Therapeutic approach of primary bone tumours by bisphosphonates

Curr Pharm Des. 2010;16(27):2981-7. doi: 10.2174/138161210793563554.

Abstract

Bone tumours can be dissociated in two main categories: i) primary bone tumours (benign or malignant) including mainly osteosarcoma and other sarcomas.ii)and giant cell tumour and bone metastases originate from others cancer (Breast, prostate, kidney cancer, etc). These tumours are able to destroy or/and induce a new calcified matrix. However, the first step of bone tumour development is associated with an induction of bone resorption and the establishment of a vicious cycle between the osteoclasts and the tumour growth. Indeed, bone resorption contributes to the pathogenesis of bone tumour by the release of cytokines (IL6, TNFα) which govern the bone tumour's development and which are trapped into the bone matrix. Bisphosphonates (BPs) are chemical compounds of P-C-P structure with a high affinity for bone hydroxyapatite crystals. Thus, they have been used as a carrier for radio nucleotides to develop novel approaches of bone imaging. BPs exert also indirect anti-tumour activities in vivo. Indeed, BPs directly interfere with the bone microenvironment and target osteoclasts, endothelial cells and immune cells (tumour-associated macrophages, γ9δ2 T cells). BPs induce tumour cell death in vitro and same activity is suspected in vivo. The present review summarizes the mechanisms of actions of BPs as well as their clinical interests in bone primary tumours.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use*
  • Bone Density Conservation Agents / pharmacology
  • Bone Density Conservation Agents / therapeutic use
  • Bone Neoplasms / diagnostic imaging
  • Bone Neoplasms / drug therapy*
  • Chondrosarcoma / drug therapy
  • Diphosphonates / pharmacology*
  • Diphosphonates / therapeutic use*
  • Drug Design*
  • Giant Cell Tumor of Bone / drug therapy
  • Humans
  • Osteosarcoma / drug therapy
  • Radiography

Substances

  • Antineoplastic Agents
  • Bone Density Conservation Agents
  • Diphosphonates