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Osteonecrosis of the Jaws

Clinicopathologic and Radiologic Characteristics, Preventive and Therapeutic Strategies

Osteonekrosen des Kiefers. Klinikopathologische Eigenschaften, radiologische Merkmale, Präventions- und Behandlungsstrategien

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Background:

Bisphosphonate (BP) use has increased dramatically in recent years, becoming an integral part of the overall antineoplastic management of patients with metastatic bone disease. Even though their application has shown to be effective in reducing pain and minimizing the risk of skeletal-related events, their administration may bring also adverse events such osteonecrosis of the jaws (ONJ).

Methods:

After a thorough review of the literature, important aspects of the pathophysiology, diagnosis, prevention, and treatment of ONJ are presented.

Results:

ONJ is evident in up to 10% of patients receiving intravenous BP treatment. Despite the fact that its exact pathophysiology is unknown, it is characterized by bone necrosis that can occur either spontaneously or after dental surgery or tooth extraction. Panoramic radiographs are useful for the diagnosis and routine assessment of patients and computed tomography can differentiate between ONJ and metastatic disease. Additionally, magnetic resonance imaging depicts local disease extension readily, and scintigraphy is the most sensitive imaging modality for detecting early involvement. Preventive measures and routine dental evaluations are essential components of the overall patient management. In the event of ONJ, stage I or II should be managed conservatively, whereas more advanced stages (III and IV) should be treated surgically.

Conclusion:

ONJ is a well-defined clinical entity that all medical and dental doctors should be aware of, since if it is not dealt with readily and effectively, it may deteriorate the clinical status and quality of life of affected patients.

Hintergrund:

Bisphosphonate haben sich in den letzten Jahren als ein integraler Bestandteil der multimodalen Therapie von Patienten mit Knochenmetastasen etabliert. Ihr erfolgreicher Einsatz in der Schmerzreduktion ossärer Läsionen sowie der Prävention skelettaler Komplikationen steht jedoch auch in Assoziation zu Osteonekrosen des Kiefers (ONJ [„osteonecrosis of the jaw“]).

Methodik:

In einem Übersichtsartikel werden die relevanten Aspekte der Pathophysiologie, Diagnostik, Prävention und Behandlung von ONJ erläutert.

Ergebnisse:

Ätiologie und Pathogenese sind nicht hinreichend geklärt, und ONJ unter Bisphosphonatbehandlung können entweder spontan oder nach Zahnextraktion bzw. kieferchirurgischen Eingriffen auftreten. Die Orthopantomographie ist die diagnostische Routinemodalität, wobei Computertomographie und Magnetresonanztomographie für die Differenzierung gegenüber Metastasen und zur Erfassung des Krankheitsausmaßes von Bedeutung sind. Die Knochenszintigraphie hat die höchste Sensitivität in der Früherkennung von ONJ, wobei sorgfältige Nachsorge und engmaschige zahnärztliche Kontrolle wichtige Präventionsmaßnahmen sind. Die Behandlung von ONJ sollte in den Stadien I und II konservativ, in den höhergradigen Stadien (III und IV) operativ erfolgen.

Schlussfolgerung:

ONJ stellen eine schwerwiegende Komplikation mit dem Risiko einer deutlichen Einschränkung der Lebensqualität dar. Eine engmaschige Patientennachsorge ist für eine frühzeitige und effektive Behandlung von elementarer Bedeutung.

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References

  1. Aapro M, Abrahamsson PA, Body JJ, et al. Guidance on the use of bisphosphonates in solid tumors: recommendations of an international expert panel. Ann Oncol 2008;19:420–32.

    Article  CAS  Google Scholar 

  2. Adamietz IA. The efficacy of pamidronate in reducing skeletal associated events in patients with advanced multiple myeloma. Strahlenther Onkol 1997;173:52–3.

    Article  CAS  Google Scholar 

  3. Adamietz IA. Retardation of progression of bone metastasis in mammary carcinoma patients by intravenous pamidronate treatment: results of a randomised, controlled multinational study. Strahlenther Onkol 1998;174:438.

    Article  CAS  Google Scholar 

  4. Adornato MC, Morcos I, Rozanski J. The treatment of bisphosphonateassociated osteonecrosis of the jaws with bone resection and autologous platelet-derived growth factors. J Am Dent Assoc 2007;138:971–7.

    Google Scholar 

  5. Bamias A, Kastritis E, Bamia C, et al. Osteonecrosis of the jaw in cancer after treatment with bisphosphonates: incidence and risk factors. J Clin Oncol 2005;23:8580–7.

    Article  Google Scholar 

  6. Bianchi SD, Scoletta M, Cassione FB, et al. Computerized tomographic findings in bisphosphonate-associated osteonecrosis of the jaw in patients with cancer. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2007;104:249–58.

    Article  Google Scholar 

  7. Body JJ, Diel IJ, Bell R, et al. Oral ibandronate improves bone pain and preserves quality of life in patients with skeletal metastases due to breast cancer. Pain 2004;111:306–12.

    Article  CAS  Google Scholar 

  8. Body JJ, Diel IJ, Lichinitser MR, et al. Intravenous ibandronate reduces the incidence of skeletal complications in patients with breast cancer and bone metastases. Ann Oncol 2003;14:1399–405.

    Article  Google Scholar 

  9. Body JJ, Diel IJ, Lichinitser MR, et al. Oral ibandronate reduces the risk of skeletal complications in breast cancer patients with metastatic bone disease: results from two randomized, placebo-controlled phase III studies. Br J Cancer 2004;90:1133–7.

    Article  CAS  Google Scholar 

  10. Bölke E, Gerber PA, Lammering G, et al. Development and management of severe cutaneous side effects in head-and-neck cancer during concurrent radiotherapy and cetuximab. Strahlenther Onkol 2008;184:105–10.

    Article  Google Scholar 

  11. Bottke D, Bathe K, Wiegel T, et al. Phase I trial of radiochemotherapy with bendamustine in patients with recurrent squamous cell carcinoma of the head and neck. Strahlenther Onkol 2007;183:128–32.

    Article  Google Scholar 

  12. Brown JE, Neville-Webbe H, Coleman RE. The role of bisphosphonates in breast and prostate cancers. Endocr Relat Cancer 2004;11:207–24.

    Article  CAS  Google Scholar 

  13. Chiandussi S, Biasotto M, Dore F, et al. Clinical and diagnostic imaging of bisphosphonate-associated osteonecrosis of the jaws. Dentomaxillofac Radiol 2006;35:236–43.

    Article  CAS  Google Scholar 

  14. Coleman RE. Bisphosphonates: clinical experience. Oncologist 2004;9:14–27.

    Article  CAS  Google Scholar 

  15. Curi MM, Cossolin GS, Koga DH, et al. Treatment of avascular osteonecrosis of the mandible in cancer patients with a history of bisphosphonate therapy by combining bone resection and autologous platelet-rich plasma: Report of 3 cases. J Oral Maxillofac Surg 2007;65:349–55.

    Article  Google Scholar 

  16. Damato K, Gralow J, Hoff A, et al. Expert panel recommendations for the prevention, diagnosis and treatment of osteonecrosis of the jaws. Dockets management, US Food and Drug Administration (available at http://www. fda.gov/ohrms/dockets/ac/05/briefing/2005-4095B2_02_12-Novartis-Zometa-App-11.pdf, accessed October 25, 2007).

  17. Diel IJ. Effectiveness of bisphosphonates on bone pain and quality of life in breast cancer patients with metastatic bone disease: a review. Support Care Cancer 2007;15:1243–9.

    Article  Google Scholar 

  18. Diel IJ, Body JJ, Lichinitser MR, et al. Improved quality of life after long-term treatment with the bisphosphonate ibandronate in patients with metastatic bone disease due to breast cancer. Eur J Cancer 2004;40:1704–12.

    Article  CAS  Google Scholar 

  19. Dunford JE, Thompson K, Coxon FP, et al. Structure-activity relationships for inhibition of bone resorption in vivo by nitrogen-containing bisphosphonates. J Pharmacol Exp Ther 2001;296:235–42.

    CAS  Google Scholar 

  20. Durie BG, Katz M, McCoy J, et al. Osteonecrosis of the jaws in myeloma: analysis of risk factors including time dependency of Aredia and Zometa use, steroid use and underlying dental problems. Haematologica 2005;90:190a.

    Google Scholar 

  21. Fleisch, H. Development of bisphosphonates. Breast Cancer Res 2002;4:30–4.

    Article  CAS  Google Scholar 

  22. Freiberger JJ, Padilla-Burgos R, Chhoeu AH, et al. Hyperbaric oxygen treatment and bisphosphonate-induced osteonecrosis of the jaw: a case series. J Oral Maxillofac Surg 2007;65:1321–7.

    Article  Google Scholar 

  23. Gibbs JB, Oliff A. The potential of farnesyltransferase inhibitors as cancer chemotherapeutics. Annu Rev Pharmacol Toxicol 1997;37:143–66.

    Article  CAS  Google Scholar 

  24. Gralow J, Tripathy DJ. Managing metastatic bone pain: the role of bisphosphonates. J Pain Symptom Manage 2007;33:462–472.

    Article  CAS  Google Scholar 

  25. Green JR, Müller K, Jaeggi KAJ. Preclinical pharmacology of CGP 42′446, a new, potent, heterocyclic bisphosphonate compound. Bone Miner Res 1994;9:745–51.

    Article  CAS  Google Scholar 

  26. Grötz KA, Walter C, Küttner C, et al. Relevance of bisphosphonate long-term therapy in radiation therapy of endosteal jaw metastases. Strahlenther Onkol 2007;183:190–4.

    Article  Google Scholar 

  27. Gutta R, Louis PJ. Bisphosphonates and osteonecrosis of the jaws: science and rationale. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2007;104:186–93.

    Article  Google Scholar 

  28. Heyman D, Ory B, Gouin F, et al. Bisphosphonates: new therapeutic agents for the treatment of bone tumors. Trends Mol Med 2004;10:337–43.

    Article  Google Scholar 

  29. Hoskin PJ. Bisphosphonates and radiation therapy for palliation of metastatic bone disease. Cancer Treat Rev 2003;29:321–7.

    Article  CAS  Google Scholar 

  30. Krempien R, Niethammer A, Harms W, Debus J. Bisphosphonates and bone metastases: current status and future directions. Expert Rev Anticancer Ther 2005;5:295–305.

    Article  CAS  Google Scholar 

  31. Landesberg R, Cozin M, Cremers S, et al. Inhibition of oral mucosal cell wound healing by bisphosphonates. J Oral Maxillofac Surg 2008;66:839–47.

    Article  Google Scholar 

  32. Marx RE, Sawatari Y, Fortin M, Broumand V. Bisphosphonate-induced exposed bone osteonecrosis/osteopetrosis of the jaws: risk factors, recognition, prevention, and treatment. J Oral Maxillofac Surg 2005;63:1567–75.

    Article  Google Scholar 

  33. Masarachia P, Weinreb M, Balena R, et al. Comparison of the distribution of 3H-aledronate and 3H-etidronate in rat and mouse bones. Bone 1996;19:281–90.

    Article  CAS  Google Scholar 

  34. Methora B, Ruggiero S. Bisphosphonates complications including osteonecrosis of the jaw. Hematology Am Soc Hematol Educ Program 2006;525:356–60.

    Google Scholar 

  35. Migliorati CA. Bisphosphonates in the treatment of bone metastases - osteonecrosis of the jaw. In: Kardamakis D, Vassiliou V, Chow E, eds. Cancer Metastasis — Biology and Treatment, Vol 12: Bone metastases: a translational and clinical approach, Springer Netherlands, 2009:251–62.

  36. Moreira MS, Katayama E, Bombana AC, Marques MM. Cytotoxicity analysis of alendronate on cultured endothelial cells and subcutaneous tissue. A pilot study. Dent Traumatol 2005;21:329–35.

    Article  CAS  Google Scholar 

  37. Olthoff A, Ewen A, Wolff HA, et al. Organ function and quality of life after transoral laser microsurgery and adjuvant radiotherapy for locally advanced laryngeal cancer. Strahlenther Onkol 2009;185:303–9.

    Article  Google Scholar 

  38. Ott SM. Long-term safety of bisphosphonates. J Clin Endocrinol Metab 2005;90:1897–9.

    Article  CAS  Google Scholar 

  39. Pavlakis N, Stocker M. Bisphosphonates for breast cancer. The Cochrane Library, issue 1. Oxford: Update Software, 2002.

    Google Scholar 

  40. Polizzotto MN, Cousins V, Schwarer AP. Bisphosphonate-associated osteonecrosis of the auditory canal. Br J Haematol 2006;132:114.

    Article  Google Scholar 

  41. Quattrocchi CC, Santini D, Dell'Aia P, et al. A prospective analysis of CT density measurements of bone metastases after treatment with zoledronic acid. Skeletal Radiol 2007;36:1121–7.

    Article  Google Scholar 

  42. Rades D, Stoehr M, Meyners T, et al. Evaluation of prognostic factors and two radiation techniques in patients treated with surgery followed by radio(chemo)therapy or definitive radio(chemo)therapy for locally advanced head-and-neck cancer. Strahlenther Onkol 2008;184:198–205.

    Article  Google Scholar 

  43. Reid IR, Bolland MJ, Grey AB. Is bisphosphonate-associated osteonecrosis of the jaw caused by soft tissue toxicity? Bone 2007;41:318–20.

    Article  CAS  Google Scholar 

  44. Rogers MJ, Brown RJ, Hodkin V, et al. Bisphosphonates are incorporated into adenine nucleotides by human aminoacyl-tRNA synthetase enzymes. Biochem Biophys Res Commun 1996;224:863–9.

    Article  CAS  Google Scholar 

  45. Rogers MJ, Gordon S, Benford HL, et al. Cellular and molecular mechanisms of action of bisphosphonates. Cancer 2000;88:2961–78.

    Article  CAS  Google Scholar 

  46. Rosen L, Gordon D, Tchekmedyian S, et al. Zoledronic acid versus placebo in the treatment of skeletal metastases in patients with lung cancer and other solid tumors: a phase III, double-blind, randomized trial — the Zoledronic Acid Lung Cancer and Other Solid Tumors Study Group. J Clin Oncol 2003;21:3150–7.

    Article  CAS  Google Scholar 

  47. Sato M, Grasser W, Endo N, et al. Bisphosphonate action. Aledronate localization in rat bone and effects on osteoclast ultrastructure. J Clin Invest 1991;88:2095–105.

    Article  CAS  Google Scholar 

  48. Sauer N, Leising D, Wild B, et al. Der Einfluss palliativer Strahlentherapie auf Schmerz und Lebensqualität bei Patienten mit Knochenmetastasen. Strahlenther Onkol 2006;182:550–6.

    Article  Google Scholar 

  49. Schwartz HC. Osteonecrosis of the jaws: a complication of cancer chemotherapy. Head Neck Surg 1982;4:251–3.

    Article  CAS  Google Scholar 

  50. Steinmann D, Schäfer C, van Oorschot B, et al. Effects of radiotherapy for brain metastases on quality of life (QoL). Prospective pilot study of the DEGRO QoL Working Party. Strahlenther Onkol 2009;185:190–7.

    Article  Google Scholar 

  51. Storm T, Steiniche T, Thamsborg G, Melsen F. Changes in bone histomorphometry after long term treatment with intermittent, cyclic etidronate for post menopausal osteoporosis. J Bone Miner Res 1993;8:199–208.

    Article  CAS  Google Scholar 

  52. Studer G, Gratz KW, Glanzmann C. Osteoradionecrosis of the mandibula in patients treated with different fractionations. Strahlenther Onkol 2004;180:233–40.

    Article  Google Scholar 

  53. Studer G, Studer SP, Zwahlen RA, et al. Osteoradionecrosis of the mandible: minimized risk profile following intensity-modulated radiation therapy (IMRT). Strahlenther Onkol 2006;182:283–8.

    Article  Google Scholar 

  54. Vassiliou V, Kalogeropoulou C, Christopoulos C, et al. Combination ibandronate and radiotherapy for the treatment of bone metastases: clinical evaluation and radiologic assessment. Int J Radiat Oncol Biol Phys 2007;67:264–72.

    CAS  Google Scholar 

  55. Vassiliou V, Kardamakis D. The management of metastatic bone disease with combination of bisphosphonates and radiotherapy: from theory to clinical practice. Anticancer Agents Med Chem 2009;9:323–35.

    Google Scholar 

  56. Vescovi P, Merigo E, Manfredi M, et al. Nd:Yag laser biostimulation in the treatment of bisphosphonate-associated osteonecrosis of the jaw: clinical experience in 28 cases. Photomed Laser Surg 2008;26:37–46.

    Article  Google Scholar 

  57. Vomvas D, Vassiliou V, Papavasileiou D, et al. Osteonecrosis of the jaw in a patient treated with ibandronate. J BUON 2008;13:441–2.

    CAS  Google Scholar 

  58. Weitzman R, Sauter N, Eriksen EF, et al. Critical review: Updated recommendations for the prevention, diagnosis and treatment of osteonecrosis of the jaw in cancer patients. Crit Rev Oncol Hematol 2007;62:148–52.

    Article  Google Scholar 

  59. Woo SB, Hellstein JW, Kalmar JR. Narrative [corrected] review: Bisphosphonates and osteonecrosis of the jaws. Ann Intern Med 2006;144:753–61.

    CAS  Google Scholar 

  60. Wyngear TV, Huizing MT, Vermoken JD. Osteonecrosis of the jaw related to the use of bisphosphonates. Curr Opin Oncol 2007;19:315–22.

    Article  Google Scholar 

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Authors and Affiliations

  1. Department of Radiation Oncology, Bank of Cyprus Oncology Centre, Nicosia, Cyprus

    Vassilios Vassiliou

  2. Department of Radiation Oncology, Klinikum Offenbach, Offenbach, Germany

    Nikolaos Tselis

  3. Department of Radiotherapy, University of Patras Medical School, Patras, Greece

    Dimitrios Kardamakis

  4. Strahlenklinik, Klinikum Offenbach, Starkenburgring 66, 63069, Offenbach am Main, Germany

    Nikolaos Tselis

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  1. Vassilios Vassiliou
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  2. Nikolaos Tselis
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  3. Dimitrios Kardamakis
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Correspondence to Nikolaos Tselis.

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Vassiliou, V., Tselis, N. & Kardamakis, D. Osteonecrosis of the Jaws. Strahlenther Onkol 186, 367–373 (2010). https://doi.org/10.1007/s00066-010-2066-9

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