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. 2001 Apr;48(4):473–477. doi: 10.1136/gut.48.4.473

Low serum and bone vitamin K status in patients with longstanding Crohn's disease: another pathogenetic factor of osteoporosis in Crohn's disease?

E Schoon 1, M Muller 1, C Vermeer 1, L Schurgers 1, R Brummer 1, R Stockbrugger 1
PMCID: PMC1728221  PMID: 11247890

Abstract

BACKGROUND—A high prevalence of osteoporosis is reported in Crohn's disease. The pathogenesis is not completely understood but is probably multifactorial. Longstanding Crohn's disease is associated with a deficiency of fat soluble vitamins, among them vitamin K. Vitamin K is a cofactor in the carboxylation of osteocalcin, a protein essential for calcium binding to bone. A high level of circulating uncarboxylated osteocalcin is a sensitive marker of vitamin K deficiency.
AIMS—To determine serum and bone vitamin K status in patients with Crohn's disease and to elucidate its relationship with bone mineral density.
METHODS—Bone mineral density was measured in 32 patients with longstanding Crohn's disease and small bowel involvement, currently in remission, and receiving less than 5 mg of prednisolone daily. Serum levels of vitamins D and K, triglycerides, and total immunoreactive osteocalcin, as well as uncarboxylated osteocalcin ("free" osteocalcin) were determined. The hydroxyapatite binding capacity of osteocalcin was calculated. Data were compared with an age and sex matched control population.
RESULTS—Serum vitamin K levels of CD patients were significantly decreased compared with normal controls (p<0.01). "Free" osteocalcin was higher and hydroxyapatite binding capacity of circulating osteocalcin was lower than in matched controls (p<0.05 and p<0.001, respectively), indicating a low bone vitamin K status in Crohn's disease. In patients, an inverse correlation was found between "free" osteocalcin and lumbar spine bone mineral density (r=−0.375, p<0.05) and between "free" osteocalcin and the z score of the lumbar spine (r=−0.381, p<0.05). Multiple linear regression analysis showed that "free" osteocalcin was an independent risk factor for low bone mineral density of the lumbar spine whereas serum vitamin D was not.
CONCLUSIONS—The finding that a poor vitamin K status is associated with low bone mineral density in longstanding Crohn's disease may have implications for the prevention and treatment of osteoporosis in this disorder.


Keywords: Crohn's disease; bone mineral density; vitamin K; osteocalcin

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Figure 1  .

Figure 1  

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Schematic representation of the vitamin K dependent carboxylation reaction. Reduced vitamin K acts as a cofactor in the carboxylation of glutamic acid residues (Glu) into gamma carboxylation acid residues (Gla). These residues render the protein osteocalcin capable of calcium binding to bone.

Figure 2  .

Figure 2  

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Serum vitamin K concentrations in patients with longstanding Crohn's disease (n=32) compared with healthy controls (n=34). Median for patients with Crohn's disease is 0.402 ng/ml; median for healthy controls is 0.610 ng/ml.

Figure 3  .

Figure 3  

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Serum concentrations of "free" (uncarboxylated) osteocalcin in patients with longstanding Crohn's disease (n=32) compared with age and sex matched healthy controls (n=34). Lines indicate median values. Median for patients with Crohn's disease is 3.89 ng/ml; median for healthy controls is 1.51 ng/ml.

Figure 4  .

Figure 4  

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Hydroxyapatite binding capacity in patients with longstanding Crohn's disease (n=32) compared with age and sex matched healthy controls (n=34). Lines indicate median values. Median for patients with Crohn's disease is 61.71%; median for healthy controls is 76.84%.

Figure 5  .

Figure 5  

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Correlation between "free" (uncarboxylated) osteocalcin and bone mineral density (BMD) of the lumbar spine in patients with longstanding Crohn's disease (n=32). Correlation coefficient (Pearson's) r=−0.375; p<0.05.

Figure 6  .

Figure 6  

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Correlation of "free" (uncarboxylated) osteocalcin and bone mineral density z score of the lumbar spine in patients with longstanding Crohn's disease (n=32). Correlation coefficient (Pearson's) r=−0.381; p<0.01.

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