Vitamin K, vertebral fractures, vascular calcifications, and mortality: VItamin K Italian (VIKI) dialysis study

Maria Fusaro, Marianna Noale, Valentina Viola, Francesco Galli, Giovanni Tripepi, Nicola Vajente, Mario Plebani, Martina Zaninotto, Giuseppe Guglielmi, Diego Miotto, Luca Dalle Carbonare, Angela D'Angelo, Agostino Naso, Cristina Grimaldi, Davide Miozzo, Sandro Giannini, Maurizio Gallieni

Research output: Contribution to journalArticle

70 Citations (Scopus)

Abstract

Vitamin K (vitamin K1 or phylloquinone and vitamin K2, a series of menaquinones [MKs]) is involved in the production of bone and matrix amino acid γ-carboxy-glutamic acid (Gla) proteins, regulating bone and vascular calcification. Low vitamin K concentrations are associated with increased risks of fractures and vascular calcification, and frequent complications in hemodialysis patients. We carried out an observational study to establish the prevalence of vitamin K deficiency and to assess the relationship between vitamin K status, vertebral fractures, vascular calcification, and survival in 387 patients on hemodialysis for ≤1 year. We determined plasma levels of vitamin K compound, bone-Gla-protein, matrix-Gla-protein, and routine biochemistry. Vertebral fractures (reduction in vertebral body height by ≤20%) and aortic and iliac calcifications were also investigated in a spine (D5-L4) radiograph. Three-year patient survival was analyzed. Important proportions of patients had deficiency of MK7 (35.4%), vitamin K1 (23.5%), and MK4 (14.5%). A total of 55.3% of patients had vertebral fractures, 80.6% had abdominal aorta calcification, and 56.1% had iliac calcification. Vitamin K1 deficiency was the strongest predictor of vertebral fractures (odds ratio [OR], 2.94; 95% confidence interval [CI], 1.38-6.26). MK4 deficiency was a predictor of aortic calcification (OR, 2.82; 95% CI, 1.14-7.01), whereas MK5 deficiency actually protected against it (OR, 0.38; 95% CI, 0.15-0.95). MK7 deficiency was a predictor of iliac calcification (OR, 1.64; 95% CI, 1.03-2.60). The presence of vertebral fractures was also a predictor of vascular calcifications (OR, 1.76; 95% CI, 1.00-3.08). Increased alkaline phosphatase and C reactive protein (CRP), age, and cerebrovascular events were predictors of mortality. Our study suggests that the vitamin K system may be important for preserving bone mass and avoiding vascular calcification in hemodialysis patients, pointing out a possible role of vitamin K in bone and vascular health. Based on our results, we suggest that the general population should also be studied for vitamin K deficiency as a possible cause of both vertebral fractures and vascular calcification.

Original languageEnglish
Pages (from-to)2271-2278
Number of pages8
JournalJournal of Bone and Mineral Research
Volume27
Issue number11
DOIs
Publication statusPublished - Nov 2012

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Vascular Calcification
Vitamin K
Vitamin K 1
Dialysis
Odds Ratio
Confidence Intervals
Mortality
Vitamin K Deficiency
Renal Dialysis
Vitamin K 2
Bone and Bones
Glutamic Acid
Avitaminosis
Fracture Fixation
Bone Matrix
Proteins
Body Height
Survival
Abdominal Aorta
Biochemistry

Keywords

  • BONE
  • CALCIFICATION
  • DIALYSIS
  • MENAQUINONE
  • PHYLLOQUINONE

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Vitamin K, vertebral fractures, vascular calcifications, and mortality : VItamin K Italian (VIKI) dialysis study. / Fusaro, Maria; Noale, Marianna; Viola, Valentina; Galli, Francesco; Tripepi, Giovanni; Vajente, Nicola; Plebani, Mario; Zaninotto, Martina; Guglielmi, Giuseppe; Miotto, Diego; Dalle Carbonare, Luca; D'Angelo, Angela; Naso, Agostino; Grimaldi, Cristina; Miozzo, Davide; Giannini, Sandro; Gallieni, Maurizio.

In: Journal of Bone and Mineral Research, Vol. 27, No. 11, 11.2012, p. 2271-2278.

Research output: Contribution to journalArticle

Fusaro, M, Noale, M, Viola, V, Galli, F, Tripepi, G, Vajente, N, Plebani, M, Zaninotto, M, Guglielmi, G, Miotto, D, Dalle Carbonare, L, D'Angelo, A, Naso, A, Grimaldi, C, Miozzo, D, Giannini, S & Gallieni, M 2012, 'Vitamin K, vertebral fractures, vascular calcifications, and mortality: VItamin K Italian (VIKI) dialysis study', Journal of Bone and Mineral Research, vol. 27, no. 11, pp. 2271-2278. https://doi.org/10.1002/jbmr.1677
Fusaro, Maria ; Noale, Marianna ; Viola, Valentina ; Galli, Francesco ; Tripepi, Giovanni ; Vajente, Nicola ; Plebani, Mario ; Zaninotto, Martina ; Guglielmi, Giuseppe ; Miotto, Diego ; Dalle Carbonare, Luca ; D'Angelo, Angela ; Naso, Agostino ; Grimaldi, Cristina ; Miozzo, Davide ; Giannini, Sandro ; Gallieni, Maurizio. / Vitamin K, vertebral fractures, vascular calcifications, and mortality : VItamin K Italian (VIKI) dialysis study. In: Journal of Bone and Mineral Research. 2012 ; Vol. 27, No. 11. pp. 2271-2278.
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T2 - VItamin K Italian (VIKI) dialysis study

AU - Fusaro, Maria

AU - Noale, Marianna

AU - Viola, Valentina

AU - Galli, Francesco

AU - Tripepi, Giovanni

AU - Vajente, Nicola

AU - Plebani, Mario

AU - Zaninotto, Martina

AU - Guglielmi, Giuseppe

AU - Miotto, Diego

AU - Dalle Carbonare, Luca

AU - D'Angelo, Angela

AU - Naso, Agostino

AU - Grimaldi, Cristina

AU - Miozzo, Davide

AU - Giannini, Sandro

AU - Gallieni, Maurizio

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N2 - Vitamin K (vitamin K1 or phylloquinone and vitamin K2, a series of menaquinones [MKs]) is involved in the production of bone and matrix amino acid γ-carboxy-glutamic acid (Gla) proteins, regulating bone and vascular calcification. Low vitamin K concentrations are associated with increased risks of fractures and vascular calcification, and frequent complications in hemodialysis patients. We carried out an observational study to establish the prevalence of vitamin K deficiency and to assess the relationship between vitamin K status, vertebral fractures, vascular calcification, and survival in 387 patients on hemodialysis for ≤1 year. We determined plasma levels of vitamin K compound, bone-Gla-protein, matrix-Gla-protein, and routine biochemistry. Vertebral fractures (reduction in vertebral body height by ≤20%) and aortic and iliac calcifications were also investigated in a spine (D5-L4) radiograph. Three-year patient survival was analyzed. Important proportions of patients had deficiency of MK7 (35.4%), vitamin K1 (23.5%), and MK4 (14.5%). A total of 55.3% of patients had vertebral fractures, 80.6% had abdominal aorta calcification, and 56.1% had iliac calcification. Vitamin K1 deficiency was the strongest predictor of vertebral fractures (odds ratio [OR], 2.94; 95% confidence interval [CI], 1.38-6.26). MK4 deficiency was a predictor of aortic calcification (OR, 2.82; 95% CI, 1.14-7.01), whereas MK5 deficiency actually protected against it (OR, 0.38; 95% CI, 0.15-0.95). MK7 deficiency was a predictor of iliac calcification (OR, 1.64; 95% CI, 1.03-2.60). The presence of vertebral fractures was also a predictor of vascular calcifications (OR, 1.76; 95% CI, 1.00-3.08). Increased alkaline phosphatase and C reactive protein (CRP), age, and cerebrovascular events were predictors of mortality. Our study suggests that the vitamin K system may be important for preserving bone mass and avoiding vascular calcification in hemodialysis patients, pointing out a possible role of vitamin K in bone and vascular health. Based on our results, we suggest that the general population should also be studied for vitamin K deficiency as a possible cause of both vertebral fractures and vascular calcification.

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KW - BONE

KW - CALCIFICATION

KW - DIALYSIS

KW - MENAQUINONE

KW - PHYLLOQUINONE

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