CLINICAL QUESTION

In women with normal bone density or osteopenia, does zoledronate (Reclast) given at baseline and 5 years later reduce the risk of fracture over 10 years?

BOTTOM LINE

Zoledronate is typically given annually for the prevention of osteoporotic fractures in adults with a high risk of fracture. This study showed a clinically and statistically meaningful benefit in lower risk postmenopausal women, even if just given once, with an additional benefit if repeated 5 years later. The cost of zoledronate ranges from $40 to $500 (goodrx.com as of January 27, 2025) and is given by infusion. (Level of Evidence = 1b)

SYNOPSIS

The authors of this study point out that most fractures in postmenopausal women occur in those without documented osteoporosis or a previous fracture. Women 50 to 60 years of age with a bone mineral density T-score between 0 and −2.5 at the lumbar spine, femoral neck, or total hip were recruited for this study; women with a previous spine or hip fracture were excluded. A value greater than −1 is considered normal; a value less than −2.5 is defined as osteoporosis. The women were randomized to receive a 5-mg intravenous infusion of zoledronate at baseline and a zoledronate infusion at 5 years, zoledronate at baseline and placebo infusion at 5 years, or placebo infusions at both times. It is not clear whether allocation was concealed, although groups were balanced at baseline and analysis was by intention to treat. The mean age of participants was 56 years, 85% were of European ancestry, and the mean T-scores were −0.36 to −0.55. A total of 1,054 women were randomized, and follow-up was 95% at 10 years. Approximately 85% of the participants received the second placebo or zoledronate infusion at 5 years. Vertebral fractures were observed less often in the two groups that received zoledronate (6.3% in the group that received zoledronate both times, 6.6% in the zoledronate and placebo group, and 11.1% in those who received placebo both times; relative risk [RR] = 0.58; 95% CI, 0.38–0.87 for both zoledronate arms vs placebo; number needed to treat [NNT] = 21–22 to prevent one fracture over 10 years). Results for those who received zoledronate at both times were only slightly better than those who received zoledronate and placebo, with no statistically significant difference between groups. Women in the zoledronate and placebo group had significantly fewer fractures (27.4% vs 35.3%; RR = 0.77; 95% CI, 0.63–0.97; NNT = 13 over 10 years) and a trend toward fewer fragility fractures than the placebo-only group (22.2% vs 28.2%; RR = 0.79; 95% CI, 0.61–1.02). Women who received zoledronate for both infusions had a slightly greater benefit, with fewer fractures overall (24.7% vs 35.3%; RR = 0.70; 95% CI, 0.56–0.88; NNT = 9) and fewer fragility fractures (20.2% vs 28.2%; RR = 0.72; 95% CI, 0.55–0.93; NNT = 12). Regarding important harms, no cases of osteonecrosis of the jaw or atypical femoral fractures occurred in any group.