BACKGROUND: Giant cell tumor of bone (GCTB) is a primary bone tumor which comprises giant cells and two types of stromal cells. Recent studies have suggested therapeutic risks of denosumab. No previous studies have reported changes in serum TRACP-5b and SUVmax of 18F-FDG-PET/CT in recurred GCTB after denosumab treatment. Therefore, we assessed the relationship between clinical and pathological features of GCTB which recurred after denosumab treatment. METHODS: We retrospectively reviewed the medical records of 26 patients with GCTB who underwent curettage between 2010 and 2018. Fourteen patients treated with denosumab were defined as the denosumab group. We evaluated TRACP-5b and SUVmax values in the denosumab group. H&E staining and immunohistochemistry for H3.3 G34W were performed for pathological assessment. Twelve patients treated without denosumab were defined as the non-denosumab group and compared with denosumab group. RESULTS: The local recurrence rate in the denosumab group was 57.4%. The mean TRACP-5b and SUVmax values were significantly decreased after denosumab therapy (P < 0.001, 1077 ± 161 to 74 ± 9 mU/dL and 8.88 ± 0.40 to 3.79 ± 0.56, respectively). Both parameters significantly increased with local recurrence. H&E staining after denosumab treatment revealed the disappearance of giant cells and histological changes in stromal cells. Specimens of local recurrence subjected to H&E staining and immunohistochemistry for H3.3 G34W demonstrated almost identical features to those in the first biopsy. CONCLUSION: Although denosumab can prevent GCTB from osteolysis, local recurrence cannot be reduced by denosumab treatment. The clinical and pathological results were almost the same as those before denosumab treatment, suggesting that the changes of GCTB by denosumab are reversible.