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

Abstract

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.

• Authors: Andrew Grey, Mark J Bolland, Anne Horne, Borislav Mihov, Greg Gamble, Ian R Reid
• Journal: CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne (CMAJ) Vol. 189 Issue 36 Pg. E1130-E1136 (Sep 11 2017) ISSN: 1488-2329 [Electronic] Canada
• PMID: 28893875 (Publication Type: Journal Article, Randomized Controlled Trial)
• Copyright: © 2017 Canadian Medical Association or its licensors.

Chemical References

• Bone Density Conservation Agents
• Diphosphonates
• Imidazoles
• Zoledronic Acid

Topics

• Bone Density (drug effects)
• Bone Density Conservation Agents (administration & dosage, therapeutic use)
• Diphosphonates (administration & dosage, therapeutic use)
• Double-Blind Method
• Drug Administration Schedule
• Female
• Humans
• Imidazoles (administration & dosage, therapeutic use)
• Infusions, Intravenous
• Middle Aged
• Osteoporosis, Postmenopausal (drug therapy)
• Spine (drug effects)
• Zoledronic Acid