McClung MR et al. (2006) Denosumab in postmenopausal women with low bone mineral density. N Engl J Med 354: 821–831

Denosumab is a fully human monoclonal antibody that targets RANKL (the receptor activator of nuclear factor κB ligand)—a protein that acts as the primary mediator of osteoclast differentiation, activity, and lifespan. In a phase II, randomized, placebo-controlled study, McClung et al. evaluated the efficacy of denosumab in postmenopausal women younger than 80 years who had a low BMD.

In total, 369 women from 29 study centers in the US completed this 12-month study. Participants were randomly assigned to receive subcutaneous denosumab, either every 3 months (6, 14, or 30 mg) or every 6 months (4, 60, 100, or 210 mg), open-label 70 mg alendronate per week, or placebo. At 12 months, women who received denosumab had a mean increase in BMD of 3.0–6.7% at the lumbar spine, compared with a 4.6% increase and a 0.8% decrease in women who received alendronate and placebo, respectively. Women who received denosumab also had a greater increase in total hip BMD and BMD in the distal third of the radius compared with the alendronate and placebo groups. Levels of serum C-TELOPEPTIDE decreased as early as 3 days in women who received denosumab. A dose of 30 mg denosumab every 3 months, or 60 mg every 6 months seemed to be the most effective regimens. Adverse events were not significantly different among the three treatment arms.

The authors conclude that denosumab administered subcutaneously to postmenopausal women causes a decrease in bone turnover and an increase in BMD. Denosumab might, therefore, be an effective treatment for osteoporosis.