An otherwise healthy 20-year-old woman was diagnosed with GCTB in February 2009, after an accidental fall while skiing. X-Ray examination showed an osteolytic area in the proximal tibia. The lesion was resected via curettage, and histological examination was positive for GCTB. Subsequent systemic staging highlighted a 5-cm large sacral primary ( Figure 1 , left panel), multiple bone (D9-11, L3, L5, right hemi-sacrum, and right femur) metastases and one single pulmonary metastasis in the superior lobe of the left lung. Diagnosis of GCTB was histologically confirmed on the sacral lesion. Family history was negative for cancer, and patient had no comorbidities at the time of the event. The patient was symptomatic for diffuse back and buttock pain, invalidating her normal daily activities and gradually determining an impairment in walking, which finally constrained her to the use of a wheelchair. Given the diagnosis and the disease extent, in November 2009, she was started with denosumab (120 mg subcutaneously, once per month, following the loading dose of 120 mg day 1-8-15), obtaining a reduction in tumor size and resolution of all GCTB-related symptoms ( Figure 1 , right panel). The disease response and clinical benefit were maintained for over 10 years. After 132 months of treatment (November 2019, at the age of 30), the drug was interrupted due to a fracture of the left femur diaphysis, after a minor trauma (low-energy fall while walking). The fracture carried the typical clinical and radiological features of a complete displaced AFF ( Figure 2 , left panel), which was related to denosumab. The patient was treated with open reduction and intramedullary nailing, along with calcium and vitamin D daily supplements, to accelerate fracture healing ( Figure 2 , right panel). However, bony callus fully consolidated only 13 months after the nailing. GCTB remained stable for 14 months after denosumab discontinuation, when a new CT scan showed progressive disease by RECIST, marked by the appearance of two new lesions in the right iliac wing and in L5 soma ( Figure 3 , left panel). After multidisciplinary evaluation and orthopedic assessment, denosumab was restarted at the previous dosage (120 mg per month, subcutaneously). At the first re-assessment, 3 months later, a new tumor stabilization was documented and confirmed at 1 year, with no evidence of AFF relapse or additional serious adverse events reported ( Figure 3 , right panel).