Zoledronic Acid and Risedronate in the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis (Health Outcomes and Reduced Incidence With Zoledronic Acid Once Yearly Trial): A Multicentre, Double-Blind, Double-Dummy, Randomized Controlled Trial

Abstract

Compliance and adherence with oral daily and weekly bisphosphonate therapy is generally poor in postmenopausal women at increased risk of glucocorticoid-induced osteoporosis. Previous studies have shown that a single yearly intravenous dose of zoledronic acid increases bone mineral density and reduces fracture risk in a similar study population. This study-part of Health Outcomes and Reduced Incidence with Zoledronic acid once yearly Trial, a 1-year multicenter, double-blind, double-dummy, randomized controlled trial-assessed whether one 5 mg infusion of zoledronic acid is inferior or not to a once daily 5 mg oral dose of risedronate for the prevention and treatment of glucocorticoid-induced osteoporosis. The study was carried out at 54 centers in 16 countries. The duration of treatment was 12 months. The primary study end point was percentage change from baseline in bone mineral density of the lumbar spine. A total of 833 study subjects were randomized to receive either a single intravenous infusion of zoledronic acid 5 mg (n = 416) or daily oral doses of risedronate 5 mg (n = 417). There were 545 women in the treatment subgroup (patients receiving glucocorticoids >3 months); of these, 272 received zoledronic acid and 273 risedronate. Of the 288 women in the prevention subgroup (patients receiving glucocorticoids ≤3 months), equal numbers of patients (n = 144) were assigned to each drug. Bone data were expressed as least square mean ± standard error. At 12 months, a single intravenous dose of zoledronic acid provided greater increases in lumbar spine bone mineral density than daily oral doses of risedronate in both the treatment subgroup (mean: 4.06% ± 0.28% vs. 2.71% ± 0.28%, mean difference: 1.36%; 95% confidence interval, 0.67%-2.05%; P = 0.0001), and the prevention subgroup (mean: 2.60% ± 0.45% vs. 0.64% ± 0.46%, mean difference: 1.96%; 95% confidence interval, 1.04%-2.88%; P = 0.0001). Zoledronic acid also produced more rapid and substantial decreases in bone turnover than did risedronate. The frequency of adverse events was higher in the patient group receiving zoledronic acid group in both subgroups, primarily because of transient symptoms within the first 3 days after infusion. There was no significant difference in overall frequency of serious adverse events between the 2 drugs or the subgroups. At the end of the study, the participants expressed a preference for zoledronic acid over oral risedronate by a nearly 10 to 1 margin. The investigators conclude from these findings that compared with oral daily doses of risedronate, zoledronic acid as a single intravenous dose is noninferior, and may be more effective and more acceptable to patients for prevention and treatment of glucocorticoid-induced osteoporosis.