Zoledronate offers protection against fractures for up to 3.5 years

Treatment with zoledronate leads to reduced fracture rates, with the protective benefit persisting for 1.5 to 3.5 years after the final dose, as reported in the extension phase of a study.

In the 6-year core trial of postmenopausal women with osteopenia, zoledronate administered at 18-month intervals had been shown to lower the incidence of fragility fractures by a third. The current 4-year extension phase included 762 of the 1,000 participants assigned to receive zoledronate in the core trial.

Participants were instructed to notify study staff of any new fractures and were contacted via phone calls at 7.5 years and 9.0 years to update their health status. At 10.0 years, the participants were invited to an onsite visit to undergo assessments of bone mineral density (BMD) and turnover markers (measured from fasting morning blood in a random subset of 50 participants).

The mean follow-up duration of the extension phase was 4.24 years, and a total of 727 participants presented for assessment at 10 years. During the extension, 92 women sustained 114 nonvertebral fractures.

Nonvertebral fracture rates increased from a nadir of 15 fractures per 1,000 woman-years in the last 2 years of the core trial to 24 fractures per 1,000 woman-years in years 6–8 and 42 fractures per 1,000 woman-years in years 8–10, similar to the rate documented in the placebo group in the last 2 years of the core trial.

Incident fractures were predicted by total hip BMD at year 6 (relative risk [RR], 0.73 per 0.1 g/cm², 95 percent confidence interval [CI], 0.57–0.93; p=0.011) and a previous history of nonvertebral fracture (RR, 1.74, 95 percent CI, 1.12–2.69; p=0.013), but not the change in total hip BMD.

Total hip BMD decreased from 4.2 percent above study baseline to 0.8 percent above baseline (p<0.0001) during the extension. Turnover markers showed no clear association with BMD loss. None of the participants had osteonecrosis of the jaw or atypical femoral fractures.