De Novo Osteosarcoma Following Prolonged Denosumab Treatment for Giant Cell Tumor of Bone at an Anatomically Distant Site: a Case Report

Denosumab is a monoclonal antibody targeting RANKL, FDA-approved for the treatment of giant cell tumor of bone (GCTB). While it has shown efficacy in tumor regression and bone preservation, rare cases of malignant transformation to osteosarcoma have been associated with denosumab treatments. Previous literature has attributed such cases to either initial misdiagnosis of a malignant giant cell tumor at baseline presentation or, more rarely, transformation of previously histologically benign GCTB to a secondary malignant GCTB. To our knowledge, these cases involved or arose from an existing giant cell tumor neoplasm. We present a unique case of a patient who developed de novo osteosarcoma at a distant location from their original GCTB tumor following prolonged denosumab therapy, highlighting the clinical course, diagnostic challenges, and therapeutic considerations.