CATEGORY: MOBILITY, BONES & JOINTS
Two infusions of zoledronate, given five years apart, brought 44% fewer new spine fractures over a decade in women aged 50 to 60. Fractures of any kind occurred in 24.7% of the women who received both infusions and 35.3% of those on placebo.1 Zoledronate belongs to a family of drugs that slow the cells whose job is to break bone down. The 1,054 women in the trial were not osteoporosis patients. Their bone density ran from roughly normal down to the milder thinning called osteopenia.
Ten Years, Three Groups, Nobody Knowing Which
Each woman landed in one of three groups by a process she had no part in, and neither did the researchers watching her. One group received an infusion at the start and a second at five years. One received an infusion at the start and a dummy infusion at five years. One received dummy infusions both times. The trial then ran a full decade, and 95% of the women were still in it at the end. For a study of that length, that is unusually high.
Fractures Found by Measuring Vertebrae, Not by Pain
The main outcome came off an X-ray rather than out of a questionnaire. Spine films taken at the start, at five years and at ten years were compared against 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 produce no obvious event, so they show up as a change in the shape of a bone instead of as a break someone noticed.
6.3% Against 11.1% on the Spine
New spine fractures appeared in 6.3% of the two-infusion group and 11.1% of the placebo group, a 44% lower risk. In counts: 22 women against 39.1 Across all fracture types the reduction was 30%, and that figure carried the tightest statistical range in the trial. Major osteoporotic fractures, meaning spine, hip, forearm and upper arm, were 40% lower. The single-infusion group landed in between, with 23% fewer fractures of any kind, though it missed the trial’s threshold on the spine measure. A companion analysis found the gap modest over the first five years and considerably wider over the second five. No jaw bone damage and no unusual thigh-bone fractures, the two complications this drug class is known for, were recorded.
Hip Fractures Were Never Within Reach
These women were aged 50 to 60, mostly in New Zealand, with bone density better than the osteoporosis threshold. The findings do not travel to men, to much older people, or to anyone with established disease. The group was also 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. This is risk reduced, not risk removed. Funding came from the Health Research Council of New Zealand, a public body, with no drug manufacturer involved. An earlier trial gave zoledronate or a placebo to 2,000 New Zealand women aged 65 and older with osteopenia, every 18 months for six years. Fragility fractures, the kind that follow a minor fall, were 37% less common among those given the drug.2 Those women were considerably older than the ones enrolled here, and the result pointed the same way.
Key Takeaways
- The women had normal to mildly reduced bone density rather than osteoporosis, were too young for hip fractures to be assessed, and came mostly from a single country.
- Over ten years, two zoledronate infusions five years apart brought 44% fewer new spine fractures and 30% fewer fractures of any kind in women aged 50 to 60.
- Neither the women nor the researchers knew who had been given the drug, which puts this well above an observational study as evidence.
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.