[Treatment of osteoporosis with Denosumab]

Denosumab is the first human monoclonal antibody for the treatment of osteoporosis. By inhibiting RANK Ligand, Denosumab prevents the development, activation and survival of osteoclasts. The FREEDOM study reported a 68 % reduction of vertebral fractures, 20 % of non-vertebral fractures and 40 % of hip fractures after 3 years in post-menopausal women with osteoporosis receiving denosumab 60 mg sc every six months vs. placebo. Five years extension of the denosumab group showed a further decrease in the rate of both vertebral and non-vertebral fractures, whereas BMD at spine and hip increased continuously. There was no increase in the rate of adverse events year after year, including of infections, cancer, atypical fractures, delayed fracture healing or ONJ. Clinical hypocalcemia was rare in the context of calcium and vitamin D supplementation. Pre-planned and post-hoc subgroup analyses have further shown the anti-fracture efficacy of denosumab in high-risk subgroups, such as older women and those with low T-scores and/or prevalent vertebral fractures. Denosumab withdrawal is accompanied by a transient rebound of bone turnover markers and a proportional BMD loss. Smaller randomized controlled studies have shown that denosumab further improves BMD after one year compared to alendronate.