Denosumab in Giant Cell Tumor of Bone: Multidisciplinary Medical Management Based on Pathophysiological Mechanisms and Real-World Evidence

(1) Despite the benign nature of the giant cell tumor of bone (GCTB), it shows a local recurrence rate of up to 50% and a chance of malignant transformation. The widely accepted local therapy in extremity GCTB is surgery, in the form of extended intralesional curettage with adequate disease clearance and retention of the limb, wherever possible. Denosumab, a human monoclonal antibody directed against the RANKL and associated inhibition of the RANKL pathway, is a relevant therapy option for advanced GCTB, to benefit tumor response and surgical down-staging. (2) The literature review of patients with GCTB treated with denosumab is performed via PubMed, using suitable keywords from January 2009 to January 2021. (3) Current indications for denosumab use are not definitively clear and unambiguous. Most GCTB patients with localized disease can be successfully treated with surgical curettage, and the role of denosumab in preoperative therapy in this patient population remains unclear. (4) However, patients with primary unresectable lesions or metastases may experience long-term clinical and radiological remission and pain control with denosumab treatment, and in this clinical situation, denosumab is currently the treatment of choice.