A longitudinal study of the effect of vitamin K2 on bone mineral density in postmenopausal women a comparative study with vitamin D3 and estrogen–progestin therapy

Iwamoto, Ichiro; Kosha, Shoichiro; Noguchi, Shinji; Murakami, Masato; Fujino, Toshinori; Douchi, Tsutomu; Nagata, Yukihiro

doi:10.1016/s0378-5122(98)00114-5

Cited by 69 publications

(40 citation statements)

References 11 publications

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“…There are several reports indicating the pharmacological amount of MK-4 supplementation that is beneficial for OC carboxylation in healthy aged people (11,12) as well as in osteoporotic postmenopausal women (21). However, in case of insufficient daily intake of vitamin K for bone metabolism, the exact amount of MK-4 supplementation required to accelerate the carboxylation of OC in healthy postmenopausal women is unclear.…”

Section: Discussionmentioning

confidence: 99%

Effect of Low Dose Vitamin K2 (MK-4) Supplementation on Bio-Indices in Postmenopausal Japanese Women

Koitaya¹,

Ezaki²,

Nishimuta³

et al. 2009

J Nutr Sci Vitaminol

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Summary It has been reported that treatment with a pharmacological dose (45 mg/d) of menaquinone-4 (MK-4) prevents bone loss in postmenopausal women. However, it is not known whether supplementation with low dose MK-4 has beneficial effects on bone metabolism in healthy women. The aim of this study is to examine the effects of the supplementation of 1.5 mg/d MK-4 for 4 wk on bone and lipid metabolism in healthy postmenopausal Japanese women. The study was performed as a randomized double blind placebo-controlled trial. The participants aged 53-65 y were randomly assigned to 2 groups and supplemented with 1.5 mg/d of MK-4 or a placebo for 4 wk ( n ϭ 20 for each group). The most marked effects of MK-4 intake were observed on serum osteocalcin (OC) concentrations. Serum undercarboxylated OC (ucOC) concentration decreased, and the ␥ -carboxylated OC (GlaOC) and GlaOC/GlaOC ϩ ucOC ratio that indicates the degree of OC ␥ -carboxylation increased significantly at 2 and 4 wk compared with that at baseline in the MK-4 group. The serum ucOC and GlaOC concentrations in the MK-4 group were significantly different from those in the placebo group at 2 wk. These results suggest that supplementation with 1.5 mg/d MK-4 accelerated the degree of OC ␥ -carboxylation. The concentrations of serum lipids and other indices were not different between the groups at either intervention period. Thus, the additional intake of MK-4 might be beneficial in the maintenance of bone health in postmenopausal Japanese women.

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Section: Discussionmentioning

confidence: 99%

Effect of Low Dose Vitamin K2 (MK-4) Supplementation on Bio-Indices in Postmenopausal Japanese Women

Koitaya¹,

Ezaki²,

Nishimuta³

et al. 2009

J Nutr Sci Vitaminol

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“…Menatetrenone (menaquinone-4, MK-4), a vitamin K 2 with four isoprene units at the 3 position of the quinone structure, has a significant therapeutic effect on involutional osteoporosis (Orimo et al 1992, Iwamoto et al 1999. The mechanism has been elucidated by in vitro studies showing that MK-4 inhibits osteoclastogenesis in murine bone marrow culture (Akiyama et al 1994).…”

Section: Introductionmentioning

confidence: 99%

Vitamin K stimulates osteoblastogenesis and inhibits osteoclastogenesis in human bone marrow cell culture

Kinoshita

Hoshi²,

Okawara³

et al. 2003

Journal of Endocrinology

124

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Accumulating evidence indicates that menaquinone-4 (MK-4), a vitamin K 2 with four isoprene units, inhibits osteoclastogenesis in murine bone marrow culture, but the reason for this inhibition is not yet clear, especially in human bone marrow culture. To clarify the inhibitory mechanism, we investigated the differentiation of colonyforming-unit fibroblasts (CFU-Fs) and osteoclasts in human bone marrow culture, to learn whether the enhancement of the differentiation of CFU-Fs from progenitor cells might relate to inhibition of osteoclast formation. Human bone marrow cells were grown in -minimal essential medium with horse serum in the presence of MK-4 until adherent cells formed colonies (CFU-Fs). Colonies that stained positive for alkaline phosphatase activity (CFU-F/ALP + ) were considered to have osteogenic potential. MK-4 stimulated the number of CFU-F/ALP + colonies in the presence or absence of dexamethasone. The stimulation was also seen in vitamin K 1 treatment. These cells had the ability to mineralize in the presence ofglycerophosphate.In contrast, both MK-4 and vitamin K 1 inhibited 1,25 dihydroxyvitamin D 3 -induced osteoclast formation and increased stromal cell formation in human bone marrow culture. These stromal cells expressed ALP and Cbfa1. Moreover, both types of vitamin K treatment decreased the expression of receptor activator of nuclear factor B ligand/osteoclast differentiation factor (RANKL/ODF) and enhanced the expression of osteoprotegerin/osteoclast inhibitory factor (OPG/OCIF) in the stromal cells. The effective concentrations were 1·0 µM and 10 µM for the expression of RANKL/ODF and OPG/OCIF respectively.Vitamin K might stimulate osteoblastogenesis in bone marrow cells, regulating osteoclastogenesis through the expression of RANKL/ODF more than through that of OPG/OCIF.

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“…Longitudinal study proved the utility of menate trenone or MK-4 as a therapeutic agent for osteoporo sis, because it suppresses the decrease in spinal BMD in postmenopausal women (30) and reduced the urinary excretion of calcium (31). Although epidemiological study showed that either vitamin K2 intake through Natto or vitamin K1 intake through lettuce had negative correlation with hip fracture incidence (15,32), their dose-effect relationships remained unknown.…”

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confidence: 99%

Promotion of Bone Formation by Fermented Soybean (Natto) Intake in Premenopausal Women

Katsuyama¹,

Ideguchi²,

Fukunaga

et al. 2004

Journal of Nutritional Science and Vitaminology, J Nutr Sci Vit

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SummaryA therapeutic agent of vitamin K2 is approved for the treatment of osteoporosis in Japan. However, little is known about the efficacy of dietary intake of vitamin K2 for bone health. We compared the effects of various levels of fermented soybeans (Natto) intake , which contains plenty of vitamin K2, on bone stiffness and bone turnover markers in healthy premenopausal women, Seventy-three healthy premenopausal women were ran domly divided into four groups matched for age and parity categories . Natto was supplied as follows: Group 1(no intake), Group 2 (once per month), Group 3 (once per week) and Group 4 (three times per week). Subjects took Natto at a lunch for 1 y , and the stiffness index by quantitative ultrasound and bone turnover markers were assessed at baseline, 6 mo and 1 y There was no statistical difference in the stiffness index during the 1 y observation . How ever, bone specific alkaline phosphatase (BAP) in Group 4 was higher than that in Group 3 at 1 y and undercarboxylated osteocalcin (Glu) in Group 4 was significantly lower than those in Groups 1, 2 and 3 at 6 mo. Logistic regression analysis showed that the risk of reduction of bone formation markers declined to 0.07 in Group 4 based on that in Group 1 . In premenopausal women who had to keep the stiffness index as high as possible before menopause, Natto intake may have contributed to the promotion of bone formation .

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A longitudinal study of the effect of vitamin K2 on bone mineral density in postmenopausal women a comparative study with vitamin D3 and estrogen–progestin therapy

Cited by 69 publications

References 11 publications

Effect of Low Dose Vitamin K2 (MK-4) Supplementation on Bio-Indices in Postmenopausal Japanese Women

Effect of Low Dose Vitamin K2 (MK-4) Supplementation on Bio-Indices in Postmenopausal Japanese Women

Vitamin K stimulates osteoblastogenesis and inhibits osteoclastogenesis in human bone marrow cell culture

Promotion of Bone Formation by Fermented Soybean (Natto) Intake in Premenopausal Women

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