Background: Giant cell tumor of bone (GCT) is a relatively rare, locally aggressive osteolytic skeletal neoplasm of young adults with uncertain behavior with recurrence rates up to 70%. Distant metastases occur approximately 2-6% of cases most often to the lungs. Nowadays denosumab is the choice of therapy for patients (pts) with unresectable or advanced disease. However the efficiency, duration or regimen and most of all safety of continuous denosumab are not established. Methods: We observed 40 advanced or unresectable GCT cases from 2005 till 2020 in N.N. Blokhin NMRCO. Patients underwent CT/MRI every 3 months during the first three years and then once every six months. Patient received subcutaneous denosumab (Db) 120 mg every 4 weeks with a loading dose of 120 mg subcutaneous on study days 8 and 15 and once in three months injection after 2 years monthly therapy. All patients received daily calcium and vitamin D supplement. Results: Median follow-up was 52,8±41,3 months (3-219). The average age of pts was 33,6±13,1 years (18-64), and the women and men ratio was about 2,1:1. The most commonly affected sites were long bones of the lower extremities (22,5%), sacrum (22,5%), long bones of the upper extremities (17,5%), spine (17,5%), pelvis (10%) and others. 70% of cases were anatomically compounded due to tumor localization and 27,5% of cases were primary disease. 37,5% of cases were with pulmonary metastases. The average Db injections were 25 ± 16 (4-85). Clinical and radiographically stabilization of the effect occurred on average at 12 ± 8 (4-32) injections. Hypocalcemia and osteonecrosis was registered in one case (2.5%) respectively. There were significant improvement of Karnofsky, VAS and Whatkins scale (p <0.001). 5-year progression-free survival for was 70.1% (95% CI: 55.7-88.0), the median was not reached. Progression of disease was observed only in subgroup A with violations in Db administration or its cancellation (32,5%). 3-year PFS subgroup A was 10% (95% CI: 15.5-64.1). In subgroup B with continuous Db and once in three months injection after 2 years monthly therapy there was no signs of progression. Conclusions: In this study we showed evidence of safety and effectiveness of continuous Db for unresectable or advanced GCT even with once in three months injection therapy. Denosumab for advanced GCT became a choice of treatment, but we need further investigation for observation long term Db effectiveness and complications.