Oral and Maxillofacial Surgery

, Volume 15, Issue 1, pp 63–66 | Cite as

Osteonecrosis of the jaw related to sunitinib

  • Felix P. Koch
  • Christian Walter
  • Torsten Hansen
  • Elke Jäger
  • Wilfried Wagner
Case Report


Case Report

A 59-year-old male patient was referred to the hospital with exposed bone measuring 10 mm in diameter in the posterior, left-side region of the lower jaw. Two months previous, the first molar had been extracted. The patient had contracted renal cell carcinoma and had been treated by nephrectomy in 2003. Soft tissue metastases occurred. After initial therapy with interferon and vinblastine, a relapse occurred and the therapy was changed to sorafenib, followed by sunitinib. Osteonecrosis of the lower jaw appeared 1 year after initial and exclusive therapy with sunitinib.


Bisphosphonates had never been applied. With increasing application of multi-kinase inhibitors, complications due to osteonecrosis could occur more frequently.


Osteonecrosis Sunitinib Multi-kinase inhibitor Side effect Tooth extraction Cancer therapy 


  1. 1.
    Chow LQ, Eckhardt SG (2007) Sunitinib: from rational design to clinical efficacy. J Clin Oncol 25:884–896CrossRefPubMedGoogle Scholar
  2. 2.
    Haas NB, Uzzo RG (2007) Tyrosine kinase inhibitors and anti-angiogenic therapies in kidney cancer. Curr Treat Options in Oncol 8:211–226CrossRefGoogle Scholar
  3. 3.
    Mendel DB, Laird AD, Xin X, Louie SG, Christensen JG, Li G, Schreck RE, Abrams TJ, Ngai TJ, Lee LB, Murray LJ, Carver J, Chan E, Moss KG, Haznedar JO, Sukbuntherng J, Blake RA, Sun L, Tang C, Miller T, Shirazian S, McMahon G, Cherrington JM (2003) In vivo antitumor activity of SU11248, a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor and platelet-derived growth factor receptors: determination of a pharmacokinetic/pharmacodynamic relationship. Clin Cancer Res 9:327–337PubMedGoogle Scholar
  4. 4.
    Arora A, Scholar EM (2005) Role of tyrosine kinase inhibitors in cancer therapy. J Pharmacol Exp Ther 315:971–979CrossRefPubMedGoogle Scholar
  5. 5.
    Sundberg C, Ljungstrom M, Lindmark G, Gerdin B, Rubin C (1993) Microvascular pericytes express platelet-derived growth factor-beta receptors in human healing wounds and colorectal adenocarcinoma. Am J Pathol 143:1377–1388PubMedGoogle Scholar
  6. 6.
    Ayllon J, Launay-Vacher V, Medioni J, Cros C, Spano JP, Oudard S (2009) Osteonecrosis of the jaw under bisphosphonate and antiangiogenic therapies: cumulative toxicity profile? Ann Oncol 20:600–601CrossRefPubMedGoogle Scholar
  7. 7.
    Brunello A, Saia G, Bedogni A, Scaglione D, Basso U (2009) Worsening of osteonecrosis of the jaw during treatment with sunitinib in a patient with metastatic renal cell carcinoma. Bone 44:173–175CrossRefPubMedGoogle Scholar
  8. 8.
    Christodoulou C, Pervena A, Klouvas G, Galani E, Falagas ME, Tsakalos G, Visvikis A, Nikolakopoulou A, Acholos V, Karapanagiotidis G, Batziou E, Skarlos DV (2009) Combination of bisphosphonates and antiangiogenic factors induces osteonecrosis of the jaw more frequently than bisphosphonates alone. Oncology 76:209–211CrossRefPubMedGoogle Scholar
  9. 9.
    Assael LA (2004) New foundations in understanding osteonecrosis of the jaws. J Oral Maxillofac Surg 62:125–126CrossRefPubMedGoogle Scholar
  10. 10.
    Chrcanovic BR, Reher P, Sousa AA, Harris M (2010) Osteoradionecrosis of the jaws—a current overview—part 1: physiopathology and risk and predisposing factors. Oral Maxillofac Surg 14:3–16CrossRefPubMedGoogle Scholar
  11. 11.
    Langer CJ (2006) Osteonecrosis of the jaw, a recently recognized sequela of bisphosphonate therapy: case report. Support Cancer Ther 3:122–124CrossRefPubMedGoogle Scholar
  12. 12.
    Walter C, Grotz KA, Kunkel M, Al-Nawas B (2007) Prevalence of bisphosphonate associated osteonecrosis of the jaw within the field of osteonecrosis. Support Care Cancer 15:197–202CrossRefPubMedGoogle Scholar
  13. 13.
    Piesold JU, Al-Nawas B, Grotz KA (2006) Osteonecrosis of the jaws by long term therapy with bisphosphonates. Mund Kiefer Gesichtschir 10:287–300CrossRefPubMedGoogle Scholar
  14. 14.
    Heinrich MC, Blanke CD, Druker BJ, CC L (2002) Inhibition of KIT tyrosine kinase activity: a novel molecular approach to the treatment of KIT-positive malignancies. J Clin Oncol 20:1692–1703CrossRefPubMedGoogle Scholar
  15. 15.
    Schmidt-Arras D, Schwable J, Bohmer FD, Serve H (2004) Flt3 receptor tyrosine kinase as a drug target in leukemia. Curr Pharm Des 10:1867–1883CrossRefPubMedGoogle Scholar
  16. 16.
    Motzer RJ, Michaelson MD, Redman BG, Hudes GR, Wilding G, Figlin RA, Ginsberg MS, Kim ST, Baum CM, DePrimo SE, Li JZ, Bello CL, Theuer CP, George DJ, Rini BI (2006) Activity of SU11248, a multitargeted inhibitor of vascular endothelial growth factor receptor and platelet-derived growth factor receptor, in patients with metastatic renal cell carcinoma. J Clin Oncol 24:16–24CrossRefPubMedGoogle Scholar
  17. 17.
    Wolter P, Dumez H, Schoffski P (2007) Sunitinib and hypothyroidism. N Engl J Med 356:1580; author reply 1580–1581Google Scholar
  18. 18.
    Roodhart JM, Langenberg MH, Witteveen E, Voest EE (2008) The molecular basis of class side effects due to treatment with inhibitors of the VEGF/VEGFR pathway. Curr Clin Pharmacol 3:132–143CrossRefPubMedGoogle Scholar
  19. 19.
    Suwattee P, Chow S, Berg BC, Warshaw EM (2008) Sunitinib: a cause of bullous palmoplantar erythrodysesthesia, periungual erythema, and mucositis. Arch Dermatol 144:123–125CrossRefPubMedGoogle Scholar
  20. 20.
    Faivre S, Delbaldo C, Vera K, Robert C, Lozahic S, Lassau N, Bello C, Deprimo S, Brega N, Massimini G, Armand JP, Scigalla P, Raymond E (2006) Safety, pharmacokinetic, and antitumor activity of SU11248, a novel oral multitarget tyrosine kinase inhibitor, in patients with cancer. J Clin Oncol 24:25–35CrossRefPubMedGoogle Scholar
  21. 21.
    Kollmannsberger C, Soulieres D, Wong R, Scalera A, Gaspo R, Bjarnason G (2007) Sunitinib therapy for metastatic renal cell carcinoma: recommendations for management of side effects. Can Urol Assoc J 1:S41–S54PubMedGoogle Scholar
  22. 22.
    Walter C, Al-Nawas B, Grotz KA, Thomas C, Thuroff JW, Zinser V, Gamm H, Beck J, Wagner W (2008) Prevalence and risk factors of bisphosphonate-associated osteonecrosis of the jaw in prostate cancer patients with advanced disease treated with zoledronate. Eur Urol 54:1066–1072CrossRefPubMedGoogle Scholar
  23. 23.
    Hansen T, Kunkel M, Springer E, Walter C, Weber A, Siegel E, Kirkpatrick CJ (2007) Actinomycosis of the jaws—histopathological study of 45 patients shows significant involvement in bisphosphonate-associated osteonecrosis and infected osteoradionecrosis. Virchows Arch 451:1009–1017CrossRefPubMedGoogle Scholar
  24. 24.
    Schwartz HC (1982) Osteonecrosis of the jaws: a complication of cancer chemotherapy. Head Neck Surg 4:251–253CrossRefPubMedGoogle Scholar
  25. 25.
    Marquet P, Lachatre G, Debord J, Eichler B, Bonnaud F, Nicot G (1992) Pharmacokinetics of vinorelbine in man. Eur J Clin Pharmacol 42:545–547CrossRefPubMedGoogle Scholar
  26. 26.
    Billiau A (1981) Pharmacokinetic and pharmacological aspects of interferon therapy in man. Acta Microbiol Acad Sci Hung 28:257–262PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Felix P. Koch
    • 1
  • Christian Walter
    • 1
  • Torsten Hansen
    • 2
  • Elke Jäger
    • 3
  • Wilfried Wagner
    • 1
  1. 1.Oral and Maxillofacial SurgeryUniversity Medical Centre of the Johannes Gutenberg UniversityMainzGermany
  2. 2.Institute of PathologyUniversity Medical Centre of the Johannes Gutenberg UniversityMainzGermany
  3. 3.Clinic for Oncology and HaematologyKrankenhaus NordwestFrankfurt a.M.Germany

Personalised recommendations