New therapy approaches for giant cell tumors

Abstract

Giant cell bone tumors (GCT) are benign but partially locally aggressive osteolytic tumors which typically occur around the knee joint in the epiphysis and metaphysis of long bones after maturation of the skeleton is completed. Due to the locally aggressive growth behavior with destruction of the bone structure, the rare possibility of pulmonary metastases in recurrent cases and a very rare possibility of malignancy, GCTs were previously also described as semimalignant bone tumors. The established therapy of these tumors at the typical locations consists of intralesional curettage, extension of resection margins using a high speed trephine and defect reconstruction with bone cement. The local recurrence rate is high (10-40 %) and lowest after using thermal extension of resection margins with a high speed trephine and defect reconstruction with bone cement. For uncommon localizations, such as the spinal column and the sacrum as well as in cases of recurrence, surgical treatment is more complicated. Histologically, GCTs consist of osteoclastic giant and oval-shaped stromal cells which show a high expression of receptor activator of nuclear factor-κB ligand (RANKL) and decisively contribute to the osteolytic activity of the tumor. Novel pharmaceutical therapy approaches with human monoclonal RANKL antibodies interfere in this osteodestructive process in an inhibitory manner and can represent alternative treatment options just as the osteosupportive therapy with bisphosphonates. After unsatisfactory attempts at surgical treatment of GCT patients, the new treatment option with denosumab is a promising alternative due to its effect as a monoclonal RANKL inhibitor.