title: Efficacy and safety of once-yearly zoledronic acid in Japanese patients with primary osteoporosis: two-year results from a randomized placebo-controlled double-blind study (ZOledroNate treatment in Efficacy to osteoporosis; ZONE study).
abstract: In a 2-year randomized, placebo-controlled study of 665 Japanese patients with primary osteoporosis, once-yearly administration of zoledronic acid (5 mg) reduced the risk of new morphometric vertebral fractures.
  
  
  
  The purpose of this study was to determine the efficacy and safety of once-yearly intravenous infusion of ZOL in Japanese patients with primary osteoporosis.
  
  
  
  This was a two-year multicenter, randomized, placebo-controlled, double-blind, parallel-group comparative study (ZONE Study). Subjects were 665 Japanese patients between the ages of 65 and 89 years who had prevalent vertebral fracture. Subjects were randomly assigned to receive once-yearly intravenous infusion of 5 mg of ZOL or placebo at baseline and 12 months.
  
  
  
  The 2-year incidence of new morphometric vertebral fracture was 3.0 % (10/330 subjects) in the ZOL group and 8.9 % (29/327) in the placebo group (p = 0.0016). The 24-month cumulative incidence of new morphometric vertebral fracture was 3.3 % in the ZOL group versus 9.7 % in the placebo group (log-rank test: p = 0.0029; hazard ratio: 0.35; 95 % confidence interval: 0.17-0.72). The cumulative incidence of any clinical fracture, clinical vertebral fracture, and non-vertebral fracture was significantly reduced in the ZOL group by 54, 70, and 45 %, respectively, compared to the placebo group. At 24 months, ZOL administration increased bone mineral density in the lumbar spine, femoral neck, and total hip (t test: p < 0.0001). No new adverse events or osteonecrosis of the jaw were observed in this study.
  
  
  
  Once-yearly administration of ZOL 5 mg to Japanese patients with primary osteoporosis reduced the risk of new morphometric vertebral fractures and was found to be safe.
authors.affiliation: Japan Osteoporosis Foundation, 11-2 Kobuna-cho, Nihonbashi, Chuo-ku, Tokyo, 103-0024, Japan. t-nak@utopia.ocn.ne.jp.
authors.forename: T
authors.initials: T
authors.lastname: Nakamura
authors.affiliation: Kawasaki Medical School, 577 Matsushima, Kurashiki City, Okayama, 701-0192, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Fukunaga
authors.affiliation: Tamana Central Hospital, 1950 Naka, Tamana City, Kumamoto, 865-0064, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Nakano
authors.affiliation: Nojima Hospital, 2714-1 Sesakimachi, Kurayoshi City, Tottori, 682-0863, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Kishimoto
authors.affiliation: Nagasaki University, 1-14 Bunkyomachi, Nagasaki City, Nagasaki, 852-8521, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Ito
authors.affiliation: School of Health Science, Tottori University, 86 Nishicho, Yonago City, Tottori, 683-8503, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Hagino
authors.affiliation: Department of Nuclear Medicine, Kawasaki Medical School, 577 Matsushima, Kurashiki City, Okayama, 701-0192, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Sone
authors.affiliation: Department of Oral and Maxillofacial Radiology, Matsumoto Dental University, 1780 Hirooka Gobara, Shiojiri City, Nagano, 399-0781, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Taguchi
authors.affiliation: Asahi Kasei Pharma Corporation, 1-105 Jinbocho, Kanda, Chiyoda-ku, Tokyo, 101-8101, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Tanaka
authors.affiliation: Asahi Kasei Pharma Corporation, 1-105 Jinbocho, Kanda, Chiyoda-ku, Tokyo, 101-8101, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Ohashi
authors.affiliation: Asahi Kasei Pharma Corporation, 1-105 Jinbocho, Kanda, Chiyoda-ku, Tokyo, 101-8101, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Ota
authors.affiliation: Research Institute and Practice for Involutional Diseases, 1610-1 Meisei, Misato, Azumino, Nagano, 399-8101, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Shiraki
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D004164:Diphosphonates / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D007262:Infusions, Intravenous; D007564:Japan / Q000453:epidemiology; D008297:Male; D010024:Osteoporosis / Q000188:drug therapy* / Q000453:epidemiology / Q000503:physiopathology; D058866:Osteoporotic Fractures / Q000453:epidemiology / Q000503:physiopathology / Q000517:prevention & control; D016103:Spinal Fractures / Q000453:epidemiology / Q000503:physiopathology / Q000517:prevention & control; D016896:Treatment Outcome; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid
keywords: Antiresorptives; Biochemical markers of bone turnover; Clinical trials; Fracture prevention; Osteoporosis