CATEGORY: MOBILITY, BONES & JOINTS
In a ten-year randomized trial of 1,054 women aged 50 to 60, two infusions of the bone drug zoledronate given five years apart were followed by 44% fewer new spine fractures than placebo, and by fractures of any kind in 24.7% of women rather than 35.3%.1 Zoledronate belongs to a class of drugs that slow the cells which break down bone. The women in the trial did not have established osteoporosis—their bone density ranged from roughly normal down to the milder thinning called osteopenia.
Three Groups Over a Decade, 95% Retained
Women were randomly assigned to one of three groups and neither they nor the researchers knew which: an infusion at the start and another at five years, an infusion at the start and a dummy infusion at five years, or dummy infusions both times. The trial then ran for a full decade, and 95% of the women stayed to the end—unusually high for a study of that length.
The main outcome was measured on X-ray rather than reported by the women. Spine films taken at the start, at five years and at ten years were compared with each woman’s own baseline film, and a new fracture was counted when a vertebra had lost at least 20% of its height. That method matters: most spine fractures cause no obvious event, so they are found by measuring the shape of the bone, not by someone noticing a break.
Spine Fractures in 6.3% Versus 11.1%
New spine fractures occurred in 6.3% of the two-infusion group compared with 11.1% of the placebo group, a 44% lower risk. In counts, 22 women in the two-infusion group had a new spine fracture, against 39 in the placebo group.1 Across all fracture types the reduction was 30%, with the tightest statistical range in the trial. Major osteoporotic fractures—spine, hip, forearm and upper arm—were 40% lower. The single-infusion group landed between the other two: 23% fewer fractures of any kind, though it did not meet the trial’s threshold on the spine measure.
Modest in the First Five Years, Larger Later
A companion analysis found the difference was modest in the first five years and considerably larger in the second five. No cases of jaw bone damage or unusual thigh-bone fractures—the two complications most associated with this drug class—were recorded during the trial.
Hip Fracture Prevention Was Not Demonstrated
These were women aged 50 to 60, mostly in New Zealand, with bone density better than the osteoporosis threshold, so the findings do not extend to men, to much older people, or to those with established disease. The group was too young to produce many hip fractures, so hip fracture prevention was not demonstrated. Between a quarter and a third of women in every group fractured something over the ten years, so this is a reduction in risk rather than its removal. The trial was funded by the Health Research Council of New Zealand, a public body, not by a drug manufacturer.
2,000 Older Women, 37% Fewer Fragility Fractures
An earlier randomized trial gave zoledronate or a placebo to 2,000 New Zealand women aged 65 and older with osteopenia—bone thinning that stops short of osteoporosis—every 18 months for six years. Fragility fractures, the kind that follow a minor fall, were 37% less common in the zoledronate group, a result pointing the same way in a considerably older group than this trial enrolled.2
Key Takeaways
- Over ten years, two zoledronate infusions five years apart were associated with 44% fewer new spine fractures and 30% fewer fractures of any kind in women aged 50 to 60.
- Because women were randomly assigned and neither they nor the researchers knew who got the drug, this is stronger evidence than an observational study.
- The women had normal to mildly reduced bone density rather than osteoporosis, were too young for hip fractures to be assessed, and were mostly from a single country.
References
- Bolland MJ, Nisa Z, Mellar A, et al. Fracture Prevention with Infrequent Zoledronate in Women 50 to 60 Years of Age. New England Journal of Medicine. 2025;392(3):239–248. link
- Reid IR, Horne AM, Mihov B, et al. Fracture prevention with zoledronate in older women with osteopenia. New England Journal of Medicine. 2018;379(25):2407–2416. link.