Three years of treatment with denosumab reduced radiographic spine fractures more than two-thirds in the randomized FREEDOM study of nearly 7,900 postmenopausal women.
Overall, those fractures appeared in 2.3 percent of the denosumab group, compared with 7.2 percent of patients taking placebo, according to Dr. Steven Cummings of California Pacific Medical Center in San Francisco and colleagues.
And a separate trial by Dr. Matthew Smith of Massachusetts General Hospital in Boston and colleagues documented a similar reduction in new vertebral fractures after two years of denosumab in 1,468 men undergoing androgen-deprivation therapy for prostate cancer, and hence at risk for bone loss.
Both studies were published online in the New England Journal of Medicine. Both sets of researchers reported increases in bone mineral density (BMD) at various body sites with denosumab, whereas no change or decreases in BMD were seen in the placebo groups.
Preliminary results from the two studies were reported last year.
Sundeep Khosla, MD, of the Mayo Clinic in Rochester, Minn., in an accompanying NEJM editorial.Although the drug did not seem to increase infection rates in either study, Khosla noted that its potential to depress immune function remained an issue.
He added that its cost could "considerably limit its use" if it turns out to be much higher than zoledronic acid (Reclast), the bisphosphonate drug that appears to be denosumab's most direct competitor.
The double-blind, randomized, placebo-controlled study by Cummings and colleagues enrolled 7,868 women 60 to 90 years old with established osteoporosis.
Patients received calcium supplements of at least 1,000 mg/day. Vitamin D supplements were provided as well. No bisphosphonates or other osteoporosis drugs were allowed.
Denosumab was given as an injection every six months for three years. Lateral spine radiographs were taken annually and analyzed at a central facility for new vertebral fractures.
At the three-year evaluation, the researchers found that the risk for new vertebral fractures detected by imaging in the group taking denosumab are only about one-third of that in those taking placebo. Similar reductions were seen in rates of vertebral fracture cases seen by doctors and the number of cases involving two or more vertebral fractures detected by X-ray. The group receiving denosumab also enjoyed better improved density.
In the other study, involving men with prostate cancer undergoing anti-androgen therapy, the basic pattern of results was similar. As in the FREEDOM trial, the drug was given every six months by injection.
Smith and colleagues found the overall incidence of new vertebral fractures in the study after three years of treatment was 1.5 percent with denosumab versus 3.9 percent among placebo patients.
Adverse effects were largely similar between treatment groups in both studies, though the male patients showed slightly higher rates (34.6 percent versus 30.6 percent for serious events and 5.9 percent versus 4.6 percent for serious events related to infections). But notably absent from the list of adverse events was osteonecrosis of the jaw, a rare but worrisome side effect of bisphosphonate drugs.