Duration of antiresorptive activity of zoledronate in postmenopausal women with osteopenia: A randomized, controlled multidose trial

Canadian Medical Association Journal | September 13, 2017

Grey A, et al. - It has been reported that intravenous zoledronate 5 mg annually reduces fracture risk, and 5 mg every 2 years prevents bone loss. This study aimed to determine the optimal dosing regimens for these indications. Investigations disclosed that the antiresorptive activity of single zoledronate doses of 1–5 mg persist for at least 3 years in postmenopausal women with osteopenia. More likewise studies were required to evaluate the effects on fracture risk of less frequent or lower doses of zoledronate than were currently recommended.

Methods

  • The physicians conducted a 3-year open-label extension of a 2-year randomized, placebo-controlled, double-blind study.
  • Late postmenopausal women with osteopenia were assigned to receive a single baseline dose of 1 mg, 2.5 mg or 5 mg of zoledronate or placebo.
  • Change in spine bone mineral density (BMD) was considered as the primary outcome.
  • Changes in hip BMD and serum markers of bone turnover were included in the secondary outcomes.

Results

  • This study enrolled 160 women.
  • Zoledronate increased BMD and reduced markers of bone turnover in a dose-dependent manner.
  • After 2 years, the 1-mg, 2.5-mg and 5-mg zoledronate doses increased spine BMD over placebo by 5.0% (95% confidence interval [CI] 3.0% to 7.0%), 5.7% (95% CI 3.7% to 7.7%) and 5.7% (95% CI 3.7% to 7.6%), respectively; after 5 years, the respective increases were 2.0% (95% CI -1.1% to 5.0%), 2.2% (95% CI -1.0% to 5.4%) and 5.1% (95% CI 2.2% to 8.1%).
  • After 2 years, the 1-mg, 2.5-mg and 5-mg zoledronate doses increased total hip BMD over placebo by 2.6% (95% CI 1.3% to 3.9%), 4.1% (95% CI 2.9% to 5.4%) and 4.7% (95% CI 3.4% to 5.9%), respectively; after 5 years, the respective increases were 1.8% (95% CI -0.1% to 3.8%), 2.8% (95% CI 0.8% to 4.8%) and 5.4% (95% CI 3.5% to 7.3%).
  • BMD remained above baseline values for 2–3 years in the 1-mg group, 3–4 years in the 2.5-mg group and at least 5 years in the 5-mg group.

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