YIJOM-4224; No of Pages 9

Int. J. Oral Maxillofac. Surg. 2019; xxx: xxx–xxx

https://doi.org/10.1016/j.ijom.2019.06.015, available online at https://www.sciencedirect.com

International News
Consensus Report

Chinese expert group Y. He1, C. Ma1,a, J. Hou2,a, X. Li1,

X. Peng3, H. Wang4, S. Wang5,
L. Liu6, B. Liu7, L. Tian8,9, Z. Liu1,
X. Liu2, X. Xu10, D. Zhang11,
consensus on diagnosis and C. Jiang12, J. Wang13, Y. Yao14,
G. Zhu15, Y. Bai15, S. Wang16,
C. Sun17, J. Li18, S. He7, C. Wang2,
clinical management of Z. Zhang1, W. Qiu1
1
Department of Oral & Maxillofacial – Head & Neck
Oncology, 9th People’s Hospital, Shanghai Jiao

osteoradionecrosis of the
Tong University School of Medicine, Shanghai Key
Laboratory of Stomatology, Shanghai, China;
2
Department of Oral and Maxillofacial Surgery,
Guanghua School of Stomatology, Hospital of
Stomatology, Sun Yat-Sen University, Guangzhou,

mandible China; 3Department of Oral and Maxillofacial

Surgery, Peking University School and Hospital of
Stomatology, Beijing, China; 4Stomatology Hospital
Affiliated to School of Medicine, Zhejiang University,
Zhejiang, China; 5Salivary Gland Disease Center
and Molecular Laboratory for Gene Therapy and
Tooth Regeneration, School of Stomatology, Capital
Y. He, C. Ma, J. Hou, X. Li, X. Peng, H. Wang, S. Wang, L. Liu, B. Liu, L. Tian, Z. Liu, Medical University, Beijing, China; 6Department of
X. Liu, X. Xu, D. Zhang, C. Jiang, J. Wang, Y. Yao, G. Zhu, Y. Bai, S. Wang, C. Sun, J. Oral and Maxillofacial Surgery, West China Hospital
of Stomatology, Sichuan University, Chengdu,
Li, S. He, C. Wang, Z. Zhang, W. Qiu: Chinese expert group consensus on diagnosis China; 7The State Key Laboratory Breeding Base of
and clinical management of osteoradionecrosis of the mandible. Int. J. Oral Basic Science of Stomatology and Key Laboratory of
Oral Biomedicine Ministry of Education, School and
Maxillofac. Surg. 2019; xxx: xxx–xxx. ã 2019 Published by Elsevier Ltd on behalf of Hospital of Stomatology, Wuhan University, Wuhan,
International Association of Oral and Maxillofacial Surgeons. Hubei, China; 8Department of Cranio-facial Trauma
and Orthognathic Surgery, School of Stomatology,
Fourth Military Medical University, Xi’an, China; 9The
State Key Laboratory of Military Stomatology,
Abstract. Osteoradionecrosis of the mandible (MORN) is one of the most devastating School of Stomatology, Fourth Military Medical
complications caused by radiation therapy in the head and neck region. It is characterized University, Xi’an, China; 10Department of Oral and
Maxillofacial Surgery, The Second Affiliated Hospital
by infection and chronic necrosis of the mandible as the main manifestation. Clinically, Zhejiang University School of Medicine, Zhejiang,
MORN-related symptoms include swelling, pain, dysphagia, trismus, masticatory or Hangzhou, China; 11Department of Oral and
Maxillofacial Surgery, Shandong Provincial Hospital
speech disorders, refractory orocutaneous fistula, bone exposure, and even pathological Affiliated to Shandong University, Jinan, Shandong,
fracture. MORN has become a challenging clinical problem for oral and maxillofacial China; 12Department of Oral and Maxillofacial
Surgery, Xiangya Hospital, Central South University,
surgeons to deal with, but thus far, this problem has not been solved due to the lack of Changsha, China; 13Department of Head and Neck
widely accepted treatment algorithms or guidelines. Surgery, Gansu Province Tumor Hospital, Lanzhou,
China; 14Department of Radiotherapy, 9th People’s
Because of the nonexistence of standardized treatment criteria, most clinical Hospital, Shanghai Jiao Tong University School of
treatment against MORN nowadays is largely based on controversial empirical Medicine, Shanghai, China; 15Department of
Radiotherapy, Renji Hospital, Shanghai Jiao Tong
understandings, while recommendations on post-therapeutic evaluations are scarce. University School of Medicine, Shanghai, China;
16
Therefore, to further unify and standardize the diagnosis and treatment of MORN, to Department of Radiation Oncology, Eye & ENT
Hospital, Fudan University, Shanghai, China;
decrease the huge waste of medical resources, and ultimately, to improve the 17
Department of Oromaxillofacial – Head and Neck
wellbeing of the patients, the Chinese Society of Oral and Maxillofacial Surgery Surgery, Department of Oral and Maxillofacial
Surgery, School of Stomatology, China Medical
(CSOMS) convened an expert panel specialized in MORN from 16 domestic University, Liaoning, China; 18Department of Oral
medical colleges and affiliated hospitals to discuss the spectrum of diagnosis and and Maxillofacial Surgery, Sun Yat-Sen Memorial
Hospital, Sun Yat-Sen University, Guangzhou, China
and formulate treatment. In addition, consensus recommendations were also revised Key words: mandible; osteoradionecrosis;
with a comprehensive literature review of the previous treatment experiences and treatment; expert consensus.
research pearls. This ‘expert consensus statement on diagnosis and clinical
management of MORN’ is for clinical reference. Accepted for publication 5 June 2019

a
These authors contributed equally to this
work. C. Ma and J. Hou are the only first
authors of the article, while Y. He is the only
corresponding author of this article.

0901-5027/000001+09 ã 2019 Published by Elsevier Ltd on behalf of International Association of Oral and Maxillofacial Surgeons.

Please cite this article in press as: He Y, et al. Chinese expert group consensus on diagnosis and clinical management of
osteoradionecrosis of the mandible, Int J Oral Maxillofac Surg (2019), https://doi.org/10.1016/j.ijom.2019.06.015
YIJOM-4224; No of Pages 9
2 He et al.
Osteoradionecrosis of the mandible
(MORN) is one of the most devastating
complications caused by radiation therapy
for the treatment of head and neck malig-
nancy. The reported incidence of MORN
has decreased from approximately 20% to
5% in modern series, due to the improve-
ments in radiotherapy techniques and pos-
sible prophylaxis on risk factors1,2.
However, once patients develop MORN,
especially those of advanced stages, the
outcomes of different treatment modalities
vary, and they will consequently affect the
health-related quality of life3. The associ-
ated complaints range from mild symp-
toms, such as swelling, local pain,
dysphagia and trismus, to severe ones,
such as suppuration, bone exposure or
even pathological fractures3,4. Without
proper and timely conservative interven-
tion, MORN will rapidly progress to a
higher stage, for which if no reconstruc-
tive methods are offered the final progno-
sis will largely fall short of expectations5.
However, controversy still exists for lack
of universally accepted treatment guide-
lines for early-stage diseases thus far6.
Besides, although many staging systems
have been proposed based on various cri-
teria, the efficacy of each system needs to
be validated by more compelling clinical
evidence with large numbers of cases7.
The post-treatment evaluation remains
elusive because there is still a lack of
the standardized protocol to comprehen-
sively assess the objective and subjective
aspects of all the therapeutic options.
Therefore, to further unify and standardize
the diagnosis and treatment of MORN, to
decrease the huge waste of medical
resources, and ultimately, to improve the
wellbeing of the patients, the Chinese
Society of Oral and Maxillofacial Surgery
(CSOMS) convened an expert panel spe-
cializing in MORN from 17 domestic
medical colleges and affiliated hospitals
to discuss the spectrum of diagnosis and
formulate treatment. In addition, consen-
sus recommendations were also revised
with a comprehensive literature review
of the previous treatment experiences
and research pearls. This ‘expert consen-
sus statement on diagnosis and clinical
management of MORN’ is largely for
clinical reference.
Definition
Regaud was the first to report the osteor-
adionecrosis of the jaws (ORNJ) about 90
years ago. Since then, numerous defini-
tions have been proposed4. In 1983, Marx
defined MORN as ‘an area greater than
1 cm of exposed bone in a field of irradia-
Please cite this article in press as: He Y, et al. Chinese expert group consensus on diagnosis and clinical management of
osteoradionecrosis of the mandible, Int J Oral Maxillofac Surg (2019), https://doi.org/10.1016/j.ijom.2019.06.015
tion that had failed to show any evidence
of healing for at least six months’8,9. Har-
ris reduced the non-healing interval to 3
months and mentioned the absence of
recurrent tumour in the same region9.
Based on Store’s findings, from a radio-
logical perspective, conditions with ne-
crotic bone and intact (unexposed)
mucosa and skin should also be incorpo-
rated into the definition10. Although the
definition is still evolving, the common
feature among all the current definitions is
the presence of nonvital bone with or
without surrounding soft tissue damage
as a result of radiotherapy. Based on the
available literature and the consensus of
the Chinese experts, we summarized the
definition of MORNJ as the devitalized
irradiated mandible with or without sur-
rounding soft tissue damage, which will
not heal spontaneously for at least 3
months, with exclusion of recurrent, met-
astatic or radio-induced tumour in the
same region.
Etiopathogenesis and risk factors
ORNJ was firstly considered as an infec-
tious disease caused by the invasion of
oral microbiological flora into the irradi-
ated bone tissue. In 1970, Meyer proposed
the classic triad theory in the pathogenesis
of ORNJ as radiation, trauma and infec-
tion4. In 1983, this theory was challenged
by Marx as hypoxia, hypovascularization
and hypocellularity, instead of trauma and
infection, were more likely to be involved
in the formation of aseptic necrotic
bone11. In 2004 and 2011, radiation-in-
duced fibroatrophic process was also
found to be one of the key mechanisms
for the development of ORNJ12. In addi-
tion, the combination of death of osteo-
blasts after irradiation, and excessive
proliferation of myofibroblasts were sug-
gested in the reduction in bony matrix and
the destruction of bony tissue13. We be-
lieve ORNJ is caused by the deregulation
of multicellular events and the existing
evidence for the explanation of ORNJ
formation is insufficient and inconclusive.
Several risk factors of ORNJ have been
proposed and can be categorized as treat-
ment factors, tumour factors, and patient
factors. Firstly, the risk for MORN is
strongly correlated to radiation doses over
60 Gy12,14,15. This risk factor can be fur-
ther aggravated by tooth extraction post-
radiotherapy in the head and neck region,
especially within the first 4 years post-
treatment16. Periosteal, marginal or seg-
mental mandibular resection will result in
an increased incidence of MORN. Patients
with oral cavity cancers have the highest
Table 1. Risk factors associated with the
development of osteoradionecrosis of the
mandible.
Primary tumor location
Mandibular angle and ramus (radiation and
bone density)
Mandibular proximity to tumour
Radiation dose volume and distribution to
mandible
Tooth problems — tooth decay and
periodontal diseases
Oral hygiene and habit(smoking and alcohol)
Radiation dose over 60 Gy
Brachytherapy or external beam radiotherapy
Nutrition status
Concurrent radio-chemotherapy
Undesirable prothesis (chronic local trauma)
Mandibulotomy or mandibulectomy
Advanced tumour stage
risk followed by those with oropharyngeal
cancers17. Smoking and dental hygiene
status are also possible predisposing fac-
tors for the occurrence of MORN18. The
risk factors are summarized in Table 1.
Diagnosis and examinations
Currently, the diagnosis of MORN is
mainly based on the following aspects:
(1) radiation history; (2) bone exposure
with or without surrounding mucosal or
epidermal damage; (3) radiological evi-
dence of bony destruction; (4) non-exis-
tence of tumour recurrence19; (5)
pathological findings of necrotic or scle-
rotic bone with empty osteocyte lacunae,
blurry or breakdown of bony trabeculae,
with loss of osteocytes and osteoblasts,
and reduced vascularity of connective tis-
sue20.
Clinical manifestation
Clinical symptoms are mainly correlated
with progressive necrosis of mandible and
soft tissue damage caused by radiation.
They may present clinically with symp-
toms such as pain, swelling, trismus, dis-
color of local skin, stiffness of muscle,
malocclusion, orocutaneous fistula, ex-
posed bone with persistent suppuration
or even facial disfiguration (Supplementa-
ry Fig. S1). Most patients seek medical
treatment for local pain and swelling,
fistula and trismus.
Radiological consideration
Panoramic X-ray
Panoramic X-ray has been widely used for
evaluation of suspected ORN, with lesser
sensitivity than computed tomography
YIJOM-4224; No of Pages 9
(CT) and magnetic resonance imaging
(MRI). Early-stage MORN is presented
with reduction in the bone mineral density,
limited loss of bone mass with resorption
of the osseous trabeculae. Intermediate- or
advanced-stage cases are presented with
expansive or fused lamellar low bone
destruction, sequestrum formation, or
even pathological fracture10,21,22 (Supple-
mentary Fig. S2).
CT or cone-beam CT (CBCT)
At CT, early-stage cases may present as
bone density reduction, sparse trabecular
structures or limited loss of trabecular in
the spongiosa. For advanced-stage cases,
large areas of osteolytic lesions or erosions
can be identified. Bone fragmentation or
sequestrum may also be encountered in
areas of ORN with clear demarcation.
Cortical involvement can lead to patho-
logical fractures in severe cases (Supple-
mentary Fig. S3). Adjacent soft tissue,
especially masticatory muscles, will form
a thickening or enhancing signal due to
local infection or swelling10,22,23.
MRI
Because MRI can meticulously depict mar-
row alterations, cortical erosions, soft-tis-
sue changes of MORN, it is recommended
as the screening examination for early-stage
cases and post-treatment follow-up. Altered
marrow signal intensity appears hypoin-
tense on T1-weighted images and hyperin-
tense on T2-weighted images. These areas
show intense post-contrast enhance-
ment4,8,10,22 (Supplementary Fig. S4).
Positron emission tomography/emission
CT/single-photon emission CT
Positron emission tomography (PET),
emission computed tomography (ECT)
or single-photon emission computed to-
mography (SPECT) can be utilized to
detect early MORN. Fludeoxyglucose
(FDG) is known to accumulate in areas
of inflammation. They show marked in-
crease in FDG uptake in the presence of
hypoxia and inflammatory mediators
(Supplementary Fig. S5). However, it
remains difficult to differentiate recurrent
tumours from MORN based solely on the
FDG-uptake signal. Besides, 99Tcm-sesta-
mibi SPECT can be used to differentiate
tumour recurrence and MORN8.
Pathology
The pathological features of MORN are
summarized as follows: microscopically,
Please cite this article in press as: He Y, et al. Chinese expert group consensus on diagnosis and clinical management of
osteoradionecrosis of the mandible, Int J Oral Maxillofac Surg (2019), https://doi.org/10.1016/j.ijom.2019.06.015
Chinese group expert consensus on diagnosis and clinical management 3
Table 2. The BS (bone/soft tissue) classification and stages of osteoradionecrosis of the
mandible (MORN).
BS classification Stages
Bone necrosis (B) Stage 0
B0No distinct changes or just osteolytic images on radiography, B0S0
but patients suffering from typical MORN-related symptoms
B1Maximal diameter of the lesion on radiography <2.0 cm Stage I
B2Maximal diameter of the lesion on radiography 2.0 cm B1S0, B1S1, B1S2
B3Pathological fracture Stage II
Soft tissue injury (S) B2S0, B2S1, B2S2
S0Mucosal and skin integrity Stage III
S1: Intraoral mucosal defect or external skin fistula B3S0, B3S1, B3S2
S2Intraoral mucosal and external skin defect; through-and-through defect
early-stage MORN shows coarse structure response to hyperbaric oxygen (HBO)
of lamellar bone, empty osteocytic lacu- therapy26. Over the years, many other
nae with microcracking areas. In terms of staging systems have been proposed to
intermediate- or advanced-stage MORN, aid treatment, though controversies still
there is an absence of osteocytes, which exist over the universal acceptance. In
have been replaced by acellular fibrotic 2000, Store defined the four distinct clini-
collagen. Necrotic or non-vital bone tis- cal stages based on the exposure of bone
sues can be observed. Normal cells in the and radiological changes6,11,27. Epstein
bone marrow cavity are damaged, proposed the staging on the progress of
replaced by a large number of fibrous the disease, in which stage I is resolving
tissues. Blood vessels are scarce within while stage III is progressive4,28. Schwartz
the radiation zone. Remnants of blood reported their staging with emphasis on
vessels are devoid of endothelial and ad- the superficial or diffuse osteolytic
ventitial cells6,20,24,25 (Supplementary Fig. changes of the mandible4,25. In a recent
S6). grading system, Lyons classified the ORN
patients according to the extent of bone
exposure, symptoms and different treat-
Diagnostic criteria
ment regimens26. In 2014, we established
The Chinese expert consensus summa- a new clinical classification for MORN
rized the diagnostic criteria for MORN as with dual focus of both hard and soft tissue
follows: (1) history of radiotherapy; (2) involvement, the so-called ‘BS’ (bone and
classic clinical symptoms; (3) no evi- soft tissue) staging system27 (Table 2).
dence of tumour recurrence or metasta- Our staging system incorporated both
sis; (4) radiologic findings of low bone the presentation of disease and radiologi-
density, bone destruction, sequestrum cal findings. The selected cut-off point of
formation or even pathological fracture; 2 cm was based on the different treatment
(5) if surgically treated, necrotic bone regimens applied. Besides, the degree of
tissue, empty bone cell lacuna, severe severity and the volume of necrotic lesions
avascular fibrosis can be found with hae- were taken into account for more compre-
motoxylin and eosin (H&E) staining. hensive evaluation. The maximal diameter
The clinical diagnosis of early-stage of the bone lesion and the status of the
MORN can be formed with the former pathological fracture were assessed by
four criteria without pathological speci- CT. The buccolingual and anteroposterior
men. diameters were measured on the trans-
verse section, and the vertical diameter
was measured on the coronal plane.
Differential diagnosis
Through sliding the bone window in the
The final diagnosis of MORN should be CT software, it was possible to determine
based on the differential diagnosis with the maximal length in different directions;
chronic osteomyelitis, medication-related the maximal length was then selected. Soft
mandibular osteonecrosis, tuberculosis of tissue involvement was determined by
mandible, tumour recurrence, radio-in- clinical examination. Different therapeu-
duced sarcoma and metastatic tumour tic options were given within our classifi-
(Supplementary Fig. S7). cation system.
As a recommendation of Chinese expert
consensus, we suggest using the ‘BS’
Staging system
staging system for a more accurate and
In 1983, Marx introduced the first staging objective evaluation of MORN and a
system for ORN patients based on the guide for related treatment protocols.
YIJOM-4224; No of Pages 9
4 He et al.
Treatment
Management of MORN includes conser-
vative (medical) and surgical interven-
tions4,6,29. The mainstay treatment of
MORN comprises primarily of symptom-
atic relief and prevention of further dis-
ease exacerbation. Without appropriate
management, early-stage MORN patients
will progress to advanced stage, which
often requires serious resection followed
by flap reconstruction30. Recent advances
in the understanding of MORN patho-
physiology have opened new perspectives
in the conservative management of mild
MORN31–33. However, due to the paucity
of level I evidence, most treatment regi-
mens depend on the severity of the condi-
tion and are different from institution to
institution. Therefore, the Chinese
experts’ group designs the treatment pro-
tocols according to the diagnosis criteria
and the ‘BS staging system’ (Fig. 1).
Conservative management
Oral care
Oral hygiene management is recom-
mended to all MORN patients. Tooth-
brushing is the first line of oral
cleansing method, which can be comple-
mented by normal saline mouthwash or
irrigation34. Chlorhexidine or hydrogen
peroxide can be used occasionally for
antibacterial activity, but they are not
recommended for daily routine rinsing
use35.
Antibiotics, steroids and analgesics
Although MORN forms as a result of non-
infective hypovascular and hypocellular
necrosis, superficial contamination or fis-
tulas with bacteria secondary to the ne-
crotic tissues are frequently seen in stage
I–III MORN patients4,6,29,36. Penicillin
and cephalosporin antibiotics can be used
in these patients, though this is not evi-
dence-based. The use of antibiotics should
be used after drug sensitivity tests. Ster-
oids are based on the anti-inflammatory
effects for local infections. Analgesics can
be prescribed to relieve the pain caused by
MORN3,7. Nevertheless, antibiotics, ster-
oids and analgesics alone may not cure the
MORN in most instances, but can be
incorporated into other treatment regi-
mens if desired.
HBO
The first application of HBO in the man-
agement of ORN dates back to 19734,37.
The rationale behind the use of HBO is
Please cite this article in press as: He Y, et al. Chinese expert group consensus on diagnosis and clinical management of
osteoradionecrosis of the mandible, Int J Oral Maxillofac Surg (2019), https://doi.org/10.1016/j.ijom.2019.06.015
Fig. 1. Algorithm of diagnosis and treatment of osteoradionecrosis of the mandible (MORN).
BS, bone andsoft tissue; CBCT, cone-beam CT; CT, computed tomography; MRI, magnetic
resonance imaging.
that intermittent elevation of tissue oxy-
gen tension promotes angiogenesis,
enhances the bacteria-killing leucocytes
and stimulates fibroblast proliferation38.
However, the results of HBO are not
convincing due to the great heterogeneity
among different studies. Annane reported
the highest level of evidence available to
date for HBO efficacy39. To our surprise,
this random, placebo-controlled, double-
blinded study was terminated due to the
worse outcome of the HBO arm. In other
retrospective studies, the response rates of
HBO alone are undesirable, indicating an
even lower effect for advanced MORN
when no or inadequate surgical manage-
ment was combined31,40. Based on the
currently available evidence, we do not
recommend the use of HBO as a mono-
therapy to MORN of any stage. It may be
used as an adjunct therapy to other types of
treatment regimens.
Pentoxifylline, tocopherol (vitamin E) and
clodronate
Pentoxifylline (PTX) was first developed
to inhibit the radiation-induced fibrosis
(RIF) in MORN patients as a targeted
drug41. In vitro studies have revealed
the antioxidant properties of PTX. The
anti-tumor necrosis factor alpha effect of
PTX can exert an inhibitory effect on the
fibroblast activation and increase collage-
nase activity42. Vitamin E can also down-
regulate procollagen gene expression,
which also reduces RIF. In recent studies,
PTX, in combination with vitamin E, can
reduce the RIF via a synergistic action43.
The addition of clodronate inhibits osteo-
clast activity and consequently on bone
destruction44. In a phase II clinical trial
conducted by Delaninan, combined PTX–
vitamin E treatment proved a striking 66%
regression of RIF45. In another phase II
trial, PTX, vitamin E and clodronate
(PENTOCLO), 16 (89%) of 18 patients
achieved complete recovery in about 14
months46. Recently, Patel also reported
comparable data showing that the use of
PTX and vitamin E has a positive impact
in the management of early MORN47.
Therefore, based on the available litera-
ture, we recommend PENTOCLO treat-
ment for stage 0 and stage I cases, and an
adjunct treatment modality to surgery for
stage II and III cases.
Ultrasound therapy
Ultrasound therapy was first introduced in
1992 as a treatment regimen for ORN.
Theoretically speaking, it can induce local
angiogenesis for revascularization of
MORN4,6,48. According to Harris’ report,
48% (10/21) of cases achieved healing
without need for surgery49. It might be a
cost-effective method. However, due to
the paucity of literature in this aspect,
therapeutic ultrasound can only be sug-
gested as an experimental option for cases
of clinical trial.
Growth factor and mesenchymal stem cell
therapy
For early-stage MORN patients, platelet
concentrate can release a large number of
cytokines, growth factors, which can stim-
ulate the healing cascade of tissues com-
promised by radiotherapy. Most of the
platelet-related treatment nowadays
YIJOM-4224; No of Pages 9
focuses on tendinopathy, the use of such
autologous blood products in MORN
patients was only recently reported. In
2015, Gallesio evaluated the effectiveness
of plasma rich in growth factors to accel-
erate healing for ORN patients50. Howev-
er, it was used as an adjunct to surgical
treatment in a small series of patients.
Bone marrow mesenchymal stem cells
(MSCs) harbour the potential for tissue
regeneration in impaired ORN cells. A
recent experiment in rats proved the effi-
cacy of the combined application of MSC
and BMP-251. However, more clinical
studies are required to reach a definitive
conclusion about the effects of these new
therapeutic options.
Surgical management
Debridement (removal of small sequestra)
Teeth with tooth mobility worse than
grade II should be extracted and affected
bone (sequestra) should be removed until
bleeding occurs27,29,52. For small bone
exposure that cannot be primarily closed,
such wounds can be packed with iodoform
gauze for 8–10 days postoperatively. This
approach can be applied to MORN
patients of BS stage I or (part of) II.
Marginal mandibulectomy
For patients with wider nonviable superfi-
cial bone or sequestra, but still limited to
alveolar ridge (with sufficient hard-tissue
buttress in case of pathological fracture),
marginal mandibulectomy (or alveolect-
omy) can be utilized as a treatment option.
This approach can be applied to patients of
BS stage I or (part of) II.
Segmental mandibulectomy
For patients with osteolysis or sequestra
exceeding the depth of lower alveolar
ridge (to the inferior border), or for those
with severe comorbidities or conditions
contraindicative to flap reconstruction,
segmental mandibulectomy should be
considered27,28. Bleeding should be clear-
ly observed in both the proximal and distal
resection margins during the operation53.
Limited soft tissue involvement without
the need for flap coverage is also required
for this surgical approach. This surgical
option is for patients of BS (part of) stage
II and III.
Radical resection and flap reconstruction
For patients with both large soft and hard
tissue involvement, which includes path-
Please cite this article in press as: He Y, et al. Chinese expert group consensus on diagnosis and clinical management of
osteoradionecrosis of the mandible, Int J Oral Maxillofac Surg (2019), https://doi.org/10.1016/j.ijom.2019.06.015
Chinese group expert consensus on diagnosis and clinical management
ological fracture or orocutaneous fistula,
or failure of conservative treatment, radi-
cal resection are required to clear away all
the infected tissues54. Significant bone and
soft tissue defects subsequent to such re-
section will necessitate flap reconstruction
to restore mandibular continuity for func-
tional and cosmetic reasons. Thus far,
vascularized bone flaps, such as fibular,
iliac and scapular flaps, are the most ef-
fective reconstructive modality for ad-
vanced MORN patients4,7. The fibula
flap has gained its popularity due to the
bone length and design flexibility. Non-
vascularized bone grafts are considered
unreliable and postoperative complication
rates can exceed 80%55. For patients with
‘frozen neck’, i.e. no suitable recipient
vessels, pedicled myocutaneous flaps, es-
pecially pectoralis major myocutaneous
flaps (PMMF), may be another alternative.
The size of the PMMF should be larger
than the defect, for radio-induced fibrosis
will cause the retraction of the residual
soft tissues. According to our experience,
the size of the soft tissue flap should be 2–
3 cm larger than the resected tissue. Be-
sides, the intra- and extra-oral defects after
MORN resection always require the fold-
ing of the PMMF. For extensive hard and
soft tissue defects caused by MORN, dou-
ble flaps with composite tissues are feasi-
ble in some circumstances56. These
approaches apply to BS stage II and III
patients.
Special attention for surgical
management
Resection margin
The resected bone of MORN is generally
larger than the signs reflected in the radio-
graphs. Guided by the preoperative CT or
panoramic X-ray, the edge of resection
should ooze fresh blood during the opera-
tion53. This is the gold standard for safe-
margin resection for osteoradionecrosis.
Recipient vessels
The key to the proper selection of recipient
vessels lies in the length and haemody-
namics (perfusion) of the vessels. The
dissection of the recipient vessels can be
extremely challenging due to the lack of
planes caused by radiation-related fibrosis
and scarring. Hence, special care should
be taken during the preparation of the
vessels. Sufficient length and no tension
anastomosis should be ensured to avoid
vasospasm during the operation. The qual-
ity of the recipient vessels may also be
compromised because thickening and
5
histological damage of the vascular walls
are frequent in irradiated patients57. To
lower the risk of reconstruction, preoper-
ative sonography or CT angiography is
recommended for vessel evaluation before
MORN operations. Candidate recipient
arteries are superior thyroid artery, facial
artery, lingual artery and transverse cervi-
cal artery. The usual preferred veins are
external jugular vein, and branches of
internal jugular vein, such as common
facial vein and superior thyroid vein. In
circumstances where no candidate vessels
are available or when quality of the can-
didate vessels is inferior, procedures can
be directly performed with external carot-
id artery for arterial, and end-to-side with
internal jugular vein for venous anastomo-
ses. In addition, for the sake of flap perfu-
sion, the haemodynamics (blood flow) of
the recipient vessels should always be
confirmed prior to anastomosis.
Airway management
The decision about airway management
during MORN surgery is critical for the
postoperative safety of the patient. The
trend towards more conservative
approaches (nasotracheal intubation and
selective tracheotomy) for major head
and neck operations regarding segmental
mandibulectomy or free flaps reconstruc-
tions. However, for MORN patients who
will receive surgery, the indications for
tracheotomy should be slightly extended.
Though not supported by the literature,
airway compromise will be more likely to
occur in MORN patients due to the dual
effects caused by radiation-induced fibro-
sis (frozen neck), radiation-related dys-
phagia and abated cough functions.
Based on experiences, we contend that
for MORN patients who will receive ex-
tended hemimandibulectomy (beyond the
midline with detachment of mylohyoid
muscles and genioglossal muscles) or
large anterior mandibulectomy from the
mental foramen to the contralateral one),
tracheotomy should be performed out of
safety concerns. Besides, for cases with
severe trismus and late-stage MORN,
elective tracheotomy should be considered
after consultation with anaesthesiologists
for potential difficult intubation. Although
the final judgment about tracheotomy is
personalized to individual patient’s con-
ditions, radical decisions for such groups
of patients are warranted.
Treatment algorithm
Generally speaking, the therapeutic
options for MORN patients should be
YIJOM-4224; No of Pages 9
6 He et al.
Table 3. Clinical staging system and corresponding treatment.
Stage B/S constitution
Stage 0 B0S0
Stage I B1S0, B1S1, B1S2
Stage II B2S0, B2S1, B2S2
Stage III B3S0, B3S1, B3S2
B, bone necrosis; S, soft tissue injury.
made with consideration of several fac-
tors, such as oral health, patient wishes,
socioeconomic status, hospital conditions
and skills of practitioners4,6,7. The treat-
ment algorithm of ours was formulated
according to the different clinical severity.
For reference, the treatment algorithm was
proposed on the basis of the BS staging
system (Table 3). Conservative treatment,
such as HBO, pentoxifylline et al., may be
considered for stage 0 patients with close
follow-up for disease progress. Stage I
patients can be surgically debrided with
fistula resection due to the small size of
affected tissues. In routine clinical set-
tings, stage II patients outnumbered those
of other stages. Except for a very small
number of patients whose alveolar ridges
were only affected (marginal mandibu-
lectomy), most stage II MORN patients
may require segmental mandibulectomy
for clearing necrotic and unhealthy bony
tissues. In terms of the stage III patients,
the same surgical approaches apply. For
bilateral late-stage MORN patients, syn-
chronous or sequential resection and re-
construction can be used for treatment
under different circumstances.
Outcome evaluation
Most MORN patients need close follow-
up for recurrence after certain kinds of
treatment. The efficacy of the treatment
employed should be subjectively and ob-
jectively evaluated on four basic dimen-
sions: local pain, trismus, wound healing
and radiographic changes. We recommend
using the simplified evaluation methods
for a rapid overview of the treatment out-
comes during the outpatient visit for fol-
low-up (Table 4).
Prevention of MORN
The prevention of MORN lies in the un-
derstanding of the specific aetiology of
Table 4. Evaluation of treatment results of osteoradionecrosis of the mandible.
Outcomes Pain
Cure None
Effective Alleviated
Ineffective Aggravated
Please cite this article in press as: He Y, et al. Chinese expert group consensus on diagnosis and clinical management of
osteoradionecrosis of the mandible, Int J Oral Maxillofac Surg (2019), https://doi.org/10.1016/j.ijom.2019.06.015
Treatment
Conservative therapy
Sequestrectomy or marginal mandibulectomy
Marginal resection without reconstruction, or segmental resection combined with
osteocutaneous flap reconstruction
Segmental resection with or without osteocutaneous/soft tissue flap reconstruction
such complications58. There are three
key factors in the development of MORN:
radiation, patient and tumour4,59,60. As for
radiation factors, using different mandi-
ble-sparing techniques, lowering total ra-
diation doses, changing radiation sources
and modifying radiation schemes, the in-
cidence of MORN can be significantly
reduced15,16. The conditions of patients
are also implicated in the formation of
MORN. Dental hygiene status, body mass
index and smoking all contribute to the
development of MORN18. For tumour
factors, oral cavity and nasopharyngeal
cancer are strong risk factors for MORN,
followed by oropharyngeal cancer16,61.
Therefore, before the start of radiotherapy
and during the post-radiation periods, pro-
phylactic measures should be taken to
prevent such complications from occur-
ring. We generalized the preventive mea-
sures into five cateogories:
Surgical prevention
For those who need postoperative radio-
therapy, we should keep in mind the pres-
ervation of mandibular periosteum during
the surgical management of head and neck
cancers. Without violating the rules of
tumour extirpation, adequate soft tissue
coverage or muscle attachment should
be kept intact for a well-nourished micro-
environment surrounding the cortical
plate. Within the radiation field, unrepair-
able teeth due to caries, periodontal dis-
ease or root lesions should be extracted to
avoid local bacterial infection63,64.
Pre-radiation preparation
Before the start of radiotherapy, patients
should be educated regarding the risks of
MORN with smoking or alcohol abuse
because recent evidence in this field is
robust. If patients have no history of prior
surgery, they are encouraged to remove or
Mouth opening Wound healing
Increased 1 cm Completely healed
Increased 0.5–1 cm Partially healed
Increased <0.5 cm Non-healed
treat the unhealthy or unviable teeth or
periodontal lesions 2 weeks before radia-
tion. In addition, complete healing of bone
exposure or wound is required before the
radiation. Metal prosthesis or denture
should be temporarily removed for dose
accumulation or potential wounding dur-
ing the radiation.
Prevention measures during radiation
Oral hygiene should be closely monitored
for avoidance or treatment of local infec-
tion. Spacer or other preventive prostheses
can be utilized for insulation of unirradi-
ated anatomies. According to Obinata’s
and Murakami’s studies, spacers are help-
ful in the prevention of MORN65,66.
Post-radiation prevention
Tooth extraction within the radiation field
puts the patient at risk of MORN in a post-
radiotherapy setting. These teeth are usu-
ally treated in a conservative way. How-
ever, if advanced teeth problems occur,
extraction should be performed as atrau-
matically as possible. Besides, alveolar
ridges should be lowered for primary clo-
sure of the exposed tooth sockets which
are vulnerable to infections. Prophylactic
antibiotics should also be applied prior to
and post the extraction procedure.
Radiation techniques and doses
With the recent advancement of radiation
techniques, radiotherapy has improved
from the conventional measure to a more
precise one. Intensity-modulated radiation
therapy (IMRT) or image-guided radiation
therapy (IGRT), which can spare the man-
dible, has become the standard of care for
head and neck cancer patients. The fre-
quent use of IMRT has already decreased
the rate of ORN to below 6%15. Consensus
has also been reached that doses <60–
Radiograph
No necrotic bone and bone healed well
No necrotic bone and bone basically healed
Necrotic bone or aggravation of necrosis
YIJOM-4224; No of Pages 9
65 Gy to the mandible represent the low
threshold for risk of MORN. Therefore,
for prevention of MORN, radio-oncolo-
gists should scheme a lower dosage to the
mandible if local tumour control is not
compromised.
In conclusion, this consensus includes
the opinions from an expert panel special-
izing in MORN. We summarized and gave
our perspectives on the definition, the
etiopathogenesis and risk factors, diagno-
sis and examination, staging system, treat-
ment, outcome evaluation and prevention
of MORN. With scarce level-I evidence
existing for MORN management, we hope
to design a brief guide for clinical refer-
ence based on the recent literature review
and our experiences. Undoubtedly, with
deeper understanding of MORN, new
therapies, such as mesenchymal stromal
cell therapy, will be put into clinical prac-
tice in the near future.
Funding
None.
Competing interests
None.
Ethical approval
The ethical exemption was given by the
Institutional Clinical Research Ethical
Committee of Shanghai 9th People’s Hos-
pital, Shanghai Jiao Tong University
School of Medicine.
Patient consent
Written patient consent was obtained to
publish clinical photographs.
Appendix A. Supplementary data
Supplementary material related to this
article can be found, in the online version,
at doi:https://doi.org/10.1016/j.ijom.2019.
06.015.
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Chinese group expert consensus on diagnosis and clinical management 9

66. Murakami S, Verdonschot RG, Kakimoto N, Address: Shanghai Key Laboratory of Stomatology
Sumida I, Fujiwara M, Ogawa K, Furukawa Yue He 639 Zhi Zao Ju Road
S. Preventing complications from high-dose Department of Oral & Maxillofacial – Head Shanghai 200011
rate brachytherapy when treating mobile & Neck Oncology China
tongue cancer via the application of a mod- 9th People’s Hospital Tel.: +86 21 2327 1699*5160;
ular lead-lined spacer. PLoS One 2016;11(4) Shanghai Jiao Tong University School Fax: +86 21 6313 6856
e0154226. of Medicine E-mail: william5218@126.com

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