Infrequent administration of zoledronate demonstrated sustained benefits in reducing vertebral fractures over a decade in early postmenopausal women. Zoledronate administered at baseline and again at 5 years was effective in preventing morphometric vertebral fractures.

In a randomized, double-blind, placebo-controlled trial, published in The New England Journal of Medicine, researchers recruited 1,054 women aged 50 to 60 with bone mineral density T-scores between 0 and −2.5, indicative of osteopenia but not osteoporosis. The participants were assigned to 1 of 3 groups: 5 mg of zoledronate at baseline and 5 years (zoledronate-zoledronate), zoledronate at baseline and placebo at 5 years (zoledronate-placebo), or placebo at both intervals (placebo-placebo).

After a follow-up of 10 years, morphometric vertebral fractures occurred in 6.3% of patients in the zoledronate-zoledronate group, 6.6% of those in the zoledronate-placebo group, and 11.1% of those in the placebo-placebo group. The relative risk (RR) of fracture was reduced by 44% in the zoledronate-zoledronate group compared to the placebo-placebo group (RR = 0.56, 95% confidence interval [CI] = 0.34–0.92, P = .04).

The researchers also evaluated fragility fractures, any fractures, and major osteoporotic fractures. Compared with those in the placebo-placebo group, the patients in the zoledronate-zoledronate group exhibited RRs of 0.72 (95% CI = 0.55–0.93) for fragility fractures, 0.70 (95% CI = 0.56–0.88) for any fractures, and 0.60 (95% CI = 0.42–0.86) for major osteoporotic fractures.

Notably, the patients in the zoledronate-placebo group demonstrated intermediate efficacy. For morphometric vertebral fractures, this group had an RR of 0.59 (95% CI = 0.36–0.97, P = .08) compared with those in the placebo-placebo group.

A robust follow-up rate of 95.2% underscored the study’s reliability, with 1,003 participants completing the trial. Adverse events were not detailed in the published results, but zoledronate’s long-lasting effects on bone density and turnover were highlighted as key advantages.

This trial suggests that infrequent zoledronate administration could serve as a practical, long-term intervention for vertebral fracture prevention in early postmenopausal women. The findings align with existing evidence for zoledronate's efficacy in older populations but extend its applicability to a younger demographic with osteopenia.

The study was funded by the Health Research Council of New Zealand. Some of the study authors disclosed financial relationships with pharmaceutical companies, including Amgen, Lilly, and Radius Health.