Physician-authored summaries and commentary on the most important medical research, provided by the NEJM Group, a division of the Massachusetts Medical Society.
© Massachusetts Medical SocietyMay 2025
Even a single dose lowered fracture risk during 10 years of follow up.
Zoledronate is administered intravenously every 12 to 18 months to prevent fractures in people with osteopenia and osteoporosis. Studies have shown that effects on bone mineral density (BMD) and markers of bone turnover persist for longer than five years after administration (J Bone Miner Res 2022; 37: 311).
In this study, researchers asked whether infrequent dosing of zoledronate could prevent fractures in early postmenopausal women who did not have BMD-defined osteoporosis (mean total hip T score at baseline, −0.5). About 1000 women (age range, 50 to 60 years) were randomised to one of three groups: zoledronate at baseline and five years (zoledronate–zoledronate), zoledronate at baseline and placebo at five years (zoledronate–placebo) or placebo at both time points (placebo–placebo).
During 10 years of follow up, the primary endpoint (i.e. new vertebral fracture defined by loss of vertebral height on spinal radiographs) occurred in 6.3% of the zoledronate–zoledronate group, 6.6% of the zoledronate–placebo group and 11.1% of the placebo–placebo group. The two zoledronate groups (combined) also suffered fewer major osteoporotic fractures than did the placebo–placebo group (13% vs 20%) and had a smaller mean decrease in BMD.
Comment: In this study, the number needed to treat to prevent one vertebral fracture during 10 years was about 20 in both zoledronate groups; however, keep in mind that vertebral fractures were defined by radiographic changes rather than clinical symptoms. These results will not affect clinical practice for now: women younger than 65 years without additional risk factors for fracture typically are not screened for osteoporosis, and women with normal BMD typically are not considered to be candidates for treatment. However, the insights from this trial probably will inform future approaches to fracture prevention.
Molly S. Brett, MD, Assistant Professor of Clinical Medicine, University of Colorado School of Medicine; Primary Care Physician, Rocky Mountain Regional VA Medical Center, Aurora, USA.
Bolland MJ, et al. Fracture prevention with infrequent zoledronate in women 50 to 60 years of age. N Engl J Med 2025; 392: 239-248.
This summary is taken from the following Journal Watch titles: General Medicine, Ambulatory Medicine, Women's Health.