Denosumab is a fully human
monoclonal antibody to the receptor activator of nuclear factor-κB
ligand (RANKL), a member of the
tumor necrosis factor receptor superfamily essential for osteoclastogenesis.
Denosumab treatment is associated with a rapid, sustained, and reversible reduction in bone turnover markers, a continuous marked increase in bone mineral density at all sites, and a marked decrease in the risk of vertebral, hip, and nonvertebral fractures in women with
postmenopausal osteoporosis. Therefore, it could be considered as an effective alternative to previous
bisphosphonate treatment as well as first-line treatment of severe
osteoporosis. Cost-effectiveness studies support this suggestion. In addition,
denosumab seems to be the safest treatment option in patients with impaired renal function.
Denosumab is characterized by reversibility of its effect
after treatment discontinuation, in contrast with
bisphosphonates. Large-scale clinical trials, including the extension of FREEDOM trial for up to 5 years, are reassuring for its safety. However, given its brief post-market period, vigilance regarding adverse events related to putative RANKL inhibition in tissues other than bone, as well as those related to bone turnover oversuppression, is advised.