Skip to main content

Advertisement

SpringerLink
Log in

Denosumab Treatment for Giant Cell Tumors, Aneurysmal Bone Cysts, and Fibrous Dysplasia—Risks and Benefits

  • Pediatrics (C Munns and F Rauch, Section Editors)
  • Published:
Current Osteoporosis Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

This review summarizes current understanding of the role of denosumab, an inhibitor of receptor activator of nuclear kappa-B ligand (RANKL), in the management of 3 skeletal neoplasms: giant cell tumors, aneurysmal bone cysts, and fibrous dysplasia.

Recent Findings

A growing body of literature supports denosumab use in giant cell tumors, a neoplasm in which RANKL plays a clear pathogenic role. Comparatively less data is available in aneurysmal bone cysts and fibrous dysplasia; however, the pathogenic similarity of these disorders to giant cell tumors, as well as encouraging preliminary data, suggests denosumab may be useful. Denosumab’s inhibitory effects on bone turnover are fully reversible after drug discontinuation. This raises important unanswered questions for clinical management, including potential risks of tumor recurrence and bone turnover rebound.

Summary

Denosumab is a promising potential treatment for skeletal neoplasms. However, its clinical use is impacted by ongoing safety concerns related to postdiscontinuation rebound, particularly in children. There is a critical need to understand denosumab treatment and discontinuation effects on tumor recurrence and to develop strategies for long-term treatment in patients who cannot be managed surgically.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Seeman E. Bone modeling and remodeling. Crit Rev Eukaryot Gene Expr. 2009;19(3):219–33.

    Article  CAS  PubMed  Google Scholar 

  2. Rauch F. Bone accrual in children: adding substance to surfaces. Pediatrics. 2007;119(Suppl 2):S137–40.

    Article  PubMed  Google Scholar 

  3. Hsu H, Lacey DL, Dunstan CR, Solovyev I, Colombero A, Timms E, et al. Tumor necrosis factor receptor family member RANK mediates osteoclast differentiation and activation induced by osteoprotegerin ligand. Proc Natl Acad Sci U S A. 1999;96(7):3540–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Ikeda T, Kasai M, Utsuyama M, Hirokawa K. Determination of three isoforms of the receptor activator of nuclear factor-kappaB ligand and their differential expression in bone and thymus. Endocrinology. 2001;142(4):1419–26.

    Article  CAS  PubMed  Google Scholar 

  5. Simonet WS, Lacey DL, Dunstan CR, Kelley M, Chang MS, Lüthy R, et al. Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell. 1997;89(2):309–19.

    Article  CAS  PubMed  Google Scholar 

  6. Dougall WC, Chaisson M. The RANK/RANKL/OPG triad in cancer-induced bone diseases. Cancer Metastasis Rev. 2006;25(4):541–9.

    Article  CAS  PubMed  Google Scholar 

  7. Xgeva (denosumab) [package insert]. Thousand Oaks: Amgen, Inc; 2010.

  8. Prolia (denosumab) [package insert]. Thousand Oaks: Amgen, Inc; 2010.

  9. Sutjandra L, Rodriguez RD, Doshi S, Ma M, Peterson MC, Jang GR, et al. Population pharmacokinetic meta-analysis of denosumab in healthy subjects and postmenopausal women with osteopenia or osteoporosis. Clin Pharmacokinet. 2011;50(12):793–807.

    Article  CAS  PubMed  Google Scholar 

  10. Gibiansky L, Sutjandra L, Doshi S, Zheng J, Sohn W, Peterson MC, et al. Population pharmacokinetic analysis of denosumab in patients with bone metastases from solid tumours. Clin Pharmacokinet. 2012;51(4):247–60.

    Article  CAS  PubMed  Google Scholar 

  11. • Cummings SR, San Martin J, MR MC, Siris ES, Eastell R, Reid IR, et al. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med. 2009;361(8):756–65 This seminal phase 3 controlled trial in patients with osteoporosis was the first to show a beneficial effect of denosumab on fracture rate.

    Article  CAS  PubMed  Google Scholar 

  12. Bone HG, Wagman RB, Brandi ML, Brown JP, Chapurlat R, Cummings SR, et al. 10 years of denosumab treatment in postmenopausal women with osteoporosis: results from the phase 3 randomised FREEDOM trial and open-label extension. Lancet Diabetes Endocrinol. 2017;5(7):513–23.

    Article  CAS  PubMed  Google Scholar 

  13. Smith MR, Egerdie B, Hernández Toriz N, Feldman R, Tammela TL, Saad F, et al. Denosumab in men receiving androgen-deprivation therapy for prostate cancer. N Engl J Med. 2009;361(8):745–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Ellis GK, Bone HG, Chlebowski R, Paul D, Spadafora S, Smith J, et al. Randomized trial of denosumab in patients receiving adjuvant aromatase inhibitors for nonmetastatic breast cancer. J Clin Oncol. 2008;26(30):4875–82.

    Article  CAS  PubMed  Google Scholar 

  15. Stopeck AT, Lipton A, Body JJ, Steger GG, Tonkin K, de Boer RH, et al. Denosumab compared with zoledronic acid for the treatment of bone metastases in patients with advanced breast cancer: a randomized, double-blind study. J Clin Oncol. 2010;28(35):5132–9.

    Article  CAS  PubMed  Google Scholar 

  16. Lewiecki EM. Bisphosphonates for the treatment of osteoporosis: insights for clinicians. Ther Adv Chronic Dis. 2010;1(3):115–28.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Bone HG, Bolognese MA, Yuen CK, Kendler DL, Miller PD, Yang YC, et al. Effects of denosumab treatment and discontinuation on bone mineral density and bone turnover markers in postmenopausal women with low bone mass. J Clin Endocrinol Metab. 2011;96(4):972–80.

    Article  CAS  PubMed  Google Scholar 

  18. Boyce AM. Denosumab: an emerging therapy in pediatric Bone disorders. Curr Osteoporos Rep. 2017;15(4):283–92.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Tsourdi E, Langdahl B, Cohen-Solal M, Aubry-Rozier B, Eriksen EF, Guañabens N, et al. Discontinuation of denosumab therapy for osteoporosis: a systematic review and position statement by ECTS. Bone. 2017;105:11–7.

    Article  PubMed  Google Scholar 

  20. Cummings SR, Ferrari S, Eastell R, Gilchrist N, Jensen JB, McClung M, et al. Vertebral fractures after discontinuation of denosumab: a post hoc analysis of the randomized placebo-controlled FREEDOM trial and its extension. J Bone Miner Res. 2018;33(2):190–8.

    Article  CAS  PubMed  Google Scholar 

  21. Reid IR, Horne AM, Mihov B, Gamble GD. Bone loss after denosumab: only partial protection with Zoledronate. Calcif Tissue Int. 2017;101(4):371–4.

    Article  CAS  PubMed  Google Scholar 

  22. •• Chawla S, Blay JY, Rutkowski P, Le Cesne A, Reichardt P, Gelderblom H, et al. Denosumab in patients with giant-cell tumour of bone: a multicentre, open-label, phase 2 study. Lancet Oncol. 2019;20(12):1719–29 This phase 2 study of denosumab treatment in GCT showed long-term disease control for patients with unresectable and resectable tumours. Results suggested an increased risk of recurrence after drug discontinuation.

    Article  CAS  PubMed  Google Scholar 

  23. Fizazi K, Carducci M, Smith M, Damião R, Brown J, Karsh L, et al. Denosumab versus zoledronic acid for treatment of bone metastases in men with castration-resistant prostate cancer: a randomised, double-blind study. Lancet. 2011;377(9768):813–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Smith MR, Saad F, Coleman R, Shore N, Fizazi K, Tombal B, et al. Denosumab and bone-metastasis-free survival in men with castration-resistant prostate cancer: results of a phase 3, randomised, placebo-controlled trial. Lancet. 2012;379(9810):39–46.

    Article  CAS  PubMed  Google Scholar 

  25. Metwally T, Burke A, Tsai JY, Collins MT, Boyce AM. Fibrous dysplasia and medication-related osteonecrosis of the jaw. J Oral Maxillofac Surg. 2016;74(10):1983–99.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Body JJ, Lipton A, Gralow J, Steger GG, Gao G, Yeh H, et al. Effects of denosumab in patients with bone metastases with and without previous bisphosphonate exposure. J Bone Miner Res. 2010;25(3):440–6.

    Article  CAS  PubMed  Google Scholar 

  27. Kong YY, Yoshida H, Sarosi I, Tan HL, Timms E, Capparelli C, et al. OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis. Nature. 1999;397(6717):315–23.

    Article  CAS  PubMed  Google Scholar 

  28. Hoyer-Kuhn H, Franklin J, Allo G, Kron M, Netzer C, Eysel P, et al. Safety and efficacy of denosumab in children with osteogenesis imperfect—a first prospective trial. J Musculoskelet Neuronal Interact. 2016;16(1):24–32.

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Wang HD, Boyce AM, Tsai JY, Gafni RI, Farley FA, Kasa-Vubu JZ, et al. Effects of denosumab treatment and discontinuation on human growth plates. J Clin Endocrinol Metab. 2014;99(3):891–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Boyce AM, Kelly MH, Brillante BA, Kushner H, Wientroub S, Riminucci M, et al. A randomized, double blind, placebo-controlled trial of alendronate treatment for fibrous dysplasia of bone. J Clin Endocrinol Metab. 2014;99(11):4133–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Whyte MP, McAlister WH, Novack DV, Clements KL, Schoenecker PL, Wenkert D. Bisphosphonate-induced osteopetrosis: novel bone modeling defects, metaphyseal osteopenia, and osteosclerosis fractures after drug exposure ceases. J Bone Miner Res. 2008;23(10):1698–707.

    Article  PubMed  Google Scholar 

  32. Mendenhall WM, Zlotecki RA, Scarborough MT, Gibbs CP, Mendenhall NP. Giant cell tumor of bone. Am J Clin Oncol. 2006;29(1):96–9.

    Article  PubMed  Google Scholar 

  33. Zheng MH, Robbins P, Xu J, Huang L, Wood DJ, Papadimitriou JM. The histogenesis of giant cell tumour of bone: a model of interaction between neoplastic cells and osteoclasts. Histol Histopathol. 2001;16(1):297–307.

    CAS  PubMed  Google Scholar 

  34. Cowan RW, Singh G. Giant cell tumor of bone: a basic science perspective. Bone. 2013;52(1):238–46.

    Article  PubMed  Google Scholar 

  35. Al-Ibraheemi A, Inwards CY, Zreik RT, Wenger DE, Jenkins SM, Carter JM, et al. Histologic spectrum of giant cell tumor (GCT) of bone in patients 18 years of age and below: a study of 63 patients. Am J Surg Pathol. 2016;40(12):1702–12.

    Article  PubMed  Google Scholar 

  36. Noh BJ, Park YK. Giant cell tumor of bone: updated molecular pathogenesis and tumor biology. Hum Pathol. 2018;81:1–8.

    Article  CAS  PubMed  Google Scholar 

  37. Jaffe HL, Lichtenstein L, Portis RB. Giant cell tumor of bone: its pathologic appearance, grading, supposed variants and treatment. Arch Pathol. 1940;30:993–1031.

    Google Scholar 

  38. Campanacci M, Baldini N, Boriani S, Sudanese A. Giant-cell tumor of bone. J Bone Joint Surg Am. 1987;69(1):106–14.

    Article  CAS  PubMed  Google Scholar 

  39. McDonald DJ, Sim FH, McLeod RA, Dahlin DC. Giant-cell tumor of bone. J Bone Joint Surg Am. 1986;68(2):235–42.

    Article  CAS  PubMed  Google Scholar 

  40. van der Heijden L, Dijkstra PDS, Blay JY, Gelderblom H. Giant cell tumour of bone in the denosumab era. Eur J Cancer. 2017;77:75–83.

    Article  PubMed  Google Scholar 

  41. 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(5):1060–7.

    Article  PubMed  Google Scholar 

  42. Errani C, Ruggieri P, Asenzio MA, Toscano A, Colangeli S, Rimondi E, et al. Giant cell tumor of the extremity: a review of 349 cases from a single institution. Cancer Treat Rev. 2010;36(1):1–7.

    Article  PubMed  Google Scholar 

  43. 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 Clin Oncol. 2008;134(9):969–78.

    Article  CAS  PubMed  Google Scholar 

  44. Mak IW, Evaniew N, Popovic S, Tozer R, Ghert M. A translational study of the neoplastic cells of giant cell tumor of bone following neoadjuvant denosumab. J Bone Joint Surg Am. 2014;96(15):e127.

    Article  PubMed  Google Scholar 

  45. Chawla S, Henshaw R, Seeger L, Choy E, Blay JY, Ferrari S, et al. Safety and efficacy of denosumab for adults and skeletally mature adolescents with giant cell tumour of bone: interim analysis of an open-label, parallel-group, phase 2 study. Lancet Oncol. 2013;14(9):901–8.

    Article  CAS  PubMed  Google Scholar 

  46. Rutkowski P, Ferrari S, Grimer RJ, Stalley PD, Dijkstra SP, Pienkowski A, et al. Surgical downstaging in an open-label phase II trial of denosumab in patients with giant cell tumor of bone. Ann Surg Oncol. 2015;22(9):2860–8.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Luengo-Alonso G, Mellado-Romero M, Shemesh S, Ramos-Pascua L, Pretell-Mazzini J. Denosumab treatment for giant-cell tumor of bone: a systematic review of the literature. Arch Orthop Trauma Surg. 2019;139(10):1339–49.

    Article  PubMed  Google Scholar 

  48. Goldschlager T, Dea N, Boyd M, Reynolds J, Patel S, Rhines LD, et al. Giant cell tumors of the spine: has denosumab changed the treatment paradigm? J Neurosurg Spine. 2015;22(5):526–33.

    Article  PubMed  Google Scholar 

  49. Muller DA, Beltrami G, Scoccianti G, Campanacci DA, Franchi A, Capanna R. Risks and benefits of combining denosumab and surgery in giant cell tumor of bone-a case series. World J Surg Oncol. 2016;14(1):281.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Rutkowski P, Gaston L, Borkowska A, Stacchiotti S, Gelderblom H, Baldi GG, et al. Denosumab treatment of inoperable or locally advanced giant cell tumor of bone—multicenter analysis outside clinical trial. Eur J Surg Oncol. 2018;44(9):1384–90.

    Article  PubMed  Google Scholar 

  51. Chinder PS, Hindiskere S, Doddarangappa S, Pal U. Evaluation of local recurrence in giant-cell tumor of bone treated by neoadjuvant denosumab. Clin Orthop Surg. 2019;11(3):352–60.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Agarwal MG, Gundavda MK, Gupta R, Reddy R. Does denosumab change the giant cell tumor treatment strategy? Lessons learned from early experience. Clin Orthop Relat Res. 2018;476(9):1773–82.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Errani C, Tsukamoto S, Leone G, Righi A, Akahane M, Tanaka Y, et al. Denosumab may increase the risk of local recurrence in patients with giant-cell tumor of bone treated with curettage. J Bone Joint Surg Am. 2018;100(6):496–504.

    Article  PubMed  Google Scholar 

  54. Urakawa H, Mizusawa J, Tanaka K, Eba J, Hiraga H, Kawai A, et al. A randomized phase III trial of denosumab before curettage for giant cell tumor of bone: Japan Clinical Oncology Group Study JCOG1610. Jpn J Clin Oncol. 2019;49(4):379–82.

    Article  PubMed  Google Scholar 

  55. Alaqaili SI, Abduljabbar AM, Altaho AJ, Khan AA, Alherabi JA. Malignant sarcomatous transformation of benign giant cell tumor of bone after treatment with denosumab therapy: a literature review of reported cases. Cureus. 2018;10(12):e3792.

    PubMed  PubMed Central  Google Scholar 

  56. Muratori F, Mondanelli N, Rizzo AR, Beltrami G, Giannotti S, Capanna R, et al. Aneurysmal bone cyst: a review of management. Surg Technol Int. 2019;35:325–35.

    PubMed  Google Scholar 

  57. Lichtenstein L. Aneurysmal bone cyst. A pathological entity commonly mistaken for giant-cell tumor and occasionally for hemangioma and osteogenic sarcoma. Cancer. 1950;3(2):279–89.

    Article  Google Scholar 

  58. Buraczewski J, Dabska M. Pathogenesis of aneurysmal bone cyst. Relationship between the aneurysmal bone cyst and fibrous dysplasia of bone. Cancer. 1971;28(3):597–604.

    Article  CAS  PubMed  Google Scholar 

  59. Martinez V, Sissons HA. Aneurysmal bone cyst. A review of 123 cases including primary lesions and those secondary to other bone pathology. Cancer. 1988;61(11):2291–304.

    Article  CAS  PubMed  Google Scholar 

  60. Vergel De Dios AM, Bond JR, Shives TC, McLeod RA, Unni KK. Aneurysmal bone cyst. A clinicopathologic study of 238 cases. Cancer. 1992;69(12):2921–31.

    Article  CAS  PubMed  Google Scholar 

  61. Baumhoer D, Amary F, Flanagan AM. An update of molecular pathology of bone tumors. Lessons learned from investigating samples by next generation sequencing. Genes Chromosomes Cancer. 2019;58(2):88–99.

    Article  CAS  PubMed  Google Scholar 

  62. Lau AW, Pringle LM, Quick L, Riquelme DN, Ye Y, Oliveira AM, et al. TRE17/ubiquitin-specific protease 6 (USP6) oncogene translocated in aneurysmal bone cyst blocks osteoblastic maturation via an autocrine mechanism involving bone morphogenetic protein dysregulation. J Biol Chem. 2010;285(47):37111–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Ye Y, Pringle LM, Lau AW, Riquelme DN, Wang H, Jiang T, et al. TRE17/USP6 oncogene translocated in aneurysmal bone cyst induces matrix metalloproteinase production via activation of NF-kappaB. Oncogene. 2010;29(25):3619–29.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Oliveira AM, Chou MM, Perez-Atayde AR, Rosenberg AE. Aneurysmal bone cyst: a neoplasm driven by upregulation of the USP6 oncogene. J Clin Oncol. 2006;24(1):e1; author reply e2.

    Article  PubMed  Google Scholar 

  65. Park HY, Yang SK, Sheppard WL, Hegde V, Zoller SD, Nelson SD, et al. Current management of aneurysmal bone cysts. Curr Rev Musculoskelet Med. 2016;9(4):435–44.

    Article  PubMed  PubMed Central  Google Scholar 

  66. Pelle DW, Ringler JW, Peacock JD, Kampfschulte K, Scholten DJ 2nd, Davis MM, et al. Targeting receptor-activator of nuclear kappaB ligand in aneurysmal bone cysts: verification of target and therapeutic response. Transl Res. 2014;164(2):139–48.

    Article  CAS  PubMed  Google Scholar 

  67. • Alhumaid I, Abu-Zaid A. Denosumab therapy in the management of aneurysmal bone cysts: a comprehensive literature review. Cureus. 2019;11(1):e3989 This review summarizes the most current clinical experience with denosumab treatment of ABCs.

    PubMed  PubMed Central  Google Scholar 

  68. Ntalos D, Priemel M, Schlickewei C, Thiesen DM, Rueger JM, Spiro AS. Therapeutic management of a substantial pelvic aneurysmatic bone cyst Including the off-label use of denosumab in a 35-year-old female patient. Case Rep Orthop. 2017;2017:9125493.

    CAS  PubMed  PubMed Central  Google Scholar 

  69. Kurucu N, Akyuz C, Ergen FB, Yalcin B, Kosemehmetoglu K, Ayvaz M, et al. Denosumab treatment in aneurysmal bone cyst: evaluation of nine cases. Pediatr Blood Cancer. 2018;65(4).

  70. Pauli C, Fuchs B, Pfirrmann C, Bridge JA, Hofer S, Bode B. Response of an aggressive periosteal aneurysmal bone cyst (ABC) of the radius to denosumab therapy. World J Surg Oncol. 2014;12:17.

    Article  PubMed  PubMed Central  Google Scholar 

  71. Lange T, Stehling C, Frohlich B, Klingenhofer M, Kunkel P, Schneppenheim R, et al. Denosumab: a potential new and innovative treatment option for aneurysmal bone cysts. Eur Spine J. 2013;22(6):1417–22.

    Article  PubMed  PubMed Central  Google Scholar 

  72. Durr HR, Grahneis F, Baur-Melnyk A, Knosel T, Birkenmaier C, Jansson V, et al. Aneurysmal bone cyst: results of an off label treatment with denosumab. BMC Musculoskelet Disord. 2019;20(1):456.

    Article  PubMed  PubMed Central  Google Scholar 

  73. Boyce AM, Collins MT. Fibrous dysplasia/McCune–Albright syndrome: a rare, mosaic disease of Galphas activation. Endocr Rev. 2020;41(2):345–70.

    Article  Google Scholar 

  74. Weinstein LS, Shenker A, Gejman PV, Merino MJ, Friedman E, Spiegel AM. Activating mutations of the stimulatory G protein in the McCune–Albright syndrome. N Engl J Med. 1991;325(24):1688–95.

    Article  CAS  PubMed  Google Scholar 

  75. Riminucci M, Liu B, Corsi A, Shenker A, Spiegel AM, Robey PG, et al. The histopathology of fibrous dysplasia of bone in patients with activating mutations of the Gs alpha gene: site-specific patterns and recurrent histological hallmarks. J Pathol. 1999;187(2):249–58.

    Article  CAS  PubMed  Google Scholar 

  76. de Castro LF, Burke AB, Wang HD, Tsai J, Florenzano P, Pan KS, et al. Activation of RANK/RANKL/OPG pathway is involved in the pathophysiology of fibrous dysplasia and associated with disease burden. J Bone Miner Res. 2019;34(2):290–4.

    Article  PubMed  Google Scholar 

  77. Kushchayeva YS, Kushchayev SV, Glushko TY, Tella SH, Teytelboym OM, Collins MT, et al. Fibrous dysplasia for radiologists: beyond ground glass bone matrix. Insights Imaging. 2018;9(6):1035–56.

    Article  PubMed  PubMed Central  Google Scholar 

  78. Burke AB, Collins MT, Boyce AM. Fibrous dysplasia of bone: craniofacial and dental implications. Oral Dis. 2017;23(6):697–708.

    Article  CAS  PubMed  Google Scholar 

  79. Kelly MH, Brillante B, Collins MT. Pain in fibrous dysplasia of bone: age-related changes and the anatomical distribution of skeletal lesions. Osteoporos Int. 2008;19(1):57–63.

    Article  CAS  PubMed  Google Scholar 

  80. Majoor BCJ, Traunmueller E, Maurer-Ertl W, Appelman-Dijkstra NM, Fink A, Liegl B, et al. Pain in fibrous dysplasia: relationship with anatomical and clinical features. Acta Orthop. 2019;90(4):401–5.

    Article  PubMed  PubMed Central  Google Scholar 

  81. Stanton RP, Ippolito E, Springfield D, Lindaman L, Wientroub S, Leet A. The surgical management of fibrous dysplasia of bone. Orphanet J Rare Dis. 2012;7 Suppl 1(Suppl 1):S1.

    Article  PubMed  Google Scholar 

  82. Florenzano P, Pan KS, Brown SM, Paul SM, Kushner H, Guthrie LC, et al. Age-related changes and effects of bisphosphonates on bone turnover and disease progression in fibrous dysplasia of Bone. J Bone Miner Res. 2019;34(4):653–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Plotkin H, Rauch F, Zeitlin L, Munns C, Travers R, Glorieux FH. Effect of pamidronate treatment in children with polyostotic fibrous dysplasia of bone. J Clin Endocrinol Metab. 2003;88(10):4569–75.

    Article  CAS  PubMed  Google Scholar 

  84. Majoor BC, Appelman-Dijkstra NM, Fiocco M, van de Sande MA, Dijkstra PS, Hamdy NA. Outcome of long-term bisphosphonate therapy in McCune–Albright syndrome and polyostotic fibrous dysplasia. J Bone Miner Res. 2017;32(2):264–76.

    Article  CAS  PubMed  Google Scholar 

  85. Collins MT, de Castro LF, Boyce AM. Denosumab for fibrous dysplasia: promising, but questions remain. J Clin Endocrinol Metab. 2020;105(11):e4179–80.

    Article  Google Scholar 

  86. Palmisano B, Spica E, Remoli C, Labella R, Di Filippo A, Donsante S, et al. RANKL inhibition in fibrous dysplasia of bone: a preclinical study in a mouse model of the human disease. J Bone Miner Res. 2019;34(12):2171–82.

    Article  CAS  PubMed  Google Scholar 

  87. Boyce AM, Chong WH, Yao J, Gafni RI, Kelly MH, Chamberlain CE, et al. Denosumab treatment for fibrous dysplasia. J Bone Miner Res. 2012;27(7):1462–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Majoor BCJ, Papapoulos SE, Dijkstra PDS, Fiocco M, Hamdy NAT, Appelman-Dijkstra NM. Denosumab in patients with fibrous dysplasia previously treated with bisphosphonates. J Clin Endocrinol Metab. 2019;104(12):6069–78.

    Article  PubMed  Google Scholar 

Download references

Funding

This work was supported by the Intramural Research Program of the NIH, National Institute of Dental and Craniofacial Research.

Author information

Authors and Affiliations

  1. Skeletal Disorders and Mineral Homeostasis Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Building 30 Room 228 MSC 4320, Bethesda, MD, 20892, USA

    Kristen S. Pan & Alison M. Boyce

  2. Department of Plastic and Reconstructive Surgery, The Johns Hopkins Medical Institutions, Baltimore, MD, USA

    Kristen S. Pan

  3. Metabolic Bone Disorders Unit, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA

    Alison M. Boyce

Authors
  1. Kristen S. Pan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alison M. Boyce
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Alison M. Boyce.

Ethics declarations

Conflict of Interest

NIDCR receives funding from Amgen, Inc. for an investigator-sponsored study of denosumab treatment for fibrous dysplasia.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical Collection on Pediatrics

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Pan, K.S., Boyce, A.M. Denosumab Treatment for Giant Cell Tumors, Aneurysmal Bone Cysts, and Fibrous Dysplasia—Risks and Benefits. Curr Osteoporos Rep 19, 141–150 (2021). https://doi.org/10.1007/s11914-021-00657-z

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11914-021-00657-z

Keywords

Search

Navigation