Zoledronic acid reduces risk for new fractures, improves survival after hip fracture surgery

Adverse events were reported at similar rates between the zoledronic acid group and the placebo group.

Administering a once-yearly infusion of zoledronic acid within 90 days after the surgical repair of a low-trauma hip fracture significantly reduces rates of new clinical fractures and significantly improves patient survival, according to a large prospective, controlled study.

Kenneth W. Lyles, MD, and colleagues at numerous centers in the United States, Europe and South America randomly assigned 2,127 patients to receive either zoledronic acid (Zometa, Novartis) infusion or placebo infusion within 90 days after undergoing the surgical repair of a hip fracture, and then annually thereafter. They reported the results of the study, called the Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly (HORIZON) Recurrent Fracture Trial, in the New England Journal of Medicine.

In addition to the assigned infusion, patients also received either vitamin D3 or D2 14 days before their first infusion if they had a serum 25-hydroxyvitamin D level of 15 ng/mL or less, or if the level was not known. All patients also received daily supplementation with calcium and vitamin D, according to the study.

Of the 2,127 patients, 1,065 were assigned to the zoledronic acid group and 1,062 were assigned to the placebo group. Overall, 71.3% of participants completed the study, with follow-up averaging 1.9 years.

Investigators identified 424 new clinical fractures in 231 patients during follow-up.

"Zoledronic acid was associated with a rate of new clinical fractures of 8.6%, as compared with 13.9% in the placebo group, an absolute risk reduction of 5.3% and a relative reduction of 35%," the authors reported.

New clinical vertebral fractures occurred in 21 patients (1.7%) in the zoledronic acid group and in 39 placebo patients (3.8%; P = .02). New clinical nonvertebral fractures occurred in 79 zoledronic acid-treated patients (7.6%) and in 107 placebo patients (10.7%; P = .03).

However, zoledronic acid did not significantly affect the risk for new hip fractures. New hip fractures occurred in 23 zoledronic acid-treated patients (2%) and in 33 placebo patients (3.5%; P = .18), according to the study.

"In the safety analysis, a total of 242 of 2,111 patients (11.5%) died during the study, of whom 101 of 1,054 (9.6%) were in the zoledronic acid group and 141 of 1,057 (13.3%) were in the placebo group (P = 0.01)," the authors reported.

"The adjudication committee determined that 11 deaths (1%) were from cardiovascular disease and seven deaths (0.7%) were from cerebrovascular disease in the zoledronic acid group, as compared with 18 deaths (1.7%) and seven deaths (0.7%), respectively, in the placebo group," they said.

Adverse events were reported at similar rates between the two groups and occurred in 867 patients (82.3%) in the zoledronic acid group and in 852 patients (80.6%) in the placebo group. Also, both groups had similar rates of serious adverse events, which occurred in 38.3% of the zoledronic acid group and 41.2% of the placebo group, according to the study.

For more information:
Lyles KW, Colón-Emeric CS, Magaziner JS, et al. Zoledronic acid and clinical fractures and mortality after hip fracture. N Engl J Med. 2007;357:1799-1809.