Denosumab: A Novel Agent for Osteoporosis

Abstract

Objective:

To review the pharmacology, pharmacokinetics, clinical efficacy, and safety of denosumab, a biologic antiresorptive agent for treatment of osteoporosis and other bone-related disorders.

Data Sources:

Primary literature and review articles were obtained via a MEDLINE search (1966–July 2008), using the following key terms: denosumab, AMG 162, and RANKL. Additional articles were identified from the bibliographies of reviewed literature.

Study Selection and Data Extraction:

English-language articles identified from the data sources were reviewed. All pertinent preclinical and clinical information was included. Randomized controlled trials were evaluated to assess the efficacy of denosumab in osteoporosis, rheumatoid arthritis (RA), and breast cancer—related bone metastases.

Data Synthesis:

Denosumab is a humanized monoclonal antibody that neutralizes receptor activator of nuclear factor-κB-ligand, thereby decreasing osteoclast-mediated bone resorption. This agent has been compared with placebo and intravenous bisphosphonates in randomized, double-blind controlled trials. In studies involving patients with osteoporosis, RA, or breast cancer—related bone metastases, denosumab significantly improved bone mineral density and markers of bone turnover when compared with placebo. Adverse events were minimal among patients receiving denosumab, although long-term safety data are not available.

Conclusions:

Denosumab is a novel therapeutic agent that improved BMD and bone turnover markers in clinical studies, suggesting that it may be promising for the treatment of a variety of bone remodeling disorders.

ACPE Universal Program Numbers:

407-000-09-051-H01-P (Pharmacists); 407-000-09-051-H01-T (Technicians)