Abstract
The purpose of the present study was to examine the effect of vitamin K2 on cancellous and cortical bone mass in rats with streptozotocin (STZ)-induced type 1 diabetes. Twenty-seven male Sprague-Dawley rats aged 12 weeks were randomized by the weight-stratified method into the following three groups: age-matched control group, STZ + vehicle group, and STZ + vitamin K2 group. STZ (40 + 50 mg/kg) was administered intravenously twice during the initial 1-week period. Vitamin K2 (menatetrenone, 30 mg/kg) was administered orally 5 days a week. After 12 weeks of treatment, the serum glucose concentration and femoral length and weight were measured and histomorphometric analysis was performed on the cancellous and cortical bone of the distal femoral metaphysis and femoral diaphysis, respectively. STZ administration induced hyperglycemia and a decrease in femoral weight. The STZ + vehicle group also showed cancellous osteopenia due to a decrease in the number of osteoblasts/bone surface (N.Ob/BS) and the osteoblast surface (ObS)/BS without any significant changes in bone-resorption parameters, but it did not have a significant decrease in cortical bone mass. Administration of vitamin K2 to STZ-treated rats prevented the development of hyperglycemia and a decrease in femoral weight. Vitamin K2 also prevented cancellous osteopenia by inhibiting the decrease in N.Ob/BS and ObS/BS without significantly affecting bone-resorption parameters, but it did not significantly increase cortical bone mass. These results suggest that vitamin K2 has beneficial effects on glucose concentration and cancellous bone mass in rats with STZ-induced type 1 diabetes.
Similar content being viewed by others
References
Adami S (2009) Health in diabetes: considerations for clinical management. Curr Med Res Opin 25:1057–1072
Hofbauer LC, Brueck CC, Singh SK, Dobnig H (2007) Osteoporosis in patients with diabetes mellitus. J Bone Miner Res 22:1317–1328
Janghorbani M, Van Dam RM, Willett WC, Hu FB (2007) Systematic review of type 1 and type 2 diabetes mellitus and risk of fracture. Am J Epidemiol 166:495–505
Shires R, Teitelbaum SL, Bergfeld MA, Fallon MD, Slatopolsky E, Avioli LV (1981) The effect of streptozotocin-induced chronic diabetes mellitus on bone and mineral homeostasis in the rat. J Lab Clin Med 97:231–240
Silva MJ, Brodt MD, Lynch MA, McKenzie JA, Tanouye KM, Nyman JS, Wang X (2009) Type 1 diabetes in young rats leads to progressive trabecular bone loss, cessation of cortical bone growth, and diminished whole bone strength and fatigue life. J Bone Miner Res 24:1618–1627
Tsuchida T, Sato K, Miyakoshi N, Abe T, Kudo T, Tamura Y, Kasukawa Y, Suzuki K (2000) Histomorphometric evaluation of the recovering effect of human parathyroid hormone (1–34) on bone structure and turnover in streptozotocin-induced diabetic rats. Calcif Tissue Int 66:229–233
Suzuki K, Miyakoshi N, Tsuchida T, Kasukawa Y, Sato K, Itoi E (2003) Effects of combined treatment of insulin and human parathyroid hormone (1–34) on cancellous bone mass and structure in streptozotocin-induced diabetic rats. Bone 33:108–114
Yamaguchi M, Uchiyama S, Lai YL (2007) Oral administration of phytocomponent p-hydroxycinnamic acid has a preventive effect on bone loss in streptozotocin-induced diabetic rats. Int J Mol Med 19:803–807
Facchini DM, Yuen VG, Battell ML, McNeill JH, Grynpas MD (2006) The effects of vanadium treatment on bone in diabetic and non-diabetic rats. Bone 38:368–377
Epstein S, Takizawa M, Stein B, Katz IA, Joffe II, Romero DF et al (1994) Effect of cyclosporin A on bone mineral metabolism in experimental diabetes mellitus in the rat. J Bone Miner Res 9:557–566
Goodman WG, Hori MT (1984) Diminished bone formation in experimental diabetes. Relationship to osteoid maturation and mineralization. Diabetes 33:825–831
Pennisi P, Clementi G, Prato A, Luca T, Martinez G, Mangiafico RA, Pulvirenti I, Muratore F, Fiore CE (2009) l-Arginine supplementation normalizes bone turnover and preserves bone mass in streptozotocin-induced diabetic rats. J Endocrinol Invest 32:546–551
Horcajada-Molteni MN, Chanteranne B, Lebecque P, Davicco MJ, Coxam V, Young A, Barlet JP (2001) Amylin and bone metabolism in streptozotocin-induced diabetic rats. J Bone Miner Res 16:958–965
Ward DT, Yau SK, Mee AP, Mawer EB, Miller CA, Garland HO, Riccardi D (2001) Functional, molecular, and biochemical characterization of streptozotocin-induced diabetes. J Am Soc Nephrol 12:779–790
Herrero S, Calvo OM, García-Moreno C, Martín E, San Román JI, Martín M, García-Talavera JR, Calvo JJ, del Pino-Montes J (1998) Low bone density with normal bone turnover in ovariectomized and streptozotocin-induced diabetic rats. Calcif Tissue Int 62:260–265
Saito M, Marumo K (2010) Collagen cross-links as a determinant of bone quality: a possible explanation for bone fragility in aging, osteoporosis, and diabetes mellitus. Osteoporos Int 21:195–214
WHO Scientific Group (2003) Prevention and management of osteoporosis. World Health Organ Tech Rep Ser 921:86–109
Iwamoto J, Matsumoto H, Takeda T (2009) Efficacy of menatetrenone (vitamin K2) against non-vertebral and hip fractures in patients with neurological diseases: meta-analysis of three randomized, controlled trials. Clin Drug Investig 29:471–479
Hauschka PV, Lian JB, Cole DEC, Gundberg CM (1989) Osteocalcin and matrix Gla protein: vitamin K-dependent proteins in bone. Physiol Rev 69:990–1047
Koshihara Y, Hoshi K (1995) Vitamin K2 enhances osteocalcin accumulation in the extracellular matrix of human osteoblasts in vitro. J Bone Miner Res 12:431–438
Shearer MJ (1995) Vitamin K. Lancet 345:229–234
Vermeer C, Jie KSG, Knapen MHJ (1995) Role of vitamin K in bone metabolism. Annu Rev Nutr 15:1–22
Tabb MM, Sun A, Zhou C, Grun F, Errandi J, Romero K, Pham H, Inoue S, Mallick S, Lin M, Forman BM, Blumberg B (2003) Vitamin K2 regulation of bone homeostasis is mediated by the steroid and xenobiotic receptor SXR. J Biol Chem 278:43919–43927
Iwamoto J, Yeh JK, Takeda T (2003) Effect of vitamin K2 on cortical and cancellous bones in orchidectomized and/or sciatic neurectomized rats. J Bone Miner Res 18:776–783
Iwamoto J, Yeh JK, Schmidt A, Rowley E, Stanfield L, Takeda T, Sato M (2005) Raloxifene and vitamin K2 combine to improve the femoral neck strength of ovariectomized rats. Calcif Tissue Int 77:119–126
Erben RG (1997) Embedding of bone samples in methylmethacrylate: an improved method suitable for bone histomorphometry, histochemistry, and immunohistochemistry. J Histochem Cytochem 45:307–313
Parfitt AM, Drezner MK, Glorieux FH, Kanis JA, Malluche H, Meunier PJ, Ott SM, Recker RR (1987) Bone histomorphometry: standardization of nomenclature, symbols, and units. Report of the ASMBR Histomorphometry Nomenclature Committee. J Bone Miner Res 2:595–610
Chen MM, Yeh JK, Aloia JF, Tierney JM, Sprintz S (1994) Effect of treadmill exercise on tibial cortical bone in aged female rats: a histomorphometry and dual energy X-ray absorptiometry study. Bone 15:313–319
Yoshida M, Booth SL, Meigs JB, Saltzman E, Jacques PF (2008) Phylloquinone intake, insulin sensitivity, and glycemic status in men and women. Am J Clin Nutr 88:210–215
Lee NK, Sowa H, Hinoi E, Ferron M, Ahn JD, Confavreux C, Dacquin R, Mee PJ, McKee MD, Jung DY, Zhang Z, Kim JK, Mauvais-Jarvis F, Ducy P, Karsenty G (2007) Endocrine regulation of energy metabolism by the skeleton. Cell 130:456–469
Ferron M, Hinoi E, Karsenty G, Ducy P (2008) Osteocalcin differentially regulates beta cell and adipocyte gene expression and affects the development of metabolic diseases in wild-type mice. Proc Natl Acad Sci USA 105:5266–5270
Iwamoto J, Takeda T, Sato Y (2004) Effects of vitamin K2 on osteoporosis. Curr Pharm Des 10:2557–2576
Iwamoto J, Takeda T, Sato Y (2006) Effects of vitamin K2 on the development of osteopenia in rats as the models of osteoporosis. Yonsei Med J 47:157–166
Hara K, Akiyama Y, Nakamura T, Murota S, Morita I (1995) The inhibitory effect of vitamin K2 (menatetrenone) on bone resorption may be related to its side chain. Bone 16:179–184
Hara K, Akiyama Y, Tajima T, Shiraki M (1993) Menatetrenone inhibits bone resorption partly through inhibition of PGE2 synthesis in vitro. J Bone Miner Res 8:535–542
Bruno G, Novelli G, Panero F, Perotto M, Monasterolo F, Bona G, Perino A, Rabbone I, Cavallo-Perin P, Cerutti F (2009) The incidence of type 1 diabetes is increasing in both children and young adults in northern Italy: 1984–2004 temporal trends. Diabetologia 52:2531–2535
Author information
Authors and Affiliations
Corresponding author
Additional information
The authors have stated that they have no conflict of interest.
Rights and permissions
About this article
Cite this article
Iwamoto, J., Seki, A., Sato, Y. et al. Vitamin K2 Prevents Hyperglycemia and Cancellous Osteopenia in Rats with Streptozotocin-Induced Type 1 Diabetes. Calcif Tissue Int 88, 162–168 (2011). https://doi.org/10.1007/s00223-010-9441-5
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00223-010-9441-5