Giant-cell tumor of bone (GCTB) is a rare osteolytic
tumor of the bone. Although classified as a benign
tumor, GCTB is characterized by local aggressiveness and risk of local recurrence. In addition, GTCB can in some cases lead to the development of so-called 'benign' chest
metastases. Surgical resection by intralesional
curettage with high-speed burring and
polymethylmethacrylate cement is the standard treatment for resectable
tumors. In cases of metastatic or unresectable disease (when planned
surgical procedure is impossible or would result in severe morbidity), medical treatments such as cytotoxic
chemotherapy or
interferon-α have limited efficacy.
Bisphosphonates have been proposed as a therapeutic option to reduce osteoclast activity. In bone, various pathological states may result from an imbalance in the RANK (
receptor activator of nuclear factor kappa-B)/RANKL (
receptor activator of nuclear factor kappa-B ligand)/OPG (
osteoprotegerin) pathway. Involvement of the RANKL pathway in pathogenesis of GCTB was first proposed in 2000.
Denosumab is a fully human
monoclonal antibody that binds and inhibits RANKL, thereby preventing the activation of the RANK pathway. As it showed the possibility to counteract osteoclast activation in GCTB and prevent the known physiopathological role of RANKL,
denosumab has been under evaluation in the clinic as a treatment for GCTB since 2005. Results of a first Phase II trial demonstrate the therapeutic potential of
denosumab to inhibit progressive bone destruction and metastatic progression in patients with unsalvageable
giant-cell tumor (GCT), and have also provided key insights into the biology of GCT.
Denosumab is currently a therapeutic option for patients with unresectable GCTB but its place in the global therapeutic strategy has not yet been defined.