CURRENT CONCEPTS IN OSTEORADIONECROSIS

AFTER HEAD AND NECK RADIOTHERAPY

J. DHANDA, D. PASQUIER , L. NEWMAN, R. SHAW
(CLINICAL ONCOLOGY 28 (2016) 459-466)

SAIFUDDIN SUHRI

Pembimbing :
dr. Arie Munandar Sp.Onk. Rad

INTRODUCTION
Osteoradionecrosis (ORN) of the jaws is a complication
of radiotherapy used for the treatment of head and neck
malignancy
There are numerous denitions of ORN and, likewise,
many classication systems have been proposed
What is common to all these denitions is the presence of
devitalized or necrotic bone in an irradiated eld, in
the absence of neoplastic disease

Fig 1. Common variables found in both the denition and classication of osteoradionecrosis

INTRODUCTION
Harriss denition is one commonly used by surgeons in
which irradiated bone becomes devitalised and
exposed through the overlying skin or mucosa,
persisting without healing for 3 months in the
absence of tumour recurrence.

Fig 2. Clinical photograph showing osteoradionecrosis with signicant

mucosal ulceration and exposed necrotic bone.

CLASSIFICATION SYSTEMS
Notanis classication :
Stage I ORN is conned to alveolar bone,
Stage II ORN is limited to the alveolar bone and/or
above the level of the inferior alveolar canal
Stage III ORN is under the lower part of the inferior
alveolar canal, with stula or bone fracture

CLASSIFICATION SYSTEMS

Fig 3. Stage III Notani osteoradionecrosis with orocutanous stulas.

IN
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The incidence of ORN reported in the literature ranges
widely from 2 to 22%.
Factors that affect the development of ORN :
> Systemic include immunodeciency, malnutrition,
peripheral vascular disease, alcohol and tobacco
misuse.
> Local features include the size and site of the
tumour, xerostomia and also the presence of a
neglected dentition with poor oral hygiene
> Treatment Factors

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Radiation-induced Osteomyelitis Theory
> Clinical observation that ORN was a manifestation
of exposure of bone to a critical dose of
radiotherapy with local injury and subsequent
infection
> This theory of secondary infection due to local
injury of devitalised bone, or radiation induced
osteomyelitis, was popularised by Meyer

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Hypoxia, Hypocellular and Hypovascular Theory
> Marx challenged this old theory with a new
pathophysiological concept
> Marx found that the composition of
microorganisms in ORN were not typical to those
in osteomyelitis of long bones represent oral
commensal colonization or contamination, rather than
infection
> A critical observation in Marxs work was the
presence of hypoxia in previously irradiated tissue

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Hypoxia, Hypocellular and Hypovascular Theory
> He concluded that ORN was a contamination of
radiation-induced metabolically and haemostatically
decient tissue in his hypoxic-hypocellularhypovascular theory
> This theory proposes that after radiotherapy a
sequence of events leads to the breakdown of cellular
and extracellular tissue, mainly collagen, which exceeds
synthesis and replication
> This loss of reparative and synthetic function causes a
chronic non healing wound with metabolic demands

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Fibroatrophic Theory
> Delanian and Lefaix radiation-induced brosis of
both soft and hard tissue was thought to result in chronic
nonhealing wounds in previously irradiated bone.
> Fibroblast activation and dysregulation is the
cornerstone of this theory
> Endothelial cell injury occurs directly from radiation
and indirectly from the free radical or reactive oxygen
species (ROS) generation

 Fibroatrophic Theory
> Subsequent cytokine production triggers an acute
inammatory response and generates further production
of ROS from inamatory cells
> Endothelial injury with small vessel thrombosis leads
to necrosis, ischaemia and tissue injury with further
cytokine production. Ultimately these cytokines
stimulate the transdifferentiation of broblasts into
myobroblasts and include broblast growth factor ,
TGF1, TNF and interleukins
> This activation results in a brotic pattern of tissue
turnover with greater proliferation and production of
abnormal extracellular matrix

RADIOTHERAPY TECHNIQUE AND

OSTEONECROSIS
Treatment factors, such as the site and dose of
radiotherapy associated with the mandible than the
maxilla and usually involves the body of the mandible
It is also more commonly associated with radiation
over 60 Gy (at 2 Gy/fraction equivalent)and when
concurrent chemotherapy is also used.
Radiation eld size, photon energy, brachytherapy
and fractionation are also well-known radiation-related
risk factors associated with ORN

RADIOTHERAPY TECHNIQUE AND

OSTEONECROSIS
Conformal three-dimensional radiation therapy and
IMRT is expected to translate into a further reduction
in ORN, by diminution of the volumes receiving higher
doses, a lower maximum dose and reduced
xerostomia
In a contemporary single centre study signicantly
more patients treated with conventional radiotherapy
exhibited ORN compared with those treated with IMRT
The use of a strict prophylactic dental care policy
and IMRT resulted in no cases of clinical ORN

RADIOTHERAPY TECHNIQUE AND

OSTEONECROSIS
The interval between extraction and initiation of
radiotherapy is important; a minimum delay of 10-21
days seems ideal

MANAGEMENT
Prevention
Head and neck cancer patients are now recommended
to have a restorative dental opinion before treatment
and any necessary extractions are carried out well in
advance of any radiotherapy
Indications for extraction include teeth with serious
dental disease or where the future prognosis is in
doubt
The role of HBOT and antimicrobial therapy has been
explored, with Marx et al

MANAGEMENT
Conservative or Simple Surgical Management of Early
Disease
reserved for symptom-free or mildly symptomatic
patients with early or moderate disease (Notani
1&2)
sequestrectomy or saucerisation
Surgical Management of Advanced Disease
Surgical resection and reconstruction with free
tissue transfer

THE MEDICAL MANAGEMENT OF

OSTEORADIONECROSIS
Several new therapeutic regimens have been proposed as a
result of the broatrophic model for the pathophysiology of
ORN
The free radical scavenger tocopherol, or vitamin E,
protects cell membranes against peroxidation of lipids,
thereby reducing ROS generation from oxidative stress.
Tocopherol can also inhibit TNFa and down regulates
procollagen gene expression, which also reduces brosis. In
combination with this, pentoxyfylline, a methylxanthine
derivative with an anti TNFa effect, has an inhibitory effect
on broblast activation as well as increasing collagenase
activity
the use of antibiotics as an induction agent to overcome

CONCLUSION
ORN is a devastating complication of radical head and neck
radiotherapy
Newer radiotherapy techniques may reduce incidence
through reduced xerostomia and respect for the mandible
as an organ at risk
Dental prevention strategies are also more widely
mandated
There is no established standard of care for ORN

THANK YOU