Serum undercarboxylated osteocalcin is a marker of the risk of hip fracture in elderly women.

Szulc, Paweł; Chapuy, M. C.; Meunier, Pierre J.; Delmas, PD

doi:10.1172/jci116387

Cited by 456 publications

(270 citation statements)

References 43 publications

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“…ucOC is a sensitive functional marker for vitamin K status [8]. Elevated concentrations of ucOC are associated with vitamin K deficiency and an increased risk of hip fractures [5,13,14,35,36]. Supplementation with vitamin K 2 promotes a decrease in ucOC, suggesting that vitamin K 2 contributes to OC carboxylation [9,37].…”

Section: Discussionmentioning

confidence: 99%

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Bioavailability and Chemical/Functional Aspects of Synthetic MK-7 vs Fermentation-Derived MK-7 in Randomised Controlled Trials

Møller

Gjelstad

Baksaas³

et al. 2017

International Journal for Vitamin and Nutrition Research

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Abstract:We investigated the bioavailability of a synthetic form of the vitamin K 2 molecule menaquinone-7 (MK-7) in a randomised single-blinded two-way cross-over study. Healthy subjects (20 -66 years of age) took a single 180 µg dose of synthetic MK-7 or fermentation-derived MK-7, and serum MK-7 concentrations were monitored for 72 hours to calculate AUC(0 -72 h) and C max . We also compared the biological effects of placebo, fermentation-derived MK-7 (90 µg) and 3 doses of synthetic MK-7 (45, 90 and 180 µg) in a randomised double-blinded parallel study. Healthy subjects (20 -60 years of age) took one of the supplements daily for 43 days, and the fraction of carboxylated osteocalcin (OC) was compared between day 1 and day 43 as a marker for vitamin K activity. In the bioavailability study, the 90 % confidence interval for the ratio of the AUC(0-72 h) values for synthetic and fermentationderived MK-7 was 83 -111, indicating bioequivalence. The 90 % confidence interval for the Cmax ratio was 83 -131. The serum concentrations of carboxylated OC and undercarboxylated OC were increased (p = 0.01) and reduced (p = 0.02), respectively, after daily intake of 180 µg of synthetic MK-7 for 43 days, indicating increased vitamin K activity. Across both studies, only 1 participant reported an adverse event (dry mouth; 180 µg synthetic MK-7 group, functional study) that was considered possibly related to synthetic MK-7 supplementation. Our findings provide evidence that the tested synthetic form of MK-7 is bioequivalent to fermentation-derived MK-7, exhibits vitamin K activity and is well tolerated in healthy subjects.

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Section: Discussionmentioning

confidence: 99%

“…Increased vitamin K intake causes a rapid decline in undercarboxylated OC (ucOC) [8,12], suggesting possible subclinical vitamin K deficiency in "healthy" bone tissue [4]. A high serum concentration of ucOC is correlated with an increased risk of hip fractures [13,14].…”

Section: Introductionmentioning

confidence: 99%

Bioavailability and Chemical/Functional Aspects of Synthetic MK-7 vs Fermentation-Derived MK-7 in Randomised Controlled Trials

Møller

Gjelstad

Baksaas³

et al. 2017

International Journal for Vitamin and Nutrition Research

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“…Elevated %ucOC has been associated with lower bone mineral density in elderly men and women (Booth et al, 2004). Low vitamin D status has also been associated with an elevated %ucOC (Szulc et al, 1993), although this association remains unconfirmed.…”

Section: Introductionmentioning

confidence: 99%

Genetic and non-genetic correlates of vitamins K and D

et al. 2007

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Objective: To assess the genetic and nongenetic correlates of circulating measures of vitamins K and D status in a communitybased sample of men and women. Subjects/Methods: A cross-sectional study of 1762 participants of the Framingham Offspring Study (919 women; mean age 59 years). Vitamin K status was measured as plasma phylloquinone and serum percent undercarboxylated osteocalcin (ucOC), and vitamin D was measured using plasma 25-hydroxyvitamin D (25(OH)D). Associations between vitamin K status and vitamin D status with biologically plausible nongenetic factors were assessed using stepwise regression. Heritability and linkage were determined using Sequential Oligogenic Linkage Analysis Routines (SOLAR). Results: Nongenetic factors accounted for 20.1 and 12.3% of the variability in plasma phylloquinone in men and women respectively, with triglycerides and phylloquinone intake being the primary correlates. In men 12.2% and in women 14.6% of the variability in %ucOC was explained by nongenetic factors in our models. Heritability estimates for these vitamin K status biomarkers were nonsignificant. Season, vitamin D intake, high-density lipoprotein (HDL) cholesterol and waist circumference explained 24.7% (men) and 24.2% (women) of the variability in plasma 25(OH)D. Of the three vitamins examined, only 25(OH)D was significantly heritable (heritability estimate ¼ 28.8%, Po0.01), but linkage analysis of 25(OH)D did not achieve genome-wide significance. Conclusions: Variability in biomarkers of vitamin K status was attributed to nongenetic factors, whereas plasma 25(OH)D was found to be significantly heritable. Further studies are warranted to investigate genetic loci influencing vitamin D status.

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“…Subclinical vitamin K deficiency, indicated by undercarboxylation of plasma osteocalcin, has been implicated in the pathogenesis of osteoporotic fracture in most investigations (Szulc et al, 1993;Binkley & Suttie 1995;Vergnaud et al, 1997;Shiraki et al, 2000). Osteocalcin is the most abundant noncollagenous protein of bone.…”

Section: Introductionmentioning

confidence: 99%

Ethnic differences in osteocalcin γ-carboxylation, plasma phylloquinone (vitamin K1) and apolipoprotein E genotype

et al. 2004

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Objective: To investigate plasma osteocalcin g-carboxylation and its relationship to plasma phylloquinone concentration and apolipoprotein E (apoE) genotype in women from three ethnic groups with differing osteoporotic fracture risk. Design and subjects: Fasted blood samples were collected from postmenopausal Gambian (n ¼ 50), British (n ¼ 31) and Chinese women (n ¼ 23), and 11 premenopausal women in each group from three cross-sectional studies. Results: After adjustment for total osteocalcin, plasma undercarboxylated osteocalcin (adjusted ucOC) was lowest in Chinese and highest in British women postmenopause (British vs Chinese 103% higher, Po0.0001; Gambian vs Chinese 66% higher, Po0.01). No differences were observed premenopause. Within each ethnic group, adjusted ucOC was similar pre-and postmenopause. Postmenopause, plasma phylloquinone was higher in Chinese women (1.0 ng/ml) than in British (0.31 ng/ml) and Gambian women (0.36 ng/ml) (Po0.0001). Premenopause, plasma phylloquinone was higher in Gambian and Chinese women (0.6 ng/ml) than in British women (0.3 ng/ml; P ¼ 0.01). Plasma phylloquinone and adjusted ucOC were inversely related in postmenopausal British women (R 2 ¼ 32.4%; P ¼ 0.0008). ApoE4 frequency was Gambian 32.6%, British 13.8% and Chinese 6%. A lower adjusted ucOC was associated with apoE2 genotype in British and Chinese women. Ethnic differences in adjusted ucOC persisted after adjustment for phylloquinone and apoE genotype. Conclusion: These preliminary data indicate suboptimal vitamin K status in postmenopausal British compared to Chinese and Gambian women. Ethnic differences in apoE genotype may also influence osteocalcin g-carboxylation status. The study highlights the need for larger epidemiological investigations of ethnic differences in vitamin K status and the possible implications to bone health. Sponsorship: This work was funded by the MRC.

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Serum undercarboxylated osteocalcin is a marker of the risk of hip fracture in elderly women.

Cited by 456 publications

References 43 publications

Bioavailability and Chemical/Functional Aspects of Synthetic MK-7 vs Fermentation-Derived MK-7 in Randomised Controlled Trials

Bioavailability and Chemical/Functional Aspects of Synthetic MK-7 vs Fermentation-Derived MK-7 in Randomised Controlled Trials

Genetic and non-genetic correlates of vitamins K and D

Ethnic differences in osteocalcin γ-carboxylation, plasma phylloquinone (vitamin K1) and apolipoprotein E genotype

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