Denosumab for the treatment of giant cell tumor of the bone

Future Oncol. 2015;11(13):1881-94. doi: 10.2217/fon.15.94.

Abstract

Giant cell tumor of bone is typically composed of neoplastic stromal cells and non-neoplastic osteoclastic giant cells. RANK-expressing osteoclastic giant cells are recruited by RANK ligand excreted by the stromal cells, and used by these neoplastic cells to create expansion space. Denosumab specifically binds to and inhibits RANK ligand, thereby eradicating osteoclastic giant cells from the tumor and thus reducing osteolytic activity. Clinical studies reported disease stabilization and clinical benefit in terms of reduced pain and analgesics use, avoided surgeries or surgeries with less morbid procedures. Adverse events observed in patients with giant cell tumor of bone were consistent with the known safety profile of denosumab with a very low incidence of hypocalcemia and osteonecrosis. Overall, denosumab was shown to suppress osteolytic activity and slow disease progression and is thus a treatment option for patients with giant cell tumor of bone.

Keywords: GCTB; RANK; RANKL; bone turnover; denosumab; giant cell tumor of bone; osteoclast activity; osteoclastic giant cells; stromal cells.

MeSH terms

  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Denosumab / adverse effects
  • Denosumab / therapeutic use*
  • Gene Expression Regulation, Neoplastic
  • Giant Cell Tumor of Bone / drug therapy*
  • Giant Cell Tumor of Bone / genetics
  • Humans
  • Osteoclasts / drug effects
  • RANK Ligand / genetics
  • Receptor Activator of Nuclear Factor-kappa B / biosynthesis*
  • Stromal Cells / drug effects
  • Stromal Cells / pathology

Substances

  • Antibodies, Monoclonal, Humanized
  • RANK Ligand
  • Receptor Activator of Nuclear Factor-kappa B
  • TNFRSF11A protein, human
  • Denosumab