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Published in: BMC Cancer 1/2010

Open Access 01-12-2010 | Research article

Bisphosphonate treatment of aggressive primary, recurrent and metastatic Giant Cell Tumour of Bone

Authors: Maurice Balke, Laura Campanacci, Carsten Gebert, Piero Picci, Max Gibbons, Richard Taylor, Pancras Hogendoorn, Judith Kroep, John Wass, Nicholas Athanasou

Published in: BMC Cancer | Issue 1/2010

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Abstract

Background

Giant cell tumour of bone (GCTB) is an expansile osteolytic tumour which contains numerous osteoclast-like giant cells. GCTB frequently recurs and can produce metastatic lesions in the lungs. Bisphosphonates are anti-resorptive drugs which act mainly on osteoclasts.

Method

In this study, we have examined clinical and radiological outcomes of treatment with aminobisphosphonates on 25 cases of aggressive primary, recurrent and metastatic GCTB derived from four European centres. We also analysed in vitro the inhibitory effect of zoledronic acid on osteoclasts isolated from GCTBs.

Results

Treatment protocols differed with several different aminobisphosphonates being employed, but stabilisation of disease was achieved in most of these cases which were refractory to conventional treatment. Most inoperable sacral/pelvic tumours did not increase in size and no further recurrence was seen in GCTBs that had repeatedly recurred in bone and soft tissues. Lung metastases did not increase in size or number following treatment. Zoledronic acid markedly inhibited lacunar resorption by GCTB-derived osteoclasts in vitro.

Conclusion

Our findings suggest that bisphosphonates may be useful in controlling disease progression in GCTB and that these agents directly inhibit GCTB - derived osteoclast resorption. These studies highlight the need for the establishment of standardised protocols to assess the efficacy of bisphosphonate treatment of GCTB.
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Literature
1.
go back to reference Reid R, Bareyce SS, Sciot R: Giant cell tumour. Pathology and Genetics of Tumours of Soft Tissue and Bone. Edited by: Fletcher L, Unni U, Mertens F. 2002, Lyon: IARC Press, 310, 312 Reid R, Bareyce SS, Sciot R: Giant cell tumour. Pathology and Genetics of Tumours of Soft Tissue and Bone. Edited by: Fletcher L, Unni U, Mertens F. 2002, Lyon: IARC Press, 310, 312
2.
go back to reference Unni KK, Inwards C, Bridge JA, Kindblom L-G, Wold LE: Tumours of the bones and joints. AFIP Atlas of Tumour Pathology Fourth Series, Fascicle 2, AFIP. 2005 Unni KK, Inwards C, Bridge JA, Kindblom L-G, Wold LE: Tumours of the bones and joints. AFIP Atlas of Tumour Pathology Fourth Series, Fascicle 2, AFIP. 2005
3.
go back to reference Lau YS, Sabokbar A, Gibbons CLMH, Athanasou NA: Phenotypic and molecular studies on giant cell tumours of bone and soft tissues. Hum Pathol. 2005, 36: 945-954. 10.1016/j.humpath.2005.07.005.CrossRefPubMed Lau YS, Sabokbar A, Gibbons CLMH, Athanasou NA: Phenotypic and molecular studies on giant cell tumours of bone and soft tissues. Hum Pathol. 2005, 36: 945-954. 10.1016/j.humpath.2005.07.005.CrossRefPubMed
4.
go back to reference Blackley HR, Wunder JS, Davis AM, White LM, Kandel R, Bell RS: Treatment of Giant-Cell Tumours of Long Bones with curettage and bone-grafting. J Bone Joint Surg. 1999, 81A: 811-20. Blackley HR, Wunder JS, Davis AM, White LM, Kandel R, Bell RS: Treatment of Giant-Cell Tumours of Long Bones with curettage and bone-grafting. J Bone Joint Surg. 1999, 81A: 811-20.
5.
6.
go back to reference Campanacci M, Baldini N, Borian S, Sudanese A: Giant-cell tumour of bone. J Bone Joint Surg. 1987, 68A: 106-14. Campanacci M, Baldini N, Borian S, Sudanese A: Giant-cell tumour of bone. J Bone Joint Surg. 1987, 68A: 106-14.
7.
go back to reference Mendenhall WM, Ziotecki RA, Scarborough MT, Gibbs CP, Mendenhall NP: Giant cell tumour of bone. Am J Clin Oncol. 2006, 29: 96-9. 10.1097/01.coc.0000195089.11620.b7.CrossRefPubMed Mendenhall WM, Ziotecki RA, Scarborough MT, Gibbs CP, Mendenhall NP: Giant cell tumour of bone. Am J Clin Oncol. 2006, 29: 96-9. 10.1097/01.coc.0000195089.11620.b7.CrossRefPubMed
8.
go back to reference Rodan GA: Mechanisms of action of bisphosphonates. Annu Rev Pharmacol Toxicol. 1998, 38: 375-388. 10.1146/annurev.pharmtox.38.1.375.CrossRefPubMed Rodan GA: Mechanisms of action of bisphosphonates. Annu Rev Pharmacol Toxicol. 1998, 38: 375-388. 10.1146/annurev.pharmtox.38.1.375.CrossRefPubMed
9.
go back to reference Kimmel DB: Mechanism of action, pharmacokinetic and pharmacodynamic profile and clinical applications of nitrogen-containing bisphosphonates. J Dent Res. 2007, 86: 1022-1033. 10.1177/154405910708601102.CrossRefPubMed Kimmel DB: Mechanism of action, pharmacokinetic and pharmacodynamic profile and clinical applications of nitrogen-containing bisphosphonates. J Dent Res. 2007, 86: 1022-1033. 10.1177/154405910708601102.CrossRefPubMed
10.
go back to reference Rogers MJ, Gordon S, Benford HL, Coxon FP, Luckman SP, Mankonnen J, Firth JC: Cellular and molecular mechanisms and action of bisphosphonates. Cancer. 2000, 88 (12 Suppl): 2961-2978. 10.1002/1097-0142(20000615)88:12+<2961::AID-CNCR12>3.0.CO;2-L.CrossRefPubMed Rogers MJ, Gordon S, Benford HL, Coxon FP, Luckman SP, Mankonnen J, Firth JC: Cellular and molecular mechanisms and action of bisphosphonates. Cancer. 2000, 88 (12 Suppl): 2961-2978. 10.1002/1097-0142(20000615)88:12+<2961::AID-CNCR12>3.0.CO;2-L.CrossRefPubMed
11.
go back to reference Lane JM, Safdar NK, O'Connor WJ, Nydlick M, Hommen JP, Schneider R, Tomin E, Brand J, Curtin J: Bisphosphonate therapy in fibrous dysplasia. Clin Orthop. 2001, 382: 6-12. 10.1097/00003086-200101000-00003.CrossRefPubMed Lane JM, Safdar NK, O'Connor WJ, Nydlick M, Hommen JP, Schneider R, Tomin E, Brand J, Curtin J: Bisphosphonate therapy in fibrous dysplasia. Clin Orthop. 2001, 382: 6-12. 10.1097/00003086-200101000-00003.CrossRefPubMed
12.
go back to reference Chapurlat RD, Delmas PD, Liens D, Meunier PJ: Long term effects of intravenous pamidronate in fibrous dysplasia of bone. J Bone Miner Res. 1997, 12: 1746-1752. 10.1359/jbmr.1997.12.10.1746.CrossRefPubMed Chapurlat RD, Delmas PD, Liens D, Meunier PJ: Long term effects of intravenous pamidronate in fibrous dysplasia of bone. J Bone Miner Res. 1997, 12: 1746-1752. 10.1359/jbmr.1997.12.10.1746.CrossRefPubMed
13.
go back to reference Farran RP, Zaretski E, Egeler M: Treatment of Langerhans Cell Histiocytosis with pamidronate. J Pediatr Hematol. 2001, 23: 54-56. 10.1097/00043426-200101000-00013.CrossRef Farran RP, Zaretski E, Egeler M: Treatment of Langerhans Cell Histiocytosis with pamidronate. J Pediatr Hematol. 2001, 23: 54-56. 10.1097/00043426-200101000-00013.CrossRef
14.
go back to reference Petra M, Gibbons CLMH, Athanasou NA: Bisphosphonate treatment of benign multifocal and unifocal primary osteolytic tumours of bone. Sarcoma. 2003, 7: 35-41. 10.1080/1357714031000114165.CrossRefPubMedPubMedCentral Petra M, Gibbons CLMH, Athanasou NA: Bisphosphonate treatment of benign multifocal and unifocal primary osteolytic tumours of bone. Sarcoma. 2003, 7: 35-41. 10.1080/1357714031000114165.CrossRefPubMedPubMedCentral
15.
go back to reference Arpornchayanon O, Leerapun T: Effectiveness of intravenous bisphosphonates in treatment of giant cell tumour: a case report and review of the literature. J Med Assoc Thai. 2008, 91: 1609-12.PubMed Arpornchayanon O, Leerapun T: Effectiveness of intravenous bisphosphonates in treatment of giant cell tumour: a case report and review of the literature. J Med Assoc Thai. 2008, 91: 1609-12.PubMed
16.
go back to reference Tse LF, Wong KC, Kumta SM, Huang L, Chow TC, Griffith JF: Bisphosphonates reduce local recurrence in extremity giant cell tumour of bone: a case-control study. Bone. 2008, 42: 68-73. 10.1016/j.bone.2007.08.038.CrossRefPubMed Tse LF, Wong KC, Kumta SM, Huang L, Chow TC, Griffith JF: Bisphosphonates reduce local recurrence in extremity giant cell tumour of bone: a case-control study. Bone. 2008, 42: 68-73. 10.1016/j.bone.2007.08.038.CrossRefPubMed
17.
go back to reference Quinn J, Matsumura Y, Tarin D, McGee JO'D, Athanasou NA: Cellular and hormonal mechanisms associated with malignant bone resorption. Lab Invest. 1994, 71: 465-471.PubMed Quinn J, Matsumura Y, Tarin D, McGee JO'D, Athanasou NA: Cellular and hormonal mechanisms associated with malignant bone resorption. Lab Invest. 1994, 71: 465-471.PubMed
18.
go back to reference Clohisy DR, Perkins SL, Romeraine MLR: Review of cellular mechanisms of tumour osteolysis. Clin Orthop. 1998, 373: 104-114.CrossRef Clohisy DR, Perkins SL, Romeraine MLR: Review of cellular mechanisms of tumour osteolysis. Clin Orthop. 1998, 373: 104-114.CrossRef
19.
go back to reference Athanasou NA, Quinn J: Immunophenotypic differences between osteoclasts and macrophage polykaryons: immunohistological distinction and implications for osteoclast ontogeny and function. J Clin Pathol. 43: 997-1004. 10.1136/jcp.43.12.997. Athanasou NA, Quinn J: Immunophenotypic differences between osteoclasts and macrophage polykaryons: immunohistological distinction and implications for osteoclast ontogeny and function. J Clin Pathol. 43: 997-1004. 10.1136/jcp.43.12.997.
21.
go back to reference Hughes DE, Wright KR, Uy HL, Sasaki A, Yoneda T, Roodman GD, Mundy GR, Boyce B: Bisphosphonates promote apoptosis in murine osteoclasts in vitro and in vivo. J Bone Mineral Res. 1995, 10: 1478-1487. 10.1002/jbmr.5650101008.CrossRef Hughes DE, Wright KR, Uy HL, Sasaki A, Yoneda T, Roodman GD, Mundy GR, Boyce B: Bisphosphonates promote apoptosis in murine osteoclasts in vitro and in vivo. J Bone Mineral Res. 1995, 10: 1478-1487. 10.1002/jbmr.5650101008.CrossRef
22.
go back to reference Nishigawa M, Akatsu T, Katayama Y, Yasumato Y, Kado S, Kugai N, Yamamoto M, Nogata N: Bisphosphonates act on osteoblast cells and inhibit osteoclast formation in mouse marrow cutures. Bone. 1996, 18: 9-14. 10.1016/8756-3282(95)00426-2.CrossRef Nishigawa M, Akatsu T, Katayama Y, Yasumato Y, Kado S, Kugai N, Yamamoto M, Nogata N: Bisphosphonates act on osteoblast cells and inhibit osteoclast formation in mouse marrow cutures. Bone. 1996, 18: 9-14. 10.1016/8756-3282(95)00426-2.CrossRef
23.
go back to reference Pandey R, Quinn J, Sabokbar A, Athanasou NA: Bisphosphonate inhibition of bone resorption by particulate biomaterial-associated macrophages. Acta Orthop Scand. 1996, 67: 221-228. 10.3109/17453679608994677.CrossRefPubMed Pandey R, Quinn J, Sabokbar A, Athanasou NA: Bisphosphonate inhibition of bone resorption by particulate biomaterial-associated macrophages. Acta Orthop Scand. 1996, 67: 221-228. 10.3109/17453679608994677.CrossRefPubMed
24.
go back to reference Chang SS, Suratwala SJ, Jung KM, Doppelt JD, Zhang HZ, Blaine TA, Kim TW, Winchester RJ, Lee FY: Bisphosphonates may reduce recurrence in giant cell tumour by inducing apoptosis. Clin Orthop Relat Res. 2004, 426: 103-9. 10.1097/01.blo.0000141372.54456.80.CrossRefPubMed Chang SS, Suratwala SJ, Jung KM, Doppelt JD, Zhang HZ, Blaine TA, Kim TW, Winchester RJ, Lee FY: Bisphosphonates may reduce recurrence in giant cell tumour by inducing apoptosis. Clin Orthop Relat Res. 2004, 426: 103-9. 10.1097/01.blo.0000141372.54456.80.CrossRefPubMed
25.
go back to reference Cheng YY, Huan L, Lee KM, Xu JK, Zheng MH, Kumta SM: Bisphosphonates induce apoptosis of stromal tumour cells in giant cell tumour of bone. Calcif Tissue Int. 2004, 75: 71-7. 10.1007/s00223-004-0120-2.CrossRefPubMed Cheng YY, Huan L, Lee KM, Xu JK, Zheng MH, Kumta SM: Bisphosphonates induce apoptosis of stromal tumour cells in giant cell tumour of bone. Calcif Tissue Int. 2004, 75: 71-7. 10.1007/s00223-004-0120-2.CrossRefPubMed
26.
go back to reference Cheng YY, Huang L, Kumta SM, Lee KM, Lai FM, Tam JS: Cytochemical and ultrastructural changes in the osteoclast-like giant cells of giant cell tumour of bone following bisphosphonate administration. Ultrastruct Pathol. 2003, 27: 385-91.CrossRefPubMed Cheng YY, Huang L, Kumta SM, Lee KM, Lai FM, Tam JS: Cytochemical and ultrastructural changes in the osteoclast-like giant cells of giant cell tumour of bone following bisphosphonate administration. Ultrastruct Pathol. 2003, 27: 385-91.CrossRefPubMed
27.
go back to reference Thomas D, Henshaw R, Skubitz K, Chawla S, Staddon A, Blay JY, Roudier M, Smith J, Ye Z, Sohn W, Dansey R, Jun S: Denosumab in patients with giant-cell tumour of bone: an open-label, phase 2 study. Lancet (Oncol). 2010, 11: 275-280. 10.1016/S1470-2045(10)70010-3.CrossRef Thomas D, Henshaw R, Skubitz K, Chawla S, Staddon A, Blay JY, Roudier M, Smith J, Ye Z, Sohn W, Dansey R, Jun S: Denosumab in patients with giant-cell tumour of bone: an open-label, phase 2 study. Lancet (Oncol). 2010, 11: 275-280. 10.1016/S1470-2045(10)70010-3.CrossRef
28.
29.
go back to reference Broom R, Du H, Clemons M, Eton D, Dranitsaris G, Simmons C, Ooi W, Cello D: Switching breast cancer patients with progressive bone metastases to third-generation bisphosphonates: measuring impact using the Functional Assessment of Cancer Therapy-Bone Pain. J Pain Symptom Manage. 2009, 38: 244-257. 10.1016/j.jpainsymman.2008.08.005.CrossRefPubMed Broom R, Du H, Clemons M, Eton D, Dranitsaris G, Simmons C, Ooi W, Cello D: Switching breast cancer patients with progressive bone metastases to third-generation bisphosphonates: measuring impact using the Functional Assessment of Cancer Therapy-Bone Pain. J Pain Symptom Manage. 2009, 38: 244-257. 10.1016/j.jpainsymman.2008.08.005.CrossRefPubMed
Metadata
Title
Bisphosphonate treatment of aggressive primary, recurrent and metastatic Giant Cell Tumour of Bone
Authors
Maurice Balke
Laura Campanacci
Carsten Gebert
Piero Picci
Max Gibbons
Richard Taylor
Pancras Hogendoorn
Judith Kroep
John Wass
Nicholas Athanasou
Publication date
01-12-2010
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2010
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-10-462

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