Denosumab Shows Bone Benefits in Two Pivotal Studies

Posted on August 11th, 2009 by

Denosumab increases bone mineral density (BMD) and reduces the risk of vertebral fractures in women with postmenopausal osteoporosis as well as men treated with androgen deprivation therapy for non-metastatic prostate cancer, according to the results of two pivotal studies published in the New England Journal of Medicine.

Denosumab is an investigational drug that targets a protein known as the RANK ligand. This protein regulates the activity of osteoclasts (cells that break down bone). Denosumab has shown promising results in the management of bone metastases, bone loss due to cancer treatment, and postmenopausal osteoporosis.

Denosumab in Men Receiving Hormonal Therapy for Non-metastatic Prostate Cancer

Hormonal therapy for prostate cancer, or androgen deprivation therapy (ADT), involves the suppression of testosterone levels—an approach that may result in loss of bone density and an increased risk of fracture. Studies show that men experience a rapid loss of bone mineral density (BMD) within the first six to 12 months of ADT.

The HALT Study involved 1,468 men undergoing ADT for non-metastatic prostate cancer.[1] Half the men were given denosumab every six months for three years and half were given a placebo. The results showed that men in the denosumab group were 62% less likely than men in the placebo group to develop a new vertebral fracture.

At 24 months, men in the denosumab group had a 5.6% increase in BMD at the lumbar spine, compared with a 1% loss in BMD among men in the placebo group; increases in BMD were observed as early as one month after initiating treatment with denosumab and continued to increase throughout the study. Men receiving denosumab also experienced increases in BMD at non-vertebral sites, including total hip, femoral neck, and distal third of the radius.

Denosumab appeared to be safe and effective, as the rate of adverse events were similar in both groups: the rate of serious adverse events were 35% for denosumab and 31% for placebo.

The researchers concluded that denosumab was safe and effective and increased BMD while decreasing the risk of fractures in men receiving ADT for non-metastatic prostate cancer. The results of denosumab were observed as early as one month into treatment and sustained for three years.

Denosumab in Women with Postmenopausal Osteoporosis

The FREEDOM Study involved more than 7,800 women between the ages of 60 and 90 years, half of whom received denosumab twice a year for three years and the other half of whom received placebo.[2] The results indicated that women who received denosumab were 68% less likely to suffer a vertebral fracture and 40% less likely to suffer a hip fracture than those who received placebo. Women who received denosumab experienced a 9.2% increase in BMD at the lumbar spine and 6.0% at the total hip compared with placebo. Rates of serious adverse events were similar for both groups: 25.8% for denosumab and 25.1% for placebo. Serious skin infections, though rare, were more common in the denosumab group than the placebo group.

The combined results of both of these studies indicate that denosumab may be an innovative new strategy for treating bone loss in different disease settings.


[1] Smith MR, Egerdie B, Hernandez Toriz N et al. Denosumab in men receiving androgen-deprivation therapy for prostate cancer. New England Journal of Medicine. Early online publication August 11, 2009.

[2] Cummings SR, San Martin J, McClung MR et al. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. New England Journal of Medicine. Early online publication August 11, 2009.

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