Low-dose Vitamin K2 (MK-4) Supplementation for 12 Months Improves Bone Metabolism and Prevents Forearm Bone Loss in Postmenopausal Japanese Women

Overview

Journal J Bone Miner Metab

Specialty Endocrinology

Date 2013 May 25

PMID 23702931

Citations 19

Authors

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 Ishimi

Affiliations

Soon will be listed here.

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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References

Tsugawa N, Shiraki M, Suhara Y, Kamao M, Ozaki R, Tanaka K . Low plasma phylloquinone concentration is associated with high incidence of vertebral fracture in Japanese women. J Bone Miner Metab. 2007; 26(1):79-85. DOI: 10.1007/s00774-007-0790-8. View

Tsugawa N, Shiraki M, Suhara Y, Kamao M, Tanaka K, Okano T . Vitamin K status of healthy Japanese women: age-related vitamin K requirement for gamma-carboxylation of osteocalcin. Am J Clin Nutr. 2006; 83(2):380-6. DOI: 10.1093/ajcn/83.2.380. View

Sokoll L, Sadowski J . Comparison of biochemical indexes for assessing vitamin K nutritional status in a healthy adult population. Am J Clin Nutr. 1996; 63(4):566-73. DOI: 10.1093/ajcn/63.4.566. View

Kaneki M, Hodges S, Hedges S, Hosoi T, Fujiwara S, Lyons A . Japanese fermented soybean food as the major determinant of the large geographic difference in circulating levels of vitamin K2: possible implications for hip-fracture risk. Nutrition. 2001; 17(4):315-21. DOI: 10.1016/s0899-9007(00)00554-2. View

Vervoort L, Ronden J, Thijssen H . The potent antioxidant activity of the vitamin K cycle in microsomal lipid peroxidation. Biochem Pharmacol. 1997; 54(8):871-6. DOI: 10.1016/s0006-2952(97)00254-2. View

Ozuru R, Sugimoto T, Yamaguchi T, Chihara K . Time-dependent effects of vitamin K2 (menatetrenone) on bone metabolism in postmenopausal women. Endocr J. 2002; 49(3):363-70. DOI: 10.1507/endocrj.49.363. View

Wang X, Shen X, Li X, Agrawal C . Age-related changes in the collagen network and toughness of bone. Bone. 2002; 31(1):1-7. DOI: 10.1016/s8756-3282(01)00697-4. View

Langenberg J, Tjaden U . Improved method for the determination of vitamin K1 epoxide in human plasma with electrofluorimetric reaction detection. J Chromatogr. 1984; 289:377-85. DOI: 10.1016/s0021-9673(00)95103-3. View

Knapen M, Schurgers L, Vermeer C . Vitamin K2 supplementation improves hip bone geometry and bone strength indices in postmenopausal women. Osteoporos Int. 2007; 18(7):963-72. PMC: 1915640. DOI: 10.1007/s00198-007-0337-9. View

10.

Ishida Y, Kawai S . RETRACTED: Comparative efficacy of hormone replacement therapy, etidronate, calcitonin, alfacalcidol, and vitamin K in postmenopausal women with osteoporosis: The Yamaguchi Osteoporosis Prevention Study. Am J Med. 2004; 117(8):549-55. DOI: 10.1016/j.amjmed.2004.05.019. View

11.

Knapen M, Nieuwenhuijzen Kruseman A, Wouters R, Vermeer C . Correlation of serum osteocalcin fractions with bone mineral density in women during the first 10 years after menopause. Calcif Tissue Int. 1998; 63(5):375-9. DOI: 10.1007/s002239900543. View

12.

Szulc P, CHAPUY M, Meunier P, Delmas P . Serum undercarboxylated osteocalcin is a marker of the risk of hip fracture in elderly women. J Clin Invest. 1993; 91(4):1769-74. PMC: 288157. DOI: 10.1172/JCI116387. View

13.

Vermeer C . Gamma-carboxyglutamate-containing proteins and the vitamin K-dependent carboxylase. Biochem J. 1990; 266(3):625-36. PMC: 1131186. DOI: 10.1042/bj2660625. View

14.

Cockayne S, Adamson J, Lanham-New S, Shearer M, Gilbody S, Torgerson D . Vitamin K and the prevention of fractures: systematic review and meta-analysis of randomized controlled trials. Arch Intern Med. 2006; 166(12):1256-61. DOI: 10.1001/archinte.166.12.1256. View

15.

Zhang Y, Zhou P, Kimondo J . Adiponectin and osteocalcin: relation to insulin sensitivity. Biochem Cell Biol. 2012; 90(5):613-20. DOI: 10.1139/o2012-022. View

16.

Takahashi M, Naitou K, Ohishi T, Kushida K, Miura M . Effect of vitamin K and/or D on undercarboxylated and intact osteocalcin in osteoporotic patients with vertebral or hip fractures. Clin Endocrinol (Oxf). 2001; 54(2):219-24. DOI: 10.1046/j.1365-2265.2001.01212.x. View

17.

Roux C, Arabi A, Porcher R, Garnero P . Serum leptin as a determinant of bone resorption in healthy postmenopausal women. Bone. 2003; 33(5):847-52. DOI: 10.1016/j.bone.2003.07.008. View

18.

Knapen M, Jie K, Hamulyak K, Vermeer C . Vitamin K-induced changes in markers for osteoblast activity and urinary calcium loss. Calcif Tissue Int. 1993; 53(2):81-5. DOI: 10.1007/BF01321883. View

19.

Okano T, Shimomura Y, Yamane M, Suhara Y, Kamao M, Sugiura M . Conversion of phylloquinone (Vitamin K1) into menaquinone-4 (Vitamin K2) in mice: two possible routes for menaquinone-4 accumulation in cerebra of mice. J Biol Chem. 2007; 283(17):11270-9. DOI: 10.1074/jbc.M702971200. View

20.

Zhang H, Xie H, Zhao Q, Xie G, Wu X, Liao E . Relationships between serum adiponectin, apelin, leptin, resistin, visfatin levels and bone mineral density, and bone biochemical markers in post-menopausal Chinese women. J Endocrinol Invest. 2010; 33(10):707-11. DOI: 10.1007/BF03346674. View