Antifracture Efficacy of 5- or 10-Yearly Zoledronate in Women Aged 50 to 60 Years: Secondary Analyses of a Randomized Trial

Abstract

Context: We recently reported that zoledronate (zol) given once at baseline or twice (every 5 years) reduced fracture risk over 10 years.

Objective: We assessed whether the effects of zol differ over time or across important baseline variables, and how they relate to changes in bone mineral density (BMD) over time.

Methods: A 10-year, prospective, randomized, double-blind, placebo-controlled trial, was conducted at a clinical research center from 2012 to 2023. Participants included 1054 postmenopausal women, aged 50 to 60 years, with BMD T-score at the lumbar spine, femoral neck, or total hip between 0 and -2.5. Intervention included either 5-yearly 5-mg zol (zol-zol), 5-mg zol infusion at baseline and placebo at 5 years (zol-placebo), or 5-yearly placebo (placebo-placebo). Main outcome measures included morphometric vertebral fractures, major osteoporotic, and any fractures.

Results: Morphometric vertebral fractures were not reduced in the years 0 to 5 following zol but were reduced in years 5 to 10 by 58% (95% CI, 21%-77%) (zol-zol) and 57% (21%-77%) (zol-placebo). For any fracture and major osteoporotic fracture, similar temporal patterns were observed. There were no interactions between treatment effect and baseline variables (including age, body mass index, BMD, falls or fracture history, and estimated fracture risk) or between treatment effect and changes in BMD with zol.

Conclusion: Fracture reductions with single-dose or 5-yearly zol appear greater during years 5 to 10 than years 0 to 5. The risk reductions are broadly consistent across this cohort and independent of baseline or change in BMD. This suggests that routine BMD monitoring may not be necessary for low-risk women considering the option of less frequent zol for long-term fracture risk reduction.

Keywords: bone mineral density; fracture; postmenopausal women; zoledronate.