Skip to main content

Vitamin K status is associated with childhood bone mineral content

  • Marieke J. H. van Summeren (a1), Silvia C. C. M. van Coeverden (a2), Leon J. Schurgers (a3), Lavienja A. J. L. M. Braam (a3), Florence Noirt (a4), Cuno S. P. M. Uiterwaal (a5), Wietse Kuis (a1) and Cees Vermeer (a3)...

In adult bone, vitamin K contributes to bone health, probably through its role as co-factor in the carboxylation of osteocalcin. In children, the significance of vitamin K in bone-mass acquisition is less well known. The objective of this longitudinal study was to determine whether biochemical indicators of vitamin K status are related to (gains in) bone mineral content (BMC) and markers of bone metabolism in peripubertal children. In 307 healthy children (mean age 11·2 years), BMC of the total body, lumbar spine and femoral neck was determined at baseline and 2 years later. Vitamin K status (ratio of undercarboxylated (ucOC) to carboxylated (cOC) fractions of osteocalcin; UCR) was also measured at both time points. Markers of bone metabolism, sex steroids, vitamin D status and growth hormones were measured at baseline only. Large variations in the levels of the UCR were found at both time-points, indicating a substantial interindividual difference in vitamin K status. Improvement of vitamin K status over 2 years (n 281 children) was associated with a marked increase in total body BMC (r − 49·1, P < 0·001). The UCR was associated with pubertal stage, markers of bone metabolism, sex hormones and vitamin D status. A better vitamin K status was associated with more pronounced increase in bone mass in healthy peripubertal children. In order to determine the significance of these findings for childhood bone health, additional paediatric studies are needed.

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

      Note you can select to send to either the or variations. ‘’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Vitamin K status is associated with childhood bone mineral content
      Available formats
      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

      Vitamin K status is associated with childhood bone mineral content
      Available formats
      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

      Vitamin K status is associated with childhood bone mineral content
      Available formats
Corresponding author
*Corresponding author: Dr Marieke J. H. van Summeren, fax +31 302505349, email
Hide All
1Braam, LA, Knapen, MH, Geusens, P, Brouns, F, Hamulyak, K, Gerichhausen, MJ & Vermeer, C (2003) Vitamin K1 supplementation retards bone loss in postmenopausal women between 50 and 60 years of age. Calcif Tissue Int 73, 2126.
2Feskanich, 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, 7479.
3Shearer, MJ (2000) Role of vitamin K and Gla proteins in the pathophysiology of osteoporosis and vascular calcification. Curr Opin Clin Nutr Metab Care 3, 433438.
4Wallin, R, Sane, DC & Hutson, SM (2002) Vitamin K 2,3-epoxide reductase and the vitamin K-dependent gamma-carboxylation system. Thromb Res 108, 221226.
5Hauschka, PV, Lian, JB & Gallop, PM (1975) Direct identification of the calcium-binding amino acid, gamma-carboxyglutamate, in mineralized tissue. Proc Natl Acad Sci USA 72, 39253929.
6Price, PA, Poser, JW & Raman, N (1976) Primary structure of the gamma-carboxyglutamic acid-containing protein from bovine bone. Proc Natl Acad Sci USA 73, 33743375.
7Koshihara, Y & Hoshi, K (1997) Vitamin K2 enhances osteocalcin accumulation in the extracellular matrix of human osteoblasts in vitro. J Bone Miner Res 12, 431438.
8Binkley, NC, Krueger, DC, Engelke, JA, Foley, AL & Suttie, JW (2000) Vitamin K supplementation reduces serum concentrations of under-gamma-carboxylated osteocalcin in healthy young and elderly adults. Am J Clin Nutr 72, 15231528.
9Binkley, NC, Krueger, DC, Kawahara, TN, Engelke, JA, Chappell, RJ & Suttie, JW (2002) A high phylloquinone intake is required to achieve maximal osteocalcin gamma-carboxylation. Am J Clin Nutr 76, 10551060.
10Sokoll, LJ, Booth, SL, O'Brien, ME, Davidson, KW, Tsaioun, KI & Sadowski, JA (1997) Changes in serum osteocalcin, plasma phylloquinone, and urinary gamma-carboxyglutamic acid in response to altered intakes of dietary phylloquinone in human subjects. Am J Clin Nutr 65, 779784.
11Szulc, 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, 487488.
12Vergnaud, 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, 719724.
13Schurgers, LJ & Vermeer, C (2000) Determination of phylloquinone and menaquinones in food. Effect of food matrix on circulating vitamin K concentrations. Haemostasis 30, 298307.
14Cockayne, 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, 12561261.
15Luukinen, H, Kakonen, SM, Pettersson, K, Koski, K, Laippala, P, Lovgren, T, Kivela, SL & Vaananen, HK (2000) Strong prediction of fractures among older adults by the ratio of carboxylated to total serum osteocalcin. J Bone Miner Res 15, 24732478.
16O'Connor, E, Molgaard, C, Michaelsen, KF, Jakobsen, J, Lamberg-Allardt, CJ & Cashman, KD (2007) Serum percentage undercarboxylated osteocalcin, a sensitive measure of vitamin K status, and its relationship to bone health indices in Danish girls. Br J Nutr 97, 661666.
17Kalkwarf, HJ, Khoury, JC, Bean, J & Elliot, JG (2004) Vitamin K, bone turnover, and bone mass in girls. Am J Clin Nutr 80, 10751080.
18van Summeren, M, Braam, L, Noirt, F, Kuis, W & Vermeer, C (2007) Pronounced elevation of undercarboxylated osteocalcin in healthy children. Pediatr Res 61, 366370.
19Coeverden, SCCMv, Netelenbos, JC, Ridder, CMd, Roos, JC, Popp-Snijders, C & Delemarre-van de Waal, HA (2002) Bone metabolism markers and bone mass in healthy pubertal boys and girls. Clin Endocrinol 57, 107116.
20Sokoll, LJ & Sadowski, JA (1996) Comparison of biochemical indexes for assessing vitamin K nutritional status in a healthy adult population. Am J Clin Nutr 63, 566573.
21Bouman, AA, Scheffer, PG, Ooms, ME, Lips, P & Netelenbos, C (1995) Two bone alkaline phosphatase assays compared with osteocalcin as a marker of bone formation in healthy elderly women. Clin Chem 41, 196199.
22Van Coeverden, SC, De Ridder, CM, Roos, JC, Van't Hof, MA, Netelenbos, JC & Delemarre-Van de Waal, HA (2001) Pubertal maturation characteristics and the rate of bone mass development longitudinally toward menarche. J Bone Miner Res 16, 774781.
23Prentice, A, Parsons, TJ & Cole, TJ (1994) Uncritical use of bone mineral density in absorptiometry may lead to size-related artifacts in the identification of bone mineral determinants. Am J Clin Nutr 60, 837842.
24Knapen, MHJ, Nieuwenhuijzen Kruseman, AC, Wouters, RS & Vermeer, C (1998) Correlation of serum osteocalcin fractions with bone mineral density in women during the first 10 years after menopause. Calcif Tissue Int 63, 375379.
25Nelson, DA & Koo, WW (1999) Interpretation of absorptiometric bone mass measurements in the growing skeleton: issues and limitations. Calcif Tissue Int 65, 13.
26Prynne, CJ, Thane, CW, Prentice, A & Wadsworth, ME (2005) Intake and sources of phylloquinone (vitamin K(1)) in 4-year-old British children: comparison between 1950 and the 1990s. Public Health Nutr 8, 171180.
27Food and Nutrition Board, Institute of Medicine (2001) Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Washington, DC: National Academy Press.
28Bounds, W, Skinner, J, Carruth, BR & Ziegler, P (2005) The relationship of dietary and lifestyle factors to bone mineral indexes in children. J Am Diet Assoc 105, 735741.
29Paredes, R, Arriagada, G, Cruzat, F, Villagra, A, Olate, J, Zaidi, K, van, WA, Lian, JB, Stein, GS, Stein, JL & Montecino, M (2004) Bone-specific transcription factor Runx2 interacts with the 1alpha,25-dihydroxyvitamin D3 receptor to up-regulate rat osteocalcin gene expression in osteoblastic cells. Mol Cell Biol 24, 88478861.
30Sato, 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, 114118.
31Bailey, DA, McKay, HA, Mirwald, RL, Crocker, PR & Faulkner, RA (1999) A six-year longitudinal study of the relationship of physical activity to bone mineral accrual in growing children: the university of Saskatchewan bone mineral accrual study. J Bone Miner Res 14, 16721679.
32Manias, K, McCabe, D & Bishop, N (2006) Fractures and recurrent fractures in children; varying effects of environmental factors as well as bone size and mass. Bone 39, 652657.
33Fournier, PE, Rizzoli, R, Slosman, DO, Theintz, G & Bonjour, JP (1997) Asynchrony between the rates of standing height gain and bone mass accumulation during puberty. Osteoporos Int 7, 525532.
34Faulkner, RA, Davison, KS, Bailey, DA, Mirwald, RL & Baxter-Jones, AD (2006) Size-corrected BMD decreases during peak linear growth: implications for fracture incidence during adolescence. J Bone Miner Res 21, 18641870.
35Knapen, MHJ, Schurgers, LJ & Vermeer, C (2007) Vitamin K(2) supplementation improves hip bone geometry and bone strength indices in postmenopausal women. Osteoporos Int 18, 963972.
36Szulc, 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, 15911595.
37Hernandez, CJ, Beaupre, GS & Carter, DR (2003) A theoretical analysis of the relative influences of peak BMD, age-related bone loss and menopause on the development of osteoporosis. Osteoporos Int 14, 843847.
38Hui, SL, Slemenda, CW & Johnston, CC (1990) The contribution of bone loss to postmenopausal osteoporosis. Osteoporos Int 1, 3034.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

British Journal of Nutrition
  • ISSN: 0007-1145
  • EISSN: 1475-2662
  • URL: /core/journals/british-journal-of-nutrition
Please enter your name
Please enter a valid email address
Who would you like to send this to? *



Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed