[The role of RANK/RANKL/osteoprotegerin (OPG) triad in cancer-induced bone diseases: physiopathology and clinical implications]

Bull Cancer. 2011 Jul;98(7):837-46. doi: 10.1684/bdc.2011.1398.
[Article in French]


Bone homeostasis is maintained by the remodelling of bone which depends on a balance between osteoclast-mediated bone resorption and osteoblast-mediated bone formation. Malignant bone lesions are very common in patients with cancer; whether they result from a tumor in bone (giant cell tumour of bone, osteosarcoma, multiple myeloma...) or they are bony metastases from advanced cancers of which the most osteotropic are breast and prostate cancer. Malignant cells within the bone disrupt the normal bone remodelling process, leading to increased bone destruction and occurence of pathological fractures. Receptor activator of NF-kB (RANK) and its ligand (RANKL) play a pivotal role in the regulation of bone remodelling; by binding to RANK, RANKL stimulates osteoclastogenesis and bone resorption, whereas its cognate decoy receptor osteoprotegerin (OPG) blocks this process by interacting with RANKL. Tumour cells produce different factors that manipulate the RANK/RANKL/OPG pathway in order to stimulate bone destruction. Furthermore, pending on the tumour type, RANKL plays a role in the migration, invasion and proliferation of malignant cells within the bone, while OPG increases survival of tumour cells. Inhibition of RANK/RANKL system may therefore offer new therapeutic perspectives for the treatment of primitive and secondary bone cancers.

Publication types

  • English Abstract
  • Review

MeSH terms

  • Bone Neoplasms / etiology*
  • Bone Neoplasms / prevention & control
  • Bone Neoplasms / secondary
  • Bone Remodeling / physiology*
  • Bone Resorption / etiology
  • Bone Resorption / physiopathology
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Female
  • Homeostasis / physiology
  • Humans
  • Male
  • Multiple Myeloma / metabolism
  • Neoplasm Proteins / antagonists & inhibitors
  • Neoplasm Proteins / physiology*
  • Osteoprotegerin / antagonists & inhibitors
  • Osteoprotegerin / physiology*
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology
  • RANK Ligand / antagonists & inhibitors
  • RANK Ligand / physiology*
  • Receptor Activator of Nuclear Factor-kappa B / antagonists & inhibitors
  • Receptor Activator of Nuclear Factor-kappa B / physiology*


  • Neoplasm Proteins
  • Osteoprotegerin
  • RANK Ligand
  • Receptor Activator of Nuclear Factor-kappa B