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Low-dose vitamin K2 (MK-4) supplementation for 12 months improves bone metabolism and prevents forearm bone loss in postmenopausal Japanese women

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Abstract

Menaquinone-4 (MK-4) administered at a pharmacological dosage of 45 mg/day has been used for the treatment of osteoporosis in Japan. However, it is not known whether a lower dose of MK-4 supplementation is beneficial for bone health in healthy postmenopausal women. The aim of this study was to examine the long-term effects of 1.5-mg daily supplementation of MK-4 on the various markers of bone turnover and bone mineral density (BMD). The study was performed as a randomized, double-blind, placebo-controlled trial. The participants (aged 50–65 years) were randomly assigned to one of two groups according to the MK-4 dose received: the placebo-control group (n = 24) and the 1.5-mg MK-4 group (n = 24). The baseline concentrations of undercarboxylated osteocalcin (ucOC) were high in both groups (>5.1 ng/ml). After 6 and 12 months, the serum ucOC concentrations were significantly lower in the MK-4 group than in the control group. In the control group, there was no significant change in serum pentosidine concentrations. However, in the MK-4 group, the concentration of pentosidine at 6 and 12 months was significantly lower than that at baseline. The forearm BMD was significantly lower after 12 months than at 6 months in the control group. However, there was no significant decrease in BMD in the MK-4 group during the study period. These results suggest that low-dose MK-4 supplementation for 6–12 months improved bone quality in the postmenopausal Japanese women by decreasing the serum ucOC and pentosidine concentrations, without any substantial adverse effects.

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Abbreviations

Gla:

γ-Carboxyglutaminate

PK:

Phylloquionone

MK:

Menaquinone

OC:

Osteocalcin

DRIs:

Dietary reference intakes

AI:

Adequate intake

ucOC:

Undercarboxylated OC

BMD:

Bone mineral density

TC:

Total cholesterol

TG:

Triacylglycerol

HDL:

High density lipoprotein

LDL:

Low density lipoprotein

E2 :

17β-Estradiol

BS-ALP:

Bone-specific alkaline phosphatase

GlaOC:

γ-Carboxylated OC

DPD:

Deoxypiridinoline

25[OH]D:

25-Hydroxyvitamin D

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Acknowledgments

We gratefully acknowledge the dedicated women who participated in this study. This study was supported by a grant from the National Institute of Health and Nutrition, Ministry of Health, Labor and Welfare, Japan and KYOWA HAKKO BIO. Co., Ltd.

Conflict of interest

The authors have no conflicts of interest to declare.

Author information

Authors and Affiliations

  1. Department of Food Function and Labeling, National Institute of Health and Nutrition, 1-23-1 Toyama, Shinjyuku-ku, Tokyo, Japan

    Noriko Koitaya, Yuko Tousen, Yoriko Nishide, Jun Yamauchi & Yoshiko Ishimi

  2. Department of Nutritional Epidemiology, National Institute of Health and Nutrition, Shinjyuku-ku, Tokyo, Japan

    Mariko Sekiguchi & Akemi Morita

  3. Department of Health Promotion and Exercise , National Institute of Health and Nutrition, Shinjyuku-ku, Tokyo, Japan

    Yuko Gando & Motohiko Miyachi

  4. Healthcare Products Development Center, Kyowa Hakko Bio Co., Ltd, Tsukuba, Ibaraki, Japan

    Mami Aoki, Miho Komatsu, Fumiko Watanabe & Koji Morishita

Authors
  1. Noriko Koitaya
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  2. Mariko Sekiguchi
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  3. Yuko Tousen
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  4. Yoriko Nishide
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  13. Yoshiko Ishimi
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Corresponding author

Correspondence to Yoshiko Ishimi.

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Koitaya, N., Sekiguchi, M., Tousen, Y. et al. Low-dose vitamin K2 (MK-4) supplementation for 12 months improves bone metabolism and prevents forearm bone loss in postmenopausal Japanese women. J Bone Miner Metab 32, 142–150 (2014). https://doi.org/10.1007/s00774-013-0472-7

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  • DOI: https://doi.org/10.1007/s00774-013-0472-7

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