Denosumab may increase bone mineral density (BMD) and reduce the incidence of new vertebral fractures in men receiving androgen-deprivation therapy (ADT) for nonmetastatic prostate cancer (PCa), a study shows.

The drug is a fully human monoclonal antibody that binds specifically to the receptor activator of a key mediator of osteoclast formation, function, and survival.

In a double-blind study of 1,468 patients (mean age 75 years) receiving ADT for nonmetastatic PCa, Matthew R. Smith, MD, PhD, of the Massachusetts General Hospital Cancer Center in Boston, randomly assigned 734 subjects to receive denosumab at a dose of 60 mg subcutaneously every six months and 734 to receive placebo. In both groups, 76% of patients had received ADT for more than six months.

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The primary end point was the percent change in BMD at the lumbar spine at 24 months.

At 24 months, the BMD of the lumbar spine had increased by 5.6% in the denosumab arm and decreased by 1% in the placebo recipients, the investigators reported in The New England Journal of Medicine (2009;361-745-755), a significant difference between the groups. In fact, the researchers observed significant differences between the groups as early as one month into the study; these differences were sustained through 36 months.

Additionally, denosumab therapy was associated with significant increases in BMD at the total hip, femoral neck, and distal third of the radius at all time points, Dr. Smith’s group noted.

The incidence of new vertebral fractures at 36 months was 1.5% in the denosumab group compared with 3.9% in the placebo group, a significant difference between the groups that translated into a 62% decrease in relative risk. The two study arms had similar rates of adverse events (AEs).

The denosumab group had 638 AEs (87.3%) and the placebo group had 627 (86.5%). In either group, the researchers observed no delay in healing of nonvertebral fractures and no cases of osteonecrosis of the jaw. Cataracts developed in 4.7% of denosumab-treated patients compared with 1.2% of placebo recipients, but none of these cases were considered related to denosumab, according to the researchers.

The authors concluded that “twice-yearly administration of denosumab was associated with increases in bone mineral density at all skeletal sites and reduction in vertebral fractures in men receiving androgen-deprivation therapy for prostate cancer.”