Evaluation of serum undercarboxylated osteocalcin in premenopausal rheumatoid arthritis patients: its correlation with disease activity and bone mineral density



There is a definite role of vitamin K and undercarboxylated osteocalcin (ucOC) on bone mineral density (BMD) in rheumatoid arthritis (RA). Up to our knowledge, no other work has discussed the relationship between ucOC and BMD in premenopausal RA patients and its correlation with disease activity.

Patients and methods

Sixty premenopausal RA female patients and 30 healthy premenopausal controls of matched age were included. All were subjected to clinical examination, laboratory investigations including serum level of ucOC, disease activity measurement using DAS-28 score, and BMD measurement using dual-energy X-ray absorptiometry.


The level of ucOC was significantly higher in patients with RA than in controls (P<0.001). BMD in patients was found to be significantly lower compared with controls in the spine, femoral neck, and distal radius areas. The most frequent osteoporotic site according to Z-score was the spine (16.7%), followed by the femoral neck (8.3%) and distal radius (6.7%). The most common commonest osteopenic site according to Z-score was the spine (31.7%), followed by the femoral neck (21.7%) and the distal radius (16.7%). Our work showed that ucOC level was found to be high in premenopausal RA patients with higher DAS values than in those with lower DAS value (P<0.001). In our work, BMD measured by means of dual-energy X-ray absorptiometry scan was found to be lower with higher DAS values and vice versa.


Serum level of ucOC (which is a mirror of vitamin K deficiency) was found to be higher in premenopausal RA patients than controls and correlated positively with disease activity and inversely with BMD measurement.


  1. 1

    Chung SJ, Kwon YJ, Park MC, Park YB, Lee SK. The correlation between increased serumconcentrations of interleukin-6 family cytokines and disease activity in rheumatoid arthritis patients. Yonsei Med J 2011; 52:113–120.

    CAS  PubMed  Article  Google Scholar 

  2. 2

    Sinnesael M, Boonen S, Claessens F, Gielen E, Vandersschueren D. Testosterone and the male skeleton: a dual mode of action. J Osteoporos 2011; 2:403–428.

    Google Scholar 

  3. 3

    Wijbrandts CA, Klaasen R, Dijkgraaf MG, Gerlag DM, van Eck-Smit BL, Tak PP. Bone mineral density in rheumatoid arthritis patients 1 year after adalimumab therapy: arrest of bone loss. Ann RheumDis 2009; 68:373–376.

    CAS  Article  Google Scholar 

  4. 4

    Aizer J, Reed G, Onofrei A, Harrison MJ. Predictors of bone density testing in patients with rheumatoid arthritis. Rheumatol Int 2009; 29:897–905.

    CAS  PubMed  Article  Google Scholar 

  5. 5

    Koshihara Y, Hoshi K. Vitamin K2 enhances osteocalcin accumulation in the extracellular matrix of human osteoblasts in vitro. J Bone Miner Res 1997; 12:431438.

    Article  Google Scholar 

  6. 6

    Funovits J, Aletaha D, Bykerk V, Combe B, Dougados M, Emery P, et al. American College of Rheumatology/European League Against Rheumatism classification criteria for rheumatoid arthritis: Methodological Report Phase I. Ann Rheum Dis 2010; 69:1589–1595.

    PubMed  Article  Google Scholar 

  7. 7

    Prevoo ML, van’t Hof MA, Kuper HH, van Leeuwen MA, van de Putte LB, van Riel PL. Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum 1995; 38:44–48.

    CAS  Google Scholar 

  8. 8

    Fransen J, Riel PL. The disease activity score and EULAR response criteria. Clinc Expr Rheuma 2005; 39:93–109.

    Google Scholar 

  9. 9

    Dacie GV, Lwis SM. Practical hematology. 6th ed. London: Churchill Livingstone; 1985. 33–35.

    Google Scholar 

  10. 10

    Westergren A. Diagnostic tests: the erythrocyte sedimentation rate range and limitations of the technique. Triangle 1957; 3:20–25.

    CAS  PubMed  Google Scholar 

  11. 11

    Nikolaisen C, Rekvig OP, Nossent HC. Rheumatoid factor by laser nephelometry and Waaler-Rose assay: prognostic value in patients with recent-onset rheumatoid arthritis. Scand J Rheumatol 2005; 34:269–276.

    CAS  PubMed  Article  Google Scholar 

  12. 12

    Dominici R, Luraschi P, Franzini C. Measurement of C-reactive protein: two high sensitivity methods compared. J Clin Lab Anal 2004; 18:280–284.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  13. 13

    Leslie WD, Adler RA, El-Hajj Fuleihan G, Hodsman AB, Kendler DL, McClung M, et al. Application of the1994 WHO classification to populations other than postmenopausal Caucasian women: the 2005 ISCD Official Positions. J Clin Densitom 2006; 9:22–30.

    PubMed  Article  Google Scholar 

  14. 14

    Sakai, Yoshitada H, Akira H, Teppei K, Yoshiko T, Chihiro S, et al. The serum level of undercarboxylated osteocalcin (ucOC) in patients with rheumatoid arthritis a high dose of predonisolone decrease the serum level of ucOC [abstract]. Arthritis Rheum 2010; 62:983–910.

    Google Scholar 

  15. 15

    Van Summeren MJ, Vermeer C, Engelbert RH, Schurgers LJ, Takken T, Fischer K, Kuis W. Extremes in vitamin K status of bone are related to bone ultrasound properties in children with juvenile idiopathic arthritis. Clin Exp Rheumatol 2008; 26:484–491.

    PubMed  Google Scholar 

  16. 16

    Iwamoto J, Takada T, Sato Y. Vitamin K nutritional status and undercarboxylated osteocalcin in postmenopausal osteoporotic women treated with bisphosphonates. Asia Pac J Clin Nutr 2014; 23:256–262.

    CAS  PubMed  Google Scholar 

  17. 17

    Lee SG, Park YE, Park SH, Kim TK, Choi HJ, Lee SJ, et al. Increased frequency of osteoporosis and BMD below the expected range for age among South Korean women with rheumatoid arthritis. Int J Rheum Dis 2012; 15:289–296.

    PubMed  Article  Google Scholar 

  18. 18

    Lodder MC, Haugeberg G, Lems WF, Uhlig T, Orstavik RE, Kostense P, et al. Radiological damage is associated with low BMD and vertebral deformities in rheumatoid arthritis. Accepted 18 January 2004 The Oslo-Truro-Amsterdam (OSTRA) collaborative study. Arthritis Rheum Arthritis Care Res 2003; 49:209–215.

    Google Scholar 

  19. 19

    Laan RF, Buijs WC, Verbeek AL, Draad MP, Corstens FH, van de Putte LB, Van Riel PL. Bone mineral density in patients with recent onset rheumatoid arthritis: influence of disease activity and functional capacity. Ann Rheum Dis 1993; 52:21–26.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  20. 20

    Haugeberg G, Uhlig T, Falch JA, Halse JI, Kvien TK. Bone mineral density and frequency of osteoporosis in female patients with rheumatoid arthritis: results from 394 patients in the Oslo County Rheumatoid Arthritis register. Arthritis Rheum 2000; 43:522–530.

    CAS  PubMed  Article  Google Scholar 

  21. 21

    Hämäläinen H, Kaarela K, Kröger H, Kauppi M, Järvenpää S, Hakala M, Kotaniemi A. Changes in bone mineral density in premenopausal women with rheumatoid arthritis during a two-year follow-up. Joint Bone Spine 2007; 74:482–487.

    PubMed  Article  Google Scholar 

  22. 22

    Hui SL, Perkins AJ, Zhou L, Longcope C, Econs MJ, Peacock M, et al. Bone loss at the femoral neck in premenopausal white women: effects of weight change and sex-hormone levels. J Clin Endocrinol Metab 2002; 87:1539–1543.

    CAS  PubMed  Article  Google Scholar 

  23. 23

    Shenstone BD, Mahmoud A, Woodward R, Elvins D, Palmer R, Ring EF, Bhalla AK. Longitudinal bone mineral density changes in early rheumatoid arthritis. Br J Rheumatol 1994; 33:541–545.

    CAS  PubMed  Article  Google Scholar 

  24. 24

    Gough AK, Lilley J, Eyre S, Holder RL, Emery P. Generalised bone loss in patients with early rheumatoid arthritis. Lancet 1994; 344:23–27.

    CAS  PubMed  Article  Google Scholar 

Download references

Author information



Corresponding author

Correspondence to Heba Ahmed Esaily MD.

Additional information

This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work noncommercially, as long as the author is credited and the new creations are licensed under the identical terms.

Rights and permissions

This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Esaily, H.A., Hewala, A.E.S.A., Soliman, S.G. et al. Evaluation of serum undercarboxylated osteocalcin in premenopausal rheumatoid arthritis patients: its correlation with disease activity and bone mineral density. Egypt Rheumatol Rehabil 43, 131–136 (2016). https://doi.org/10.4103/1110-161X.189822

Download citation


  • disease activity
  • osteoporosis
  • premenopause
  • rheumatoid arthritis
  • undercarboxylated osteocalcin