Denosumab Approved for Bone Loss in Men With Osteoporosis

Emma Hitt, PhD


September 27, 2012

September 27, 2012 — The US Food and Drug Administration (FDA) has approved denosumab (Prolia, Amgen) for the treatment of bone loss in men with osteoporosis who are at high risk for fracture, according to an announcement from the manufacturer.

Denosumab is the first FDA-approved receptor activator of nuclear factor-κB (RANK) ligand inhibitor and is given subcutaneously every 6 months. Denosumab is already approved for the treatment of postmenopausal women with osteoporosis who are at high risk for fracture, in men receiving androgen deprivation therapy for nonmetastatic prostate cancer who are at high risk for fracture, and in women receiving adjuvant aromatase inhibitor therapy for breast cancer who are at high risk for fracture.

The new indication is based on results from the ADAMO randomized trial, which compared the efficacy and safety of denosumab 60 mg every 6 months with that of placebo in men with osteoporosis. The study involved 242 men with low bone mineral density (BMD).

Compared with placebo, denosumab significantly increased bone mass at the lumbar spine (5.7% vs 0.9%). These effects took place independent of age, baseline testosterone levels, BMD status, and estimated fracture risk. Improvements were also observed at the "total" hip (2.4% vs 0.3%) and femoral neck (2.1% vs 0.0%). The trial did not include a formal endpoint assessing fractures, but the reported numbers were 2 fractures (1.7%) in the placebo group and 1 (0.8%) in the denosumab-treated group at 12 months.

The most common adverse reactions reported, at an incidence of more than 5%, were back pain, arthralgia, and nasopharyngitis. The adverse events were similar to those observed in other studies and settings.

"[O]steoporosis in men is a significant issue that is increasing in prevalence as life expectancies rise," noted Sean E. Harper, MD, executive vice president of Research and Development at Amgen, in the company news release.

"According to the National Osteoporosis Foundation, two million men in the U.S. have osteoporosis and another 12 million are at risk. Osteoporosis and osteoporotic fractures in men remain underdiagnosed and undertreated," the release notes.