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Previous Volume 356:1809-1822 May 3, 2007 Number 18 Next

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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 [ClinicalTrials.gov] .)

Source Information

From the University of California, San Francisco, San Francisco (D.M.B., T.F.H., D.S.); Université Claude Bernard Lyon 1 and INSERM Research Unit 831, Lyon, France (P.D.D.); University of Sheffield, Sheffield, United Kingdom (R.E.); University of Auckland, Auckland, New Zealand (I.R.R.); Katholieke Universiteit Leuven, Leuven, Belgium (S.B.); University of Pittsburgh, Pittsburgh (J.A.C.); Helen Hayes Hospital, West Haverstraw, NY (F.C.); Semmelweis University Medical School, Budapest, Hungary (P.L.); the Chinese University of Hong Kong, Hong Kong (P.C.L.); Centro Tratamiento Integral Endocrinología Metabolismo Patología Ósea, Buenos Aires (Z.M.); Centro de Osteopatías Médicas, Buenos Aires (C.M.); Novartis Pharmaceuticals, East Hanover, NJ (P.M., H.H., J.C., K.T., T.R.-J., J.K.); Novartis Pharma, Basel, Switzerland (E.F.E.); and San Francisco Coordinating Center, San Francisco (S.R.C.).

Address reprint requests to Dr. Black at the Department of Epidemiology and Biostatistics, University of California, San Francisco, 185 Berry St., Lobby 4, Suite 5700, San Francisco, CA 94107, or at dblack{at}psg.ucsf.edu.

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