title: Comparison of concurrent treatment with vitamin K2and risedronate compared with treatment with risedronate alone in patients with osteoporosis: Japanese Osteoporosis Intervention Trial-03.
abstract: The aim of this study was to investigate the efficacy of concurrent treatment with vitamin K2and risedronate compared with treatment with risedronate alone in patients with osteoporosis and to explore subsets of patients for which concurrent treatment is particularly efficacious. Women with osteoporosis aged 65 years or older were recruited from 123 institutes in Japan and allocated to take either vitamin K2(45 mg/day) and risedronate (2.5 mg/day or 17.5 mg/week) or risedronate (2.5 mg/day or 17.5 mg/week) alone. The primary end point was the incidence of any fracture (vertebral and nonvertebral). The secondary end points were bone mineral density, height, undercarboxylated osteocalcin concentration, quality of life, and safety. Over a 2-year follow-up, vertebral or nonvertebral fractures occurred in 117 or 22 sites respectively among 931 patients in the risedronate and vitamin K2group and in 104 or 26 sites respectively among 943 patients in the risedronate alone group. The rates of any incident fracture were similar between the two groups (incidence rate ratio 1.074, 95 % confidence interval 0.811-1.422, p = 0.62), implying that the primary end point was not met. There were no differences in the degree of increase in bone mineral density between the two groups. Undercarboxylated osteocalcin concentration decreased from 5.81 ± 3.93 ng/mL to 2.59 ± 1.52 ng/mL at 6 months in the risedronate and vitamin K2group, whereas the change in the risedronate alone group was minimal (from 5.96 ± 4.36 ng/mL to 4.05 ± 3.40 ng/mL at 6 months) (p < 0.01). The treatment discontinuation rate was higher in the risedronate and vitamin K2group than in the risedronate alone group (10.0 % vs 6.7 %). No unknown adverse drug reactions were reported. In conclusion, concurrent treatment with vitamin K2and risedronate was not efficacious compared with monotherapy with risedronate in terms of fracture prevention.
authors.affiliation: Department of Pharmacoepidemiology, Graduate School of Medicine and Public Health, Kyoto University, Kyoto, Japan. tanaka.shiro.8n@kyoto-u.ac.jp.
authors.forename: Shiro
authors.initials: S
authors.lastname: Tanaka
authors.affiliation: Public Health Research Foundation, Tokyo, Japan.
authors.forename: Teruhiko
authors.initials: T
authors.lastname: Miyazaki
authors.affiliation: Biostatistics Division, Clinical Research Support Center, University of Tokyo Hospital, Tokyo, Japan.
authors.forename: Yukari
authors.initials: Y
authors.lastname: Uemura
authors.affiliation: Public Health Research Foundation, Tokyo, Japan.
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Miyakawa
authors.affiliation: Department of Obstetrics and Gynecology, Hori Hospital, Yokohama, Japan.
authors.forename: Itsuo
authors.initials: I
authors.lastname: Gorai
authors.affiliation: Department of Orthopedic Surgery, University of Occupational and Environmental Health School of Medicine, Fukuoka, Japan.
authors.forename: Toshitaka
authors.initials: T
authors.lastname: Nakamura
authors.affiliation: Kawasaki Medical School, Okayama, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Fukunaga
authors.affiliation: Department of Integrated Science and Engineering for Sustainable Society, Chuo University, Tokyo, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Ohashi
authors.affiliation: Department of Obstetrics and Gynecology, International University of Health and Welfare, Tokyo, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Ohta
authors.affiliation: Bone and Joint Surgery, Seirei Hamamatu General Hospital, Shizuoka, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Mori
authors.affiliation: School of Health Science, Tottori University Faculty of Medicine, Tottori, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hagino
authors.affiliation: Kenkoin Clinic, Tokyo, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Hosoi
authors.affiliation: Internal Medicine 1, Shimane University Faculty of Medicine, Shimane, Japan.
authors.forename: Toshitsugu
authors.initials: T
authors.lastname: Sugimoto
authors.affiliation: Department of Orthopaedic Surgery, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Itoi
authors.affiliation: Japan Osteoporosis Foundation, Tokyo, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Orimo
authors.affiliation: Department of Internal Medicine, Research Institute and Practice for Involutional Diseases, Nagano, Japan.
authors.forename: Masataka
authors.initials: M
authors.lastname: Shiraki
mesh_terms: D000368:Aged; D050071:Bone Density Conservation Agents / Q000009:adverse effects / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D023381:Endpoint Determination; D005260:Female; D006801:Humans; D015994:Incidence; D007564:Japan; D055118:Medication Adherence; D008875:Middle Aged; D010024:Osteoporosis / Q000188:drug therapy*; D058866:Osteoporotic Fractures / Q000188:drug therapy / Q000453:epidemiology; D011788:Quality of Life; D000068296:Risedronic Acid / Q000009:adverse effects / Q000627:therapeutic use*; D024482:Vitamin K 2 / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D050071:Bone Density Conservation Agents; D024482:Vitamin K 2; D000068296:Risedronic Acid
keywords: Osteoporosis; Risedronate; Undercarboxylated osteocalcin; Vitamin K2