Background: Treatment with bisphosphonates reduces the risk of new fractures and is the treatment of choice for osteoporosis. Denosumab inhibits bone resorption via a different mechanism than bisphosphonates, and is a new option in the treatment of osteoporosis. In this paper we give an overview of the mode of action and clinical effects.
Material and methods: The paper is based on a non-systematic literature search in Pubmed/Medline.
Results: Denosumab is a human monoclonal antibody to receptor-activated nuclear factor kappa B (RANKL), a member of the TNF family that is formed in the osteoblast. Binding to RANKL results in reduced recruitment and activity of osteoclasts. Denosumab 60 mg given subcutaneously every six months is shown to inhibit bone resorption to a greater degree than bisphosphonates. In a three-year study of 7,868 women with postmenopausal osteoporosis, a reduction in the relative risk of vertebral, non-vertebral and hip fractures compared to placebo was found (68. 20 and 40 %, correspondingly). In the clinical trials with denosumab, the safety profile was similar to placebo, except for a slightly higher incidence of cellulitis and exanthema. Denosumab has also shown promising skeletal effects in the treatment of cancer and rheumatoid arthritis.
Interpretation: Treatment with denosumab has an effect on postmenopausal osteoporosis and may be an alternative to treatment with bisphosphonates. There are few adverse effects and it is simple to administer.