Modern Rheumatology

, Volume 23, Issue 5, pp 1001–1007 | Cite as

Vitamin K2 administration is associated with decreased disease activity in patients with rheumatoid arthritis

  • Kosuke Ebina
  • Kenrin ShiEmail author
  • Makoto Hirao
  • Shoichi Kaneshiro
  • Tokimitsu Morimoto
  • Kota Koizumi
  • Hideki Yoshikawa
  • Jun Hashimoto
Original Article



Vitamin K2 (VitK2) is reported to induce not only bone mineralization of human osteoblasts and apoptosis of osteoclasts, but also apoptosis of rheumatoid arthritis (RA) synovial cells, while its clinical effect on disease activity of RA remains unknown.


158 female RA patients (mean age 62.5 years) who had not been treated with warfarin, biologics, or teriparatide were enrolled in this study. VitK2 (45 mg/day) was administered in 70 patients with a serum undercarboxylated osteocalcin level of >4.5 ng/ml or with decreased bone mineral density in spite of the treatment with other anti-osteoporosis medications, regardless of RA disease activity. A longitudinal study was conducted in 52 patients who were additionally treated with VitK2 without changing their other medications for three months.


In the cross-sectional study, as compared to the VitK2-naïve group (n = 88), the VitK2-treated group (n = 70) showed lower serum CRP (1.7 ± 0.2 vs. 0.5 ± 0.1 mg/dl; P < 0.001), MMP-3 (220.4 ± 21.9 vs. 118.0 ± 14.4 ng/ml; P < 0.001), and DAS28-CRP (2.9 ± 0.1 vs. 2.4 ± 0.1; P < 0.05). In the longitudinal study, patients who were additionally treated with VitK2 showed significant decreases in serum CRP (1.1 ± 0.2 to 0.6 ± 0.2 mg/dl; P < 0.001), MMP-3 (160.1 ± 25.6 to 125.0 ± 17.8 ng/ml; P < 0.05), and DAS28-CRP (3.1 ± 0.2 to 2.4 ± 0.1; P < 0.001).


VitK2 may have the potential to improve disease activity besides osteoporosis in RA.


C-reactive protein Disease Activity Score assessing 28 joints with CRP Matrix metalloproteinase-3 Rheumatoid arthritis Vitamin K2 



The authors thank Tadashi Koga (Biometrics Department, Shin Nippon Biomedical Laboratories, Ltd., Kagoshima, Japan) and Sayaka Aoki (Department of Medical Informatics at Osaka University Medical Hospital) for their excellent help with the statistical analysis.

Conflict of interest



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Copyright information

© Japan College of Rheumatology 2012

Authors and Affiliations

  • Kosuke Ebina
    • 1
  • Kenrin Shi
    • 1
    Email author
  • Makoto Hirao
    • 2
  • Shoichi Kaneshiro
    • 1
  • Tokimitsu Morimoto
    • 1
  • Kota Koizumi
    • 1
  • Hideki Yoshikawa
    • 1
  • Jun Hashimoto
    • 3
  1. 1.Department of OrthopaedicsOsaka University Graduate School of MedicineSuitaJapan
  2. 2.Department of OrthopaedicsNational Hospital Organization Osaka Minami Medical CenterKawachinaganoJapan
  3. 3.Department of RheumatologyNational Hospital Organization Osaka Minami Medical CenterKawachinaganoJapan

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