Zoledronate, a bisphosphonate infusion approved to treat osteoporosis, has been shown to prevent fractures in women aged 65 and older with osteopenia (T-score -1 to -2.5). To explore its effects in younger women with bone loss in the osteopenia or less range, researchers randomized 1054 postmenopausal women aged 50 to 60 (average age 56) with a T-score between 0 and -2.5 at the lumbar spine, femoral neck, or total hip (average lumbar spine T-score: -0.43; average total hip T-score: -0.51) to one of three treatments: zoledronate 5 mg at baseline and in 5 years, zoledronate 5 mg at baseline and placebo in 5 years, or placebo at baseline and in 5 years. At 10 years, the primary outcome, morphometric vertebral fracture (fractures identified by their shape on X-ray as opposed to symptoms), occurred in 6.3% (Zoledronate-Zoledronate), 6.6% (Zoledronate-Placebo), and 11.1% (Placebo-Placebo) of patients (p<0.05). Incidences of any fracture were 24.7%, 27.4%., and 35.3%, respectively. (p<0.05). No cases of osteonecrosis of the jaw or atypical femoral fracture, two concerning bisphosphonate side effects, were reported during the trial.

Zoledronate reduced the 10-year fracture risk in postmenopausal women aged 50 to 60 with an average T-score of around -0.46. Two infusions were slightly more effective than one, and both were superior to placebo. A secondary analysis stratifying effect size by baseline bone mineral density (BMD) would have been informative but was not performed. With 45% of women aged 50 to 60 having T-scores less than 0, these results apply to a large population. Current USPSTF guidelines recommend BMD screening in women under 65 at increased risk of osteoporosis, which they loosely define as a 10-year fracture risk of 10% or more.

Providers wanting to incorporate this study into their practice could follow these steps:

1. Screen postmenopausal women aged 50 to 60 with the FRAX tool
2. If the 10-year risk of a major osteoporotic fracture is greater than 10%, order a BMD test
3. If the T-score is 0 to -2.5 at the lumbar spine, femoral neck, or total hip, offer a one-time infusion of zoledronate 5 mg, with an anticipated effect of reducing the absolute risk of any fracture over 10 years by 8%

• Zoledronate vs Placebo in Postmenopausal Women Aged 50 to 60, NEJM (2025)
• Osteoporosis review
• Osteoporosis medications