Denosumab is an investigational fully human monoclonal antibody against receptor activator of nuclear factor-κB ligand, a mediator of osteoclastogenesis and osteoclast survival.Objective:
This study evaluated the ability of denosumab to increase bone mineral density (BMD) and decrease bone turnover markers (BTMs) in early and later postmenopausal women with low BMD.Design and Setting:
This 2-yr randomized, double-blind, placebo-controlled study was conducted in North America.Participants:
Subjects included 332 postmenopausal women with lumbar spine BMD T-scores between −1.0 and −2.5.Interventions:
Subjects were randomly assigned to receive denosumab sc, 60 mg every 6 months, or placebo. Randomization was stratified by time since onset of menopause (≤5 yr or > 5 yr).Main Outcome Measures:
The primary end point was the percent change in lumbar spine BMD by dual-energy x-ray absorptiometry at 24 months. Additional end points were percent change in volumetric BMD of the distal radius by quantitative computed tomography; percent change in BMD by dual-energy x-ray absorptiometry for the total hip, one-third radius, and total body; hip structural analysis; percent change in BTMs; and safety.Results:
Denosumab significantly increased lumbar spine BMD, compared with placebo at 24 months (6.5 vs. −0.6%; P<0.0001) with similar results for both strata. Denosumab also produced significant increases in BMD at the total hip, one-third radius, and total body (P < 0.0001 vs. placebo); increased distal radius volumetric BMD (P < 0.01); improved hip structural analysis parameters; and significantly suppressed serum C-telopeptide, tartrate-resistant acid phosphatase-5b, and intact N-terminal propeptide of type 1 procollagen. The overall incidence of adverse events was similar between both study groups.Conclusions:
Twice-yearly denosumab increased BMD and decreased BTMs in early and later postmenopausal women.