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Research question Is once yearly intravenous zoledronic acid an effective treatment for postmenopausal osteoporosis?
Answer Yes. Yearly treatment prevents fractures and increases bone mineral density compared with a placebo.
Why did the authors do the study? Oral bisphosphonates help prevent fractures in postmenopausal women, but they can be inconvenient to take and many women stop their treatment. These authors wanted to test whether a more convenient yearly infusion of intravenous zoledronic acid would also reduce the risk of fractures.
What did they do? 7765 postmenopausal women with osteoporosis took part in a randomised, double blind trial, sponsored by the manufacturers of zoledronic acid. Participants were given three infusions of zoledronic acid (5 mg) or a placebo at yearly intervals. They were followed up for 12 months after their last infusion. The authors looked for vertebral fractures in yearly spinal radiographs. Other fractures, including hip, were reported by participants and confirmed by radiographs. The authors monitored participants' bone mineral density using dual energy x ray absorptiometry and used serum markers to monitor bone turnover. An adjudication committee reviewed serious adverse events. The authors compared treatment and placebo groups using intention to treat analysis, but confined their analysis of vertebral fractures to women not taking any other treatments for osteoporosis at baseline.
What did they find? 3.3% (92/2822) of the women given zoledronic acid had a vertebral fracture, a reduction of 70% compared with the 10.9% (310/2853) of those given placebo (relative risk 0.30 (95% CI 0.24 to 0.38)). Zoledronic acid also significantly reduced the risk of hip fracture (1.4% v 2.5%, hazard ratio 0.59 (0.42 to 0.83)), all non-vertebral fractures, all clinical fractures, and clinical vertebral fractures. It also significantly increased women's bone mineral density at the hip, lumbar spine, and femoral neck compared with placebo (by 6%, 6.7%, and 5.1%) and reduced bone turnover.
Infusion of zoledronic acid was associated with a higher incidence of fever, myalgia, flu-like symptoms, headache, and arthralgia. It was also associated with a higher risk of serious atrial fibrillation (5% v 1.3%, P<0.001), but no long term renal toxicity. One woman in each group developed osteonecrosis of the jaw, a rare side effect of intravenous bisphosphonates given in high doses to patients with cancer.
What does it mean? A single yearly infusion of 5 mg zoledronic acid helped prevent important osteoporotic fractures in this vulnerable population of postmenopausal women. It seems reasonably safe, although the excess of atrial fibrillation is a worry and needs further investigation. Some women might find a yearly infusion easier and more convenient than regular oral drugs, and it's possible the two routes are equally effective. But we won't know for certain until researchers do a large, head to head trial.