title: Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis.
abstract: BACKGROUND
  A single infusion of intravenous zoledronic acid decreases bone turnover and improves bone density at 12 months in postmenopausal women with osteoporosis. We assessed the effects of annual infusions of zoledronic acid on fracture risk during a 3-year period.
  
  
  METHODS
  In this double-blind, placebo-controlled trial, 3889 patients (mean age, 73 years) were randomly assigned to receive a single 15-minute infusion of zoledronic acid (5 mg) and 3876 were assigned to receive placebo at baseline, at 12 months, and at 24 months; the patients were followed until 36 months. Primary end points were new vertebral fracture (in patients not taking concomitant osteoporosis medications) and hip fracture (in all patients). Secondary end points included bone mineral density, bone turnover markers, and safety outcomes.
  
  
  RESULTS
  Treatment with zoledronic acid reduced the risk of morphometric vertebral fracture by 70% during a 3-year period, as compared with placebo (3.3% in the zoledronic-acid group vs. 10.9% in the placebo group; relative risk, 0.30; 95% confidence interval [CI], 0.24 to 0.38) and reduced the risk of hip fracture by 41% (1.4% in the zoledronic-acid group vs. 2.5% in the placebo group; hazard ratio, 0.59; 95% CI, 0.42 to 0.83). Nonvertebral fractures, clinical fractures, and clinical vertebral fractures were reduced by 25%, 33%, and 77%, respectively (P<0.001 for all comparisons). Zoledronic acid was also associated with a significant improvement in bone mineral density and bone metabolism markers. Adverse events, including change in renal function, were similar in the two study groups. However, serious atrial fibrillation occurred more frequently in the zoledronic acid group (in 50 vs. 20 patients, P<0.001).
  
  
  CONCLUSIONS
  A once-yearly infusion of zoledronic acid during a 3-year period significantly reduced the risk of vertebral, hip, and other fractures. (ClinicalTrials.gov number, NCT00049829.)
authors.affiliation: University of California, San Francisco, San Francisco, CA 94107, USA. dblack@psg.ucsf.edu
authors.forename: Dennis M
authors.initials: DM
authors.lastname: Black
authors.forename: Pierre D
authors.initials: PD
authors.lastname: Delmas
authors.forename: Richard
authors.initials: R
authors.lastname: Eastell
authors.forename: Ian R
authors.initials: IR
authors.lastname: Reid
authors.forename: Steven
authors.initials: S
authors.lastname: Boonen
authors.forename: Jane A
authors.initials: JA
authors.lastname: Cauley
authors.forename: Felicia
authors.initials: F
authors.lastname: Cosman
authors.forename: Péter
authors.initials: P
authors.lastname: Lakatos
authors.forename: Ping Chung
authors.initials: PC
authors.lastname: Leung
authors.forename: Zulema
authors.initials: Z
authors.lastname: Man
authors.forename: Carlos
authors.initials: C
authors.lastname: Mautalen
authors.forename: Peter
authors.initials: P
authors.lastname: Mesenbrink
authors.forename: Huilin
authors.initials: H
authors.lastname: Hu
authors.forename: John
authors.initials: J
authors.lastname: Caminis
authors.forename: Karen
authors.initials: K
authors.lastname: Tong
authors.forename: Theresa
authors.initials: T
authors.lastname: Rosario-Jansen
authors.forename: Joel
authors.initials: J
authors.lastname: Krasnow
authors.forename: Trisha F
authors.initials: TF
authors.lastname: Hue
authors.forename: Deborah
authors.initials: D
authors.lastname: Sellmeyer
authors.forename: Erik Fink
authors.initials: EF
authors.lastname: Eriksen
authors.forename: Steven R
authors.initials: SR
authors.lastname: Cummings
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001281:Atrial Fibrillation / Q000139:chemically induced; D015415:Biomarkers / Q000378:metabolism; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000008:administration & dosage* / Q000009:adverse effects; D004164:Diphosphonates / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D050723:Fractures, Bone / Q000453:epidemiology / Q000517:prevention & control*; D006620:Hip Fractures / Q000453:epidemiology / Q000517:prevention & control; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage* / Q000009:adverse effects; D015994:Incidence; D007262:Infusions, Intravenous; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy*; D012306:Risk; D016103:Spinal Fractures / Q000453:epidemiology / Q000517:prevention & control; D000077211:Zoledronic Acid
chemical_list: D015415:Biomarkers; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid