Background It has been reported that Vitamin K2 (VitK2) is a key inducer of bone mineralization in human osteoblasts and also inhibits osteoclastogenesis by induction of the osteoclast apoptosis (1). Human studies have demonstrated that VitK2 is proposed to be an effective treatment for osteoporosis and prevention of fractures (2), and is frequently used for the treatment of osteoporosis in Japan and other Asian countries. In addition, VitK2 has antitumor effects through its proapoptotic effects. Recent study showed that VitK2 also induces apoptosis of synovial cells of RA patients in vitro and inhibits development of collagen-induced arthritis of rats in vivo (3), although no clinical studies have been shown.

Objectives The aim of this study is to assess the effect of oral VitK2 intake (45mg/day) on RA disease activity.

Methods 129 female RA patients without biologics (mean age 62.4 years old, mean disease duration 14.7 years, mean DAS28-CRP 2.7, 65.9% taking methotrexate (MTX) with average dose 4.4mg/week, 65.1% taking prednisolone (PSL) with average dose 2.9mg/day) were enrolled. Cross-sectional study was conducted by investigating correlation with VitK2 intake and serum CRP, Matrix Metalloproteinase-3 (MMP-3), IL-6 levels, Bone mineral density (BMD) of lumbar spine and hip, and bone metabolism markers.

Results Serum CRP levels were significantly low in VitK2-treated group compared to VitK2-naïve group (0.5±0.7 mg/dl versus 1.7±2.0 mg/dl; R=-0.34, P<0.001) as well as serum MMP-3 levels (127.6±127.6 ng/ml versus 220.4±205.7 ng/ml; R=-0.28, P<0.01). Among variables which showed significant correlation with CRP and MMP-3 (VitK2 dosage, PSL dosage, IL-6, and DAS28-CRP), VitK2 dosage and PSL dosage showed significant correlation (R=-0.28 P<0.05). After adjustment with PSL dosage by two-way analysis of variance, VitK2 dosage still showed significant correlation with CRP and MMP-3. In addition, 22 patients showed tendency to decrease in both CRP (1.0±1.7$→ $0.6±1.2 mg/dl) and MMP-3 (107.1±69.0$→ $81.2±75.5 ng/ml) after VitK2 treatment for 3 months without change of other prescription. VitK2 showed no significant correlation with IL-6, BMD, and bone metabolism markers in this period.

Conclusions In female RA patients, serum CRP and MMP-3 levels were significantly low in VitK2-treated group compared to VitK2-naïve group. VitK2 may represent a new strategy for the treatment of RA presumably in the setting of combination therapy with other disease-modifying antirheumatic drugs.

1. Yamaguchi, M., Taguchi, H., Gao, Y. H., Igarashi, A., and Tsukamoto, Y. (1999) Effect of vitamin K2 (menaquinone-7) in fermented soybean (natto) on bone loss in ovariectomized rats. J. Bone Miner. Metab. 17, 23–29.

2. Shiraki, M., Shiraki, Y., Aoki, C., and Miura, M. (2000) Vitamin K2 (menatetrenone) effectively prevents fractures and sustains lumbar bone mineral density in osteoporosis. J. Bone Miner. Res. 15, 515–521.

3. Okamoto H. (2008) Vitamin K and rheumatoid arthritis. IUBMB Life. Jun;60(6):355-61.

Disclosure of Interest None Declared