Korean J Nutr.  2011 Jun;44(3):189-195. 10.4163/kjn.2011.44.3.189.

Effect of Dietary Vitamin K2 Supplementation on Bone Mineral Density in Ovariectomized Rats

• Choi MJ
• Kim MS

• KMID: 2268507
• DOI: http://doi.org/10.4163/kjn.2011.44.3.189

Abstract

Vitamin K has been suggested to plays a role in bone metabolism. The objective of this study was to determine whether vitamin K2 supplementation is related to bone mineral density, bone formation markers, and bone resorption in ovariectomized (OVX) rats. Forty Sprague-Dawley female rats (body weight, 200 +/- 10 g) were divided into four groups: a sham group fed a control diet, a sham group fed a vitamin K2 supplemented diet, OVX fed a control diet, and OVX fed a vitamin K2 supplemented diet (3.5 mg vitamin K2/kg diet). All rats were fed the experimental diets for 6 weeks, and deionized water was provided ad libitum. Serum alkaline phosphatase activity (ALP), osteocalcin, and urinary deoxypyridinoline crosslink values were measured as markers of bone formation and resorption. Bone mineral density (BMD) and bone mineral content were measured in the spine and femur using PIXImus (GE Lunar Co., Madison, WI, USA). No significant differences in body weight gain, food intake, or food efficiency ratio were observed between the control and experimental groups. Serum ALP, osteocalcin, and urinary crosslink values were not significantly different between the vitamin K2 supplemented groups. No significant differences were observed for any of the variables in the sham group. Spine BMD values were significantly lower in the OVX than those in the sham groups. Spine and femur BMD per weight of vitamin K2 tended to be higher than the control diet group within the OVX group, but no significant differences were observed. In conclusion, dietary vitamin K2 supplementation may have a beneficial effect on spine and femur BMD in OVX rats. Further research is needed to understand the potential benefits of vitamin K2 on bone loss in OVX rats.

Keyword

vitamin K2; BMD; BMC; ovariectomized rats

MeSH Terms

Alkaline Phosphatase
Amino Acids
Animals
Body Weight
Bone Density
Bone Resorption
Diet
Eating
Female
Femur
Humans
Osteocalcin
Osteogenesis
Rats
Salicylamides
Spine
Vitamin K
Vitamin K 2
Vitamins
Water
Alkaline Phosphatase
Amino Acids
Osteocalcin
Salicylamides
Vitamin K
Vitamin K 2
Vitamins
Water

Reference

1. Koshihara Y, Hoshi K, Okawara R, Ishibashi H, Yamamoto S. Vitamin K stimulates osteoblastogenesis and inhibits osteoclastogenesis in human bone marrow cell culture. J Endocrinol. 2003. 176(3):339–348.

2. Orimo H, Shiraki M, Tomita A, Morii H, Fujita T, Ohata M. Effects of menatetrenone on the bone and calcium metabolism in osteoporosis: a double-blind placebo-controlled study. J Bone Miner Metab. 1998. 16(2):106–112.

3. Hong JY, Choue R. The effects of vitamin K supplements on serum osteocalcin carboxylation in postmenopausal women. Korean J Nutr. 1999. 32(6):726–731.

4. Kalkwarf HJ, Khoury JC, Bean J, Elliot JG. Vitamin K, bone turnover, and bone mass in girls. Am J Clin Nutr. 2004. 80(4):1075–1080.

5. Booth SL, Broe KE, Gagnon DR, Tucker KL, Hannan MT, McLean RR, Dawson-Hughes B, Wilson PW, Cupples LA, Kiel DP. Vitamin K intake and bone mineral density in women and men. Am J Clin Nutr. 2003. 77(2):512–516.

6. Kanai T, Takagi T, Masuhiro K, Nakamura M, Iwata M, Saji F. Serum vitamin K level and bone mineral density in post-menopausal women. Int J Gynaecol Obstet. 1997. 56(1):25–30.

7. Shiraki M, Shiraki Y, Aoki C, Miura M. Vitamin K₂ (menatetrenone) effectively prevents fractures and sustains lumbar bone mineral density in osteoporosis. J Bone Miner Res. 2000. 15(3):515–521.

8. Iwamoto I, Kosha S, Noguchi S, Murakami M, Fujino T, Douchi T, Nagata Y. 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. Maturitas. 1999. 31(2):161–164.

9. Hong JY, Choue R. Correlation of dietary vitamin K intakes and bone mineral density in postmenopausal women. Korean J Nutr. 1997. 30(3):299–306.

10. Iwamoto J, Yeh JK, Takeda T, Ichimura S, Sato Y. Comparative effects of vitamin K and vitamin D supplementation on prevention of osteopenia in calcium-deficient young rats. Bone. 2003. 33(4):557–566.

11. Koshihara Y, Hoshi K. Vitamin K2 enhances osteocalcin accumulation in the extracellular matrix of human osteoblasts in vitro. J Bone Miner Res. 1997. 12(3):431–438.

12. Iwamoto J, Takeda T, Ichimura S, Sato Y, Yeh JK. Differential effect of vitamin K and vitamin D supplementation on bone mass in young rats fed normal or low calcium diet. Yonsei Med J. 2004. 45(2):314–324.

13. Iwamoto J, Yeh JK, Takeda T, Sato Y. Effects of vitamin K₂ administration on calcium balance and bone mass in young rats fed normal or low calcium diet. Horm Res. 2005. 63(5):211–219.

14. Hara K, Kobayashi M, Akiyama Y. Vitamin K₂ (menatetrenone) inhibits bone loss induced by prednisolone partly through enhancement of bone formation in rats. Bone. 2002. 31(5):575–581.

15. Binkley N, Krueger D, Engelke J, Crenshaw T, Suttie J. Vitamin K supplementation does not affect ovariectomy-induced bone loss in rats. Bone. 2002. 30(6):897–900.

16. Mawatari T, Miura H, Higaki H, Moro-Oka T, Kurata K, Murakami T, Iwamoto Y. Effect of vitamin K₂ on three-dimensional trabecular microarchitecture in ovariectomized rats. J Bone Miner Res. 2000. 15(9):1810–1817.

17. Akiyama Y, Hara K, Ohkawa I, Tajima T. Effects of menatetrenone on bone loss induced by ovariectomy in rats. Jpn J Pharmacol. 1993. 62(2):145–153.

18. Iwamoto J, Takeda T, Yeh JK, Ichimura S, Toyama Y. Effect of vitamin K₂ on cortical and cancellous bones in orchidectomized young rats. Maturitas. 2003. 44(1):19–27.

19. Onodera K, Takahashi A, Sakurada S, Okano Y. Effects of phenytoin and/or vitamin K₂ (menatetrenone) on bone mineral density in the tibiae of growing rats. Life Sci. 2002. 70(13):1533–1542.

20. Mitruka BM, Rawnsley HM. Clinical biochemical and hematological reference values in normal experimental animals and normal humans. 1987. 2nd edition. New York: Masson;160.

21. Kobayashi M, Hara K, Akiyama Y. Effects of vitamin K₂ (menatetrenone) and alendronate on bone mineral density and bone strength in rats fed a low -magnesium diet. Bone. 2004. 35(5):1136–1143.

22. Douglas AS, Robins SP, Hutchison JD, Porter RW, Stewart A, Reid DM. Carboxylation of osteocalcin in post-menopausal osteoporotic women following vitamin K and D supplementation. Bone. 1995. 17(1):15–20.

23. Ushiroyama T, Ikeda A, Ueki M. Effect of continuous combined therapy with vitamin K(2) and vitamin D(3) on bone mineral density and coagulofibrinolysis function in postmenopausal women. Maturitas. 2002. 41(3):211–221.

24. Szulc P, Chapuy MC, Meunier PJ, Delmas PD. Serum undercarboxylated osteocalcin is a marker of the risk of hip fracture in elderly women. J Clin Invest. 1993. 91(4):1769–1774.

25. Vergnaud P, Garnero P, Meunier PJ, Breart G, Kamihagi K, Delmas PD. Undercarboxylated osteocalcin measured with a specific immunoassay predicts hip fracture in elderly women: the EPIDOS Study. J Clin Endocrinol Metab. 1997. 82(3):719–724.

26. Arjmandi BH, Getlinger MJ, Goyal NV, Alekel L, Hasler CM, Juma S, Drum ML, Hollis BW, Kukreja SC. Role of soy protein with normal or reduced isoflavone content in reversing bone loss induced by ovarian hormone deficiency in rats. Am J Clin Nutr. 1998. 68:Suppl. 1358S–1363S.

27. Bunyaratavej N, Penkitti P, Kittimanon N, Boonsangsom P, Bonjongsat A, Yunoi S. Efficacy and safety of Menatetrenone-4 postmenopausal Thai women. J Med Assoc Thai. 2001. 84:Suppl 2. S553–S559.

28. 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):363–370.

29. Sogabe N, Maruyama R, Baba O, Hosoi T, Goseki-Sone M. Effects of long-term vitamin K(1) (phylloquinone) or vitamin K(2) (menaquinone-4) supplementation on body composition and serum parameters in rats. Bone. 2011. 48(5):1036–1042.

30. Koshihara Y, Hoshi K. Vitamin K2 enhances osteocalcin accumulation in the extracellular matrix of human osteoblasts in vitro. J Bone Miner Res. 1997. 12(3):431–438.

31. Peters BS, Martini LA. Nutritional aspects of the prevention and treatment of osteoporosis. Arq Bras Endocrinol Metabol. 2010. 54(2):179–185.