and harmful sun exposure times during the year for major Australian population centres. Med J Aust. 2006;184(7):338–41.
Chesney RW. Vitamin D: can an upper limit be defined? J Nutr. 1989;119 Suppl 12:1825–8.
Cranney A, Horsley T, O’Donnell S, et al. Effectiveness and safety of vitamin D in relation to bone health. Evid Rep Technol Assess (Full Rep). 2007;158:1–235.
Acknowledgement
Funding: AC is funded by a NHMRC practitioner fellowship (grant number 545216).
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2012 Springer Science+Business Media, LLC
About this chapter
Cite this chapter
Buntain, H.M., Chang, A.B. (2012). Cystic Fibrosis. In: Litonjua, A. (eds) Vitamin D and the Lung. Respiratory Medicine, vol 3. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-61779-888-7_12
Download citation
DOI: https://doi.org/10.1007/978-1-61779-888-7_12
Published:
Publisher Name: Humana Press, Totowa, NJ
Print ISBN: 978-1-61779-887-0
Online ISBN: 978-1-61779-888-7
eBook Packages: MedicineMedicine (R0)