title: Vitamin K2 administration is associated with decreased disease activity in patients with rheumatoid arthritis.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  VitK2 may have the potential to improve disease activity besides osteoporosis in RA.
authors.affiliation: Department of Orthopaedics, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Ebina
authors.forename: Kenrin
authors.initials: K
authors.lastname: Shi
authors.forename: Makoto
authors.initials: M
authors.lastname: Hirao
authors.forename: Shoichi
authors.initials: S
authors.lastname: Kaneshiro
authors.forename: Tokimitsu
authors.initials: T
authors.lastname: Morimoto
authors.forename: Kota
authors.initials: K
authors.lastname: Koizumi
authors.forename: Hideki
authors.initials: H
authors.lastname: Yoshikawa
authors.forename: Jun
authors.initials: J
authors.lastname: Hashimoto
mesh_terms: D000368:Aged; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy*; D015519:Bone Density / Q000187:drug effects; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008875:Middle Aged; D015675:Osteocalcin / Q000097:blood; D012720:Severity of Illness Index; D016896:Treatment Outcome; D024482:Vitamin K 2 / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D015675:Osteocalcin; D024482:Vitamin K 2