Denosumab Effective Over 2 Years in Men with Low Bone Density

By Reuters Staff

NEW YORK (Reuters Health) - Treatment with the antiresportive denosumab proved safe and effective over two years in men with low bone mineral density (BMD) in the ADAMO trial.

BMD continued to increase at all sites assessed and bone resportion decreased in the second year of treatment, Dr. Bente Langdahl from Aarhus University Hospital in Denmark and colleagues report.

Denosumab is a fully human monoclonal antibody that targets the receptor activator of the nuclear factor-kappa-B ligand (RANKL) protein, which contributes to bone maintenance.

The phase 3 ADAMO study had two consecutive 12-month treatment phases: a previously reported double-blind, placebo-controlled phase in which 242 men with low BMD received placebo or denosumab 60 mg subcutaneously every six months, and an open-label phase reported online now in the Journal of Clinical Endocrinology and Metabolism.

In the open-label phase, 111 men from the denosumab arm continued on treatment for a second year and 117 patients on placebo crossed over to denosumab. All of the men took 1000 mg elemental calcium and at least 800 IU vitamin D daily during the study.

During the open-label phase, BMD continued to increase in the denosumab group at all sites (2.2% lumbar spine; 0.9% total hip; 1.3% femoral neck; 1.3% trochanter; and 0.2% 1/3 radius), resulting in cumulative 24-month gains from baseline of 8.0%, 3.4%, 3.4%, 4.6%, and 0.7%, respectively (all p<0.01), the study team reports.

The men who crossed over to denosumab had gains in BMD after 12 months of denosumab treatment similar to the long-term denosumab group during the first treatment year, they note.

Rapid and significant reductions in serum C-telopeptide (sCT), a marker of bone resorption, were observed with denosumab treatment. Rates of adverse events were similar between groups and no new safety signals were identified.

The authors note that one in four men in the U.S. over age 50 will suffer an osteoporosis-related fracture.

The bone-building effects of denosumab in this study of men with low BMD are similar to those previously seen in postmenopausal women with osteoporosis and men with prostate cancer on androgen deprivation therapy, Dr. Langdahl and colleagues say.

In a study of postmenopausal women, denosumab therapy significantly reduced the risk of new vertebral and nonvertebral fractures, including hip fractures. "It is reasonable to anticipate that the effect on fracture risk is likely to be similar in men with osteoporosis treated with denosumab," the researchers conclude.

The study was funded by Amgen, which markets denosumab. Several of the researchers have financial relationships or are employees of the company.

SOURCE: https://bit.ly/1JImX0q

J Clin Endocrinol Metab 2015.

(c) Copyright Thomson Reuters 2015. Click For Restrictions - https://about.reuters.com/fulllegal.asp