CORR Insights®: Is a Short-course of Preoperative Denosumab as Effective as Prolonged Therapy for Giant Cell Tumor of Bone?

Giant cell tumor of bone (GCTB) is a locally aggressive, rarely metastasizing lesion that is usually found in the epiphyseal-metaphyseal region of the long bones. Surgical management most often consists of extended intralesional curettage to remove all disease. Because of the infiltrative nature of GCTB as well as the desire to preserve articular cartilage and subchondral bone to facilitate joint salvage, microscopic disease may persist after intralesional treatment. In the past, this has resulted in a substantial risk of local recurrence, as high as 40% in a recent study [5]. To reduce this risk, intralesional, cytotoxic chemical adjuvants have sometimes been used at the time of curettage. These include ethanol, phenol, hydrogen peroxide, and liquid nitrogen cryotherapy. The local recurrence rates in case series using these adjuvants are usually comparable to those in which no adjuvants are used [7, 10, 14]. Denosumab is a human monoclonal antibody that inhibits the receptor activator of nuclear factor-kappa b ligand. This receptor blockade inactivates osteoclastic giant cells in GCTB, thereby promoting bone formation rather than aggressive lytic bone destruction. It has shown promise in decreasing skeletal events in patients with metastatic breast cancer [12] and those with multiple myeloma [15]. As a result, there was substantial initial enthusiasm to use denosumab in patients with GCTB to facilitate joint salvage in large periarticular tumors that would otherwise be treated with en bloc resection and prosthetic reconstruction, decrease the local recurrence rate, and provide stability for inoperable tumors, such as those in the axial skeleton. The initial treatment recommendation was 120 mg of denosumab on Days 1, 8, and 15 of Month 1, followed by monthly dosing of 120 mg for a further 5 months [8]. Despite initial promising results using this regimen [13], other authors have since noted a substantially higher local recurrence rate after intralesional curettage than in previous series without denosumab [3]. Furthermore, toxicities and malignant degeneration of GCTB have been reported [1, 2]. These findings have prompted some centers to consider a shorter course of treatment before surgical management in the hope that the purported benefits may outweigh the risks outlined above [11]. Hindiskere et al. [6] undertook a single-center, retrospective study to determine whether a shorter course of denosumab of three or fewer doses before surgical management of GCTB is associated with a higher risk of local recurrence or a difference in the clinical and radiographic response compared with the conventional longer regimen. The authors concluded that a short course of denosumab was no different from a long course in terms of Musculoskeletal Tumor Society scores, radiologic and histologic response, and recurrence-free survival. Based on this, they concluded that short-course denosumab treatment therefore may be considered in patients with GCTB when the benefit of joint This CORR Insights is a commentary on the article “Is a Short-course of Preoperative Denosumab as Effective as Prolonged Therapy for Giant Cell Tumor of Bone? ” by Hindiskere and colleagues available at: 10. 1097/CORR.0000000000001285. The author certifies that neither he, nor any members of his immediate family, has any commercial associations (such as consultancies, stock ownership, equity interest, patent/licensing arrangements, etc.) that might pose a conflict of interest in connection with the submitted article. All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research editors and board members are on file with the publication and can be viewed on request. The opinions expressed are those of the writer, and do not reflect the opinion or policy of CORR or The Association of Bone and Joint Surgeons. P. C. Ferguson MD, MSc, FRCSC, FAOA ✉, Mount Sinai Hospital, 600 University Avenue, Suite 476G, Toronto, ON, Canada, M5G 1X5, Email: pferguson@mtsinai.on. ca P. C. Ferguson,Mount Sinai Hospital, Toronto, ON, Canada