Fracture Prevention with Infrequent Zoledronate in Women 50 to 60 Years of Age.

Background: Zoledronate prevents fractures in older women when administered every 12 to 18 months, but its effects on bone density and bone turnover persist beyond 5 years. Whether infrequent zoledronate administration would prevent vertebral fractures in early postmenopausal women is unknown.

Methods: We conducted a 10-year, prospective, double-blind, randomized, placebo-controlled trial involving early postmenopausal women (50 to 60 years of age) with bone mineral density T scores lower than 0 and higher than -2.5 (scores of -1 or higher typically indicate normal bone mineral density) at the lumbar spine, femoral neck, or hip. Participants were randomly assigned to receive an infusion of zoledronate at a dose of 5 mg at baseline and at 5 years (zoledronate-zoledronate group), zoledronate at a dose of 5 mg at baseline and placebo at 5 years (zoledronate-placebo group), or placebo at both baseline and 5 years (placebo-placebo group). Spinal radiographs were obtained at baseline, 5 years, and 10 years. The primary end point was morphometric vertebral fracture, which was assessed semiquantitatively and defined as at least a 20% change in vertebral height from that seen on the baseline radiograph. Secondary end points were fragility fracture, any fracture, and major osteoporotic fracture.

Results: Of 1054 women with a mean age of 56.0 years at baseline, 1003 (95.2%) completed 10 years of follow-up. A new morphometric fracture occurred in 22 women (6.3%) in the zoledronate-zoledronate group, in 23 women (6.6%) in the zoledronate-placebo group, and in 39 women (11.1%) in the placebo-placebo group (relative risk, zoledronate-zoledronate vs. placebo-placebo, 0.56 [95% confidence interval {CI}, 0.34 to 0.92; P = 0.04]; and zoledronate-placebo vs. placebo-placebo, 0.59 [95% CI, 0.36 to 0.97; P = 0.08]). The relative risk of fragility fracture, any fracture, and major osteoporotic fracture was 0.72 (95% CI, 0.55 to 0.93), 0.70 (95% CI, 0.56 to 0.88), and 0.60 (95% CI, 0.42 to 0.86), respectively, when zoledronate-zoledronate was compared with placebo-placebo and 0.79 (95% CI, 0.61 to 1.02), 0.77 (95% CI, 0.62 to 0.97), and 0.71 (95% CI, 0.51 to 0.99), respectively, when zoledronate-placebo was compared with placebo-placebo.

Conclusions: Ten years after trial initiation, zoledronate administered at baseline and 5 years was effective in preventing morphometric vertebral fracture in early postmenopausal women. (Funded by the Health Research Council of New Zealand; Australian New Zealand Clinical Trials Registry number, ACTRN12612000270819.).