PT  - JOURNAL ARTICLE
AU  - Andrew Grey
AU  - Mark J. Bolland
AU  - Anne Horne
AU  - Borislav Mihov
AU  - Greg Gamble
AU  - Ian R. Reid
TI  - Duration of antiresorptive activity of zoledronate in postmenopausal women with osteopenia: a randomized, controlled multidose trial
AID  - 10.1503/cmaj.161207
DP  - 2017 Sep 11
TA  - Canadian Medical Association Journal
PG  - E1130--E1136
VI  - 189
IP  - 36
4099  - http://www.cmaj.ca/content/189/36/E1130.short
4100  - http://www.cmaj.ca/content/189/36/E1130.full
SO  - CMAJ2017 Sep 11; 189
AB  - BACKGROUND: Intravenous zoledronate 5 mg annually reduces fracture risk, and 5 mg every 2 years prevents bone loss, but the optimal dosing regimens for these indications are uncertain.METHODS: We 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. The primary outcome was change in spine bone mineral density (BMD). Secondary outcomes were changes in hip BMD and serum markers of bone turnover.RESULTS: The study involved 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.INTERPRETATION: The antiresorptive activity of single zoledronate doses of 1–5 mg persist for at least 3 years in postmenopausal women with osteopenia. Clinical trials would be justified to evaluate the effects on fracture risk of less frequent or lower doses of zoledronate than are currently recommended.Trial registration: www.anzctr.org.au, no. ACTRN12607000576426