The Antiresorptive Effects of a Single Dose of Zoledronate Persist for Two Years: A Randomized, Placebo-Controlled Trial in Osteopenic Postmenopausal Women

Abstract

In a previous study, 12 months after a single annual intravenous dose of 5-mg zoledronate, mean levels of bone resorption markers were 50% to 60% less than the placebo. In another trial, a placebo-controlled randomized study of osteopenic HIV-infected men, bone turnover markers stably decreased for up to 24 months after the second of two annual intravenous doses of 4 mg zoledronate. The duration of action of the currently recommended dose of 5 mg is not known. This double-blind, randomized, placebo-controlled trial, evaluated the duration of the antiresorptive action of a single dose of 5 mg intravenous zoledronate in a volunteer sample of 50 postmenopausal women with osteopenia over a period of 2-year at an academic research center. The participants were randomly assigned to receive a single intravenous infusion of either 5 mg zoledronate (n = 25) or placebo (n = 25). Biochemical markers of bone turnover measured included β-C-terminal telopeptide of type I collagen, N-telopeptide of type 1 collagen, procollagen type-I N-terminal propeptide and serum osteocalcin. Bone mineral density (BMD) of the lumbar spine, proximal femur, and total body was also measured. Compared to the placebo, at 12, 18, and 24 months after administration of the drug, the mean level of each of the 4 bone markers was decreased by at least 38% (range: 38%-64%) (P < 0.0001 for each marker). At 24 months, bone mineral density was higher in the zoledronate group by an average of 5.7% (95% confidence interval [CI], 4.0-7.4) at the lumbar spine; 3.9% (95% CI, 2.2-5.7) at the proximal femur; and 1.7% (95% CI, 0.8-2.5 at the total body (P < 0.0001 for each site). For all markers of bone turnover and BMD measured, between groups, differences were similar at 12 and 24 months. Treatment with zoledronate induced a mild secondary hyperparathyroidism throughout the study. These findings show that the antiresorptive actions of a 5-mg dose of zoledronate persist for 24 months and may be associated with anti-fracture efficacy. There was no evidence that the treatment effect changed over time.