[Antiresorption - same goal, different ways]

[2009;12(01) Moot News]

[According to the results of a recent clinical trial, the antiresorptive effect of a single 60-mg injection of denosumab, a monoclonal antibody specific to RANKL (receptor activator of NFκB ligand) substantially exceeds the effect of alendronate (70 mg weekly). Despite these differences, 1-year increases in bone density at the lumbar spine are virtually identical for both agents. The author summarizes experimental and clinical observations illustrating potential consequences of osteoclast deficiency and a constantly low rate of bone resorption for osteoblast function, bone mineralization, bone quality parameters, and mechanical properties, which all may have important implications for bone fragility. These observations also raise the question whether treatment efficiency is truly improved by aggressively pushing the limits of antiresorptive action.]

[Denosumab is a fully human monoclonal antibody to RANKL modifying bone resorption in a rapid, sustained and reversible way. In postmenopausal women with low bone mineral density, denosumab 60 mg every 6 months increased mineral density, and reduced bone turnover. In postmenopausal women, it reduced the risk of vertebral, hip, and non-vertebral fractures. Increase in body mass index and reduction in bone turnover was more pronounced with denosumab than with alendronate. In patients who were switched from alendronate to denosumab, positive effects on bone were more pronounced than in those continuing alendronate. Denosumab was safe and well tolerated, and it holds the promise of becoming an efficacious therapy for postmenopausal osteoporosis.]