Denosumab for the treatment of osteoporosis

Denosumab, a specific inhibitor of receptor activator of nuclear factor kappa-β ligand, is a novel therapy for postmenopausal osteoporosis and related disorders. An extensive and robust clinical development program evaluated the clinical efficacy and safety of denosumab with several thousand patients being followed for up to 10 years. In patients with osteoporosis, denosumab therapy rapidly and persistently reduced fracture risk with relatively few safety concerns with long-term therapy. In accord with its pharmacology, the effects of denosumab on bone remodeling wane quickly upon stopping therapy, necessitating follow-on therapy to prevent the rapid loss of bone density and fracture protection. Combined with almost 10 years of experience in the clinic, the clinical trials described here provide substantial confidence that denosumab is an important component of any long-term treatment strategy for patients with osteoporosis at high risk for fracture. This chapter will summarize the clinical development of denosumab and lessons learned since its approval for clinical use in 2010.