Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Minerals, trace elements, vitamin D and bone health

Vitamin D and K status influences bone mineral density and bone accrual in children and adolescents with celiac disease

European Journal of Clinical Nutrition volume 66, pages 488–495 (2012)Cite this article

Abstract

Background/Objectives:

Children with celiac disease (CD) are at risk for decreased bone mineral density (BMD) because of fat-soluble vitamin malabsorption, inflammation and/or under-nutrition. The study objective was to determine the interrelationships between vitamin K/D status and lifestyle variables on BMD in children and adolescents with CD at diagnosis and after 1 year on the gluten-free diet (GFD).

Subjects/Methods:

Children and adolescents aged 3–17 years with biopsy proven CD at diagnosis and after 1 year on the GFD were studied. BMD was measured using dual-energy X-ray absorptiometry. Relevant variables included: anthropometrics, vitamin D/K status, diet, physical activity and sunlight exposure.

Results:

Whole-body and lumbar-spine BMD-z scores were low (⩽−1) at diagnosis (10–20%) and after 1 year (30–32%) in the children, independent of symptoms. Whole-body BMD-z scores (−0.55±0.7 versus 0.72±1.5) and serum levels of 25(OH) vitamin D (90.3±24.8 versus 70.5±19.8 nmol/l) were significantly lower in older children (>10 years) when compared with younger children (⩽10 years) (P<0.001). Forty-three percent had suboptimal vitamin D status (25(OH)-vitamin D <75 nmol/l) at diagnosis; resolving in nearly half after 1 year on the GFD. Twenty-five percent had suboptimal vitamin K status at diagnosis; all resolved after 1 year.

Conclusions:

Children and adolescents with CD are at risk for suboptimal bone health at time of diagnosis and after 1 year on GFD; likely due in part to suboptimal vitamin D/K status. Therapeutic strategies aimed at optimizing vitamin K/D intake may contribute to improved BMD in children with CD.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  • Bailey DA (1997). The Saskatchewan pediatric bone mineral accrual study: bone mineral acquisition during the growing years. Int J Sports Med 18 (Suppl 3), S191–S194.

    Article  PubMed  Google Scholar 

  • Blazina S, Bratanic N, Campa AS, Blagus R, Orel R (2010). Bone mineral density and importance of strict gluten-free diet in children and adolescents with celiac disease. Bone 47, 598–603.

    Article  PubMed  Google Scholar 

  • Booth SL (1997). Skeletal functions of vitamin K-dependent proteins: not just for clotting anymore. Nutr Rev 55, 282–284.

    Article  CAS  PubMed  Google Scholar 

  • Cashman KD (2005). Vitamin K status may be an important determinant of childhood bone health. Nutr Rev 63, 284–289.

    Article  PubMed  Google Scholar 

  • Cavallaro R, Iovino P, Castiglione F, Palumbo A, Marino M, Di Bella S et al. (2004). Prevalence and clinical associations of prolonged prothrombin time in adult untreated coeliac disease. (See comment). Eur J Gastroenterol Hepatol 16, 219–223.

    Article  PubMed  Google Scholar 

  • Ciacci C, Maurelli L, Klain M, Savino G, Salvatore M, Mazzacca G et al. (1997). Effects of dietary treatment on bone mineral density in adults with celiac disease: factors predicting response. Am J Gastroenterol 92, 992–996.

    CAS  PubMed  Google Scholar 

  • Cockayne S, Adamson J, Lanham-New S, Shearer MJ, Gilbody S, Torgerson DJ (2006). Vitamin K and the prevention of fractures: systematic review and meta-analysis of randomized controlled trials. Arch Int Med 166, 1256–1261.

    Article  CAS  Google Scholar 

  • Crocker PR, Bailey DA, Faulkner RA, Kowalski KC, Mcgrath R (1997). Measuring general levels of physical activity: preliminary evidence for the physical activity questionnaire for older children. Med Sci Sports Exerc 29, 1344–1349.

    Article  CAS  PubMed  Google Scholar 

  • El Hayek J, Egeland G, Weiler H (2010). Vitamin D status of Inuit preschoolers reflects season and vitamin D intake. J Nutr 140, 1839–1845.

    Article  CAS  PubMed  Google Scholar 

  • Fasano A, Catassi C (2001). Current approaches to diagnosis and treatment of celiac disease: an evolving spectrum. (See comment). Gastroenterology 120, 636–651.

    Article  CAS  PubMed  Google Scholar 

  • Genuis SJ, Schwalfenberg GK, Hiltz MN, Vaselenak SA (2009). Vitamin D status of clinical practice populations at higher latitudes: analysis and applications. Int J Environ Res Public Health 6, 151–173.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Greulich W, Pyle S (1959). Radiographic Atlas of Skeletal Development of the Hand and Wrist, 2nd edn, Stanford University Press: Stanford, CA.

    Book  Google Scholar 

  • Holick MF (2007). Optimal vitamin D status for the prevention and treatment of osteoporosis. Drugs Aging 24, 1017–1029.

    Article  CAS  PubMed  Google Scholar 

  • Kavak US, Yuce A, Kocak N, Demir H, Saltik IN, Gurakan F et al. (2003). Bone mineral density in children with untreated and treated celiac disease. (See comment). J Pediatric Gastroenterol Nutr 37, 434–436.

    Article  CAS  Google Scholar 

  • Kobayashi M, Hara K, Akiyama Y (2002). Effects of vitamin K2 (menatetrenone) on calcium balance in ovariectomized rats. Jpn J Pharmacol 88, 55–61.

    Article  CAS  PubMed  Google Scholar 

  • Koshihara Y, Hoshi K, Ishibashi H, Shiraki M (1996). Vitamin K2 promotes 1alpha,25(OH)2 vitamin D3-induced mineralization in human periosteal osteoblasts. Calcified Tissue Int 59, 466–473.

    CAS  Google Scholar 

  • Lerner A, Shapira Y, Agmon-Levin N, Pacht A, Ben-Ami shor D, Lopez HM et al. (2011). The clinical significance of 25OH-vitamin D status in celiac disease. Clin Rev Allergy Immunol; e-pub ahead of print 7 January 2011; doi:10.1007/S12016-010-8237-8.

  • Lewiecki EM, Gordon CM, Baim S, Leonard MB, Bishop NJ, Bianchi ML et al. (2008). International Society for Clinical Densitometry 2007 Adult and Pediatric Official Positions. Bone 43, 1115–1121.

    Article  PubMed  Google Scholar 

  • Mager DR, Mcgee PL, Furuya KN, Roberts EA (2006). Prevalence of vitamin K deficiency in children with mild to moderate chronic liver disease. J Pediatr Gastroenterol Nutr 42, 71–76.

    Article  CAS  PubMed  Google Scholar 

  • Mark S, Lambert M, Delvin EE, O’Loughlin J, Tremblay A, Gray-Donald K (2011). Higher vitamin D intake is needed to achieve serum 25(OH)D levels greater than 50 nmol/l in Quebec youth at high risk of obesity. Eur J Clin Nutr 65, 486–492.

    Article  CAS  PubMed  Google Scholar 

  • Marsh MN (1992). Gluten, major histocompatibility complex, and the small intestine. A molecular and immunobiologic approach to the spectrum of gluten sensitivity (‘celiac sprue’). Gastroenterology 102, 330–354.

    Article  CAS  PubMed  Google Scholar 

  • Mautalen C, Gonzalez D, Mazure R, Vazquez H, Lorenzetti MP, Maurino E et al. (1997). Effect of treatment on bone mass, mineral metabolism, and body composition in untreated celiac disease patients. Am J Gastroenterol 92, 313–318.

    CAS  PubMed  Google Scholar 

  • Motta ME, Faria ME, Silva GA (2009). Prevalence of low bone mineral density in children and adolescents with celiac disease under treatment. Sao Paulo Med J 127, 278–282.

    Article  PubMed  Google Scholar 

  • Oberhuber G, Granditsch G, Vogelsang H (1999). The histopathology of coeliac disease: time for a standardized report scheme for pathologists. Eur J Gastroenterol Hepatol 11, 1185–1194.

    Article  CAS  PubMed  Google Scholar 

  • Ohlund K, Olsson C, Hernell O, Ohlund I (2010). Dietary shortcomings in children on a gluten-free diet. J Hum Nutr Diet 23, 294–300.

    Article  CAS  PubMed  Google Scholar 

  • Otten J, Pitzi Hellwig J, Meyers LD (ed) (2006). Dietary (DRI) Reference Intakes. Institute of Medicine, The National Academies Press: Washington, DC, USA.

  • Pazianas M, Butcher GP, Subhani JM, Finch PJ, Ang L, Collins C et al. (2005). Calcium absorption and bone mineral density in celiacs after long term treatment with gluten-free diet and adequate calcium intake. Osteoporosis Int 16, 56–63.

    Article  CAS  Google Scholar 

  • Rajani S, Huynh HQ, Turner J (2010). The changing frequency of celiac disease diagnosed at the Stollery Children's Hospital. Can J Gastroenterol 24, 109–112.

    Article  PubMed  PubMed Central  Google Scholar 

  • Ross AC, Manson JE, Abrams SA, Aloia JF, Brannon PM, Clinton SK et al. (2011). The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. J Clin Endocrinol Metab 96, 53–58.

    Article  CAS  PubMed  Google Scholar 

  • Roth DE, Martz P, Yeo R, Prosser C, Bell M, Jones AB (2005). Are national vitamin D guidelines sufficient to maintain adequate blood levels in children? Can J Public Health 96, 443–449.

    PubMed  PubMed Central  Google Scholar 

  • Scotta MS, Salvatore S, Salvatoni A, De Amici M, Ghiringhelli D, Broggini M et al. (1997). Bone mineralization and body composition in young patients with celiac disease. (See comment). Am J Gastroenterol 92, 1331–1334.

    CAS  PubMed  Google Scholar 

  • Sylvester FA, Wyzga N, Hyams JS, Davis PM, Lerer T, Vance K et al. (2007). Natural history of bone metabolism and bone mineral density in children with inflammatory bowel disease. Inflamm Bowel Dis 13, 42–50.

    Article  PubMed  Google Scholar 

  • Tanner JM, Whitehouse RH (1976). Clinical longitudinal standards for height, weight, height velocity, weight velocity, and stages of puberty. Arch Dis Child 51, 170–179.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Termorshuizen F, Wijga A, Garssen J, Den Outer PN, Slaper H, van Loveren H (2002). Exposure to solar ultraviolet radiation in young Dutch children: assessment by means of a 6-week retrospective questionnaire. J Expo Anal Environ Epidemiol 12, 204–213.

    Article  PubMed  Google Scholar 

  • Tremblay MS, Leblanc AG, Janssen I, Kho ME, Hicks A, Murumets K et al. (2011a). Canadian sedentary behaviour guidelines for children and youth. Appl Physiol Nutr Metab 36, 59–64; 65–71.

    Article  PubMed  Google Scholar 

  • Tremblay MS, Warburton DE, Janssen I, Paterson DH, Latimer AE, Rhodes RE et al. (2011b). New Canadian physical activity guidelines. Appl Physiol Nutr Metab 36, 36–46; 47–58.

    Article  PubMed  Google Scholar 

  • Treuth MS, Hou N, Young DR, Maynard LM (2005). Validity and reliability of the Fels physical activity questionnaire for children. Med Sci Sports Exerc 37, 488–495.

    Article  PubMed  Google Scholar 

  • Turner J, Pellerin G, Mager D (2009). Prevalence of metabolic bone disease in children with celiac disease is independent of symptoms at diagnosis. J Pediatr Gastroenterol Nutr 49, 589–593.

    Article  PubMed  Google Scholar 

  • Valdimarsson T, Toss G, Lofman O, Strom M (2000). Three years’ follow-up of bone density in adult coeliac disease: significance of secondary hyperparathyroidism. Scand J Gastroenterol 35, 274–280.

    Article  CAS  PubMed  Google Scholar 

  • Wild D, Robins GG, Burley VJ, Howdle PD (2010). Evidence of high sugar intake, and low fibre and mineral intake, in the gluten-free diet. Aliment Pharmacol Ther 32, 573–581.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors gratefully acknowledge the assistance of Leanne Shirton RN in data collection. Funding for this project was provided by the JA Campbell Award, Canadian Celiac Association, Food and Health Innovative Initiative, University for Alberta (JQ). We also wish to gratefully acknowledge the children and parents and/or caregivers for participating in this study.

Author information

Authors and Affiliations

  1. Department of Agriculture, Food and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada

    D R Mager, J Qiao & J Turner

  2. Department of Pediatric Gastroenterology and Nutrition, University of Alberta, Edmonton, Alberta, Canada

    D R Mager & J Turner

Authors
  1. D R Mager
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J Qiao
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J Turner
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to D R Mager.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mager, D., Qiao, J. & Turner, J. Vitamin D and K status influences bone mineral density and bone accrual in children and adolescents with celiac disease. Eur J Clin Nutr 66, 488–495 (2012). https://doi.org/10.1038/ejcn.2011.176

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ejcn.2011.176

Keywords

This article is cited by

Search

Advanced search

Quick links