Top

Published in:

01-02-2013 | Original Contribution

Serum level of under-carboxylated osteocalcin and bone mineral density in early menopausal Norwegian women

Authors: Nina Emaus, Nguyen D. Nguyen, Bjørg Almaas, Gro K. Berntsen, Jacqueline R. Center, Monika Christensen, Clara G. Gjesdal, Anne S. Grimsgaard, Tuan V. Nguyen, Laila Salomonsen, John A. Eisman, Vinjar M. Fønnebø

Published in: European Journal of Nutrition | Issue 1/2013

Abstract

Purpose

Serum level of under-carboxylated osteocalcin (ucOC) is considered a sensitive measure of vitamin K status, and ucOC levels are associated with bone mineral density (BMD) and fracture risk in elderly persons. The aim of this study was to assess the relationship between ucOC and BMD in early menopausal women.

Methods

The data reported here come from the enrolment in a double-blinded placebo-controlled randomized trial comprising 334 healthy Norwegian women between 50 and 60 years, 1–5 years after menopause, not using warfarin or medication known to affect bone metabolism. Total hip, femoral neck, lumbar spine, and total body BMD and serum level of ucOC and total osteocalcin were measured, and information of lifestyle was collected through questionnaires. The association between ucOC and BMD at all measurement sites was assessed by multiple regression analyses adjusting for possible confounding variables.

Results

The absolute serum level of ucOC was significantly and negatively associated with BMD at all measurements sites, both in univariate analyses (p < 0.01) and in multivariate analyses adjusting for years since menopause, smoking status and weight (p < 0.01). However, serum ucOC, expressed as percentage of the total osteocalcin level, was not associated with BMD at any site.

Conclusions

Achievement of adequate vitamin K nutritional intake is important, but ucOC expressed as percentage of total osteocalcin levels as reflection of vitamin K status does not seem to play a central role in determining BMD levels in early menopausal women.

Vermeer C, Braam L (2001) Role of K vitamins in the regulation of tissue calcification. J Bone Miner Metab 19:201–206CrossRef

Cockayne S, Adamson J, Lanham-New S, Shearer MJ, Gilbody S, Torgerson DJ (2006) Vitamin K and the prevention of fractures: systematic review and meta-analysis of randomized controlled trials. Arch Intern Med 166:1256–1261CrossRef

Katsuyama H, Otsuki T, Tomita M, Fukunaga M, Fukunaga T, Suzuki N, Saijoh K, Fushimi S, Sunami S (2005) Menaquinone-7 regulates the expressions of osteocalcin, OPG, RANKL and RANK in osteoblastic MC3T3E1 cells. Int J Mol Med 15:231–236

Katsuyama H, Saijoh K, Otsuki T, Tomita M, Fukunaga M, Sunami S (2007) Menaquinone-7 regulates gene expression in osteoblastic MC3T3E1 cells. Int J Mol Med 19:279–284

Schurgers LJ, Vermeer C (2000) Determination of phylloquinone and menaquinones in food. Effect of food matrix on circulating vitamin K concentrations. Haemostasis 30:298–307

Shea MK, Booth SL (2008) Update on the role of vitamin K in skeletal health. Nutr Rev 66:549–557CrossRef

Kaneki M, Hedges SJ, Hosoi T, Fujiwara S, Lyons A, Crean SJ, Ishida N, Nakagawa M, Takechi M, Sano Y, Mizuno Y, Hoshino S, Miyao M, Inoue S, Horiki K, Shiraki M, Ouchi Y, Orimo H (2001) 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 17:315–321CrossRef

Zittermann A (2001) Effects of vitamin K on calcium and bone metabolism. Curr Opin Clin Nutr Metab Care 4:483–487CrossRef

Weber P (2001) Vitamin K and bone health. Nutrition 17:880–887CrossRef

10.

Nimptsch K, Hailer S, Rohrmann S, Gedrich K, Wolfram G, Linseisen J (2007) Determinants and correlates of serum undercarboxylated osteocalcin. Ann Nutr Metab 51:563–570CrossRef

11.

Gundberg CM, Nieman SD, Abrams S, Rosen H (1998) Vitamin K status and bone health: an analysis of methods for determination of undercarboxylated osteocalcin. J Clin Endocrinol Metab 83:3258–3266CrossRef

12.

McKeown NM, Jacques PF, Gundberg CM, Peterson JW, Tucker KL, Kiel DP, Wilson PW, Booth SL (2002) Dietary and nondietary determinants of vitamin K biochemical measures in men and women. J Nutr 132:1329–1334

13.

Szulc P, Arlot M, Chapuy MC, Duboeuf F, Meunier PJ, Delmas PD (1994) Serum undercarboxylated osteocalcin correlates with hip bone mineral density in elderly women. J Bone Miner Res 9:1591–1595CrossRef

14.

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

15.

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

16.

Binkley N, Harke J, Krueger D, Engelke J, Vallarta-Ast N, Gemar D, Checovich M, Chappell R, Suttie J (2009) Vitamin K treatment reduces undercarboxylated osteocalcin but does not alter bone turnover, density, or geometry in healthy postmenopausal North American women. J Bone Miner Res 24:983–991CrossRef

17.

Booth SL, Dallal G, Shea MK, Gundberg C, Peterson JW, Dawson-Hughes B (2008) Effect of vitamin K supplementation on bone loss in elderly men and women. J Clin Endocrinol Metab 93:1217–1223CrossRef

18.

Emaus N, Gjesdal CG, Almas B, Christensen M, Grimsgaard AS, Berntsen GK, Salomonsen L, Fonnebo V (2010) Vitamin K2 supplementation does not influence bone loss in early menopausal women: a randomised double-blind placebo-controlled trial. Osteoporos Int 21:1731–1740CrossRef

19.

Gundberg CM (2009) Vitamin K and bone: past, present, and future. J Bone Miner Res 24:980–982CrossRef

20.

Fang Y, Hu C, Tao X, Wan Y, Tao F (2011) Effect of vitamin K on bone mineral density: a meta-analyses of randomized controlled trials. J Bone Miner Metab (E-pub ahead of print)

21.

Bischoff-Ferrari HA, Willett WC, Wong JB, Giovannucci E, Dietrich T, Dawson-Hughes B (2005) Fracture prevention with vitamin D supplementation: a meta-analysis of randomized controlled trials. JAMA 293:2257–2264CrossRef

22.

Booth SL, Broe KE, Peterson JW, Cheng DM, Dawson-Hughes B, Gundberg CM, Cupples LA, Wilson PW, Kiel DP (2004) Associations between vitamin K biochemical measures and bone mineral density in men and women. J Clin Endocrinol Metab 89:4904–4909CrossRef

23.

Booth SL, Al RA (2008) Determinants of vitamin K status in humans. Vitam Horm 78:1–22CrossRef

24.

De Laet C, Kanis JA, Oden A, Johanson H, Johnell O, Delmas P, Eisman JA, Kroger H, Fujiwara S, Garnero P, McCloskey EV, Mellstrom D, Melton LJ III, Meunier PJ, Pols HA, Reeve J, Silman A, Tenenhouse A (2005) Body mass index as a predictor of fracture risk: a meta-analysis. Osteoporos Int 16:1330–1338CrossRef

25.

Kanis JA, Borgstrom F, De Laet C, Johansson H, Johnell O, Jonsson B, Oden A, Zethraeus N, Pfleger B, Khaltaev N (2005) Assessment of fracture risk. Osteoporos Int 16:581–589CrossRef

26.

Law MR, Hackshaw AK (1997) A meta-analysis of cigarette smoking, bone mineral density and risk of hip fracture: recognition of a major effect. BMJ 315:841–846CrossRef

27.

Wallace BA, Cumming RG (2000) Systematic review of randomized trials of the effect of exercise on bone mass in pre- and postmenopausal women. Calcif Tissue Int 67:10–18CrossRef

28.

Szulc P, Chapuy MC, Meunier PJ, Delmas PD (1996) Serum undercarboxylated osteocalcin is a marker of the risk of hip fracture: a three year follow-up study. Bone 18:487–488CrossRef

29.

Liu G, Peacock M (1998) Age-related changes in serum undercarboxylated osteocalcin and its relationships with bone density, bone quality, and hip fracture. Calcif Tissue Int 62:286–289CrossRef

30.

Zofkova I, Hill M, Palicka V (2003) Association between serum undercarboxylated osteocalcin and bone density and/or quality in early postmenopausal women. Nutrition 19:1001–1003CrossRef

31.

Feskanich D, Weber P, Willett WC, Rockett H, Booth SL, Colditz GA (1999) Vitamin K intake and hip fractures in women: a prospective study. Am J Clin Nutr 69:74–79

32.

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

33.

Sato Y, Honda Y, Kuno H, Oizumi K (1998) Menatetrenone ameliorates osteopenia in disuse-affected limbs of vitamin D- and K-deficient stroke patients. Bone 23:291–296CrossRef

34.

Sato Y, Honda Y, Kaji M, Asoh T, Hosokawa K, Kondo I, Satoh K (2002) Amelioration of osteoporosis by menatetrenone in elderly female Parkinson’s disease patients with vitamin D deficiency. Bone 31:114–118CrossRef

35.

Sato Y, Kanoko T, Satoh K, Iwamoto J (2005) Menatetrenone and vitamin D2 with calcium supplements prevent nonvertebral fracture in elderly women with Alzheimer’s disease. Bone 36:61–68CrossRef

36.

Shiomi S, Nishiguchi S, Kubo S, Tamori A, Habu D, Takeda T, Ochi H (2002) Vitamin K2 (menatetrenone) for bone loss in patients with cirrhosis of the liver. Am J Gastroenterol 97:978–981CrossRef

37.

Yonemura K, Kimura M, Miyaji T, Hishida A (2000) Short-term effect of vitamin K administration on prednisolone-induced loss of bone mineral density in patients with chronic glomerulonephritis. Calcif Tissue Int 66:123–128CrossRef

38.

Yonemura K, Fukasawa H, Fujigaki Y, Hishida A (2004) Protective effect of vitamins K2 and D3 on prednisolone-induced loss of bone mineral density in the lumbar spine. Am J Kidney Dis 43:53–60CrossRef

39.

Ishida Y, Kawai S (2004) 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 117:549–555CrossRef

40.

Iwamoto J, Takeda T, Ichimura S (2000) Effect of combined administration of vitamin D3 and vitamin K2 on bone mineral density of the lumbar spine in postmenopausal women with osteoporosis. J Orthop Sci 5:546–551CrossRef

41.

Iwamoto J, Takeda T, Ichimura S (2001) Effect of menatetrenone on bone mineral density and incidence of vertebral fractures in postmenopausal women with osteoporosis: a comparison with the effect of etidronate. J Orthop Sci 6:487–492CrossRef

42.

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

43.

Purwosunu Y, Muharram G, Rachman IA, Reksoprodjo S, Sekizawa A (2006) Vitamin K2 treatment for postmenopausal osteoporosis in Indonesia. J Obstet Gynaecol Res 32:230–234

44.

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

45.

Katsuyama H, Ideguchi S, Fukunaga M, Fukunaga T, Saijoh K, Sunami S (2004) Promotion of bone formation by fermented soybean (Natto) intake in premenopausal women. J Nutr Sci Vitaminol (Tokyo) 50:114–120CrossRef

46.

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

47.

Ozuru R, Sugimoto T, Yamaguchi T, Chihara K (2002) Time-dependent effects of vitamin K2 (menatetrenone) on bone metabolism in postmenopausal women. Endocr J 49:363–370CrossRef

48.

Knapen MH, Schurgers LJ, Vermeer C (2007) Vitamin K2 supplementation improves hip bone geometry and bone strength indices in postmenopausal women. Osteoporos Int 18:963–972CrossRef

49.

Yamauchi M, Yamaguchi T, Nawata K, Takaoka S, Sugimoto T (2010) Relationships between undercarboxylated osteocalcin and vitamin K intakes, bone turnover, and bone mineral density in healthy women. Clin Nutr 29:761–765CrossRef

50.

Koshihara Y, Hoshi K, Ishibashi H, Shiraki M (1996) Vitamin K2 promotes 1alpha, 25(OH)2 vitamin D3-induced mineralization in human periosteal osteoblasts. Calcif Tissue Int 59:466–473

51.

Miyake N, Hoshi K, Sano Y, Kikuchi K, Tadano K, Koshihara Y (2001) 1, 25-Dihydroxyvitamin D3 promotes vitamin K2 metabolism in human osteoblasts. Osteoporos Int 12:680–687CrossRef

52.

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

53.

Yasui T, Miyatani Y, Tomita J, Yamada M, Uemura H, Miura M, Irahara M (2006) Effect of vitamin K2 treatment on carboxylation of osteocalcin in early postmenopausal women. Gynecol Endocrinol 22:455–459CrossRef

54.

Lee NK, Sowa H, Hinoi E, Ferron M, Ahn JD, Confavreux C, Dacquin R, Mee PJ, McKee MC, Jung DY, Zhang Z, Kim JK, Mauvais-Jarvis F, Ducy P, Karsenty G (2007) Endocrine regulation of energy metabolism by the skeleton. Cell 130:456–469CrossRef

55.

Ferron M, Wei J, Yoshizawa T, Fattore AD, DePinho RA, Teti A, Ducy P, Karsenty G (2010) Insulin signaling in osteoblasts integrates bone remodeling and energy metabolism. Cell 142:296–308CrossRef

Title: Serum level of under-carboxylated osteocalcin and bone mineral density in early menopausal Norwegian women
Authors: Nina Emaus
Nguyen D. Nguyen
Bjørg Almaas
Gro K. Berntsen
Jacqueline R. Center
Monika Christensen
Clara G. Gjesdal
Anne S. Grimsgaard
Tuan V. Nguyen
Laila Salomonsen
John A. Eisman
Vinjar M. Fønnebø
Publication date: 01-02-2013
Publisher: Springer-Verlag
Published in: European Journal of Nutrition / Issue 1/2013
Print ISSN: 1436-6207
Electronic ISSN: 1436-6215
DOI: https://doi.org/10.1007/s00394-011-0285-1

ACC 2024 Congress Coverage

Heart Failure Video

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Serum level of under-carboxylated osteocalcin and bone mineral density in early menopausal Norwegian women

Abstract

Purpose

Methods

Results

Conclusions

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2013

Comparison of the effects of weight loss from a high-protein versus standard-protein energy-restricted diet on strength and aerobic capacity in overweight and obese men

Effect of a combination of genistein, polyunsaturated fatty acids and vitamins D3 and K1 on bone mineral density in postmenopausal women: a randomized, placebo-controlled, double-blind pilot study

A comparison of the accuracy of self-reported intake with measured intake of a laboratory overeating episode in overweight and obese women with and without binge eating disorder

Neuroprotective effects of digested polyphenols from wild blackberry species

Adherence to Mediterranean diet and close dietetic supervision increase total dietary antioxidant intake and plasma antioxidant capacity in subjects with abdominal obesity

Erratum to: Hexane fraction from Laminaria japonica exerts anti-inflammatory effects on lipopolysaccharide-stimulated RAW 264.7 macrophages via inhibiting NF-kappaB pathway

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page