Journal of Bone and Mineral Metabolism

, Volume 32, Issue 2, pp 142–150 | Cite as

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

  • Noriko Koitaya
  • Mariko Sekiguchi
  • Yuko Tousen
  • Yoriko Nishide
  • Akemi Morita
  • Jun Yamauchi
  • Yuko Gando
  • Motohiko Miyachi
  • Mami Aoki
  • Miho Komatsu
  • Fumiko Watanabe
  • Koji Morishita
  • Yoshiko IshimiEmail author
Original Article


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.


MK-4 Osteocalcin Postmenopausal women Bone mineral density Pentosidine 











Dietary reference intakes


Adequate intake


Undercarboxylated OC


Bone mineral density


Total cholesterol




High density lipoprotein


Low density lipoprotein




Bone-specific alkaline phosphatase


γ-Carboxylated OC




25-Hydroxyvitamin D



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.


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Copyright information

© The Japanese Society for Bone and Mineral Research and Springer Japan 2013

Authors and Affiliations

  • Noriko Koitaya
    • 1
  • Mariko Sekiguchi
    • 2
  • Yuko Tousen
    • 1
  • Yoriko Nishide
    • 1
  • Akemi Morita
    • 2
  • Jun Yamauchi
    • 1
  • Yuko Gando
    • 3
  • Motohiko Miyachi
    • 3
  • Mami Aoki
    • 4
  • Miho Komatsu
    • 4
  • Fumiko Watanabe
    • 4
  • Koji Morishita
    • 4
  • Yoshiko Ishimi
    • 1
    Email author
  1. 1.Department of Food Function and LabelingNational Institute of Health and NutritionTokyoJapan
  2. 2.Department of Nutritional EpidemiologyNational Institute of Health and NutritionTokyoJapan
  3. 3.Department of Health Promotion and Exercise National Institute of Health and NutritionTokyoJapan
  4. 4.Healthcare Products Development Center, Kyowa Hakko Bio Co., LtdTsukubaJapan

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