Zoledronate effective for prevention of vertebral fracture in postmenopausal women on long-term basis: Study

A new study published in The New England Journal of Medicine revealed that in early postmenopausal women, zoledronate given at baseline and 5 years proved successful in avoiding morphometric vertebral fractures 10 years after the start of the trial.

Bisphosphonates are the main class of drugs used to treat postmenopausal osteoporosis and have been demonstrated to reduce the risk of fractures. The properties of zoledronate make it a desirable medication for osteopenia in women. despite most people preferring oral bisphosphonates, the intravenous injection at periods of one year or more has an excellent safety profile.

When given every 12 to 18 months, zoledronate helps older women avoid fractures, but its effects on bone turnover and density last longer than five years. It is uncertain if giving zoledronate seldom might shield early postmenopausal women from vertebral fractures. Thus, this study was carried out by Mark Bolland and colleagues to evaluate the effectiveness of zoledronate administration in postmenopausal women.

Early postmenopausal women (50 to 60 years old) with bone mineral density T scores that were below 0 and higher than −2.5 (scores of −1 or higher generally indicate normal bone mineral density) at the femoral neck, lumbar spine, or hip participated in a 10-year prospective, randomized, double-blind, placebo-controlled trial for this study.

The participants were randomized to receive either a placebo at baseline and at 5 years (placebo–placebo group), zoledronate at a dose of 5 mg at baseline and at 5 years (zoledronate–zoledronate group), or zoledronate at a dose of 5 mg at baseline and placebo at 5 years (zoledronate–placebo group). Radiographs of the spine were taken at baseline, 5, and 10 years.

Morphometric vertebral fracture was the main outcome, and it was measured semi-quantitatively. It was defined as a change in vertebral height of at least 20% from the baseline radiograph. Fragility fracture, any fracture, and significant osteoporotic fracture were secondary end goals.

A total of 1003 (95.2%) of the 1054 women who had a baseline mean age of 56.0 years finished the 10-year follow-up. 22 women (6.3%) in the zoledronate–zoledronate group, 23 women (6.6%) in the zoledronate–placebo group, and 39 women (11.1%) in the placebo–placebo group experienced a new morphometric fracture.

When comparing zoledronate–zoledronate with placebo–placebo, the relative risk of fragility fracture, any fracture, and severe osteoporotic fracture was 0.72, 0.70, and 0.60, respectively, while comparing zoledronate–placebo with placebo–placebo, it was 0.79, 0.77, and 0.71, respectively. Overall, Vertebral fractures were decreased shortly after menopause by infrequent zoledronate infusions.

Reference:

Bolland, M. J., Nisa, Z., Mellar, A., Gasteiger, C., Pinel, V., Mihov, B., Bastin, S., Grey, A., Reid, I. R., Gamble, G., & Horne, A. (2025). Fracture prevention with infrequent zoledronate in women 50 to 60 years of age. The New England Journal of Medicine, 392(3), 239–248. https://doi.org/10.1056/nejmoa2407031