Osteoclast Inhibitory Effects of Vitamin K₂ Alone or in Combination with Etidronate or Risedronate in Patients with Rheumatoid Arthritis: 2-Year Results

MINORU MORISHITA, MASAKAZU NAGASHIMA, KOICHI WAUKE, HIROSHI TAKAHASHI, and KENJI TAKENOUCHI

ABSTRACT.

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-kB 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.

Conclusion. 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. (First Release Feb 1 2008; J Rheumatol 2008;35:407-13)

Key Indexing Terms:

RHEUMATOID ARTHRITIS
VITAMIN K₂
ETIDRONATE
RISEDRONATE
RECEPTOR ACTIVATOR OF NUCLEAR FACTOR-kB LIGAND
OSTEOPROTEGERIN

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From the Department of Rheumatology, Tokyo Metropolitan Bokutoh Hospital; and Department of Joint Disease and Rheumatism, Nippon Medical School, Tokyo, Japan.

Supported by the Japan Osteoporosis Foundation.

M. Morishita, MD; K. Takenouchi, MD, Department of Joint Disease and Rheumatism, Nippon Medical School; K. Wauke, MD, PhD; H. Takahashi, MD, PhD, Department of Rheumatology, Tokyo Metropolitan Bokutoh Hospital; M. Nagashima, MD, PhD, Director, Department of Rheumatology, Tokyo Metropolitan Bokutoh Hospital and Department of Joint Disease and Rheumatism, Nippon Medical School.

Address reprint requests to Dr. M. Nagashima, Department of Rheumatology, Tokyo Metropolitan Bokutoh Hospital, 4-23-15 Kotobashi, Sumida-ku, Tokyo 130-8575, Japan. E-mail: m_nagashima@bokutoh-hp.metro.tokyo.jp

Accepted for publication October 15, 2007.

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