Osteoradionecrosis of the jaws: de finition, epidemiology, staging and clinical and radiological findings. A concise review
Aristeidis Chronopoulos
1, Theodora Zarra
2, Michael Ehrenfeld
1and Sven Otto
11Department of Oral and Maxillofacial Surgery, Ludwig-Maximilians-University of Munich, Munich, Germany;2Department of Endodontology, Dental School, Aristotle University of Thessaloniki, Thessaloniki, Greece.
Osteoradionecrosis (ORN) of the jaws is a pernicious complication of radiation therapy for head and neck tumours. This article aims to provide an update on data related to the definition, epidemiology, staging, and clinical and radiological findings of ORN of the jaws. Using certain keywords, an electronic search was conducted spanning the period from Jan- uary 1922 to April 2014 to identify the available related investigations. Pooled data were then analysed. ORN is described as exposed irradiated bone that fails to heal over a period of 3 months without evidence of persisting or recur- rent tumour. The prevalence of ORN varies in the literature. Several staging or scoring systems of ORN have been pro- posed. Clinical findings include ulceration or necrosis of the mucosa with exposure of necrotic bone. Radiological findings are not evident in the early stages of ORN. Furthermore ORN may not be apparent in imaging even when the disease is advanced. Taking into account the severity of ORN and the difficulties in diagnosing it early and accurately, the clinician should be aware of this complex entity in order to prevent its appearance or the development of more sev- ere complications.
Key words: Clinical findings, epidemiology, jaw, osteoradionecrosis, radiation therapy
INTRODUCTION
Osteoradionecrosis (ORN) is a pernicious complica- tion of radiotherapy in head and neck cancer. It was first described by Regaud
1in 1922 and is still a clini- cal challenge. According to the most recent literature, ORN of the jaws is defined as exposed irradiated bone that fails to heal over a period of 3 months without any evidence of persisting or recurrent tumour
2–4. The mechanism of pathogenesis is still under investigation. However, the most frequently reported reason is radiation arteritis. Radiation arteri- tis leads to the development of a hypocellular, hypo- vascular and hypoxic environment, which results in a pathological outcome
5.
The purpose of this paper is to explore the current theories on the definition and staging systems of ORN of the jaws. In addition, the epidemiology and the clin- ical and radiological findings of ORN of the jaws, are critically reviewed based on the available literature.
Finally, critical issues and considerations are discussed and pathways for future research are proposed.
METHODS
An electronic search of three databases (PubMed, Sco- pus and the Cochrane Library) was performed using the keywords ‘osteoradionecrosis’, ‘radiotherapy’, ‘os- teonecrosis’, ‘osteoradionecrosis’ and ‘mandible’, ‘os- teoradionecrosis’ and ‘jaw’, ‘osteoradionecrosis’ and
‘radiotherapy’, ‘osteoradionecrosis’ and ‘staging’, ‘os- teoradionecrosis’ and ‘clinical findings’, ‘osteora- dionecrosis’ and ‘radiological findings’, to identify literature published in English and German between January 1922 and April 2014 (Table 1). Abstracts were obtained for all the titles identified during the electronic search. Two reviewers (A.C. and T.Z.) independently screened titles and abstracts to elimi- nate articles that were completely off-topic. No other exclusion criteria were utilised. Following exclusion of
doi: 10.1111/idj.12318
the articles irrelevant to the topic and the removal of duplicating papers, the remaining articles were care- fully reviewed and their findings were critically anal- ysed.
RESULTS Definition
Several attempts have been made in order to define ORN. Ewing
6was the first to use the term ‘radiation osteitis’ to describe changes in bone after radiother- apy. In the following years, several terms were used to name these changes in bone, such as radiation osteitis, ORN and avascular bone necrosis
7. In 1974, Guttenberg
8proposed the term ‘septic ORN of the mandible’ to describe the stage of necrosis when irra- diated bone becomes superficially infected, ending up with a high risk of involvement of deeper structures.
In 1983, Marx
5defined ORN as ‘an area >1 cm of exposed bone in a field of irradiation that failed to show any evidence of healing for at least 6 months’.
Marx also reported that superficial contamination and no interstitial infection was present. In 1987, Marx and Johnson
3suggested the definition of ORN as: ‘The exposure of nonviable bone which fails to heal without intervention’. Epstein et al.
9defined ORN as ‘an ulcer- ation or necrosis of the mucous membrane, with expo- sure of necrotic bone for more than 3 months’.
Widmark et al.
10described ORN as ‘a non-healing mucosal or cutaneous ulcer with denuded bone, last- ing for more than 3 months’. Both Widmark and Marx excluded from their definition conditions with necrotic bone for which the mucosa and skin were intact. Store and Boysen
11reported that exposed bone is sporadically present; radiological findings are evi- dent in all cases of ORN. In 1997, Wong et al.
12defined ORN as ‘a slow-healing radiation-induced ischemic necrosis of variable extent occurring in the absence of local primary tumor necrosis, recurrence or metastatic disease’.
According to the literature published in the last 15 years, ORN of the jaws is defined as exposed irra- diated bone that fails to heal over a period of
3 months without evidence of persisting or recurrent tumour
2–4,13–15. At the time of diagnosis, the necrosis might involve the bone superficially or deeply. It might be a process that progresses slowly or an active progressive state that can lead to a pathological frac- ture
16–18.
Epidemiology
The prevalence of ORN varies widely in the literature (Table 2)
16,17,19–48and ranges from 0.4% to 56%
19,20,22,24,30–33,36,49. ORN usually affects patients over 55 years of age
14,36,50,51. However, the most fre- quently reported prevalence rate is 5–15%
7,36,52. In up to 20% of patients with persistent ORN which does not respond to aggressive treatment, bone dam- age is reported to be caused by recurrent disease or a second primary tumour
16,53.
Staging
Several staging or scoring systems of ORN have been proposed (Table 3)
2,11,32,54–59. These systems are based on response to hyperbaric oxygen (HBO) ther- apy, degree of bone damage, clinical–radiological find- ings, duration of bone exposure and treatment required.
Coffin
55divided cases of ORN into two groups:
minor and major. Morton and Simpson
56subdivided ORN into three groups – ‘minor’, ‘moderate’ and
‘major’. In 1983, Marx
2proposed a three-stage sys- tem for ORN. According to his protocol, patients are categorised as Stage I if they exhibit exposed bone in a field of radiation that has failed to heal for at least 6 months and do not have a pathological fracture, cutaneous fistula or osteolysis to the inferior border.
In Stage I, all patients receive 30 sessions of HBO at 2.4 atmospheres absolute for 90 minutes at depth.
Patients who respond to HBO alone (Stage I respon- der) demonstrate a softening of the radiated tissues and spontaneous sequestration of exposed bone with formation of granulation tissue. Each Stage I respon- der undergoes an additional 10 HBO sessions and then the tissues are allowed to heal completely. Stage II patients are those who do not respond to the 30 sessions of HBO. This group is characterised by a large amount of non-viable bone that makes resorp- tion and sequestration from HBO-induced angiogene- sis alone impossible. Consequently, careful surgical debridement is required. Stage II patients undergo transoral resection with limited soft-tissue reflection.
In particular, surgical treatment includes extraction of involved dentition and a non-continuity bone resec- tion to clinically bleeding bone. Wound flaps are closed primarily and the patient is given 10 postsurgi- cal sessions of HBO. Tissues that heal without Table 1 Example of electronic search strategy in
PubMed
Search strategy Results
Osteoradionecrosis 1,980
Radiotherapy 286,652
Osteonecrosis 15,087
Osteoradionecrosis and mandible 636
Osteoradionecrosis and jaw 738
Osteoradionecrosis and radiotherapy 1,332
Osteoradionecrosis and staging 76
Osteoradionecrosis and clinical findings 177 Osteoradionecrosis and radiological findings 30
complication are treated with a prosthesis when required, similarly to Stage I responders. Stage III patients are characterised by having a large quantity of non-viable bone and/or soft tissue unable to be managed by HBO-induced angiogenesis alone or HBO combined with local sequestrectomy. In addition to 30 presurgical HBO treatments, each Stage III patient requires a continuity resection, stabilisation and 10 postsurgical sessions of HBO, and are sched- uled for later (usually 3 months) reconstruction (Stage III-R). Stage III patients are therefore those who fail to respond to Stage I and Stage II treatment and those who initially present with a pathological fracture, cutaneous fistula or osteolysis to the inferior bor- der
2,60.
Epstein et al.
32suggested a new staging system for ORN with three tiers based on clinical findings.
Glanzmann and Gratz
57proposed a system based on the duration of bone exposure and necessity of treat- ment. Clayman
54introduced a classification of ORN related to the integrity of the overlying mucosa.
According to this classification, type I includes cases of ORN in which bone lysis occurs under intact gin- giva or mucosa. Type II includes more aggressive cases of ORN in which soft tissues break down and
the bone is exposed to saliva, causing secondary con- tamination. This is defined as radiation osteomyelitis.
Type I cases heal with conservative therapy; type II cases do not. In 2000, Store and Boysen
16introduced a new classification of ORN that is based on the pres- ence or absence of clinical and radiological signs.
The most recently designed staging systems are these of Schwartz and Kagan
58and Notani et al.
59The system of Schwartz and Kagan
58is based on clin- ical and radiological findings. Notani et al.
59divided the cases into three grades based on the extent of the ORN lesion. Grade I is defined as ORN confined to the alveolar bone. Grade II is defined as ORN limited to the alveolar bone and/or the mandible above the level of the mandibular alveolar canal. In Grade III the ORN extends to the mandible under the level of the mandibular alveolar canal and a skin fistula and/
or a pathological fracture is present.
Clinical findings
Clinical signs and symptoms of ORN include ulcera- tion or necrosis of the mucosa with exposure of necrotic bone for longer than 3 months, pain, trismus and suppuration in the area (Figure 1a)
32,61–64. Table 2 Incidence of osteoradionecrosis (ORN) in different studies
Study Year Period Total number
of patients
Prevalence of ORN (%)
Mean irradiation dose
Watson and Scarborough20 1938 1930–1937 1,819 12.9
Martin and Sugarbaker21 1940 103 25
MacComb22 1962 1952–1959 251 37.1
MacDougall et al.23 1963 364 5
Grant and Fletcher24 1966 1954–1962 176 37.5 10,000*
Rahn and Drane25 1967 1960–1962 120 44.2
Rankow and Weissman26 1971 176 6.3 5,000*
Wang27 1972 262 5.8
Cheng and Wang28 1974 76 17.1 2,500*
Marciani and Plezia29 1974 220 10.5
Bedwinek et al.30 1976 1966–1971 381 14.2 7,000*
Murray et al.31 1980 1966–1975 653 21.1 5,000*
Morrish et al.19 1981 1971–1977 100 22 7,500*
Epstein et al.32 1987 1977–1984 1,000 2.7 6,000*
Withers et al.33 1995 1976–1985 676 4.7 65†
Turner et al.34 1996 1980–1987 333 5.9 55†
Thorn et al.16 2000 1992–1998 80 74 60†
Storey et al.35 2001 1965–1995 83 6 60†
Reuther et al.36 2003 1969–1999 830 8.2 60†
Oh et al.37 2004 1989–2004 81 4.9 52.6†
Studer et al.38 2004 1980–1998 268 12.5 60†
Ben-David et al.39 2007 1996–2005 176 0 65†
Jham et al.40 2008 2003–2005 207 5.5 58.9†
Katsura et al.41 2008 1996–2003 39 15 60.7†
Gomez et al.42 2009 2000–2006 35 5 60†
Lee et al.43 2009 1990–2000 198 6.6 60†
Stenson et al.44 2010 1994–2008 27 18.4 62†
Gomez et al.45 2011 2000–2007 168 1.2 67.9†
Monnier et al.17 2011 2000–2007 73 40 66†
Crombie et al.46 2012 2000–2007 54 36 69.7†
Niewald et al.47 2013 1993–2001 99 12 72
Tsai et al.48 2013 2000–2008 402 7.5 70†
*Radiation dose given in rads.
†Radiation dose given in Grays (Gy).
Neurological symptoms, such as pain, dysaesthesia or anaesthesia, as well as fetor oris, dysgeusia and food impaction in the area, are also usually present. Expo- sure of rough and irregular bone can result in physical irritation of adjacent tissues. Progression of ORN may lead to pathological fractures, intra-oral or extra-oral fistulae and local or systemic infection. Difficulties in mouth opening, mastication and speech frequently arise
9,65–67. In patients treated with external beam
radiation therapy (EBRT), osseous alterations usually appear in the body of the mandible (premolar and molar regions), whereas in those managed with brachytherapy, the lingual or buccal surfaces are affected
68.
The diagnosis of septic ORN appears to be easier.
Marked pain is the primary symptom. A thorough clinical examination will reveal intra- or extra-oral draining fistulae, ulcerations of the mucous Table 3 Classification systems of osteoradionecrosis (ORN)
Study Stages Description of stages Basis of stage
Coffin55 2 Minor A series of small sequestra which separate spontaneously after varying periods of weeks or months. These areas cannot be demonstrated radiologically
Clinical and radiological findings
Major Necrosis occurring to an extent that involves the entire thickness of the jaw, and a pathological fracture is inevitable. This form can be obviously seen radiologically
Marx2 3 Stage I Exposed alveolar bone without pathologic fracture, which responds to HBO therapy
Response to HBO therapy Stage II Disease does not respond to HBO therapy, and requires sequestrectomy and
saucerisation
Stage III Full-thickness bone damage or pathological fracture, usually requires complete resection and reconstruction with free tissue
Morton and Simpson56
3 Minor Ulceration with exposed bone and a history of bony spicules that healed spontaneously over a period of months
Clinical findings and response to treatment Moderate Exposed bone and small sequestra limited in nature and healing spontaneously
with conservative treatment within 6–12 months
Major Large areas of exposed bone, with formation of large sequestra, possible fracture and sinus formation. These cases often require radical treatment Epstein
et al.32
3 Stage I Ia Ib
Resolved, healed No pathological fracture Pathological fracture
Disease progression
Stage II IIa IIb
Chronic, persistent non-progressive No pathological fracture Pathological fracture Stage III
IIIa IIIb
Active, progressive No pathological fracture Pathological fracture Glanzmann
and Gratz57
5 Stage 1 Bone exposure without signs of infection and persisting for at least 3 months Duration of bone exposure and treatment necessity
Stage 2 Bone exposure with signs of infection or sequester and without the signs of Grades 3–5
Stage 3 Bone necrosis treated with mandibular resection with a satisfactory result Stage 4 Bone necrosis with persisting problems despite mandibular resection Stage 5 Death from ORN
Clayman54 2 Type I Bone lysis occurs under intact gingiva or mucosa Clinical findings Type II A more aggressive type in which soft tissues break down, exposing the bone to
saliva, and causing secondary contamination Store and
Boysen11
4 Stage 0 Mucosal defects only Combination of
radiological and clinical parameters
Stage 1 Radiological evidence of necrotic bone with intact mucosa Stage 2 Positive radiological findings with denuded bone intra-orally
Stage 3 Clinically exposed radionecrotic bone, verified by imaging techniques, along with skin fistulae and infection
Schwartz and Kagan58
3 Stage I Minimal soft-tissue ulceration and limited exposed cortical bone. Patients are treated with conservative management
Imaging and clinical findings
Stage II IIa IIb
Localised involvement of the mandibular cortex and underlying medullary bone
Minimal soft tissue ulceration
Presence of an oro-cutaneous fistula and mild soft-tissue necrosis Stage III Full-thickness involvement of the bone, including the inferior border.
Pathological fractures may also be present Notani
et al.59
3 Stage I ORN confined to alveolar bone Clinical findings
Stage II ORN limited to the alveolar bone and/or mandible above the level of the inferior alveolar canal
Stage III ORN involving the mandible below the level of the inferior alveolar canal and/
or skin fistula and/or pathological fracture HBO, hyperbaric oxygen.
membrane, exposed devitalised bone, haemorrhage, cellulitis or pathological fractures. A biopsy is manda- tory for final diagnosis in order to exclude metastatic cancer
8.
Radiological findings
Radiographs, computed tomography (CT) scans, mag- netic resonance imaging (MRI), Doppler ultrasound, nuclear medicine and near-infrared spectroscopy are often indicated in order to detect ORN
18.
ORN is not usually detectable radiographically in early stages
69. Imaging features are not correlated to the severity of ORN
8,23,70,71. The described radio- graphic features range from normal appearance, to localised osteolytic areas, extensive osteolytic areas, sequestra and fracture (Figure 1b). Radioluncies indi- cating post extraction sockets will often remain visible for longer than 12 months (Figure 2a). The most defi- nitive radiographic alterations in early disease are increased radiodensity, as well as a mixed radio- opaque/radiolucent lesion in which radiolucent areas represent bone destruction (Figure 2b)
8.
Orthopantomogram (OPT) is the most frequently used imaging method for the diagnosis of ORN and is usually supplemented with other extra-oral or intra- oral radiographs. In an OPT, ORN is depicted as an undefined radiolucency, without sclerotic demarca- tion, which surrounds necrotic zone. Radiopaque areas can be identified when bone sequestra are formed. In order to be visible in an OPT, a substantial alteration in mineral content and extensive involve- ment of bone is required and this only occurs in later stages of ORN
9. Ardran
72noted that a 30% loss of bone mineral content is necessary before any radio- graphic change can be seen.
CT
73shows osseous abnormalities, such as focal lytic areas, cortical interruptions and loss of the spon- giosa trabeculation on the symptomatic side, fre- quently accompanied by soft-tissue thickening. Such a picture may cause difficulties in differential diagnosis between ORN and recurrent tumour
68. In MRI with gadolinium administration, an abnormal marrow sig- nal, cortical destruction and slight-to-mild irregular enhancement is demonstrated
35,74–76. MRI has the advantage of excellent tissue contrast and high spatial resolution
77.
Bone scintigraphy permits estimation of the exten- sion and location of the lesion. It shows high sensitiv- ity (up to 100%) but low specificity (about 60%) for the diagnosis of ORN
77. Scintigraphy using 99mTc-
(a)(b)
Figure 1. A 69-year-old man presented with pain and a non-healing wound in the left lower jaw. The patient was an active smoker, suffered from pharynx cancer and had received radiotherapy (external beam radio-
therapy with standardfield sizes, conventional fractionation and mean dose 64 Gy) and chemotherapy. Clinically, exposed necrotic bone in the left lower jaw, inflammation, swelling and inferior alveolar nerve hypes- thesia was present (a). The orthopantomogram revealed pathologic frac-
ture of the left lower jaw (b). The patient was diagnosed with osteoradionecrosis of the lower jaw and was scheduled to be treated
surgically.
(a)
(b)
Figure 2. Orhtopantomograms of patients who have received radiother- apy (external beam radiotherapy with standardfield sizes, conventional
fractionation and mean dose 64 Gy) for oropharyngeal cancers. The patients underwent extractions of teeth of the lower jaw after completion
of radiotherapy. The orthopantomogram revealed radiolucencies indicat- ing post extraction sockets, which remained visible for longer than 12 months (a), as well as increased radiodensity with mixed radio-opa-
que/radiolucent lesions, where the radiolucent areas represent bone destruction (b).
marked diphosphonates (99mTc-MDP) allows highly sensitive depiction of mandibular lesions as a result of their altered phosphate metabolism. Pathophysiologi- cal changes in bone can be identified sooner when using 99mTc-MDP than when using conventional radiography because scan changes reflect osteoblastic activity and good blood flow
78. Low spatial resolution and over-projection by soft tissues are the major dis- advantages of the method, which can be overcome with the use of single photon emission computed tomography (SPECT)
77. Finally, positron emission tomography (PET), which is a promising method for pretherapeutic assessment of the spread of squa- mous cell carcinomas, has been advocated as being efficient for differentiating between ORN and tumour recurrence
79.
Discussion and Conclusion
Irradiation of bone is the main prerequisite for devel- opment of ORN. A differential diagnosis is required to exclude recurrence of tumour and bisphosphonate- related osteonecrosis of the jaws. In contrast to the findings of Store and Boysen
11, mucosal breakdown or failure of healing is necessary for the diagnosis of ORN
3,9,10.
The duration of bone exposure is still a matter of controversy. Some authors did not state the period of time that bone was exposed
71. Other authors recom- mended a 2-month period of exposed bone before diagnosis
73,80,81, or even 3
19,82,83to 6
2,5months.
There are also cases in which a late diagnosis is pre- sent. Berger and Symington
84reported two late pre- sentations: one 45 years after radium implant therapy; and the other 38 years after external beam treatment.
A very short waiting period can lead to over-diagno- sis as mucosal radionecrosis can occur without ORN.
Moreover, any surgery and/or extraction usually takes up to 1 month to heal. On the other hand, monitoring a trauma for a longer period (such as 6 months) is con- traindicated; intervention prior to this time is certainly needed. For the aforementioned reasons, in order to diagnose ORN, recent literature
2–4,13–15indicates that bone exposure should be at least 3 months in duration.
The variability in prevalence of ORN can probably be attributed to differences in the study populations observation periods and existence of pretreatment dental assessment and dental management of cohorts.
The literature reports numerous factors which are associated with the risk of ORN development and also affect its prevalence. Total radiation dose, brachytherapy, fractionation, poor oral hygiene, alco- hol, tobacco use, dental extractions, tumour size and location, staging and chemotherapy have been high- lighted
7,19,36,44,47,53,85–90.
The late onset of ORN can be attributed to the late occurrence of oropharyngeal cancers (OPCs) and their complications (mean age of patients over 60 years).
This can be explained by the fact that oral tissues tend to undergo prolonged exposure to potential carcinogens with advancing age. In addition, aging cells may be more susceptible to DNA damage. ORN is predomi- nant in the mandible (the ratio between ORN in the mandible and ORN in the maxilla is 24:1)
91. The rea- son for this could be that the mandible has a restricted localised blood supply, which is often completely within the radiation field, whereas the maxilla has many anastomoses located outside the area of irradia- tion. Furthermore, mandibular bone density is different from maxillary bone density, and the mandible absorbs a higher amount of radiation during radiotherapy.
The prevalence of ORN has decreased since the 1990s
92. Recent studies have shown a decrease in the prevalence of ORN to levels lower than 5%. Accord- ing to Clayman
54, the application of megavoltage therapy resulted in a significant reduction of the over- all prevalence of ORN from 11.8% before 1968 to 5.4% after this time. Wahl
93described similar results and noted a prevalence of ORN of 3% during the period 1997 to 2006. Lee et al.
43found that the fre- quency of ORN was 6.6% among 198 patients with either oral cavity or OPCs treated with radiation between 1990 and 2000. The overall reduction of ORN can be attributed to the advent of megavoltage radiotherapy, improved dental-preventive care and improved radiation techniques, including three-dimen- sional conformal radiotherapy (3D-CRT) and inten- sity-modulated radiotherapy (IMRT)
7,36,38.
Marx’s staging system
2is based on the use of, and response to, HBO. The advantages of this protocol include selection of patients who are able to respond to less aggressive treatments, use of minimal levels of HBO, resolution of the disease and preparation of patients’ tissues for reconstruction without further HBO
2,60.
Even though Marx’s staging system is the one still used by surgeons, it has been used less frequently from the mid-1990s to date. The reasons for this are that HBO is nowadays recommended for use as adju- vant therapy, its effectiveness has been questioned and most cases of ORN can be managed successfully with- out HBO according to the most recent literature
58,94–96. The staging system of Epstein et al.
32is an improve- ment, but it is focussed on the presence or absence of a pathological fracture
58.
The classification system of Notani et al.
59seems to
be more accurate as it is based on: (i) the presence or
absence of clinical and radiological signs, in contrast
to other systems that are non-specific and are partly
based on patients’ subjective interpretation; and (ii)
pretreatment evaluation, not on treatment response or
refractoriness. It is also simple and easily recalled
97. (For review see Chronopoulos
98.)
During the past 80 years, a number of theories about the origin of ORN have been proposed. Despite the controversy, the majority of authors agree that prereq- uisites for the diagnosis of ORN are: (i) previous irradi- ation of the affected bone; (ii) absence of recurrent tumour; (iii) presence of mucosal breakdown or failure of healing, resulting in bone exposure; and (iv) ‘necro- sis’ of the overlying bone. The presence of pathological fracture, fistula formation or cellulitis is not necessary for the diagnosis. Mandibular ORN is predominant over maxillary ORN. ORN can lead to pain, fracture and sequestration of the bone, as well as to fistulae.
Although the prevalence of ORN has decreased to levels lower than 5%, it still remains a pernicious com- plication of radiotherapy and a challenge to the clini- cian because of difficulty in its management. Owing to the severity of ORN and the difficulties in its early and accurate diagnosis and treatment, increased awareness of this complex entity among clinicians is desirable, with the aim to prevent its appearance or the develop- ment of severe complications. Further research is required in order to clarify its complex etiology, and guide new treatment strategies.
Acknowledgements
This review is included in the doctoral thesis of the first author, entitled ‘Clinical presentation and risk factors of osteoradionecrosis’.
Patient data were anonymised and de-identified before analysis. The clinical photograph and three radiographs were derived from the archive of the Department of Oral and Maxillofacial Surgery in Munich (LMU).
Conflicts of interest
We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome. There was no funding received for this study.
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