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

Context: Annual iv administration of 5 mg zoledronate decreases fracture risk. The optimal dosing interval of 5 mg zoledronate is not known. Objective: Our objective was to determine the duration of antiresorptive action of a single 5-mg dose of iv zoledronate. Design, Setting, and Participants: We conducted a double-blind, randomized, placebo-controlled trial over 2 yr at an academic research center, in a volunteer sample of 50 postmenopausal women with osteopenia. Intervention: Intervention included 5 mg zoledronate. Main Outcome Measures: Biochemical markers of bone turnover and bone mineral density of the lumbar spine, proximal femur, and total body. Results: Compared with placebo, zoledronate treatment decreased mean levels of each of four markers of bone turnover by at least 38% (range 38-45%) for the duration of the study (P < 0.0001 for each marker). After 2 yr, bone mineral density was higher in the zoledronate group than the placebo group by an average of 5.7% (95% confidence interval = 4.0-7.4) at the lumbar spine, 3.9% (2.2-5.7) at the proximal femur, and 1.7% (0.8-2.5) at the total body (P < 0.0001 for each skeletal site). Between-groups differences in markers of bone turnover and bone mineral density were similar at 12 and 24 months. Mild secondary hyperparathyroidism was present throughout the study in the zoledronate group. Conclusion: The antiresorptive effects of a single 5-mg dose of zoledronate are sustained for at least 2 yr. The magnitudes of the effects on markers of bone turnover and bone mineral density are comparable at 12 and 24 months. Administration of zoledronate at intervals of up to 2 yr may be associated with antifracture efficacy; clinical trials to investigate this possibility are justified. (J Clin Endocrinol Metab 94: 538-544, 2009)