Exploring Denosumab in the Treatment of Giant Cell Tumors: Clinical Evidence and Controversies

Giant cell tumors (GCTs) are benign but locally aggressive bone neoplasms that primarily affect skeletally mature individuals. They are characterized by a tendency for recurrence and being associated with significant morbidity. Traditional treatment has focused on surgical resection; however, the role of medical therapies, such as Denosumab, a bone anti-resorptive drug, which has been Food and Drug Administration (FDA)-approved for unresectable GCTs since 2013, recently has gained prominence. Denosumab is a human monoclonal antibody that inhibits receptor activator of nuclear factor kappa B ligand (RANKL). This article aims to consolidate the current literature on Denosumab's efficacy in treating GCTs, highlighting its mechanism of action, clinical evidence, and potential complications. Clinical studies have demonstrated that Denosumab effectively reduces tumor size improving patient outcomes. Yet, some clinicians maintain concerns and reservations regarding local recurrence and malignant transformation. This review discusses the biochemical background of GCTs, current treatment guidelines, challenges, and future directions for research. Ultimately, Denosumab represents a potentially viable advancement in the management of GCTs, particularly in cases where surgical options are limited.