Osteoporosis International

, Volume 20, Issue 6, pp 935–942 | Cite as

High prevalence of vitamin K and D deficiency and decreased BMD in inflammatory bowel disease

  • A. Kuwabara
  • K. Tanaka
  • N. Tsugawa
  • H. Nakase
  • H. Tsuji
  • K. Shide
  • M. Kamao
  • T. Chiba
  • N. Inagaki
  • T. Okano
  • S. Kido
Original Article

Abstract

Summary

Vitamin K and D deficiency and decreased bone mineral density (BMD) were highly prevalent in patients with inflammatory bowel disease (IBD), especially Crohn’s disease (CD). Dietary intakes of these vitamins, however, were above the Japanese adequate intakes in IBD patients, suggesting that malabsorption is the basis for hypovitaminosis K and D and decreased BMD.

Introduction

We have studied the possible involvement of vitamin K and D deficiency in the pathogenesis of decreased BMD in IBD.

Methods

Seventy patients with IBD were evaluated for their BMD; plasma levels of vitamin K; phylloquinone (PK), menaquinone-7 (MK-7), and 25OH-D; serum PTH, protein induced by vitamin K absence (PIVKA-II), and undercarboxylated osteocalcin (ucOC) levels; and their food intake.

Results

Compared with ulcerative colitis (UC) patients, CD patients had significantly lower plasma vitamin K and 25OH-D concentrations; significantly higher serum levels of PTH, PIVKA-II, and ucOC; and significantly lower BMD scores at almost all measurement sites. More IBD patients were vitamin K deficient in bone than in liver. Multiple regression analyses revealed that low plasma concentrations of vitamin K and 25OH-D were independent risk factors for low BMD and that they were associated with the patients’ fat intake, but not with their intake of these vitamins.

Conclusion

IBD patients have high prevalence of decreased BMD and vitamin K and D deficiency probably caused by malabsorption of these vitamins.

Keywords

Inflammatory bowel disease Malabsorption Vitamin K Vitamin D 

References

  1. 1.
    Compston JE, Judd D, Crawley EO et al (1987) Osteoporosis in patients with inflammatory bowel disease. Gut 28:410–415PubMedCrossRefGoogle Scholar
  2. 2.
    Bjarnason I, Macpherson A, Mackintosh C et al (1997) Reduced bone density in patients with inflammatory bowel disease. Gut 40:228–233PubMedGoogle Scholar
  3. 3.
    Ardizzone S, Bollani S, Bettica P et al (2000) Altered bone metabolism in inflammatory bowel disease: there is a difference between Crohn’s disease and ulcerative colitis. J Intern Med 247:63–70PubMedCrossRefGoogle Scholar
  4. 4.
    Bjarnason I (1999) Metabolic bone disease in patients with inflammatory bowel disease. Rheumatology 38:801–804PubMedCrossRefGoogle Scholar
  5. 5.
    Bartram SA, Peaston RT, Rawlings DJ et al (2006) Multifactorial analysis of risk factors for reduced bone mineral density in patients with Crohn’s disease. World J Gastroenterol 12:5680–5686PubMedGoogle Scholar
  6. 6.
    Schoon EJ, Müller MC, Vermeer C et al (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 48:473–477PubMedCrossRefGoogle Scholar
  7. 7.
    Vermeer C (1990) γ-Carboxyglutamate-containing proteins and the vitamin K-dependent carboxylasa. Biochem J 266:625–636PubMedGoogle Scholar
  8. 8.
    Booth SL (1997) Skeletal functions of vitamin K-dependent proteins: not just for clotting anymore. Nutr Rev 55:282–284PubMedCrossRefGoogle Scholar
  9. 9.
    Feskanich D, Weber P, Willett WC et al (1999) Vitamin K intake and hip fractures in women: a prospective study. Am J Clin Nutr 69:74–79PubMedGoogle Scholar
  10. 10.
    Booth SL, Tucker KL, Chen H et al (2000) Dietary vitamin K intakes are associated with hip fracture but not with bone mineral density in elderly men and women. Am J Clin Nutr 71:1201–1208PubMedGoogle Scholar
  11. 11.
    Booth SL, Broe KE, Peterson JW et al (2004) Associations between vitamin K biochemical measures and bone mineral density in men and women. J Clin Endocrinol Metab 89:4904–4909PubMedCrossRefGoogle Scholar
  12. 12.
    Szulc P, Chapuy M-C, Meunier PJ et al (1993) Serum undercarboxylated osteocalcin is a marker of the risk of hip fracture in elderly women. J Clin Invest 91:1769–1774PubMedCrossRefGoogle Scholar
  13. 13.
    Cockayne S, Adamson J, Lanham-New S et al (2006) Vitamin K and the prevention of fractures: systematic review and meta-analysis of randomized controlled trials. Arch Intern Med 166:1256–1261PubMedCrossRefGoogle Scholar
  14. 14.
    Bernstein CN, Bector S, Leslie W (2003) Lack of relationship of calcium and vitamin D intake to bone mineral density in premenopausal women with inflammatory bowel disease. Am J Gastroenterol 98:2468–2473PubMedCrossRefGoogle Scholar
  15. 15.
    Duggan P, O’Brien M, Kiely M et al (2004) Vitamin K status in patients with Crohn’s disease and relationship to bone turnover. Am J Gastroenterol 99:2178–2185PubMedCrossRefGoogle Scholar
  16. 16.
    Abreu MT, Kantorovich EA, Vasiliauskas EA et al (2004) Measurement of vitamin D levels in inflammatory bowel disease patients reveals a subset of Crohn’s disease patients with elevated 1,25-dihydroxyvitamin D and low bone mineral density. Gut 53:1129–1136PubMedCrossRefGoogle Scholar
  17. 17.
    Driscoll RH, Meredith SC, Sitrin M et al (1982) Vitamin D deficiency and bone disease in patients with Crohn’s disease. Gastroenterology 83:1252–1258PubMedGoogle Scholar
  18. 18.
    Jahnsen J, Falch JA, Mowinckel P et al (2002) Vitamin D status, parathyroid hormone and bone mineral density in patients with inflammatory bowel disease. Scand J Gastroenterol 37:192–199PubMedCrossRefGoogle Scholar
  19. 19.
    Vogelsang H, Klamert M, Resch H et al (1995) Dietary vitamin D intake in patients with Crohn’s disease. Wien Klin Wochenschr 107:578–581PubMedGoogle Scholar
  20. 20.
    Silvennoinen J (1996) Relationships between vitamin D, parathyroid hormone and bone mineral density in inflammatory bowel disease. J Intern Med 239:131–137PubMedCrossRefGoogle Scholar
  21. 21.
    Bikle DD (2001) Osteoporosis in gastrointestinal, pancreatic, and hepatic diseases. In: Marcus R, Feldman D, Kelsey J (eds) Osteoporosis. 2nd edn. Academic, San Diego, CA, pp 237–258Google Scholar
  22. 22.
    Haderslev KV, Jeppesen PV, Sorensen HA et al (2003) Vitamin D status and measurements of markers of bone metabolism in patients with small intestinal resection. Gut 52:653–658PubMedCrossRefGoogle Scholar
  23. 23.
    Lo CW, Paris PW, Clemens TL, Nolan J, Holick MF (1985) Vitamin D absorption in healthy subjects and in patients with intestinal malabsorption syndromes. Am J Clin Nutr 42:644–649PubMedGoogle Scholar
  24. 24.
    Krasinsk SD, Russell RM, Furie BC et al (1985) The prevalence of vitamin K deficiency in chronic gastrointestinal disorders. Am J Clin Nutr 41:639–643Google Scholar
  25. 25.
    Suhara Y, Kamao M, Tsugawa N et al (2005) Method for the determination of vitamin K homologues in human plasma using high-performance liquid chromatography-tandem mass spectrometry. Anal Chem 77:757–763PubMedCrossRefGoogle Scholar
  26. 26.
    Kanis JA, Melton LJ 3rd, Christiansen C et al (1994) The diagnosis of osteoporosis. J Bone Miner Res 9:1137–1141PubMedCrossRefGoogle Scholar
  27. 27.
    Todd KS, Hudes M, Calloway DH (1983) Food intake measurement: problems and approaches. Am J Clin Nutr 37:139–146PubMedGoogle Scholar
  28. 28.
    Davies M, Berry JL, Mee AP (2005) Bone disorders associated with gastrointestinal and hepatobiliary disease. In: Feldman D, Pike JW, Glorieux FG (eds) Vitamin D. 2nd edn. Academic, San Diego CA, pp 1293–1311Google Scholar
  29. 29.
    Holick MF (2007) Vitamin D deficiency. N Engl J Med 357:266–281PubMedCrossRefGoogle Scholar
  30. 30.
    Ministry of Health, Labour, and Welfare, Japan (2005) Dietary reference intakes for Japanese. Daiichi Shuppan, TokyoGoogle Scholar
  31. 31.
    Silvennoinen JA, Karttunen TJ, Niemelä SE et al (1995) A controlled study of bone mineral density in patients with inflammatory bowel disease. Gut 37:71–76PubMedCrossRefGoogle Scholar
  32. 32.
    Motley RJ, Clements D, Evans WD et al (1993) A four-year longitudinal study of bone loss in patients with inflammatory bowel disease. Bone Miner 23:95–104PubMedCrossRefGoogle Scholar
  33. 33.
    Sambrook PN (2006) Glucocorticoid-induced osteoporosis. In: Favus MJ (ed) (2006) Primers on the metabolic bone diseases and disorders of mineral metabolism. 6th edn. American Society for Bone and Mineral Research, Washington DC, pp 296–302Google Scholar
  34. 34.
    Nemetz A, Tóth M, García-González MA et al (2001) Allelic variation at the interleukin 1β gene is associated with decreased bone mass in patients with inflammatory bowel diseases. Gut 49:644–649PubMedCrossRefGoogle Scholar
  35. 35.
    Moschen AR, Kaser A, Enrich B et al (2005) The RANKL/OPG system is activated in inflammatory bowel disease and relates to the state of bone loss. Gut 54:479–487PubMedCrossRefGoogle Scholar
  36. 36.
    Sylvester FA, Wyzga N, Hyams JS et al (2002) Effect of Crohn’s disease on bone metabolism in vitro: a role for interleukin-6. J Bone Miner Res 17:695–702PubMedCrossRefGoogle Scholar
  37. 37.
    Héla S, Nihel M, Faten L et al (2005) Osteoporosis and Crohn’s disease. Joint Bone Spine 72:403–407PubMedCrossRefGoogle Scholar
  38. 38.
    Schurgers LJ, Teunissen KJ, Hamulyák K et al (2007) Vitamin K-containing dietary supplements: comparison of synthetic vitamin K1 and natto-derived menaquinone-7. Blood 109:3279–3283PubMedCrossRefGoogle Scholar
  39. 39.
    Kaneki M, Hedges SJ, Hosoi T et al (2001) Japanese fermented soybean food as the major determination of the large geographic difference in circulating levels of vitamin K2: possible implications for hip-fracture risk. Nutrition 17:315–321PubMedCrossRefGoogle Scholar
  40. 40.
    Beavan SR, Prentice A, Stirling DM et al (2005) Ethnic differences in osteocalcin γ-carboxylation, plasma phylloquinone (vitamin K1) and apolipoprotein E genotype. Eur J Clin Nutr 59:72–81PubMedCrossRefGoogle Scholar
  41. 41.
    Tsugawa N, Shiraki M, Suhara Y et al (2006) Vitamin K status of healthy Japanese women: age-related vitamin K requirement for γ-carboxylation of osteocalcin. Am J Clin Nutr 83:380–386PubMedGoogle Scholar
  42. 42.
    Booth SL, Martini L, Peterson JW et al (2003) Dietary phylloquinone depletion and repletion in older women. J Nutr 133:2565–2569PubMedGoogle Scholar
  43. 43.
    Vermeer C, Gijsbers BL, Crācium AM et al (1996) Effects of vitamin K on bone mass and bone metabolism. J Nutr 126:1187S–1191SPubMedGoogle Scholar
  44. 44.
    Tangpricha V, Koutkia P, Rieke SM et al (2003) Fortification of orange juice with vitamin D: a novel approach for enhancing vitamin D nutritional health. Am J Clin Nutr 77:1478–1483PubMedGoogle Scholar
  45. 45.
    Bernstein CN, Blanchard JF, Leslie W, Wajda A, Yu N (2000) The incidence of fracture among patients with inflammatory bowel disease. A population-based cohort study. Ann Intern Med 133:795–799PubMedGoogle Scholar

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2008

Authors and Affiliations

  • A. Kuwabara
    • 1
  • K. Tanaka
    • 1
  • N. Tsugawa
    • 2
  • H. Nakase
    • 3
  • H. Tsuji
    • 4
  • K. Shide
    • 4
  • M. Kamao
    • 2
  • T. Chiba
    • 3
  • N. Inagaki
    • 4
  • T. Okano
    • 2
  • S. Kido
    • 1
  1. 1.Department of Food and NutritionKyoto Women’s UniversityHigashiyamaJapan
  2. 2.Department of Hygienic SciencesKobe Pharmaceutical UniversityKobeJapan
  3. 3.Department of Gastroenterology, Graduate School of MedicineKyoto UniversityKyotoJapan
  4. 4.Department of Diabetes and Clinical Nutrition, Graduate School of MedicineKyoto UniversityKyotoJapan

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