Infrequent administration of zoledronate demonstrated sustained benefits in reducing vertebral fractures over a decade in early postmenopausal women.
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 years with bone mineral density T scores between 0 and −2.5, indicative of osteopenia but not osteoporosis. The participants were assigned to one of three 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 the patients in the zoledronate-zoledronate group, 6.6% of those in the zoledronate-placebo group, and 11.1% of those in the the placebo-placebo group. The relative risk of fracture was reduced by 44% in the zoledronate-zoledronate group compared with the placebo-placebo group (relative risk [RR] = 0.56, 95% confidence interval [CI] = 0.34–0.92, P = .04).
Zoledronate administered at baseline and 5 years was effective in preventing morphometric vertebral fractures in early postmenopausal women.
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.
"Ten years after trial initiation, zoledronate administered at baseline and 5 years was effective in preventing morphometric vertebral fracture in early postmenopausal women," lead study author Mark J. Bolland, MB, ChB, PhD, explained.
This trial suggested that infrequent zoledronate administration could serve as a practical, long-term intervention for vertebral fracture prevention in early postmenopausal women. The findings aligned with existing evidence for zoledronate's efficacy in older populations but extended 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.