Osteoclast inhibitory effects of vitamin K2 alone or in combination with etidronate or risedronate in patients with rheumatoid arthritis: 2-year results.
OBJECTIVE
To investigate the effects of vitamin K2 (Vit K2) alone or in combination with etidronate and risedronate on bone loss, osteoclast induction, and inflammation in patients with rheumatoid arthritis (RA).


METHODS
Subjects comprised 79 patients with RA who were receiving prednisolone, divided into 3 groups: Group K, Vit K2 alone; Group KE, Vit K2 plus etidronate; and Group KR, Vit K2 plus risedronate. During a 24-month treatment and followup period, levels of N-terminal telopeptide of type I collagen (NTx) and bone alkaline phosphatase were measured. Bone mineral density (BMD) of the 3 groups was measured using dual-energy x-ray absorptiometry. Damage score to fingers on radiographic findings were measured according to the Larsen method. Serum levels of receptor activator of nuclear factor-kappaB ligand (RANKL) and osteoprotegerin (OPG) were measured.


RESULTS
Falls in rate of change of BMD decreased after 18 months in groups KR and KE. Larsen damage scores indicated a significant difference between Group KE and other groups. Significant decreases in serum NTx were observed in groups KE and KR at all timepoints, but not in Group K. Levels of RANKL decreased significantly in all 3 groups.


CONCLUSIONS
Vit K2 alone or in combination with bisphosphonates for treatment of osteoporosis in patients with RA may inhibit osteoclast induction via decreases in levels of RANKL.
Morishita
Minoru
M
Department of Joint Disease and Rheumatism, Nippon Medical School, Tokyo, Japan.
Nagashima
Masakazu
M
Wauke
Koichi
K
Takahashi
Hiroshi
H
Takenouchi
Kenji
K
D000368:Aged; D000469:Alkaline Phosphatase / Q000187:drug effects; D001172:Arthritis, Rheumatoid / Q000188:drug therapy; D015519:Bone Density / Q000187:drug effects*; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D015331:Cohort Studies; D024042:Collagen Type I / Q000187:drug effects; D004359:Drug Therapy, Combination; D012968:Etidronic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010010:Osteoclasts / Q000187:drug effects; D010024:Osteoporosis / Q000139:chemically induced / Q000188:drug therapy*; D053244:Osteoprotegerin / Q000187:drug effects; D010455:Peptides / Q000187:drug effects; D011239:Prednisolone / Q000009:adverse effects; D011446:Prospective Studies; D053245:RANK Ligand / Q000187:drug effects; D000068296:Risedronic Acid; D024482:Vitamin K 2 / Q000494:pharmacology*
D050071:Bone Density Conservation Agents; D024042:Collagen Type I; D053244:Osteoprotegerin; D010455:Peptides; D053245:RANK Ligand; C505688:TNFSF11 protein, human; C052929:collagen type I trimeric cross-linked peptide; D024482:Vitamin K 2; D011239:Prednisolone; D000469:Alkaline Phosphatase; D000068296:Risedronic Acid; D012968:Etidronic Acid