Systemic Adjuvant Therapies in the Management of Giant Cell Tumor of Bone: Current State of Understanding and Practice

Vol 3 | Issue 2 | Sep-Dec 2017 | Page 6-9 | Shekhar Kumta, Carol Lau, K C Wong.

Authors: Shekhar Kumta [1], Carol Lau [1], K C Wong [2].

[1] Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Hong Kong,
[2] Department of Orthopaedics& Traumatology, The Prince of Wales Hospital, Hong Kong.

Address of Correspondence
Dr. Shekhar Kumta,
103-E, Learning Resource Centre, Block A, Prince of Wales Hospital, Shatin, Hong Kong.


GCT of bone is a locally aggressive bone-destroying tumor. The primary neoplastic tumor cell is a RANKL over expressing cell that drives osteoclast recruitment and activation, ultimately leading to bone resorption at the site of the lesion. Osteoclast driven destruction in GCT may be ameliorated with the use of drugs such as Bisphophonates, which target Osteoclasts as well as the primary neoplastic stromal cells. Denusomab, is a monoclonal antibody against RANKL and it has a dramatic effect on Osteoclasts. Adjuvant therapies have reduced recurrence rates in GCT of bone, but uncertainties remain as to the optimum dose-intensity of the drugs and the duration of treatment.
Keywords: Tumor, bone destruction, Giant Cell Tumor of Bone.


1. Balke M, Schremper L, Gebert C, Ahrens H, Streitbuerger A, Koehler G, et al. Giant cell tumor of bone: Treatment and outcome of 214 cases. J Cancer Res ClinOncol2008;134:969-78.
2. Becker WT, Dohle J, Bernd L, Braun A, Cserhati M, Enderle A, et al. Local recurrence of giant cell tumor of bone after intralesional treatment with and without adjuvant therapy. J Bone Joint Surg Am 2008;90:1060-7.
3. Malawer MM, Bickels J, Meller I, Buch RG, Henshaw RM, Kollender Y, et al. Cryosurgery in the treatment of giant cell tumor. A long-term followup study. ClinOrthopRelat Res 1999;359:176-88.
4. Marcove RC, Weis LD, Vaghaiwalla MR, Pearson R. Cryosurgery in the treatment of giant cell tumors of bone: A report of 52 consecutive cases. ClinOrthopRelat Res 1978;134:275-89.
5. Gortzak Y, Kandel R, Deheshi B, Werier J, Turcotte RE, Ferguson PC, et al. The efficacy of chemical adjuvants on giant-cell tumour of bone. An in vitro study. J Bone Joint Surg Br 2010;92:1475-9.
6. Lin WH, Lan TY, Chen CY, Wu K, Yang RS. Similar local control between phenol- and ethanol-treated giant cell tumors of bone. ClinOrthopRelat Res 2011;469:3200-8.
7. Theoleyre S, Wittrant Y, Tat SK, Fortun Y, Redini F, Heymann D, et al. The molecular triad OPG/RANK/RANKL: Involvement in the orchestration of pathophysiological bone remodeling. Cytokine Growth Factor Rev 2004;15:457-75.
8. Yasuda H, Shima N, Nakagawa N, Yamaguchi K, Kinosaki M, Mochizuki S, et al. Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL. Proc Natl AcadSci U S A 1998;95:3597-602.
9. Yasuda H, Shima N, Nakagawa N, Mochizuki SI, Yano K, Fujise N, et al. Identity of osteoclastogenesis inhibitory factor (OCIF) and osteoprotegerin (OPG): A mechanism by which OPG/OCIF inhibits osteoclastogenesisin vitro. Endocrinology 1998;139:1329-37.
10. Huang L, Xu J, Wood DJ, Zheng MH. Gene expression of osteoprotegerin ligand, osteoprotegerin, and receptor activator of NF-kappaB in giant cell tumor of bone: Possible involvement in tumor cell-induced osteoclast-like cell formation. Am J Pathol2000;156:761-7.
11. Nancollas GH, Tang R, Phipps RJ, Henneman Z, Gulde S, Wu W, et al. Novel insights into actions of bisphosphonates on bone: Differences in interactions with hydroxyapatite. Bone 2006;38:617-27.
12. Rogers MJ, Crockett JC, Coxon FP, Mönkkönen J. Biochemical and molecular mechanisms of action of bisphosphonates. Bone 2011;49:34-41.
13. Ebetino FH, Francis MD, Rogers MJ, Russell RG. Mechanisms of actions of etidronate and other bisphosphonates. Rev ContempPharmacother1998;9:233-43.
14. Balke M, Campanacci L, Gebert C, Picci P, Gibbons M, Taylor R, et al. Bisphosphonate treatment of aggressive primary, recurrent and metastatic giant cell tumour of bone. BMC Cancer 2010;10:462.
15. Tse LF, Wong KC, Kumta SM, Huang L, Chow TC, Griffith JF, et al. Bisphosphonates reduce local recurrence in extremity giant cell tumor of bone: A case-control study. Bone 2008;42:68-73.
16. Yu X, Xu M, Xu S, Su Q. Clinical outcomes of giant cell tumor of bone treated with bone cement filling and internal fixation, and oral bisphosphonates. Oncol Lett 2013;5:447-51.
17. Cheng YY, Huang L, Lee KM, Xu JK, Zheng MH, Kumta SM, et al. Bisphosphonates induce apoptosis of stromal tumor cells in giant cell tumor of bone. Calcif Tissue Int2004;75:71-7.
18. Coleman RE, Major P, Lipton A, Brown JE, Lee KA, Smith M, et al. Predictive value of bone resorption and formation markers in cancer patients with bone metastases receiving the bisphosphonate zoledronic acid. J ClinOncol2005;23:4925-35.
19. Weitzman R, Sauter N, Eriksen EF, Tarassoff PG, Lacerna LV, Dias R, et al. Critical review: Updated recommendations for the prevention, diagnosis, and treatment of osteonecrosis of the jaw in cancer patients-May 2006. Crit Rev OncolHematol2007;62:148-52.
20. Perazella MA, Markowitz GS. Bisphosphonate nephrotoxicity. Kidney Int2008;74:1385-93.
21. Kostenuik PJ, Nguyen HQ, McCabe J, Warmington KS, Kurahara C, Sun N, et al. Denosumab, a fully human monoclonal antibody to RANKL, inhibits bone resorption and increases BMD in knock-in mice that express chimeric (murine/human) RANKL. J Bone Miner Res 2009;24:182-95.
22. Thomas D, Henshaw R, Skubitz K, Chawla S, Staddon A, Blay JY, et al. Denosumab in patients with giant-cell tumour of bone: An open-label, Phase 2 study. Lancet Oncol2010;11:275-80.
23. Lewiecki EM, Miller PD, McClung MR, Cohen SB, Bolognese MA, Liu Y, et al. Two-year treatment with denosumab (AMG 162) in a randomized Phase 2 study of postmenopausal women with low BMD. J Bone Miner Res 2007;22:1832-41.

How to Cite this article: Kumta S, Lau C, Wong K C. Systemic Adjuvant Therapies in the Management of Giant Cell Tumor of Bone: Current State of Understanding and Practice. Journal of Bone and Soft Tissue Tumors Sep-Dec 2017;3(2): 6-9..


      (Abstract    Full Text HTML)      (Download PDF)