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Year : 2014  |  Volume : 1  |  Issue : 1  |  Page : 42-49

Maxillofacial osteoradionecrosis

Department of Oral and Maxillofacial Surgery, DPU, Dr. D. Y. Patil Dental College and Hospital, Pimpri, Pune, Maharashtra, India

Date of Web Publication31-Jan-2014

Correspondence Address:
Amit T Suryawanshi
Department of Oral and Maxillofacial Surgery, DPU, Dr. D. Y. Patil Dental College and Hospital, Pimpri, Pune, Maharashtra
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/2348-3172.126171

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Osteoradionecrosis is a severe and delayed radiation-induced injury, characterized by bone tissue necrosis and failure to heal. Cases of osteoradionecrosis present to the clinician with features of pain, drainage, and fistulation of the mucosa or skin related to exposed bone in the previously irradiated area. The tumour size and location, radiation dose, occurrence of local trauma, dental extractions, infection, immune defects, and malnutrition are predisposing factors. A better understanding of risk factors leading to the development osteoradionecrosis and of the underlying pathophysiology may improve the ability of the clinician to prevent the occurrence and help improve the prognosis of this complication. Although the frequency of osteoradionecrosis has declined since the introduction of newer methods of radiotherapy, this review focuses on the etiology, pathophysiology, clinical features, radiological features, diagnosis, and treatment modalities including the newer modalities.

Keywords: Jaws, management, osteoradionecrosis, physiopathology, risk factors

How to cite this article:
Suryawanshi AT, Kumar SS, Dolas R S, Khindria R, Pawar V, Singh M. Maxillofacial osteoradionecrosis. J Dent Res Rev 2014;1:42-9

How to cite this URL:
Suryawanshi AT, Kumar SS, Dolas R S, Khindria R, Pawar V, Singh M. Maxillofacial osteoradionecrosis. J Dent Res Rev [serial online] 2014 [cited 2023 Mar 30];1:42-9. Available from: https://www.jdrr.org/text.asp?2014/1/1/42/126171

  Introduction Top

The global incidence of oral cancer is 5,00,000 cases per year with mortality of 2,70,000 cases per year. The incidence of oral cancer in India is 40% among all cancers and about 1,00,000 patients suffer from oral cancer in any year. Oral cancer is responsible for 7% of all cancer deaths in males and 3% in females. [1]

The recent protocol for management of oral cancer includes multimodal therapy, such as surgery with radiotherapy and/or chemotherapy. Radiation therapy is one of the major treatment modalities for the management of oral malignancies. Like with any treatment modality, even radiation therapy is associated with various complications. A long-term side effect of radiotherapy that is also the most serious is osteoradionecrosis. [2],[3] Literature reveals many terminologies to represent the same disease, such as radiation osteitis, radio-osteonecrosis, radiation osteomyelitis, osteomyelitis of irradiated bone, osteonecrosis, radio-osteomyelitis, septic osteoradionecrosis, and post-radiotherapy osteonecrosis. [4]

This review focuses on the general information on maxillofacial osteoradionecrosis for general practitioners.

  Historical perspective Top

In 1922, Regaud published the first report about osteoradionecrosis of jaws after radiotherapy. [4] In 1926, further description of osteoradionecrosis was given by Ewing under the name Radiation Osteitis. [5] In 1970, Meyer classified osteoradionecrosis as one special type of osteomyelitis. In 1975, Mainous advocated the use of hyperbaric oxygen therapy (HBO) for late radiation tissue injury. In 1983, Robert Marx proposed the hypoxic, hypocellular, and hypovascular theory as a new way of understanding the pathophysiology of osteoradionecrosis. In 1992, Harris introduced the use of Ultrasound as one of the modes to treat osteoradionecrosis. [6] In 1998, Marx gave the 30/10 protocol that was employed in the treatment of established osteoradionecrosis. In 2004, Delanian and Lefaix put forward a new theory named radiation-induced fibrosis that accounts for the damage to normal tissues, including bone after radiotherapy. [7]


In literature, osteoradionecrosis has been defined in many ways [Table 1]. [8],[9] However, the authors feel that the definition given by Wong, Wood, and McLean (1997) [8] is the most appropriate and complete:
Table 1: Definitions of osteoradionecrosis

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"A slow-healing radiation-induced ischemic necrosis of bone with associated soft tissue necrosis of variable extent occurring in the absence of local primary tumour necrosis, recurrence, or metastatic disease that may or may not:

  1. Be superinfected (and accompanied by fistulation or cellulitis)
  2. End in pathologic fracture
  3. Resolve without surgery, hyperbaric oxygen therapy or both."

Classification and staging systems

There have been several staging or scoring systems that have been proposed. These systems are based on response to HBO therapy, degree of bone damage, clinical-radiological findings, length of bone exposure through the overlying skin or mucosa, and treatment needed [Table 2] and [Table 3]. [8],[9],[10],[11],[12],[13],[14],[15]
Table 2: Classification systems of osteoradionecrosis

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Table 3: Classification of osteoradionecrosis

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Risk factors

The existing articles in literature fail to give an exact etiology for osteoradionecrosis. The etiology of osteoradionecrosis is considered to be multifactorial. These factors may increase the risk of the patient for development of osteoradionecrosis. The factors are classified into four groups as shown in [Table 4]. [15],[16],[17],[18]
Table 4: Risk factors of osteoradionecrosis

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The pathophysiology of osteoradionecrosis is not very clear till date. However, literature reveals three theories that have been put forward since 1970, as mentioned in the following:

  • Meyer's Radiation, trauma and infection theory [19]
  • Marx's Hypoxic, hypocellular, and hypovascular theory [20]
  • Delanian's Radiation-induced fibroatrophic theory. [21]

Meyer's radiation, trauma, and infection theory

In 1970, in an excellent monograph on infectious disease of the jaws, Meyer defined the classic triad of osteoradionecrosis as radiation, trauma, and infection [Figure 1]. [19] Meyer portrayed that the trauma provided the portal for invasion by oral microbiological flora into the underlying irradiated bone. Meyer's theory lasted for a decade and became the foundation for the popular use of antibiotics with surgery to treat osteoradionecrosis. [19]
Figure 1: Meyer's radiation, trauma and infection theory

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Marx's hypoxic, hypocellular, and hypovascular theory

Robert E Marx in his landmark study noted that there was no injury before the onset of osteoradionecrosis in 35% of his cases. He also found that composite irradiated tissues were more hypoxic than those that had not been irradiated [Figure 2]. [20] Marx concluded that "Osteoradionecrosis is not a primary infection of irradiated bone, but a complex metabolic and homeostatic deficiency of tissue that is created by radiation-induced cellular injury; micro-organisms play only a contaminating role in osteoradionecrosis; and trauma may or may not be an initiating factor." [20]
Figure 2: Marx's hypoxic-hypocellular-hypovascular theory

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Delanian's radiation-induced fibroatrophic theory

Radiation-induced fibrosis is a new theory that accounts for the damage to normal tissues, including bone, after radiotherapy. It was introduced in 2004 when recent advances in cellular and molecular biology explained the progression of microscopically observed osteoradionecrosis [Figure 3]. [21] Three distinct phases are seen:
Figure 3: Delanian's radiation-induced fibroatrophic theory

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  • The initial prefibrotic phase in which changes in endothelial cells predominate together with the acute inflammatory response
  • The constitutive organised phase in which abnormal fibroblastic activity predominates, and there is disorganisation of the extracellular matrix
  • The late fibroatrophic phase, when attempted tissue remodelling occurs with the formation of fragile healed tissues that carry a serious inherent risk of late reactivated inflammation in the event of local injury. [10]


Osteoradionecrosis was earlier attributed to secondary infection in the traumatized irradiated tissue following the nonhealing wounds and exposed bone. However, this was challenged by Robert Marx in 1983. [20] The detailed description of various microorganisms detected in osteoradionecrosis is given in [Table 5]. [8],[22],[23],[24],[25],[26],[27] Further studies on bacterial flora associated with osteoradionecrosis are required, which may contribute to a more precise use of antibiotics.
Table 5: Microbiology of osteoradionecrosis

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Clinical features

The incidence of osteoradionecrosis varies from 0.95% to 35% as shown in [Table 6]. [28],[29],[30],[31],[32],[33],[34],[35],[36] The patient is usually asymptomatic. Pain and evidence of exposed bone are the most common chief complaints. Trismus, fetor oris, and elevated body temperature are usually present during the initial period although acute infection is usually not present. Other clinical features of osteoradionecrosis are swelling, nonresolving painful mucosal ulcer, dysgeusia, dysguesia, xerostomia, food impaction, malocclusion, telangiectasia, orocutaneous fistula, and missing hair follicles. The tissues surrounding the bone may be indurated. Surface texture changes such as cutaneous flaking and keratinisation may be present. Surface colour changes may also be seen. Pathologic fracture of the jaws may be evident in severe cases. Rarely, Deep cellulitis of face and neck may be present. [28]
Table 6: Incidence of osteoradionecrosis

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Radiological features

The presence of osteoradionecrosis cannot always be diagnosed radiographically and often clinically obvious signs of exposed necrotic may not be accompanied by significant radiologic changes.

Plain radiography shows an ill-defined cortical destruction without sequestration. The periphery may be ill-defined as in osteomyelitis. Bone pattern can be granular. Scattered regions of radiolucency may be seen, with or without central sequestra. The most common effect on surrounding bone is stimulation of sclerosis.

Computed tomography plays an important role in diagnosis of osteoradionecrosis since it is hard tissue lesion. Anterior-posterior and supero-inferior extent of the osteolytic lesion is best judged with CT scans comparatively. Hence, from diagnostic purpose to the surgical intervention, CT is recommended as far as osteoradionecrosis is concerned. [29]

MRI reveals development of new heterogeneous signal within the marrow of an irradiated area (intermediate or low T1 signal, intermediate or high T2 signal). Adjacent muscles may appear oedematous and show intense enhancement, which can be difficult to differentiate from recurrent tumour if bone changes are not visible on CT. [28]

PET scan is helpful to differentiate between osteoradionecrosis and recurrent tumour. [28]

Radionuclide bone scanning with technetium methylene diphosphonate (99mTc-MDP) can identify pathophysiologic changes in bone earlier than conventional radiography because scan changes reflect osteoblastic activity and good blood flow. [28]

Infrared spectroscopy is a noninvasive method. This shows a reduction of the amount of deoxygenated haemoglobin at sites of osteoradionecrosis, confirming that it is a hypovascular and hypoxic tissue with decreased metabolic rate. [28]

Histologic features

The histological findings noted by Marx showed endothelial death, hyalinisation, and thrombosis of vessels with a fibrotic periosteum. [25]

Diagnostic criteria

In 1997, Wong, Wood, and McLean have given diagnostic criteria for osteoradionecrosis that seem to be agreed by the majority of the authors:

  • The affected site should have been previously irradiated
  • There should be absence of recurrent tumour on the affected site
  • Mucosal breakdown or failure to heal should occur, resulting in bone exposure
  • The overlying bone should be 'dead', usually due to a hypoxic necrosis
  • Cellulitis, fistulation, or pathologic fracture need not be present to be considered as osteoradionecrosis. [30]

Osteoradionecrosis usually develops after 3-6 months having bone exposure at least for 3 months. [30]


The management of osteoradionecrosis is divided into two methods.

  1. Preventive management
  2. Therapeutic management.

Preventive management

The prevention of osteoradionecrosis begins as early as the head and neck malignancy is diagnosed. The patient should be reviewed by the multidisciplinary team consisting of a dentist/oral and maxillofacial surgeon. The measures taken to prevent osteoradionecrosis, as per Donoff's protocol, are mentioned in [Table 7]. [37] The precautions that are to be taken during dental extraction are summarized in [Table 8]. [38]
Table 7: Preventive management of osteoradionecrosis

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Table 8: Precautions to be taken for dental extractions in osteoradionecrosis

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Therapeutic management

The nonsurgical and surgical management with a note on recent medications are summarized in [Table 9]. [39]
Table 9: Therapeutic management of osteoradionecrosis

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  Conclusion Top

Osteoradionecrosis can be a cruel blow to patients and their families who have been enduring radiotherapy for the treatment of cancer. Prevention of osteoradionecrosis by regular follow-up and early diagnosis should be the goal of every health care professional managing head and neck cancer patients. Improved radiotherapy protocols, multidisciplinary preventive care and reconstructive surgery can help to improve the quality of life of patients suffering from osteoradionecrosis.

  References Top

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2.Peterson DE, Doerr W, Hovan A. Osteoradionecrosis in cancer patients: The evidence base for treatment-dependent frequency, current management strategies, and future studies. Support Care Cancer 2010;18:1089-98.   Back to cited text no. 2
3.Silverman S Jr: Complications of treatment. In: Silverman S Jr, ed.: Oral Cancer. 5 th ed. Hamilton, Canada: BC Decker Inc, 2003, pp 113-28.   Back to cited text no. 3
4.Lyons A, Ghazali N. osteoradionecrosis of the jaws: current understanding of its pathophysiology and treatment. Br J Oral Maxillofac Surg 2008;46:653-60.   Back to cited text no. 4
5.Murray CG, Herson J, Daly TE, Zimmerman S 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 1980b;6:549-53.  Back to cited text no. 5
6.Kluth EV, Jain PR, Stuchell RN, Frich JC Jr. A study of factors contributing to the development of osteoradionecrosis of the jaws. J Prosthet Dent 1988;59:194-201.  Back to cited text no. 6
7.Granström G, Fagerberg-Mohlin B, Fomander J. Aspects on the management of patients with osteoradionecrosis after therapy of head and neck cancer. XVIIIth Annual Meeting of EUBS, 1992a. pp. 163-9.  Back to cited text no. 7
8.Marx RE. A new concept in the treatment of osteoradionecrosis. J Oral Maxillofac Surg 1983;41:351.  Back to cited text no. 8
9.Reher P. Evidence for the use of ultrasound therapy for the management of mandibular osteoradionecrosis. Doctorate Thesis, University of London; 1999.  Back to cited text no. 9
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13.Meghji S. Bone remodelling. Br Dent J 1992;172:235-42.  Back to cited text no. 13
14.Van Merkesteyn JP, Bakker DJ, Borgmeijer-Hoelen AM. Hyperbaric oxygen treatment of osteoradionecrosis of the mandible: experience in 29 patients. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1995;80:12-6.  Back to cited text no. 14
15.Regaud C (1922a) Sur la necrose des os attenté par un processus cancereux et traites par les radiaions. Compt Rend Soc Biol 1992a;87:427.  Back to cited text no. 15
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19.Meyer I. Infectious diseases of the jaws. J Oral Surg 1970;28:17-26.  Back to cited text no. 19
20.Marx RE. Osteoradionecrosis: A new concept of its pathophysiology. J Oral Maxillofac Surg 1983a;41:283-8.  Back to cited text no. 20
21.Delanian S, Lefaix JL. The radiation-induced fibroatrophic process: Therapeutic perspective via thantioxidant pathway. Radiother Oncol 2004;73:119-31.  Back to cited text no. 21
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23.Hansen T, Kunkel M, Weber A, James Kirkpatrick C.Osteonecrosis of the jaws in patients treated with bisphosphonates - histomorphologic analysis in comparison with infected osteoradionecrosis. J Oral Pathol Med 2006 Mar;35:155-60.  Back to cited text no. 23
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28.Chrcanovic BR, Reher P, Sousa AA, Harris M. Osteoradionecrosis of the jaws - a current overview - Part 1. Physiopathology and risk and predisposing factors. J Oral Maxillofac Surg 2010;14:3-16.  Back to cited text no. 28
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30.Wang, Schaaf, Chen. 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 1974;61:1123-31.  Back to cited text no. 30
31.Bedwinck, Hutchinson IL. Complications of radiotherapy in the head and neck: an orofacial surgeon's view. In: Tobias JS, Thomas PRM (eds) Current radiation oncology. Arnold, London, 1976. pp 144-77.   Back to cited text no. 31
32.Thorn JJ, Hansen HS, Specht L, Bastholt L. Osteoradionecrosis of the jaws: Clinical characteristics and relation to the field of irradiation. J Oral Maxillofac Surg 2000;58:1088-93.  Back to cited text no. 32
33.Hutchison IL, Cope M, Delpy DT, Richardson CE, Harris M. The investigation of osteoradionecrosis of the mandible by near infrared spectroscopy. Br J Oral Maxillofac Surg 1995;28:150-4.  Back to cited text no. 33
34.van der Meij, Beumer J 3rd, Harrison R, Sanders B, Kurrasch M. Preradiation dental extractions and the incidence of bone necrosis. Head Neck Surg 1997;5:514-21.   Back to cited text no. 34
35.Harris M. The conservative management of osteoradionecrosis of the mandible with ultrasound therapy. Br J Oral Maxillofac Surg 1997;30:313-8.   Back to cited text no. 35
36.Morrish RB Jr, Chan E, Silverman S Jr, Meyer J, Fu KK, Greenspan D. Osteonecrosis in patients irradiated for head and neck carcinoma. Cancer 1981;47:1980-3.   Back to cited text no. 36
37.Tong AC, Leung AC, Cheng JC, Sham J. Incidence of complicated healing and osteoradionecrosis following tooth extraction in patients receiving radiotherapy for treatment of nasopharyngeal carcinoma. Aust Dent J 1999;44:187-94.  Back to cited text no. 37
38.Ramli R, Ngeow WC, Rahman RA, Chai WL. Managing complications of radiation therapy in head and neck cancer patients: Part IV. Management of osteoradionecrosis. Singapore Dent J 2006;28:11-5.   Back to cited text no. 38
39.Vanderpuye V, Goldson A. Osteoradionecrosis of the mandible. J Natl Med Assoc 2000;92:579-84.  Back to cited text no. 39


  [Figure 1], [Figure 2], [Figure 3]

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8], [Table 9]

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