Zoledronate 5 mg every 18 months reduces fragility fractures in women over 65 with osteopenia (NNT = 15 over 6 years)

Reference

Reid IR, Horne AM, Mihov B, et al. Fracture prevention with zoledronate in older women with osteopenia. N Engl J Med 2018;379(25):2407-2416.

Synopsis

There remains uncertainty regarding the benefit of pharmacotherapy for women with osteopenia, defined as a T score of -1.0 to -2.5 at either the total hip or femoral neck on at least one side. A total of 2000 women, 65 years or older, with osteopenia were randomized to receive a 5-mg zoledronate infusion every 18 months or a saline infusion; 1861 completed the 6-year follow-up. Patients with osteoporosis in one hip, but osteopenia in the other could be included (we aren't told how many fell into this category). All women received 100,000 IU oral cholecalciferol at the start of the trial and then 50,000 IU monthly during the trial. One gram of calcium daily was recommended but no supplements were given. The mean age of the women was 71 years, 94% were of European descent, 24% had a previous nonvertebral fracture after age 45 years, and 13% had a vertebral fracture at the time of enrollment. Their median 10-year risk of osteoporotic fracture was 12%, and their 10-year risk of hip fracture was 2.3%. Groups were balanced at the start of the study, and analysis was by intention to treat. After 6 years, there were significantly fewer fragility fractures (38.5 vs 22.1 per 1000 person-years) and symptomatic fractures (46.9 vs 31.2 per 1000 person-years) in the zoledronate group. This corresponds to an NNT of 15 women over 6 years to prevent a fragility fracture in one woman, or an NNT of 10 over 6 years to prevent a single fragility fracture (some women had more than one). The effect was consistent for vertebral and nonvertebral fractures, with the exception that there was no significant reduction in hip fractures (12 with placebo vs 8 with zoledronate). There was no significant difference between groups in serious adverse events, and no cases of osteonecrosis of the jaw reported. The cost of a single vial of zoledronate ranges from $31 to $295 in the United States (www.goodrx.com, 12-28-18), but this does not include infusion charges. A previous study showed that a similar group of postmenopausal women not selected for having osteoporosis also found fracture reduction with the bisphosphonate clodronate.