Level 1: Likely reliable evidence
The efficacy of zoledronic acid after hip fracture was evaluated in 2,127 patients (1,619 women and 508 men) aged 50 years and older (N Engl J Med. 2007;357:1799-1809). The Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly (HORIZON) Recurrent Fracture Trial randomized patients within 90 days after surgical repair of hip fracture to zoledronic acid 5 mg vs. placebo IV (given over 15 minutes) annually for up to five years. Patients had to be previously ambulatory and have both legs; hip fracture had to be due to minimal trauma (fall from standing height or lower). All patients were given calcium (1,000-1,500 mg/day orally) and vitamin D (50,000-125,000 units 14 days before first study drug infusion if serum 25-hydroxyvitamin D level was ≤15 ng/mL or not available, then 800-1,200 units/day). The trial was stopped early when prespecified interim analysis demonstrated efficacy. After median follow-up 1.9 years (a few patients were followed for more than three years), 71.3% of patients completed the trial (counting deaths as dropouts), 82.7% completed the trial or died.
Zoledronic acid was associated with decreased rate of any clinical fracture (8.6% vs. 13.9%), nonvertebral clinical fracture (7.6% vs. 10.7%), clinical vertebral fracture (1.7% vs. 3.8%), and mortality (9.6% vs. 13.3%). There were no significant differences in rates of hip fracture, adverse events, or discontinuation due to adverse event. Myalgia and pyrexia occurred within three days after infusion, more frequently with zoledronic acid. No cases of osteonecrosis of the jaw were reported.