• Andrew Grey, Mark J Bolland, Diana Wattie, Anne Horne, Greg Gamble, and Ian R Reid.
• Department of Medicine, University of Auckland, Private Bag 92 019, Auckland, New Zealand. a.gray@auckland.ac.nz
• J. Clin. Endocrinol. Metab. 2009 Feb 1; 94 (2): 538-44.

ContextAnnual iv administration of 5 mg zoledronate decreases fracture risk. The optimal dosing interval of 5 mg zoledronate is not known.ObjectiveOur objective was to determine the duration of antiresorptive action of a single 5-mg dose of iv zoledronate.Design, Setting, And ParticipantsWe 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.InterventionIntervention included 5 mg zoledronate.Main Outcome MeasuresBiochemical markers of bone turnover and bone mineral density of the lumbar spine, proximal femur, and total body.ResultsCompared 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.ConclusionThe 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.

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