Low-dose zoledronate in osteopenic postmenopausal women: a randomized controlled trial.

Context: Annual iv administration of 5 mg zoledronate decreases fracture risk. The skeletal effects of annual treatment with doses of zoledronate under 4 mg have not been assessed.

Objective: Our objective was to determine the skeletal effects of single doses of zoledronate of 5 mg or less.

Design, Setting, And Participants: This was a double-blind, randomized, placebo-controlled trial over 1 yr at an academic research center in 180 postmenopausal women with osteopenia.

Intervention: Intervention was a single baseline administration of iv zoledronate in doses of 1, 2.5, or 5 mg, or placebo.

Main Outcome Measures: The primary endpoint was change in bone mineral density (BMD) at the lumbar spine. Secondary endpoints were change in BMD at the proximal femur and total body and changes in biochemical markers of bone turnover.

Results: After 12 months, change in spine BMD was greater in each of the zoledronate groups than in the placebo group [mean (95% confidence interval) difference vs. placebo was 3.5% (2.2-4.8%) for 1 mg, 4.0% (2.7-5.3%) for 2.5 mg, and 3.6% (2.3-4.9%) for 5 mg zoledronate, P < 0.001 for each dose]. Change in BMD at the total hip was greater in each of the zoledronate groups than the placebo group [mean (95% confidence interval) difference vs. placebo was 2.7% (1.9-3.5%) for 1 mg, 3.6% (2.8-4.4%) for 2.5 mg, and 3.6% (2.8-4.4%) for 5 mg zoledronate, P < 0.001 for each dose]. Each of the bone turnover markers, β-C-terminal telopeptide of type I collagen and procollagen type I N-terminal propeptide, was lower by at least 40% in each of the zoledronate groups than the placebo group throughout the trial (P < 0.001 vs. placebo for each marker for each dose). There was evidence for a dose-dependent effect of zoledronate on each of the markers (P for trend <0.001).

Conclusion: Annual administration of doses of iv zoledronate lower than 5 mg produces substantial antiresorptive effects. Trials assessing the antifracture efficacy of low doses of zoledronate are justified.