Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis.
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.)
Black
Dennis M
DM
University of California, San Francisco, San Francisco, CA 94107, USA. dblack@psg.ucsf.edu
Delmas
Pierre D
PD
Eastell
Richard
R
Reid
Ian R
IR
Boonen
Steven
S
Cauley
Jane A
JA
Cosman
Felicia
F
Lakatos
Péter
P
Leung
Ping Chung
PC
Man
Zulema
Z
Mautalen
Carlos
C
Mesenbrink
Peter
P
Hu
Huilin
H
Caminis
John
J
Tong
Karen
K
Rosario-Jansen
Theresa
T
Krasnow
Joel
J
Hue
Trisha F
TF
Sellmeyer
Deborah
D
Eriksen
Erik Fink
EF
Cummings
Steven R
SR
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
D015415:Biomarkers; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid