European Spine Journal

, Volume 27, Supplement 3, pp 446–452 | Cite as

Neoadjuvant denosumab for the treatment of a sacral osteoblastoma

  • Jeremy J. Reynolds
  • Dominique A. Rothenfluh
  • Nick Athanasou
  • Shaun Wilson
  • David C. Kieser
Case Report



To present a case of aggressive sacral osteoblastoma (OB) treated with neoadjuvant denosumab therapy and en bloc resection.


Case report of a 14-year-old male with an aggressive OB affecting the superior articular process of the left first sacral segment. The lesion was lytic and metabolically active and involved the left-sided posterior elements of S1–S3 with extension into the spinal canal, affecting the left S1, S2, S3, S4 and S5 nerve roots. He was treated for 1 month with neoadjuvant denosumab followed by en bloc resection.


Denosumab therapy caused regression of the tumour and converted the diffuse infiltrative mass into a well-defined solid (osteoma-like) structure, aiding surgical resection and preserving the S1, S4 and S5 nerve roots. Histologically, the treated lesion showed abundant sclerotic woven bone and osteoblasts with absence of osteoclasts.


A short course of denosumab caused tumour regression, ossification and conversion of an aggressive OB into a sclerotic, well-defined lesion thus aiding surgical resection and preservation of neural structures. Neoadjuvant therapy reduced osteoclast numbers but PET showed that the lesion remained FDG avid post-therapy.


Osteoblastoma Denosumab RANK Tumour 



Glynny Kieser for her editorial input and Sarah Turton for typing the manuscript.

Compliance with ethical standards

Conflict of interest

None of the authors has any potential conflict of interest.


  1. 1.
    Berry M, Mankin H, Gebhardt M et al (2008) Osteoblastoma: a 30-year study of 99 cases. J Surg Oncol 98:179–183CrossRefPubMedGoogle Scholar
  2. 2.
    Harrop JS, Schmidt MH, Boriani S et al (2009) Aggressive “benign” primary spine neoplasms: osteoblastoma, aneurysmal bone cyst, and giant cell tumour. Spine 34(22S):39–47CrossRefGoogle Scholar
  3. 3.
    De Andrea CE, Bridge JA, Schiller A (2013) Osteoblastoma. In: Fletcher CDM, Bridge JA, Hogerdoorn PCW, Mertens F (eds) WHO classification of tumours of soft tissue and bone. IARC, Lyons, pp 279–280Google Scholar
  4. 4.
    Azouz EM, Kozlowski K, Marton D et al (1986) Osteoid osteoma and osteoblastoma of the spine in children: report of 22 cases with brief literature review. Pediatr Radiol 16:25–31CrossRefPubMedGoogle Scholar
  5. 5.
    Murphey MD, Andrews CL, Flemming DJ et al (1996) Primary tumors of the spine: radiologic pathologic correlation. Radiographics 16:1131–1158CrossRefPubMedGoogle Scholar
  6. 6.
    Thakur NA, Daniels AH, Schiller J et al (2012) Benign tumors of the spine. J Am Acad Orthop Surg 20:715–724PubMedGoogle Scholar
  7. 7.
    Schajowicz F, Lemos C (1970) Osteoid osteoma and osteoblastoma. Closely related entities of osteoblastic derivation. Acta Orthop Scand 41:272–291CrossRefPubMedGoogle Scholar
  8. 8.
    Chan P, Boriani S, Fourney DR et al (2009) An assessment of the reliability of the Enneking and Weinstein–Boriani–Biagini classifications for staging of primary spinal tumors by the Spine Oncology Study Group. Spine 34:384–391CrossRefPubMedGoogle Scholar
  9. 9.
    Lucas DR (2010) Osteoblastoma. Arch Pathol Lab Med 134(10):1460–1466PubMedGoogle Scholar
  10. 10.
    Lucas DR, Unni KK, McLeod RA et al (1994) Osteoblastoma: clinicopathologic study of 306 cases. Hum Pathol 25:117–134CrossRefPubMedGoogle Scholar
  11. 11.
    Dorfman HD, Weiss SW (1984) Borderline osteoblastic tumors: problems in the differential diagnosis of aggressive osteoblastoma and low-grade osteosarcoma. Semin Diagn Pathol 1:215–234PubMedGoogle Scholar
  12. 12.
    Gertzbein SD, Cruickshank B, Hoffman H et al (1973) Recurrent benign osteoblastoma of the second thoracic vertebra: a case report. JBJS [Br] 55:841–847CrossRefGoogle Scholar
  13. 13.
    Marsh BW, Bonfiglio M, Brady LP et al (1975) Benign osteoblastoma: range of manifestations. JBJS [Am] 57:1–9CrossRefGoogle Scholar
  14. 14.
    Rehnitz C, Sprengel SD, Lehner B et al (2012) CT-guided radiofrequency ablation of osteoid osteoma and osteoblastoma: clinical success and long-term follow up in 77 patients. Eur J Radiol 81(11):3426–3434CrossRefPubMedGoogle Scholar
  15. 15.
    Weber MA, Sprengel SD, Omlor GW et al (2015) Clinical long-term outcome, technical success, and cost analysis of radiofrequency ablation for the treatment of osteoblastomas and spinal osteoid osteomas in comparison to open surgical resection. Skeletal Radiol 44(7):981–993CrossRefPubMedGoogle Scholar
  16. 16.
    Martel VJ, Bueno HA, Ortiz CEJ (2009) Percutaneous radiofrequency ablation of benign bone tumours: osteoid osteoma, osteoblastoma, and chondroblastoma. Radiologia 51(6):549–558CrossRefGoogle Scholar
  17. 17.
    Singer JM, Deutsch GP (1993) The successful use of radiotherapy for osteoblastoma: case report. Clin Oncol 5(2):124–125CrossRefGoogle Scholar
  18. 18.
    Bertoni F, Unni KK, Lucas DR et al (1993) Osteoblastoma with cartilaginous matrix. An unusual morphologic presentation in 18 cases. Am J Surg Pathol 17:69–74CrossRefPubMedGoogle Scholar
  19. 19.
    Eisenbrey AB, Huber PJ, Rachmaninoff N (1969) Benign osteoblastoma of the spine with multiple recurrences: case report. J Neurosurg 31:468–473CrossRefPubMedGoogle Scholar
  20. 20.
    Mayer L (1967) Malignant degeneration of so-called benign osteoblastoma. Bull Hosp Joint Dis 28:4–13PubMedGoogle Scholar
  21. 21.
    Beyer WF, Kuhn H (1985) Can an osteoblastoma become malignant? Virchows Arch A Pathol Anat Histopathol 408:297–305CrossRefPubMedGoogle Scholar
  22. 22.
    Merryweather R, Middlemiss JH, Sanerkin NG (1980) Malignant transformation of osteoblastoma. JBJS [Br] 62:381–384Google Scholar
  23. 23.
    De Souza Dias L, Frost HM (1973) Osteoblastoma of the spine. A review and report of eight new cases. Clin Orthop Relat Res 91:141–151CrossRefGoogle Scholar
  24. 24.
    Jones DN, Marion M, Rozenbilds MA (1993) Bone scan appearances of a metastasizing aggressive osteoblastoma: a case report. Clin Nucl Med 18:567–569CrossRefPubMedGoogle Scholar
  25. 25.
    Berberoglu S, Oguz A, Aribal E et al (1997) Osteoblastoma response to radiotherapy and chemotherapy. Med Pediatr Oncol 28:305–309PubMedGoogle Scholar
  26. 26.
    Zileli M, Cagli S, Basdemir G et al (2003) Osteoid osteomas and osteoblastomas of the spine. Neurosurg Focus 15:E5PubMedGoogle Scholar
  27. 27.
    Janin Y, Epstein JA, Carras R et al (1981) Osteoid osteomas and osteoblastomas of the spine. Neurosurgery 8:31–38CrossRefPubMedGoogle Scholar
  28. 28.
    Camitta B, Wells R, Segura A et al (1991) Osteoblastoma response to chemotherapy. Cancer 68:999–1003CrossRefPubMedGoogle Scholar
  29. 29.
    Schajowicz F, Lemos C (1976) Malignant osteoblastoma. JBJS [Br] 58:202–211Google Scholar
  30. 30.
    Tonai M, Campbell CJ, Ahn GH et al (1982) Osteoblastoma: classification and report of 16 patients. Clin Orthop Relat Res 167:222–235Google Scholar
  31. 31.
    Kroon HM, Schurmans J (1990) Osteoblastoma: clinical and radiologic findings in 98 new cases. Radiology 175:783–790CrossRefPubMedGoogle Scholar
  32. 32.
    Jackson RP, Reckling FW, Mants FA (1977) Osteoid osteoma and osteoblastoma. Similar histologic lesions with different natural histories. Clin Orthop Relat Res 128:303–313Google Scholar
  33. 33.
    Jackson RP (1978) Recurrent osteoblastoma: a review. Clin Orthop Relat Res 131:229–233Google Scholar
  34. 34.
    Lucas DR (2010) Osteoblastoma. Arch Pathol Lab Med 134:1460–1466PubMedGoogle Scholar
  35. 35.
    Boriani S, Amendola L, Bandiera S et al (2012) Staging and treatment of osteoblastoma in the mobile spine: a review of 51 cases. Eur Spine J 21:2003–2010CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Versteeg AL, Dea N, Boriani S et al (2017) Surgical management of spinal osteoblastomas. JNS Spine 27:321–327Google Scholar
  37. 37.
    Takami M, Woo JT, Nagai K (1999) Osteoblastic cell induce fusion and activation of osteoclasts through a mechanism independent of macrophage-colony-stimulating factor production. Cell Tissue Res 298(2):327–334CrossRefPubMedGoogle Scholar
  38. 38.
    Thomas D, Henshaw R, Skubitz K et al (2010) Densoumab in patients with giant-cell tumour of bone: an open-label, phase 2 study. Lancet Oncol 11(3):275–280CrossRefPubMedGoogle Scholar
  39. 39.
    Lewiecki EM (2010) Clinical use of denosumab for the treatment for post-menopausal osteoporosis. Curr Med Res Opin 26:2807–2812CrossRefPubMedGoogle Scholar
  40. 40.
    Pageau SC (2009) Denosumab. MAbs 1(3):210–215CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    McClung MR, Lewiecki EM, Cohen SB et al (2006) Denosumab in postmenopausal women with low bone mineral density. N Engl J Med 354(8):821–831CrossRefPubMedGoogle Scholar
  42. 42.
    Fizazi K, Carducci M, Smith M et al (2011) Denosumab versus zoledronic acid for treatment of bone metastases in men with castration resistant prostate cancer: a randomised, double blind study. Lancet 377:813–822CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Lipton A, Fizazi K, Stopeck AT et al (2016) Effect of denosumab versus zoledronic acid in preventing skeletal-related events in patients with bone metastases by baseline characteristics. Eur J Cancer 53(1):75–83CrossRefPubMedGoogle Scholar
  44. 44.
    Lange T, Stehling C, Frohlich B et al (2013) Denosumab: a potential new and innovative treatment option for aneurysmal bone cysts. Eur Spine J 22(6):1417–1422CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Goldschlager T, Dea N, Boyd M et al (2015) Giant cell tumors of the spine: has denosumab changed the treatment paradigm. Neurosurg Spine 22(5):526–533CrossRefPubMedGoogle Scholar
  46. 46.
    Lau YS, Sabokbar A, Gibbons CL et al (2005) Phenotypic and molecular studies of giant-cell tumours of bone and soft tissue. Hum Pathol 36:945–954CrossRefPubMedGoogle Scholar
  47. 47.
    Gibbons CL, Petra M, Smith R et al (2003) Bisphosphonate treatment of benign multifocal and unifocal osteolytic tumours of bone. Sarcoma 7(1):35–41CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Cornelis F, Truchetet ME, Amoretti N et al (2014) Bisphosphonate therapy for unresectable symptomatic bone tumors: a long-term prospective study of tolerance and efficacy. Bone 58:11–16CrossRefPubMedGoogle Scholar
  49. 49.
    Yamagishi T, Kawashima H, Ogose A et al (2016) Receptor-activator of nuclear KappaB ligand expression as a new therapeutic target in primary bone tumours. PLoS One 11(5):e0154680CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Boyce AM, Chong WH, Galfri RI et al (2012) Denosumab treatment for fibrous dysplasia. J Bone Miner Res 27:1462–1470CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Inwards C, Squire J (2013) Low-grade central osteosarcoma. In: Fletcher CDM, Bridge JA, Hogerdoorn PCW, Mertens F (eds) WHO classification of tumours of soft tissue and bone. IARC, Lyon, pp 281–282Google Scholar
  52. 52.
    Aghaloo TL, Felsenfeld AL, Sotirios T (2010) Osteonecrosis of the jaw in a patient on denosumab. J Oral Maxillofac Surg 68(5):959–963CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Cummings SR, Martin JS, McClung MR et al (2009) Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med 361(8):756–765CrossRefPubMedGoogle Scholar
  54. 54.
    Papapoulos S, Lippuner K, Roux C et al (2015) The effect of 8 or 5 years of denosumab treatment in postmenopausal women with osteoporosis: results from the FREEDOM Extension study. Osteoporos Int 26(12):2773–2783CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Jeremy J. Reynolds
    • 1
  • Dominique A. Rothenfluh
    • 1
  • Nick Athanasou
    • 1
  • Shaun Wilson
    • 1
  • David C. Kieser
    • 1
    • 2
  1. 1.Division of Spinal SurgeryUniversity of OxfordOxfordUK
  2. 2.Department of Orthopaedic Surgery and Musculoskeletal MedicineCanterbury District Health BoardChristchurchNew Zealand

Personalised recommendations