title: Clinical Trials Express: fracture risk reduction with denosumab in Japanese postmenopausal women and men with osteoporosis: denosumab fracture intervention randomized placebo controlled trial (DIRECT).
abstract: BACKGROUND
  Denosumab 60 mg sc injection every 6 months for 36 months was well tolerated and effective in reducing the incidence of vertebral, nonvertebral, and hip fracture in predominantly Caucasian postmenopausal women with osteoporosis.
  
  
  OBJECTIVE
  The objective of this phase 3 fracture study was to examine the antifracture efficacy and safety of denosumab 60 mg in Japanese women and men with osteoporosis compared with placebo.
  
  
  METHODS
  A randomized, double-blind, placebo-controlled trial with an open-label active comparator as a referential arm was conducted.
  
  
  METHODS
  Subjects were 1262 Japanese patients with osteoporosis aged 50 years or older, who had one to four prevalent vertebral fractures.
  
  
  METHODS
  Subjects were randomly assigned to receive denosumab 60 mg sc every 6 months (n = 500), placebo for denosumab (n = 511), or oral alendronate 35 mg weekly (n = 251). All subjects received daily supplements of calcium and vitamin D.
  
  
  METHODS
  The primary endpoint was the 24-month incidence of new or worsening vertebral fracture for denosumab vs placebo.
  
  
  RESULTS
  Denosumab significantly reduced the risk of new or worsening vertebral fracture by 65.7%, with incidences of 3.6% in denosumab and 10.3% in placebo at 24 months (hazard ratio 0.343; 95% confidence interval 0.194-0.606, P = .0001). No apparent difference in adverse events was found between denosumab and placebo during the first 24 months of the study.
  
  
  CONCLUSIONS
  These results provide evidence of the efficacy and safety of denosumab 60 mg sc every 6 months in Japanese subjects with osteoporosis.
authors.affiliation: National Center for Global Health and Medicine (T.Nakam.), Tokyo 162-8655, Japan; Department of Medicine and Bioregulatory Sciences (T.Matsu.), University of Tokushima Graduate School of Medical Sciences, Tokushima 770-8503, Japan; Internal Medicine 1 (T.Su.), Shimane University Faculty of Medicine, Izumo 693-8501, Japan; Kenkoin Clinic (T.H.), Tokyo 104-0061, Japan; Department of Geriatric (T.Mi.), Osaka City University Medical School, Osaka 545-8585, Japan; Hori Hospital (I.G.), Yokohama 246-0021, Japan; Department of Orthopedic Surgery (H.Y.), Osaka University Graduate School of Medicine, Suita 565-0871, Japan; The First Department of Internal Medicine (Y.T.), University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan; Department of Orthopaedic Surgery Faculty of Medicine (S.T.), The University of Tokyo, Tokyo 113-8655, Japan; Department of Nuclear Medicine (T.So.), Kawasaki Medical School (M.F.), Kurashiki 701-0192, Japan; Tamana Central Hospital (T.Nakan.), Tamana 865-0064, Japan; Division of Radiology (M.I.), Nagasaki University School of Medicine, Nagasaki 852-8501, Japan; Department of Biostatistics (S.M.), Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan; Osaka University Graduate School of Dentistry (T.Y.), Suita 565-0871, Japan; Daiichi Sankyo Co Ltd (H.T., K.W., T.O.), Tokyo 140-8710, Japan; and Research Institute and Practice for Involutional Diseases (M.S.), Azumino 399-8101, Japan.
authors.forename: Toshitaka
authors.initials: T
authors.lastname: Nakamura
authors.forename: Toshio
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Toshitsugu
authors.initials: T
authors.lastname: Sugimoto
authors.forename: Takayuki
authors.initials: T
authors.lastname: Hosoi
authors.forename: Takami
authors.initials: T
authors.lastname: Miki
authors.forename: Itsuo
authors.initials: I
authors.lastname: Gorai
authors.forename: Hideki
authors.initials: H
authors.lastname: Yoshikawa
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Sakae
authors.initials: S
authors.lastname: Tanaka
authors.forename: Teruki
authors.initials: T
authors.lastname: Sone
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Nakano
authors.forename: Masako
authors.initials: M
authors.lastname: Ito
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Matsui
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Yoneda
authors.forename: Hideo
authors.initials: H
authors.lastname: Takami
authors.forename: Ko
authors.initials: K
authors.lastname: Watanabe
authors.forename: Taisuke
authors.initials: T
authors.lastname: Osakabe
authors.forename: Masataka
authors.initials: M
authors.lastname: Shiraki
authors.forename: Masao
authors.initials: M
authors.lastname: Fukunaga
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D019386:Alendronate / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000069448:Denosumab; D005260:Female; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D010024:Osteoporosis / Q000188:drug therapy* / Q000453:epidemiology; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy* / Q000453:epidemiology; D058866:Osteoporotic Fractures / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control*; D010919:Placebos; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D010919:Placebos; D000069448:Denosumab; D019386:Alendronate