DENOSUMAB EFFECTIVE IN MALE OSTEOPOROSIS 

NEW YORK (Reuters Health) Jul 06 - Denosumab has now been shown in a randomized trial to improve osteoporosis in men, too.

Whether the men's improvements in bone mineral density and reductions in bone resorption will translate to fewer fractures remains unknown, however.

The drug is better known for its results in women. But about 2 million men in the United States have osteoporosis, and another 12 million are at risk for it.

A variety of bisphosphonates are approved for treating osteoporosis in men, but the researchers who conducted the current study say compliance with long-term bisphosphonate therapy is poor.

Denosumab, a monoclonal antibody that binds to the protein receptor activator of nuclear factor kappa-B (RANK) ligand, reduces fractures in postmenopausal women with osteoporosis and in men receiving androgen deprivation therapy for prostate cancer.

In a new report online June 21 in The Journal of Clinical Endocrinology & Metabolism, Dr. Eric Orwoll from Oregon Health and Science University in Portland and colleagues present the 12-month findings from the 24-month phase III ADAMO trial of denosumab vs placebo in men with low BMD.

Of the 242 patients who enrolled, 228 completed the first 12 months. Their mean age was 65 years.

At 12 months, lumbar spine BMD - the primary endpoint - had increased by significantly more in the denosumab group than in the placebo group (5.7% vs 0.9%). Lumbar spine BMD was already significantly higher in the denosumab group by six months of treatment.

Denosumab also significantly increased BMD at the total hip, femoral neck, hip trochanter, and one third radius at month 12.

Denosumab's superiority persisted after the authors adjusted for baseline testosterone level, lumbar spine BMD T-score, 10-year major osteoporotic fracture risk, serum C-telopeptide of type I collagen (sCTX), age, race, geographic region, and previous osteoporotic fracture.

"The consistent results across subgroups demonstrated that denosumab therapy is effective across a spectrum of men," the researchers say.

Median concentrations of sCTX, a marker of bone turnover, decreased by 81% in the denosumab group, compared with a 7% decrease in the placebo group (p<0.0001).

Although the study design did not include a formal assessment of fractures, clinical fractures occurred in two (1.7%) placebo patients and one (0.8%) denosumab patient during the study; one man in each group had a rib fracture, and in the placebo group there was one man with a humerus fracture and one with a new vertebral fracture.

Rates of adverse events, serious adverse events, and fatal adverse events were similar in the treatment groups, and there were no cases of hypocalcemia, jaw osteonecrosis, complications of fracture healing, or atypical femoral fractures during the study.

"The increases in BMD were similar to those observed in previous studies that demonstrated fracture risk reduction," the investigators note, "suggesting that denosumab is efficacious in the treatment of men with osteoporosis."

Other trials will have to answer the question of whether these increases in BMD will actually translate into fewer fractures for men with low BMD.

Dr. Orwoll did not respond to a request for comments.

The study was supported by Amgen, which employed five of the authors and had various types of relationships with all 15 of the remaining authors.

SOURCE: http://bit.ly/RtQIHb

J Clin Endocrinol Metab 2012.