RANK-Ligand and Mode of Action of denosumab (XGEVA®)

RANK-Ligand (RANKL) is a primary mediator of the activation of osteoclasts and of tumor associated bone disease. RANKL is responsible for the differentiation and activity of osteoclasts that are active in bone reduction. The protein OPG (osteoprotegerin), that is produced by osteoblasts, prevents the binding of RANKL to the osteoclasts, and establishes a physiological equilibrium between bone loss and bone construction. This balance is destroyed in tumor induced bone disease. The increased amount of RANKL increases the activity of osteoclasts, starting a vicious cycle: excessive osteoclast activity drives increased bone resorption; this in turn releases growth factors from the bone matrix that may perpetuate tumor activity.


Mode of action of denosumab
Denosumab is a fully human monoclonal antibody directed against RANKL, preventing the activation and differentiation of the osteoclasts by binding to its receptor RANK on the osteoclast surface.
The mode of action of denosumab in the bone metastatic environment is shown in this video.

Bone remodeling in multiple myeloma


This video describes the pathogenesis of osteolytic bone lesions in patients with multiple myeloma. Specifically, the RANK-Ligand-pathway plays an essential role in the resorption of the bone.

Denosumab Oncology presentations

Denosumab (XGEVA®) in Clinical Guidelines
Denosumab Oncology in Breast Cancer
Denosumab Oncology in Prostate Cancer
Denosumab (XGEVA®) and Giant Cell Tumor of the Bone
Denosumab in the ‘482 SRE Multiple Myeloma trial*
Denosumab and Immune Oncology Therapies
Bone Therapies in metastatic Prostate Cancer Landscape

Denosumab (XGEVA) Support Materials for physicians and patients

XGEVA® (Denosumab) Patienten-Informationskarte
XGEVA® (denosumab) scheda paziente-informazione
Individual slide decks and speaker slide decks can be requested with MedInfo.
These support materials for the dentist and the patients can be ordered directly with your product specialist representative - Verena Schmutz; Sonja Jehle Schwertfeger; Carmen Schwizer and Guy Perret.
*Denosumab is not licensed in Switzerland for the treatment of bone lesions in patients with Multiple Myeloma