The Role of Denosumab in the Modern Treatment of Giant Cell Tumor of Bone

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Giant cell tumor of bone (GCTB) is a typically benign, locally aggressive, and osteolytic primary bone tumor1,2. Without treatment, uncontrolled growth can result in osseous destruction of the affected region and invasion into surrounding soft tissues1. Patients with GCTB usually present with functional limitations, swelling at the affected site, and pain. GCTB comprises approximately 3% to 6% of all biopsy-analyzed primary bone tumors in Western countries, but, in Asian countries, it represents up to 20%1,3,4. Adults 20 to 50 years of age are typically affected, with an increased propensity for development in women over men1,3. Most GCTB lesions are solitary and the vast majority occur in the distal part of the femur, the proximal part of the tibia, or the distal part of the radius (Fig. 1)2,3,5,6.
The operative management for GCTB is extended intralesional curettage with or without physical or surgical adjuvants1,2. En bloc resection is an acceptable treatment option for bones considered expendable, such as the proximal part of the fibula, when expendable bones demonstrate well-composed bone stock1,2. Lesions can also be considered unresectable, when the rate of morbidity and mortality predicted for such a procedure would represent an unjustifiable risk1,2. Typically, unresectable lesions refer to those of the axial skeleton such as the sacrum and posterior elements of the spine1,2. Systemic therapy and local radiation are generally not considered the standard of care, given the nonmalignant nature of GCTB1,2. Local recurrence rates of GCTB vary widely depending on the initial treatment modality pursued. Local recurrence rates have been reported as low as 0% to 12% for en bloc excision and extended intralesional procedures with physical and chemical adjuvants and as high as 56% following intralesional curettage and defect cementing1,5. Furthermore, up to 10.5% of recurrent lesions, depending on the initial treatment modality (such as previous radiation therapy), may develop malignant properties and may metastasize to the lungs1,5.
GCTB exhibits 3 major cell types: spindle-shaped mesenchymal stromal cells, mononuclear monocytes, and multinucleated osteoclast-like giant cells, which are a part of the monocyte and macrophage lineage (Figs. 2-A and 2-B)1,7,8. The spindle-shaped stromal cells are the main neoplastic component of the tumor and express high levels of receptor activator of nuclear factor-κB ligand (RANKL), whereas the giant cells overexpress the RANK receptor9. RANK and RANKL interaction is the dominant cause of robust osteoclastogenesis and extensive bone resorption seen in GCTB1,4,7-9.
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