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.).
| Discipline Area | Score |
|---|---|
| Family Medicine (FM)/General Practice (GP) |  |
| General Internal Medicine-Primary Care(US) | |
| Endocrine | |
| Geriatrics | |
| Public Health | |
| Internal Medicine | |
These data may tip clinicians to treat women with osteopenia. The changes in bone turnover markers and bone mineral density would support this.
A provocative study looking at women without significant osteoporosis. It's unclear whether 2 doses is really better than 1 dose. Also, the primary outcome is radiologic evidence of spinal fracture and it's unclear how many of these are clinically significant fractures.
Interesting findings that suggest another option for early post-menopausal women who do not want to commit to bisphosphonates therapy yearly (with IV zoledronic acid) or weekly oral therapy.
Large long-term trial showing that very infrequent dosing of zoledronate can prevent both radiographic and clinical fractures in early postmenopausal women with decreased bone density.
Interesting on 2 main clinical fronts: 1. potentially a very cost-effective option for osteoporosis where medication compliance is a problem; and 2. it was accomplished without any attention to or use of routine calcium and vitamin D.
This is a well conducted RCT with very little to criticize. It should change clinical practice and allow physicians to give this drug less often, which should save adverse events for patients and reduce costs to the health system while improving outcomes. The only question I'm left with is: what difference does giving zolendronate every 5 years instead of every year have on BMD?
