title: The HORIZON Recurrent Fracture Trial: design of a clinical trial in the prevention of subsequent fractures after low trauma hip fracture repair.
abstract: OBJECTIVE
  To present the novel design of a trial testing the safety and efficacy of a yearly bisphosponate, zoledronic acid, in preventing new clinical fractures in patients with recent low trauma hip fracture repair.
  
  
  METHODS
  Randomized, placebo-controlled, triple-blind study. One hundred and fifteen clinical centers worldwide are recruiting approximately 1714 subjects aged 50 years and over (no upper age limit, median age of enrolled subjects to date 79 years) who have undergone surgical repair of a low trauma hip fracture in the preceding 90 days. Patients will be assigned at random to an intervention group (5 mg zoledronic acid intravenously yearly) or a control group (placebo infusion yearly). Both groups receive a loading dose of Vitamin D2 or D3 IM or orally, followed by 800-1200 IU Vitamin D and 1000-1500 mg elemental calcium orally on a daily basis. Concomitant therapy with calcitonin, hormone replacement therapy, selective estrogen receptor modulators, tibolone, and external hip protectors are allowed.
  
  
  METHODS
  The primary endpoint is subsequent skeletal fractures as adjudicated by a clinical endpoints committee blinded to intervention status. Secondary outcomes include delayed hip fracture healing, changes in bone mineral density, and health resource utilization. Subjects will be recruited over a 3-4 year period and will be followed until 211 primary endpoints are accrued and adjudicated.
  
  
  CONCLUSIONS
  This randomized clinical trial is novel among osteoporosis therapies as it (1). targets hip fracture patients, a previously understudied group, and (2). uses only clinically evident fractures as the primary outcome. Ethical and practical considerations in studying this frail population are discussed.
authors.affiliation: Center for the Study of Aging and Human Development, Box 3003, Duke University Medical Center, Durham, NC 27710, USA. colon001@mc.duke.edu
authors.forename: Cathleen S
authors.initials: CS
authors.lastname: Colón-Emeric
authors.forename: John
authors.initials: J
authors.lastname: Caminis
authors.forename: Theodore T
authors.initials: TT
authors.lastname: Suh
authors.forename: Carl F
authors.initials: CF
authors.lastname: Pieper
authors.forename: Cheri
authors.initials: C
authors.lastname: Janning
authors.forename: Jay
authors.initials: J
authors.lastname: Magaziner
authors.forename: Jonathan
authors.initials: J
authors.lastname: Adachi
authors.forename: Theresa
authors.initials: T
authors.lastname: Rosario-Jansen
authors.forename: Peter
authors.initials: P
authors.lastname: Mesenbrink
authors.forename: Zeb D
authors.initials: ZD
authors.lastname: Horowitz
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Lyles
mesh_terms: D015519:Bone Density; D002118:Calcium / Q000008:administration & dosage; D019049:Developed Countries; D004164:Diphosphonates / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006620:Hip Fractures / Q000188:drug therapy* / Q000601:surgery; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010919:Placebos; D016032:Randomized Controlled Trials as Topic; D014807:Vitamin D / Q000008:administration & dosage; D000077211:Zoledronic Acid
chemical_list: D004164:Diphosphonates; D007093:Imidazoles; D010919:Placebos; D014807:Vitamin D; D000077211:Zoledronic Acid; D002118:Calcium