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Investigators for the Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly (HORIZON) Pivotal Fracture Trial are listed in the Appendix.
Fractures are an important cause of disability among postmenopausal women, and the costs of medical care associated with osteoporosis are estimated to be more than $18 billion annually in the United States alone.1 Bisphosphonates, the most commonly used treatment for established osteoporosis, inhibit osteoclast-mediated bone resorption and reduce the risk of vertebral fracture. Two bisphosphonates, alendronate and risedronate, also have been shown to reduce nonvertebral and hip fractures in women with osteoporosis.2 -6 However, adherence to oral treatment is problematic, and about half of patients for whom oral treatment is prescribed do not adhere to it after 1 year.7 ,8 Poor adherence has been shown to compromise the effectiveness of treatment against fracture and to increase the costs of medical care.9 ,10
A single infusion of intravenous zoledronic acid has been reported to decrease bone turnover and improve bone density for at least 12 months after infusion,11 suggesting an enduring effect. In our study, annual infusions of zoledronic acid (5 mg) for 3 years were evaluated to determine whether they reduced the risk of vertebral, hip, and other types of fracture.
Methods
Study Design
The Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly (HORIZON) Pivotal Fracture Trial was an international, multicenter, randomized, double-blind, placebo-controlled trial involving postmenopausal women with osteoporosis. Patients were randomly assigned to receive either a 15-minute intravenous administration of zoledronic acid (5 mg) or placebo at baseline (day 0), at 12 months, and at 24 months. In addition, all patients received oral daily calcium (1000 to 1500 mg) and vitamin D (400 to 1200 IU). Patients were monitored for 3 years with quarterly telephone interviews and clinic visits at months 6, 12, 24, and 36.
The study was jointly designed by members of the steering committee and the sponsor. The sponsor had responsibility for data collection and quality control. An independent data and safety monitoring board met semiannually to oversee the conduct of the study and monitor the safety of patients. A copy of the study database was periodically transferred to the University of California, San Francisco (UCSF), for reports to the data and safety monitoring board. Analyses...