Denosumab for treating giant cell tumor of bone

Introduction: Giant cell tumor of bone (GCTB) is usually a locally aggressive tumor with low metastatic potential. Giant cells are known to express receptor activator of NF-B ligand (RANKL) and are responsible for its aggressive osteolytic nature. Overexpression of RANKL by mononuclear neoplastic stromal cells promotes recruitment of numerous reactive multinucleated giant cells.Areas covered: In patients with high-risk or locally advanced/surgically unsalvageable GCTB or in rare cases of metastatic disease, systemic targeted therapy with the RANKL inhibitor - monoclonal antibody denosumab - is highly effective and may lead to long-term responses or down staging facilitating resection of the tumor. Several studies with denosumab in patients with advanced or unresectable GCTB have shown objective reductions of bone destruction and clinical benefits. The literature focusing on denosumab and GCTB is reviewed here and the most important questions related to the future management of GCTB are discussed.Expert opinion: Denosumab, which inhibits RANK - RANKL interaction, is a new promising actor among molecular-targeted therapeutic agents for GCTB. Ideally, all patients should be treated with local/intralesional excision followed by adjuvant treatment or preceded by neoadjuvant denosumab in selected cases, achieving joint salvage and optimal function outcome.