Clinical Health Updates

Zoledronic acid reduces fracture risk in osteoporosis, osteopenia with previous fracture

Clinical Question:
Is zoledronic a safe and effective drug for preventing fractures in women with osteoporosis?

Bottom Line:
Zoledronic acid (Zometa) given once a year via intravenous infusion reduces the risk of clinical fracture in women with osteoporosis or osteopenia and previous fracture. Approximately 1 in 100 women will develop atrial fibrillation, though, as a result of treatment.

Black DM, Delmas PD, Eastell R, et al, for the HORIZON Pivotal Fracture Trial. Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med 2007;356:1809-1822.

Study Design:
Randomized controlled trial (double-blinded)

Zoledronic acid is a bisphosphonate that has primarily been used in patients with multiple myeloma and in cancer patients with hypercalcemia. In this study, 7765 women between the ages of 65 years and 89 years with either osteoporosis (T score at femoral neck < -2.5) or osteopenia (T score < -1.5) and evidence of previous vertebral fracture were randomly assigned to receive either zoledronic acid 5 mg given intravenously at baseline, 12 months, and 24 months or matching placebo. All patients received 1000 mg to 1500 mg of calcium and 400 IU to 1200 IU of vitamin D daily. Patients were allowed to take nonbisphosphonate drugs for the treatment of osteoporosis. Approximately 600 women in each group did not return for the final evaluation. Groups were similar at baseline and analysis was by intention to treat. Approximately 80% of the women were not taking any other osteoporosis drugs; of those who were, raloxifene was the most commonly used (42%).

Patients receiving zoledronic acid had fewer hip fractures (1.4% vs 2.5%; P = .002; number needed to treat [NNT] = 111 for 3 years) and fewer clinical vertebral fractures (0.5% vs 2.6%; P < .001; NNT = 48) and fewer clinical fractures of any type (8.4% vs 12.8%; P < .001; NNT = 23). Although patients taking the drug had transient increases in serum creatinine, at the end of the study there was no difference in renal function between groups. Atrial fibrillation was also more common in women taking zoledronic acid (1.3% vs 0.5%; P < .001; NNH = 125). This has also been previously reported in a study of alendronate, although more data are needed. There was no difference between groups regarding other cardiovascular events or all-cause mortality and no instances of osteonecrosis of the jaw.