Skip to main content
Log in

Osteocalcin carboxylation is not associated with body weight or percent fat changes during weight loss in post-menopausal women

Endocrine Aims and scope Submit manuscript

Abstract

Osteocalcin (OC) is a vitamin K-dependent bone protein used as a marker of bone formation. Mouse models have demonstrated a role for the uncarboxylated form of OC (ucOC) in energy metabolism, including energy expenditure and adiposity, but human data are equivocal. The purpose of this study was to determine the associations between changes in measures of OC and changes in body weight and percent body fat in obese, but otherwise healthy post-menopausal women undergoing a 20-week weight loss program. All participants received supplemental vitamins K and D and calcium. Body weight and body fat percentage (%BF) were assessed before and after the intervention. Serum OC [(total (tOC), ucOC, percent uncarboxylated (%ucOC)], and procollagen type 1N-terminal propeptide (P1NP; a measure of bone formation) were measured. Women lost an average of 10.9 ± 3.9 kg and 4 %BF. Serum concentrations of tOC, ucOC, %ucOC, and P1NP did not significantly change over the twenty-week intervention, nor were these measures associated with changes in weight (all p > 0.27) or  %BF (all p > 0.54). Our data do not support an association between any serum measure of OC and weight or %BF loss in post-menopausal women supplemented with nutrients implicated in bone health.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

References

  1. P.V. Hauschka, F.H. Wians, Osteocalcin-hydroxyapatite interaction in the extracellular organic matrix of bone. Anat. Rec. 224, 180–188 (1989)

    Article  CAS  PubMed  Google Scholar 

  2. S.L. Booth, A. Centi, S.R. Smith, C. Gundberg, The role of osteocalcin in human glucose metabolism: marker or mediator? Nat. Rev. Endocrinol. 9, 43–55 (2013)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  3. J.P. Brown, P.D. Delmas, L. Malaval, C. Edouard, M.C. Chapuy, P.J. Meunier, Serum bone Gla-protein: a specific marker for bone formation in postmenopausal osteoporosis. Lancet 1, 1091–1093 (1984)

    Article  CAS  PubMed  Google Scholar 

  4. E. O’Connor, C. Mølgaard, K.F. Michaelsen, J. Jakobsen, C.J.E. Lamberg-Allardt, K.D. Cashman, 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, 661–666 (2007)

    Article  PubMed  Google Scholar 

  5. N.C. Binkley, D.C. Krueger, T.N. Kawahara, J.A. Engelke, R.J. Chappell, J.W. Suttie, A high phylloquinone intake is required to achieve maximal osteocalcin gamma-carboxylation. Am. J. Clin. Nutr. 76, 1055–1060 (2002)

    CAS  PubMed  Google Scholar 

  6. N.K. Lee, H. Sowa, E. Hinoi, M. Ferron, J.D. Ahn, C. Confavreux, R. Dacquin, P.J. Mee, M.D. McKee, D.Y. Jung, Z. Zhang, J.K. Kim, F. Mauvais-Jarvis, P. Ducy, G. Karsenty, Endocrine regulation of energy metabolism by the skeleton. Cell 130, 456–469 (2007)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  7. M. Ferron, E. Hinoi, G. Karsenty, P. Ducy, 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 (2008)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  8. J. Wei, M. Ferron, C.J. Clarke, Y.A. Hannun, H. Jiang, W.S. Blaner, G. Karsenty, Bone-specific insulin resistance disrupts whole-body glucose homeostasis via decreased osteocalcin activation. J. Clin. Invest. 124, 1781–1793 (2014)

    Article  PubMed Central  CAS  Google Scholar 

  9. F. Oury, L. Khrimian, C.A. Denny, A. Gardin, A. Chamouni, N. Goeden, Y. Huang, H. Lee, P. Srinivas, X.-B. Gao, S. Suyama, T. Langer, J.J. Mann, T.L. Horvath, A. Bonnin, G. Karsenty, Maternal and offspring pools of osteocalcin influence brain development and functions. Cell 155, 228–241 (2013)

    Article  CAS  PubMed  Google Scholar 

  10. F. Oury, G. Sumara, O. Sumara, M. Ferron, H. Chang, C.E. Smith, L. Hermo, S. Suarez, B.L. Roth, P. Ducy, G. Karsenty, Endocrine regulation of male fertility by the skeleton. Cell 144, 796–809 (2011)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  11. R.C. Riddle, J.L. Frey, R.E. Tomlinson, M. Ferron, Y. Li, D.J. Digirolamo, M.-C. Faugere, M.A. Hussain, G. Karsenty, T.L. Clemens, Tsc2 is a molecular checkpoint controlling osteoblast development and glucose homeostasis. Mol. Cell. Biol. 34, 1850–1862 (2014)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  12. K. Fulzele, R.C. Riddle, D.J. DiGirolamo, X. Cao, C. Wan, D. Chen, M.-C. Faugere, S. Aja, M.A. Hussain, J.C. Brüning, T.L. Clemens, Insulin receptor signaling in osteoblasts regulates postnatal bone acquisition and body composition. Cell 142, 309–319 (2010)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  13. J. Lacombe, G. Karsenty, M. Ferron, In vivo analysis of the contribution of bone resorption to the control of glucose metabolism in mice. Mol. Metab. 2, 498–504 (2013)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

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

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. S.L. Booth, A. Al Rajabi, Determinants of vitamin K status in humans. Vitam. Horm. 78, 1–22 (2008)

    Article  CAS  PubMed  Google Scholar 

  16. S.A. New, Bone health: the role of micronutrients. Br. Med. Bull. 55, 619–633 (1999)

    Article  CAS  PubMed  Google Scholar 

  17. E. Huskisson, S. Maggini, M. Ruf, The role of vitamins and minerals in energy metabolism and well-being. J. Int. Med. Res. 35, 277–289 (2007)

    Article  CAS  PubMed  Google Scholar 

  18. B.N. Ames, The metabolic tune-up: metabolic harmony and disease prevention. J. Nutr. 133, 1544S–1548S (2003)

    CAS  PubMed  Google Scholar 

  19. B.J. Nicklas, X. Wang, T. You, M.F. Lyles, J. Demons, L. Easter, M.J. Berry, L. Lenchik, J.J. Carr, Effect of exercise intensity on abdominal fat loss during calorie restriction in overweight and obese postmenopausal women: a randomized, controlled trial. Am. J. Clin. Nutr. 89, 1043–1052 (2009)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  20. P. Tarallo, M. Balland, J. Henny, Effect of long-term storage on human plasma osteocalcin level. Clin. Chim. Acta 208, 237–239 (1992)

    Article  CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  22. J.A. Sadowski, S.J. Hood, G.E. Dallal, P.J. Garry, Phylloquinone in plasma from elderly and young adults: factors influencing its concentration. Am. J. Clin. Nutr. 50, 100–108 (1989)

    CAS  PubMed  Google Scholar 

  23. B.W. Hollis, J.Q. Kamerud, S.R. Selvaag, J.D. Lorenz, J.L. Napoli, Determination of vitamin D status by radioimmunoassay with an 125I-labeled tracer. Clin. Chem. 39, 529–533 (1993)

    CAS  PubMed  Google Scholar 

  24. J. Melkko, S. Kauppila, S. Niemi, L. Risteli, K. Haukipuro, A. Jukkola, J. Risteli, Immunoassay for intact amino-terminal propeptide of human type I procollagen. Clin. Chem. 42, 947–954 (1996)

    CAS  PubMed  Google Scholar 

  25. M.J. Shearer, P. Newman, Metabolism and cell biology of vitamin K. Thromb. Haemost. 100, 530–547 (2008)

    CAS  PubMed  Google Scholar 

  26. C.W. Thane, C.J. Bates, M.J. Shearer, N. Unadkat, D.J. Harrington, A.A. Paul, A. Prentice, C. Bolton-Smith, Plasma phylloquinone (vitamin K1) concentration and its relationship to intake in a national sample of British elderly people. Br. J. Nutr. 87, 615–622 (2002)

    Article  CAS  PubMed  Google Scholar 

  27. C.W. Thane, L.Y. Wang, W.A. Coward, Plasma phylloquinone (vitamin K1) concentration and its relationship to intake in British adults aged 19-64 years. Br. J. Nutr. 96, 1116–1124 (2006)

    Article  CAS  PubMed  Google Scholar 

  28. A. Looker, B. Dawson-Hughes, M. Calvo, E. Gunter, N. Sahyoun, Serum 25-hydroxyvitamin D status of adolescents and adults in two seasonal subpopulations from NHANES III. Bone 30, 771–777 (2002)

    Article  CAS  PubMed  Google Scholar 

  29. R.P. Heaney, Vitamin D in health and disease. Clin. J. Am. Soc. Nephrol. 3, 1535–1541 (2008)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  30. E.M. Alissa, W.A. Alnahdi, N. Alama, G.A. Ferns, Serum osteocalcin is associated with dietary vitamin D, body weight and serum magnesium in postmenopausal women with and without significant coronary artery disease. Asia Pac. J. Clin. Nutr. 23, 246–255 (2014)

    CAS  PubMed  Google Scholar 

  31. U. Saleem, T.H. Mosley Jr, I.J. Kullo, Serum osteocalcin is associated with measures of insulin resistance, adipokine levels, and the presence of metabolic syndrome. Arter. Thromb. Vasc. Biol. 30, 1474–1478 (2010)

    Article  CAS  Google Scholar 

  32. Y. Bao, X. Ma, R. Yang, F. Wang, Y. Hao, J. Dou, H. He, W. Jia, Inverse relationship between serum osteocalcin levels and visceral fat area in Chinese men. J. Clin. Endocrinol. Metab. 98, 345–351 (2013)

    Article  CAS  PubMed  Google Scholar 

  33. S.W. Lee, H.H. Jo, M.R. Kim, Y.O. You, J.H. Kim, Association between obesity, metabolic risks and serum osteocalcin level in postmenopausal women. Gynecol. Endocrinol. 28, 472–477 (2012)

    Article  CAS  PubMed  Google Scholar 

  34. C.M. Lenders, P.D.K. Lee, H.A. Feldman, D.M. Wilson, S.H. Abrams, S.E. Gitelman, W.J. Klish, M.S. Wertz, G.A. Taylor, R.T. Alongi, T.C. Chen, M.F. Holick, A cross-sectional study of osteocalcin and body fat measures among obese adolescents. Obesity (Silver Spring) 21, 808–814 (2013)

    Article  CAS  Google Scholar 

  35. B.B. Yeap, S.A. Chubb, L. Flicker, K.A. McCaul, P.R. Ebeling, J.P. Beilby, P.E. Norman, Reduced serum total osteocalcin is associated with metabolic syndrome in older men via waist circumference, hyperglycemia, and triglyceride levels. Eur. J. Endocrinol. 163, 265–272 (2010)

    Article  CAS  PubMed  Google Scholar 

  36. A. Movahed, B. Larijani, I. Nabipour, M. Kalantarhormozi, K. Asadipooya, K. Vahdat, S. Akbarzadeh, M. Farrokhnia, M. Assadi, R. Amirinejad, A. Bargahi, Z. Sanjdideh, Reduced serum osteocalcin concentrations are associated with type 2 diabetes mellitus and the metabolic syndrome components in postmenopausal women: the crosstalk between bone and energy metabolism. J. Bone Miner. Metab. 30, 683–691 (2012)

    Article  CAS  PubMed  Google Scholar 

  37. A.A. Alfadda, A. Masood, S.A. Shaik, H. Dekhil, M. Goran, Association between osteocalcin, metabolic syndrome, and cardiovascular risk factors: role of total and undercarboxylated osteocalcin in patients with type 2 diabetes. Int. J. Endocrinol. 2013, 197519 (2013)

    Article  PubMed Central  PubMed  Google Scholar 

  38. I. Kanazawa, T. Yamaguchi, M. Yamauchi, M. Yamamoto, S. Kurioka, S. Yano, T. Sugimoto, Serum undercarboxylated osteocalcin was inversely associated with plasma glucose level and fat mass in type 2 diabetes mellitus. Osteoporos. Int. 22, 187–194 (2011)

    Article  CAS  PubMed  Google Scholar 

  39. M.K. Karlsson, J.M. Kindblom, C. Ohlsson, Plasma osteocalcin is inversely related to fat mass and plasma glucose in elderly Swedish Men. J. Bone Miner. Res. 24, 785–791 (2009)

    Article  PubMed  Google Scholar 

  40. M.K. Shea, S.L. Booth, C.M. Gundberg, J.W. Peterson, C. Waddell, B. Dawson-Hughes, E. Saltzman, Adulthood obesity is positively associated with adipose tissue concentrations of vitamin K and inversely associated with circulating indicators of vitamin K status in men and women. J. Nutr. 140, 1029–1034 (2010)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  41. M.H.J. Knapen, L.J. Schurgers, M.J. Shearer, P. Newman, E. Theuwissen, C. Vermeer, Association of vitamin K status with adiponectin and body composition in healthy subjects: uncarboxylated osteocalcin is not associated with fat mass and body weight. Br. J. Nutr. 108, 1017–1024 (2012)

    Article  CAS  PubMed  Google Scholar 

  42. A.L. Schafer, D.E. Sellmeyer, A.V. Schwartz, C.J. Rosen, E. Vittinghoff, L. Palermo, J.P. Bilezikian, D.M. Shoback, D.M. Black, Change in undercarboxylated osteocalcin is associated with changes in body weight, fat mass, and adiponectin: parathyroid hormone (1-84) or alendronate therapy in postmenopausal women with osteoporosis (the PaTH study). J. Clin. Endocrinol. Metab. 96, E1982–E1989 (2011)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  43. L. Welsh, O.M. Rutherford, I. James, C. Crowley, M. Comer, R. Wolman, The acute effects of exercise on bone turnover. Int. J. Sports Med. 18, 247–251 (1997)

    Article  CAS  PubMed  Google Scholar 

  44. A. Tosun, N. Bölükbaşı, E. Çıngı, M. Beyazova, M. Ünlü, Acute effects of a single session of aerobic exercise with or without weight-lifting on bone turnover in healthy young women. Mod. Rheumatol. 16, 300–304 (2006)

    Article  PubMed  Google Scholar 

  45. B. Tartibian, B. Hajizadeh Maleki, J. Kanaley, K. Sadeghi, Long-term aerobic exercise and omega-3 supplementation modulate osteoporosis through inflammatory mechanisms in post-menopausal women: a randomized, repeated measures study. Nutr. Metab. (Lond.) 8, 71 (2011)

    Article  CAS  Google Scholar 

  46. M.E. Lester, M.L. Urso, R.K. Evans, J.R. Pierce, B.A. Spiering, C.M. Maresh, D.L. Hatfield, W.J. Kraemer, B.C. Nindl, Influence of exercise mode and osteogenic index on bone biomarker responses during short-term physical training. Bone 45, 768–776 (2009)

    Article  PubMed  Google Scholar 

  47. H.W. Woitge, B. Friedmann, S. Suttner, I. Farahmand, M. Müller, H. Schmidt-Gayk, P. Baertsch, R. Ziegler, M.J. Seibel, Changes in bone turnover induced by aerobic and anaerobic exercise in young males. J. Bone Miner. Res. 13, 1797–1804 (1998)

    Article  CAS  PubMed  Google Scholar 

  48. J. Bowen, M. Noakes, P.M. Clifton, A high dairy protein, high-calcium diet minimizes bone turnover in overweight adults during weight loss. J. Nutr. 134, 568–573 (2004)

    CAS  PubMed  Google Scholar 

  49. J.W. Nieves, Osteoporosis: the role of micronutrients. Am. J. Clin. Nutr. 81, 1232S–1239S (2005)

    CAS  PubMed  Google Scholar 

  50. J.T. Truong, X. Fu, E. Saltzman, A. Al Rajabi, G.E. Dallal, C.M. Gundberg, S.L. Booth, Age group and sex do not influence responses of vitamin K biomarkers to changes in dietary vitamin K. J. Nutr. 142, 936–941 (2012)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  51. A.C. Ross, J.E. Manson, S.A. Abrams, J.F. Aloia, P.M. Brannon, S.K. Clinton, R.A. Durazo-Arvizu, J.C. Gallagher, R.L. Gallo, G. Jones, C.S. Kovacs, S.T. Mayne, C.J. Rosen, S.A. Shapses, The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. J. Clin. Endocrinol. Metab. 96, 53–58 (2011)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

Supported by NIH/NIDDK Grant No. R01AGDK20583, Wake Forest University Claude D. Pepper Older Americans Independence Center (P30-AG21332), Wake Forest University General Clinical Research Center (M01-RR07122) and USDA Agricultural Research Service under Cooperative Agreement No. 58-1950-7-707.

Conflict of interest

The authors have no conflicts of interest to disclose.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Sarah L. Booth.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 13 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Centi, A.J., Booth, S.L., Gundberg, C.M. et al. Osteocalcin carboxylation is not associated with body weight or percent fat changes during weight loss in post-menopausal women. Endocrine 50, 627–632 (2015). https://doi.org/10.1007/s12020-015-0618-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12020-015-0618-6

Keywords

Navigation