When and how to stop denosumab therapy in a patient with osteoporosis.

Abstract

Denosumab is a human monoclonal antibody that competitively inhibits the receptor activator of nuclear factor kappa B ligand which regulates osteoclast activity. It is an effective treatment for osteoporosis with a reduced cumulative rate of vertebral fractures, hip and nonvertebral fractures as well as an increase in bone mineral density. The benefits have been shown to be maintained when treatment is continued up to and likely after 10 years of therapy, but the effects are lost rapidly if treatment is discontinued abruptly. There are rare medical indications for discontinuation of treatment. Discontinuation of denosumab is often driven by concern about complications such as osteonecrosis of the jaw, atypical femoral fractures and hypocalcaemia, which remain rare events. Further studies are required to confirm safety and efficacy beyond 10 years of treatment, but it is likely that patients will have ongoing benefits from therapy beyond this. We aim to present a personal perspective of why and how denosumab should be discontinued in patients with osteoporosis.