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The effect of vitamin K supplementation on biochemical markers of bone formation in children and adolescents with cystic fibrosis

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Abstract

Introduction

Impaired vitamin K status in cystic fibrosis (CF) has been considered as a newly emerged pathogenetic factor for reduced bone mineral density (BMD).

Objectives

Our aim was to evaluate the effectiveness of vitamin K supplementation in managing bone formation abnormalities in children and adolescents with CF.

Materials and methods

The statuses of vitamins K and D in relation to biochemical markers of bone metabolism and BMD were examined in 20 CF children receiving vitamin D supplements but not vitamin K supplements. Laboratory tests were carried out at the beginning of the study period and after 1 year of vitamin K supplementation (10 mg single oral dose/week) and the results were compared; the results were also compared with those of 25 healthy controls.

Results and discussion

Ten of the CF patients had BMD z-score ≤2.5 (n=5) or between −1 and −2.5 (n=5). Biochemical tests on patients before vitamin K supplementation revealed that the levels of osteoblastic activity markers, namely, bone alkaline phosphatase (BAP), serum osteocalcin (Gla-OC), serum carboxy-terminal propeptide of type I procollagen (PICP) and serum amino-terminal propeptide of type I procollagen (PINP), were significantly reduced compared with those of the controls. These patients had also lower 25-hydroxy-vitamin D (25(OH)D) and vitamin K serum levels, higher undercaboxylated osteocalcin (Glu-OC) and parathormone (PTH) levels and a higher calcium to creatinine ratio (Ca/Cr) than the controls. Vitamin K intake was associated with an increase in Gla-OC, PINP, PICP levels and a decrease in Glu-OC levels. PTH levels were lower after vitamin K supplementation without any difference in BMD z-scores.

Conclusion

Our data indicate that vitamin K supplementation may have a beneficial role in bone health in CF children.

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References

  1. Aris RM, Ontjes DA, Buell HE, Blackwood AD, Lark RK, Caminiti M, Brown SA, Renner JB, Chalermskulrat W, Lester GE (2002) Abnormal bone turnover in cystic fibrosis adults. Osteoporos Int 13:151–157

    Article  PubMed  CAS  Google Scholar 

  2. Aris RM, Ontjes DA, Brown SA, Chalermskulrat W, Neuringer I, Lester GE (2003) Carboxylated osteocalcin levels in cystic fibrosis. Am J Respir Crit Care Med 168:1129

    PubMed  Google Scholar 

  3. Aris RM, Merkel PA, Bachrach LK, Borowitz DS, Boyle MP, Elkin SL, Guise TA, Hardin DS, Haworth CS, Holick MF, Joseph PM, O’Brien K, Tullis E, Watts NB, White TB (2005) Guide to bone health and disease in cystic fibrosis. J Clin Endocrinol Metab 90:1888–1896

    Article  PubMed  CAS  Google Scholar 

  4. Baroncelli GI, De Luca F, Magazzu G, Arrigo T, Sferlazzas C, Catena C, Bertelloni S, Saggese G (1997) Bone demineralization in cystic fibrosis: evidence of imbalance between bone formation and degradation. Pediatr Res 41:397–403

    Article  PubMed  CAS  Google Scholar 

  5. Beker LT, Ahrens RA, Fink RJ, O’Brien ME, Davidson KW, Sokoll LJ, Sadowski JA (1997) Effect of vitamin K1 supplementation on vitamin K status in cystic fibrosis patients. J Pediatr Gastroenterol Nutr 24:512–517

    Article  PubMed  CAS  Google Scholar 

  6. Bhudhikanok GS, Lim J, Marcus R, Harkins A, Moss RB, Bachrach LK (1996) Correlates of osteopenia in patients with cystic fibrosis. Pediatrics 97:103–111

    PubMed  CAS  Google Scholar 

  7. Bhudhikanok GS, Wang MC, Marcus R, Harkins A, Moss RB, Bachrach LK (1998) Bone acquisition and loss in children and adults with cystic fibrosis: a longitudinal study. J Pediatr 133:18–27

    Article  PubMed  CAS  Google Scholar 

  8. Conway SP, Morton AM, Oldroyd B, Truscott JG, White H, Smith AH, Haigh I (2000) Osteoporosis and osteopenia in adults and adolescents with cystic fibrosis: prevalence and associated factors. Thorax 55:798–804

    Article  PubMed  CAS  Google Scholar 

  9. Conway SP, Wolfe SP, Brownlee KG, White H, Oldroyd B, Truscott JG, Harvey JM, Shearer MJ (2005) Vitamin K status among children with cystic fibrosis and its relationship to bone mineral density and bone turnover. Pediatrics 115:1325–1331

    Article  PubMed  Google Scholar 

  10. Donovan DS Jr, Papadopoulos A, Staron RB, Addesso V, Schulman L, McGregor C, Cosman F, Lindsay RL, Shane E (1998) Bone mass and vitamin D deficiency in adults with advanced cystic fibrosis lung disease. Am J Respir Crit Care Med 157:1892–1899

    PubMed  Google Scholar 

  11. Douglas AS, Robins SP, Hutchison JD, Porter RW, Stewart A, Reid DM (1995) Carboxylation of osteocalcin in post-menopausal osteoporotic women following vitamin K and D supplementation. Bone 17:15–20

    Article  PubMed  CAS  Google Scholar 

  12. Hahn TJ, Spuires AE, Halstead LR, Strominger DB (1979) Reduced serum 25-hydroxyvitamin D concentrations and disordered mineral metabolism in patients with cystic fibrosis. J Pediatr 94:38–42

    Article  PubMed  CAS  Google Scholar 

  13. Hanly JG, McKenna MJ, Quigley C, Freaney R, Muldowney FP, FitzGerald MX (1985) Hypovitaminosis D and response to supplementation in older patients with cystic fibrosis. Q J Med 56:377–385

    PubMed  CAS  Google Scholar 

  14. Henderson RC, Madsen CD (1996) Bone density in children and adolescents with cystic fibrosis. J Pediatr 128:28–34

    Article  PubMed  CAS  Google Scholar 

  15. Ionescu AA, Nixon LS, Evans WD, Stone MD, Lewis-Jenkins V, Chatham K, Shale DJ (2000) Bone density, body composition, and inflammatory status in cystic fibrosis. Am J Respir Crit Care Med 162:789–794

    PubMed  CAS  Google Scholar 

  16. Iwamoto J, Yeh JK, Takeda T, Ichimura S, Sato Y (2003) Comparative effects of vitamin K and vitamin D supplementation on prevention of osteopenia in calcium-deficient young rats. Bone 33:557–566

    Article  PubMed  CAS  Google Scholar 

  17. Iwamoto J, Yeh JK, Takeda T, Sato Y (2005) Effects of vitamin K2 administration on calcium balance and bone mass in young rats fed normal or low calcium diet. Horm Res 63:211–219

    Article  PubMed  CAS  Google Scholar 

  18. Leifke E, Friemert M, Heilmann M, Puvogel N, Smaczny C, von zur Muhlen A, Brabant G (2003) Sex steroids and body composition in men with cystic fibrosis. Eur J Endocrinol 148:551–557

    Article  PubMed  CAS  Google Scholar 

  19. Mortensen LA, Chan GM, Alder SC, Marshall BC (2000) Bone mineral status in prepubertal children with cystic fibrosis. J Pediatr 136:648–652

    Article  PubMed  CAS  Google Scholar 

  20. Nakashima A, Yorioka N, Doi S, Masaki T, Ito T, Harada S (2004) Effects of vitamin K2 in hemodialysis patients with low serum parathyroid hormone levels. Bone 34:579–583

    Article  PubMed  CAS  Google Scholar 

  21. Potts TJ (2005) Parathyroid hormone: past and present. J Endocrinol 187:311–325

    Article  PubMed  CAS  Google Scholar 

  22. Ramsey BW, Farrell PM, Pencharz P (1992) Nutritional assessment and management in cystic fibrosis: a consensus report. The Consensus Committee. Am J Clin Nutr 55:108–116

    PubMed  CAS  Google Scholar 

  23. Schoon EJ, Muller MC, Vermeer C, Schurgers LJ, Brummer RJ, Stockbrugger RW (2001) Low serum and bone vitamin K status in patients with longstanding Crohn’s disease: another pathogenetic factor of osteoporosis in Crohn’s disease? Gut 48:473–477

    Article  PubMed  CAS  Google Scholar 

  24. Shwachman H, Kulczycki LL (1958) Long-term study of 105 patients with cystic fibrosis. Am J Dis Child 96:6–15

    CAS  Google Scholar 

  25. Takahashi M, Naitou K, Ohishi T, Kushida K, Miura M (2001) Effect of vitamin K and / or D on undercarboxylated and intact osteocalcin in osteoporotic patients with vertebral or hip fractures. Clin Endocr 54:219–224

    Article  PubMed  CAS  Google Scholar 

  26. UK Cystic Fibrosis Trust, Nutrition Working Group (2002) Nutritional management of Cystic Fibrosis. A consensus report. UK Cystic Fibrosis Trust, Bromley, Kent, UK

  27. Ushiroyama T, Ikeda A, Ueki M (2002) Effect of continuous combined therapy with vitamin K(2) and vitamin D(3) on bone mineral density and coagulofibrinolysis function in postmenopausal women. Maturitas 41:211–221

    Article  PubMed  CAS  Google Scholar 

  28. van Hoorn JH, Hendriks JJ, Vermeer C, Forget PP (2003) Vitamin K supplementation in cystic fibrosis. Arch Dis Child 88:974–975

    Article  PubMed  Google Scholar 

  29. Wilson DC, Rashid M, Durie PR, Tsang A, Kalnins D, Andrew M, Corey M, Shin J, Tullis E, Pencharz PB (2001) Treatment of vitamin K deficiency in cystic fibrosis: effectiveness of a daily fat-soluble vitamin combination. J Pediatr 138:851–855

    Article  PubMed  CAS  Google Scholar 

  30. Zittermann A (2001) Effects of vitamin K on calcium and bone metabolism. Curr Opin Clin Nutr Metab Care 4:483–487

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Third Department of Pediatrics, Athens University Medical School, University General Hospital “Attikon”, Athens, Greece

    Polyxeni Nicolaidou, Anna Papadopoulou & Konstantinos Douros

  2. Second Department of Pediatrics, Athens University Medical School, “P. and A. Kyriakou” Children’s Hospital, Athens, Greece

    Ilias Stavrinadis, Helen Georgouli & Dimitrios Gourgiotis

  3. Cystic Fibrosis Unit, “Aghia Sophia” Children’s Hospital, Athens, Greece

    Ioanna Loukou & Stavros Doudounakis

  4. Allergy-Pneumonology Department, Penteli Children’s Hospital, Athens, Greece

    Kostas N. Priftis

  5. Department of Environmental Sciences, University of the Aegean, Mytilene, Greece

    Yiannis G. Matsinos

  6. Third Department of Pediatrics, University of Athens Medical School, “Attikon” Hospital, 1 Rimini St., Chaidari, 12464, Greece

    Polyxeni Nicolaidou

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  1. Polyxeni Nicolaidou
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  2. Ilias Stavrinadis
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  3. Ioanna Loukou
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  4. Anna Papadopoulou
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  7. Kostas N. Priftis
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  8. Dimitrios Gourgiotis
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Correspondence to Polyxeni Nicolaidou.

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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 165, 540–545 (2006). https://doi.org/10.1007/s00431-006-0132-1

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  • DOI: https://doi.org/10.1007/s00431-006-0132-1

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