This six-year, double-blind trial studied the effects of zoledronate on 2,000 women aged 65 and older with osteopenia. Participants were randomly assigned to receive either a 5 mg infusion of zoledronate or a placebo (saline) every 18 months. While all participants were advised to consume 1 g of dietary calcium daily, calcium supplements were not provided. Those not already taking vitamin D supplements received an initial high dose followed by monthly supplementation. The primary outcome measured was the time to the first occurrence of a nonvertebral or vertebral fragility fracture.
At the study’s conclusion, women receiving zoledronate had significantly lower fracture rates than those in the placebo group. Specifically, fragility fractures occurred in 122 women in the zoledronate group compared to 190 in the placebo group, reflecting a 37% risk reduction. Additionally, the treatment lowered the risk of nonvertebral fractures (by 34%), symptomatic fractures (by 27%), and vertebral fractures (by 55%). Women on zoledronate also experienced less height loss compared to those receiving the placebo. Notably, 15 women would need treatment to prevent a single fracture, suggesting a meaningful benefit.
These findings challenge the current paradigm, as bisphosphonates like zoledronate are approved only for osteoporosis, not osteopenia. Since most fractures in postmenopausal women occur in those with osteopenia, effective treatments for this population are crucial. This study presents strong evidence that zoledronate can significantly reduce fracture risk in women with osteopenia, raising the question of whether treatment guidelines should be expanded to include these patients.
If zoledronate were approved for osteopenia, it could transform fracture prevention strategies for millions of women worldwide. However, questions remain about long-term safety, cost-effectiveness, and patient adherence. Should all women with osteopenia receive treatment, or should therapy be reserved for those at the highest risk? Further research and policy discussions are needed to determine how best to incorporate these findings into clinical practice.
