Giant cell tumor of bone (GCTB) is a locally aggressive primary bone
tumor that contains numerous osteoclasts formed from marrow-derived precursors through receptor activator of nuclear factor κ-B
ligand (RANKL), an
osteoclast differentiation factor expressed in neoplastic cells of GCTB.
Denosumab, a fully human
monoclonal antibody targeting RANKL, has recently been used for the treatment of GCTB, and superior treatment effects have been reported. The aim of this work was to elucidate the mechanism of action of
denosumab, and the differences between
denosumab and
zoledronic acid at the level of GCTB cells. We isolated GCTB cells from 3 patients and separated them into osteoclasts, osteoclast precursors and proliferating spindle-shaped stromal cells (the true neoplastic component), and examined the action of
denosumab on differentiation, survival and
bone resorption activity of osteoclasts.
Denosumab and
zoledronic acid inhibited osteoclast differentiation from mononuclear cells containing osteoclast precursors.
Zoledronic acid inhibited osteoclast survival, whereas an inhibitory effect of
denosumab on osteoclast survival was not observed. The inhibitory effect on
bone resorption by both agents was confirmed in culture on dentin slices. Furthermore,
zoledronic acid showed dose-dependent inhibition of cell growth of neoplastic cells whereas
denosumab had no inhibitory effect on these cells.
Denosumab has an inhibitory effect on osteoclast differentiation, but no inhibitory effects on survival of osteoclasts or growth of neoplastic cells in GCTBs.