Oral and Maxillofacial Surgery

, Volume 14, Issue 1, pp 3–16

Osteoradionecrosis of the jaws—a current overview—part 1

Physiopathology and risk and predisposing factors
  • Bruno Ramos Chrcanovic
  • Peter Reher
  • Alexandre Andrade Sousa
  • Malcolm Harris
Review Article

Abstract

Purpose

The aim of this paper is to explore the current theories about definition, classification, incidence and physiopathology of osteoradionecrosis (ORN) of the jaws. Moreover, it is discussed the predisposing and risk factors for the development of osteoradionecrosis based on the literature review.

Discussion

Osteoradionecrosis is one of the most serious oral complications of head and neck cancer treatment. Osteoradionecrosis is a severe delayed radiation-induced injury, characterised by bone tissue necrosis and failure to heal. Osteoradionecrosis either stabilises or gradually worsens and is notoriously difficult to manage. The most widely accepted theory to explain its cause until recently was the theory of hypoxia, hypovascularity and hypocellularity. A new theory for the pathogenesis of osteoradionecrosis was proposed. The clinical presentations of osteoradionecrosis are pain, drainage and fistulation of the mucosa or skin that is related to exposed bone in an area that has been irradiated. The tumour size and location, radiation dose, local trauma, dental extractions, infection, immune defects and malnutrition can predispose its development.

Conclusions

A better understanding of risk factors for the development ORN and of the underlying pathophysiology may improve our ability to prevent this complication and help to improve the prognosis for those being treated for osteoradionecrosis.

Keywords

Osteoradionecrosis Jaw Physiopathology Risk factors 

References

  1. 1.
    Jansma J, Vissink A, Spijkervet FKL, Roodenburg JLN, Panders AK, Vermey A, Szabó BG, Gravenmade EJ (1992) Protocol for the prevention and treatment of oral sequelae resulting from head and neck radiation therapy. Cancer 70:2171–2180CrossRefPubMedGoogle Scholar
  2. 2.
    Jansma J, Vissink A, Bouma J, Vermey A, Panders AK, Gravenmade EJ (1992) A survey of prevention and treatment regimens for oral sequelae resulting from head and neck radiotherapy used in Dutch radiotherapy institutes. Int J Radiat Onc Biol Phys 24:359–367Google Scholar
  3. 3.
    Sulaiman F, Huryn JM, Zlotolow IM (2003) Dental extractions in irradiated head and neck patient: a retrospective analysis of Memorial Sloan-Kettering Cancer Center protocols, criteria and end results. J Oral Maxillofac Surg 61:1123–1131CrossRefPubMedGoogle Scholar
  4. 4.
    Hutchinson IL (1996) Complications of radiotherapy in the head and neck: an orofacial surgeon's view. In: Tobias JS, Thomas PRM (eds) Current radiation oncology. Arnold, London, pp 144–177Google Scholar
  5. 5.
    Thorn JJ, Hansen HS, Specht L, Bastholt L (2000) Osteoradionecrosis of the jaws: clinical characteristics and relation to the field of irradiation. J Oral Maxillofac Surg 58:1088–1093CrossRefPubMedGoogle Scholar
  6. 6.
    Marx RE, Johnson RP (1987) Studies in the radiobiology of osteoradionecrosis and their clinical significance. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 644:379–390Google Scholar
  7. 7.
    Katsura K, Sasai K, Sato K, Saito M, Hoshina H, Hayashi T (2008) Relationship between oral health status and development of osteoradionecrosis of the mandible: a retrospective longitudinal study. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 105:731–738CrossRefPubMedGoogle Scholar
  8. 8.
    Marx RE (1983) Osteoradionecrosis: a new concept of its pathophysiology. J Oral Maxillofac Surg 41:283–288CrossRefPubMedGoogle Scholar
  9. 9.
    Epstein JB, Wong FLW, Stevenson-Moore P (1987) Osteoradionecrosis: clinical experience and a proposal for classification. J Oral Maxillofac Surg 45:104–110CrossRefPubMedGoogle Scholar
  10. 10.
    Kluth EV, Jain PR, Stuchell RN, Frich JC Jr (1988) A study of factors contributing to the development of osteoradionecrosis of the jaws. J Prosthet Dent 59:194–201CrossRefPubMedGoogle Scholar
  11. 11.
    Reuther T, Schuster T, Mende U, Kübler A (2003) Osteoradionecrosis of the jaws as a side effect of radiotherapy of head and neck tumour patients—a report of a thirty-year retrospective review. Int J Oral Maxillofac Surg 32:289–295CrossRefPubMedGoogle Scholar
  12. 12.
    Regaud C (1922) Sur la necrose des os attenté par un processus cancereux et traites par les radiaions. Compt Rend Soc Biol 87:427Google Scholar
  13. 13.
    Ewing J (1926) Radiation osteitis. Acta Radiol 6:399–412CrossRefGoogle Scholar
  14. 14.
    Meyer I (1970) Infectious diseases of the jaws. J Oral Surg 28:17–26PubMedGoogle Scholar
  15. 15.
    Titterington WP (1971) Osteomyelitis and osteoradionecrosis of the jaws. J Oral Med 26:7–16PubMedGoogle Scholar
  16. 16.
    Marx RE (1983) A new concept in the treatment of osteoradionecrosis. J Oral Maxillofac Surg 41:351–357CrossRefPubMedGoogle Scholar
  17. 17.
    Wong JK, Wood RE, McLean M (1997) Conservative management of osteoradionecrosis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 84:16–21CrossRefPubMedGoogle Scholar
  18. 18.
    Epstein JB, Wong FLW, Dickens A, Szasz I, Lepawsky M (1992) Bone and gallium scans in postradiotherapy osteonecrosis of the jaw. Head Neck 14:288–292CrossRefPubMedGoogle Scholar
  19. 19.
    Beumer J 3rd, Curtis T, Harrison RE (1979) Radiation therapy of the oral cavity: sequelae and management. Part 2. Head Neck Surg 1:392–400CrossRefPubMedGoogle Scholar
  20. 20.
    Hutchinson IL, Colpe M, Delpy DT, Richardson CE, Harris M (1990) The investigation of osteoradionecrosis of the mandible by near infrared spectroscopy. Br J Oral Maxillofac Surg 28:150–154CrossRefGoogle Scholar
  21. 21.
    Beumer J 3rd, Harrison R, Sanders B, Kurrasch M (1983) Preradiation dental extractions and the incidence of bone necrosis. Head Neck Surg 5:514–521CrossRefPubMedGoogle Scholar
  22. 22.
    Harris M (1992) The conservative management of osteoradionecrosis of the mandible with ultrasound therapy. Br J Oral Maxillofac Surg 30:313–318CrossRefPubMedGoogle Scholar
  23. 23.
    Morrish RB Jr, Chan E, Silverman S Jr, Meyer J, Fu KK, Greenspan D (1981) Osteonecrosis in patients irradiated for head and neck carcinoma. Cancer 47:1980–1983CrossRefPubMedGoogle Scholar
  24. 24.
    Clayman L (1997) Clinical controversies in oral and maxillofacial surgery: part two. Management of dental extractions in irradiated jaws: a protocol without hyperbaric oxygen therapy. J Oral Maxillofac Surg 55:275–281CrossRefPubMedGoogle Scholar
  25. 25.
    Berger RP, Symington JM (1990) Long-term clinical manifestation of osteoradionecrosis of the mandible: report of two cases. J Oral Maxillofac Surg 48:82–84CrossRefPubMedGoogle Scholar
  26. 26.
    Lyons A, Ghazali N (2008) Osteoradionecrosis of the jaws: current understanding of its pathophysiology and treatment. Br J Oral Maxillofac Surg 46:653–660CrossRefPubMedGoogle Scholar
  27. 27.
    Reher P (1999) Evidence for the use of ultrasound therapy for the management of mandibular osteoradionecrosis. Doctorate thesis, University of LondonGoogle Scholar
  28. 28.
    Murray CG, Daly TE, Zimmerman SO (1980) The relationship between dental disease and radiation necrosis of the mandible. Oral Surg Oral Med Oral Pathol 49:99–104CrossRefPubMedGoogle Scholar
  29. 29.
    Murray CG, Herson J, Daly TE, Zimmerman S (1980) Radiation necrosis of the mandible: a 10 year study. Part II. Dental factors; onset, duration and management of necrosis. Int J Radiat Oncol Biol Phys 6:549–553PubMedGoogle Scholar
  30. 30.
    Murray CG, Herson J, Daly TE, Zimmerman S (1980) Radiation necrosis of the mandible: a 10 year study. Part I. Factors influencing the onset of necrosis. Int J Radiat Oncol Biol Phys 6:543–548PubMedGoogle Scholar
  31. 31.
    Mainous EG, Hart GB (1975) Osteonecrosis of the mandible: treatment with hyperbaric oxygen. Arch Otolaryngol 101:173–177PubMedGoogle Scholar
  32. 32.
    Bedwinek JM, Shukowsky LJ, Fletcher GH, Daley TE (1976) Osteoradionecrosis in patients treated with definitive radiotherapy for squamous cell carcinomas of the oral cavity and naso- and oropharynx. Radiology 119:665–667PubMedGoogle Scholar
  33. 33.
    Van Merkesteyn JPR, Bakker DJ, Borgmeijer-Hoelen AMMJ (1995) Hyperbaric oxygen treatment of osteoradionecrosis of the mandible: experience in 29 patients. Oral Surg Oral Med Oral Patho1 Oral Radiol Endod 80:12–16CrossRefGoogle Scholar
  34. 34.
    Curi MM, Dib LL (1997) Osteoradiadionecrosis of the jaws: a retrospective study of the background factors and treatment in 104 cases. J Oral Maxillofac Surg 55:540–544CrossRefPubMedGoogle Scholar
  35. 35.
    Granström G, Fagerberg-Mohlin B, Fomander J (1992a) Aspects on the management of patients with osteoradionecrosis after therapy of head and neck cancer. XVIIIth Annual Meeting of EUBS, pp 163–169Google Scholar
  36. 36.
    Daly TE, Drane JB, MacComb WS (1972) Management of problems of the teeth and jaw in patients undergoing irradiation. Am J Surg 124:539–542CrossRefPubMedGoogle Scholar
  37. 37.
    Coffin F (1983) The incidence and management of osteoradionecrosis of the jaws following head and neck radiotherapy. Br J Radiol 56:851–857CrossRefPubMedGoogle Scholar
  38. 38.
    Morton ME, Simpson W (1986) The management of osteoradionecrosis of the jaws. Br J Oral Maxillofac Surg 24:332–341CrossRefPubMedGoogle Scholar
  39. 39.
    Gowgiel JM (1960) Experimental radio-osteonecrosis of the jaws. J Dent Res 39:176–197PubMedGoogle Scholar
  40. 40.
    Stevens MR, Marx RE (1981) Complete resolution of osteoradionecrosis with a new protocol combining hyperbaric oxygen and resection. Scientific Abstracts session 63rd Annual AAOMS MeetingGoogle Scholar
  41. 41.
    Jereczek-Fossa BA, Orecchia R (2002) Radiotherapy-induced mandibular bone complications. Cancer Treat Rev 28:65–74CrossRefPubMedGoogle Scholar
  42. 42.
    Pasquier D, Hoelscher T, Schmutz J, Dische S, Mathieu D, Baumann M, Lartigau E (2004) Hyperbaric oxygen therapy in the treatment of radio-induced lesions in normal tissues: a literature review. Radiother Oncol 72:1–13CrossRefPubMedGoogle Scholar
  43. 43.
    Mainous EG, Boyne PJ, Hart GB (1973) Elimination of sequestrum and healing of osteoradionecrosis of the mandible after hyperbaric oxygen therapy: report of case. J Oral Surg 31:336–339PubMedGoogle Scholar
  44. 44.
    Assael LA (2004) New foundations in understanding osteonecrosis of the jaws. J Oral Maxillofac Surg 62:125–126CrossRefPubMedGoogle Scholar
  45. 45.
    Al-Nawas B, Duschner H, Grötz KA (2004) Early cellular alterations in bone after radiation therapy and its relation to osteoradionecrosis. J Oral Maxillofac Surg 62:1045CrossRefPubMedGoogle Scholar
  46. 46.
    Delanian S, Depondt J, Lefaix JL (2005) Major healing of refractory mandible osteoradionecrosis after treatment combining pentoxifylline and tocopherol: a phase II trial. Head Neck 27:114–123CrossRefPubMedGoogle Scholar
  47. 47.
    Store G, Eribe ERK, Olsen I (2005) DNA–DNA hybridization demonstrates multiple bacteria in osteoradionecrosis. Int J Oral Maxillofac Surg 34:193–196CrossRefPubMedGoogle Scholar
  48. 48.
    Delanian S, Lefaix JL (2004) The radiation-induced fibroatrophic process: therapeutic perspective via the antioxidant pathway. Radiother Oncol 73:119–131CrossRefPubMedGoogle Scholar
  49. 49.
    Vozenin-Brotons MC, Milliat F, Sabourin JC, de Gouville AC, François A, Lasser P, Morice P, Haie-Meder C, Lusinchi A, Antoun S, Bourhis J, Mathé D, Girinsky T, Aiqueperse J (2003) Fibrogenic signals in patients with radiation enteritis are associated with increased connective tissue growth factor expression. Int J Radiat Oncol Biol Phys 56:561–572CrossRefPubMedGoogle Scholar
  50. 50.
    Dambrain R (1993) The pathogenesis of osteoradionecrosis. Rev Stomatol Chir Maxillofac 94:140–147PubMedGoogle Scholar
  51. 51.
    Delanian S, Baillet F, Huart J, Lefaix JL, Maulard C, Housset M (1994) Successful treatment of radiation-induced fibrosis using liposomal Cu/Zn superoxide dismutase: clinical trial. Radiother Oncol 32:12–20CrossRefPubMedGoogle Scholar
  52. 52.
    Riley P (1994) Free radicals in biology: oxidative stress and the effects of ionizing radiation. Int J Radiat Biol 65:27–33CrossRefPubMedGoogle Scholar
  53. 53.
    Scully C, Epstein JB (1996) Oral health care for the cancer patient. Eur J Cancer B Oral Oncol 32B:281–292CrossRefPubMedGoogle Scholar
  54. 54.
    Meghji S (1992) Bone remodelling. Br Dent J 172:235–242PubMedGoogle Scholar
  55. 55.
    Jones SJ, Boyde A, Ali NN (1984) The resorption of biological and non biological substrates by cultured avian and mammalian osteoclasts. J Anat Embriol 170:247–256CrossRefGoogle Scholar
  56. 56.
    Beumer J 3rd, Curtis T, Harrison RE (1979) Radiation therapy of the oral cavity: sequelae and management, part 1. Head Neck Surg 1:301–312CrossRefPubMedGoogle Scholar
  57. 57.
    Store G, Boysen M (2000) Mandibular osteoradionecrosis: clinical behaviour and diagnostic aspects. Clin Otolaryngol Allied Sci 25:378–384CrossRefPubMedGoogle Scholar
  58. 58.
    Epstein JB, Rea G, Wong FLW, Spinelli J, Stevenson-Moore P (1987) Osteonecrosis: study of the relationship of dental extractions in patients receiving radiotherapy. Head Neck Surg 10:48–54CrossRefPubMedGoogle Scholar
  59. 59.
    Ardran G (1951) Bone destruction not demonstrable by radiography. Br J Radiol 24:107–109CrossRefPubMedGoogle Scholar
  60. 60.
    Fujita M, Harada K, Masaki N, Shimizutani K, Kim SW, Fujita N, Sakurai K, Fuchihata H, Inoue T, Kozuka T (1991) MR imaging of osteoradionecrosis of the mandible following radiotherapy for head and neck cancers. Nippon Acta Radiologic 51:892–900Google Scholar
  61. 61.
    Minn H, Aitasalo K, Happonen R-P (1993) Detection of cancer recurrence in irradiated mandible using positron emission tomography. Eur Arch Oto Rhin Laryngol 250:312–315Google Scholar
  62. 62.
    Alexander JM (1976) Radionuclide bone scanning in the diagnosis of lesions of the maxillofacial region. J Oral Surg 34:249–256PubMedGoogle Scholar
  63. 63.
    Weiner R (1990) The role of transferrin and other receptors in the mechanism of GA-67 localization. Nucl Med Biol 17:141–149Google Scholar
  64. 64.
    Matcher SJ, Cooper CE (1994) Absolute quantification of deoxyhaemoglobin concentration in tissue using near infrared spectroscopy. Phys Med Biol 39:1295–1312CrossRefPubMedGoogle Scholar
  65. 65.
    Beumer J 3rd, Brady FA (1978) Dental management of the irradiated patient. Int J Oral Surg 73:208–220CrossRefGoogle Scholar
  66. 66.
    Beumer J 3rd, Harrison R, Sanders B, Kurrasch M (1984) Osteoradionecrosis: predisposing factors and outcomes of therapy. Head Neck Surg 64:819–827CrossRefGoogle Scholar
  67. 67.
    MacDougall RH, Orr JA, Kerr GR, Duncan W (1990) Fast neuron treatment for squamous cell carcinoma of the head and neck: final report of Edinburgh randomised trial. Br Med J 301:1241–1242CrossRefGoogle Scholar
  68. 68.
    Beumer J 3rd, Harrison R, Sanders B, Kurrasch M (1983) Postradiation dental extractions: a review of the literature and a report of 72 episodes. Head Neck Surg 6:581–586CrossRefPubMedGoogle Scholar
  69. 69.
    Tong AC, Leung AC, Cheng JC, Sham J (1999) Incidence of complicated healing and osteoradionecrosis following tooth extraction in patients receiving radiotherapy for treatment of nasopharyngeal carcinoma. Aust Dent J 44:187–194CrossRefPubMedGoogle Scholar
  70. 70.
    Oh HK, Chambers MS, Garden AS, Wong PF, Martin JW (2004) Risk of osteoradionecrosis after extraction of impacted third molars in irradiated head and neck cancer patients. J Oral Maxillofac Surg 62:139–144CrossRefPubMedGoogle Scholar
  71. 71.
    Goldwaser BR, Chuang SK, Kaban LB, August M (2007) Risk factor assessment for the development of osteoradionecrosis. J Oral Maxillofac Surg 65:2311–2316CrossRefPubMedGoogle Scholar
  72. 72.
    Hehr T, Classen J, Welz S, Ganswindt U, Scheithauer H, Koitschev A, Bamberg M, Budach W (2006) Hyperfractionated, accelerated chemoradiation with concurrent mitomycin-C and cisplatin in locally advanced head and neck cancer, a phase I/II study. Radiother Oncol 80:33–38CrossRefPubMedGoogle Scholar
  73. 73.
    Studer G, Studer SP, Zwahlen RA, Huquenin P, Grätz KW, Lütolf UM, Glanzmann C (2006) Osteoradionecrosis of the mandible: minimized risk profile following intensity-modulated radiation therapy (IMRT). Strahlenther Onkol 182:283–288CrossRefPubMedGoogle Scholar
  74. 74.
    Johnson RP (1997) Discussion: osteoradionecrosis of the jaws: a retrospective study of the background factors and treatment in 104 cases. J Oral Maxillofac Surg 556:545–546CrossRefGoogle Scholar
  75. 75.
    Pigott KH, Dische S, Saunders MI (1993) The long-term outcome after radical radiotherapy for advanced head and neck cancer. Clin Oncol 5:343–349CrossRefGoogle Scholar
  76. 76.
    Koga DH, Salvajoli JV, Alves FA (2008) Dental extractions and radiotherapy in head and neck oncology: review of the literature. Oral Dis 14:40–44PubMedCrossRefGoogle Scholar
  77. 77.
    Sader R, Zimmermann V, Zeilhofer HF, Deppe H, Herzog M, Auberger T et al (1996) Die allikreinaktivität im Speichel als möglicher Prognosefaktor bei der Osteoradionekrose des Unterkiefers. Dtsch Z für Mund-Kiefer Gesichtschirurg 20:285–291Google Scholar
  78. 78.
    Watson WL, Scarborough JE (1938) Osteoradionecrosis in intra-oral cancer. Am J Roentgen 40:524–534Google Scholar
  79. 79.
    Chavez JA, Adkinson CD (2001) Adjunctive hyperbaric oxygen in irradiated patients requiring dental extractions: outcomes and complications. J Oral Maxillofac Surg 59:518–522CrossRefPubMedGoogle Scholar
  80. 80.
    Celik NC, Wei FC, Chen HC, Cheng MH, Huang WC, Tsai FC, Chen YC (2002) Osteoradionecrosis of the mandible after oromandibular cancer surgery. Plast Reconstr Surg 109:1875–1881CrossRefPubMedGoogle Scholar
  81. 81.
    Epstein JB, Stevenson-Moore P (2001) Periodontal disease and periodontal management in patients with cancer. Oral Oncol 37:613–619CrossRefPubMedGoogle Scholar
  82. 82.
    Schiødt M, Hermund NU (2002) Management of oral disease prior to radiation therapy. Support Care Cancer 101:40–43Google Scholar
  83. 83.
    Silverman S, Chierici G (1965) Radiation therapy of oral carcinoma. I. Effects on oral tissues and management of the periodontium. J Periodontol 36:478–484PubMedGoogle Scholar
  84. 84.
    Rohrer MD, Kim Y, Fayos JV (1979) The effect of cobalt-60 irradiation on monkey mandibles. Oral Surg Oral Med Oral Pathol 48:424–440CrossRefPubMedGoogle Scholar
  85. 85.
    Galler C, Epstein JB, Guze KA, Buckles D, Stevenson-Moore P (1992) The development of osteoradionecrosis from sites of periodontal disease activity: report of 3 cases. J Periodontol 63:310–316PubMedGoogle Scholar
  86. 86.
    Eggert JH, Dumbach J, Steinhäuser EW (1985) Zur Etiologie und Therapie der Osteoradionekrose des Unterkiefers. Dtsch Zahnärztl Z 40:2–11PubMedGoogle Scholar
  87. 87.
    Bras J, de Jonge HKT, van Merkensteyn JPR (1990) Osteoradionecrosis of the mandible: pathogenesis. Am J Otolaryngol 11:244–250CrossRefPubMedGoogle Scholar
  88. 88.
    Buchbinder D, St Hilaire H (2006) The use of free tissue transfer in advanced osteoradionecrosis of the mandible. J Oral Maxillofac Surg 64:961–964CrossRefPubMedGoogle Scholar
  89. 89.
    Mounsey RA, Brown DH, O'Dwyer TP, Gullane PJ, Koch GH (1993) Role of hyperbaric oxygen therapy in the management of mandibular osteoradionecrosis. Laryngoscope 103:605–608CrossRefPubMedGoogle Scholar
  90. 90.
    Rankow RM, Weissman B (1971) Osteoradionecrosis of the mandible. Annals of Otolaryngology 80:603–611Google Scholar
  91. 91.
    Marx RE (1994) Radiation injury to tissue. In: Kindwall EP (ed) Hyperbaric medicine practice. Best, Flagstaff, pp 445–503Google Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Bruno Ramos Chrcanovic
    • 1
  • Peter Reher
    • 2
    • 3
  • Alexandre Andrade Sousa
    • 4
    • 5
  • Malcolm Harris
    • 6
  1. 1.Belo HorizonteBrazil
  2. 2.School of Dentistry and Oral Health, Gold Coast CampusGriffith UniversitySouthportAustralia
  3. 3.Department of Oral and Maxillofacial Surgery, School of DentistryPontifícia Universidade Católica de Minas GeraisBelo HorizonteBrazil
  4. 4.Hospital das Clínicas UFMG, Instituto Alfa de GastroenterologiaHead and Neck SurgeryBelo HorizonteBrazil
  5. 5.Belo HorizonteBrazil
  6. 6.Oral and Maxillofacial Surgery, Eastman Dental InstituteUniversity College LondonLondonUK

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