1. Introduction Osteoradionecrosis (ORN) of the mandible is a serious and debilitating complication that arises following radiation therapy, particularly in patients treated for head and neck cancers. First described by Regaud in 1922, ORN is characterized by the death of bone tissue due to radiation-induced damage, without evidence of persistent or recurrent tumor. It is most commonly seen in the mandible due to its relatively poor vascularity compared to the maxilla and its greater susceptibility to radiation damage. With advancements in radiation techniques and better understanding of tissue response, the incidence of ORN has decreased, but it remains a significant clinical concern. The condition not only impacts oral function and quality of life but also poses challenges in treatment due to poor healing capacity of irradiated tissues. 2. Epidemiology The reported incidence of mandibular ORN varies from 2% to 22% depending on the population studied, type and dose of radiation, use of concurrent chemotherapy, and preventive measures employed. The mandible is involved in more than 85% of ORN cases, likely due to its dense cortical bone, poor blood supply, and exposure to high radiation doses in oropharyngeal cancers. 3. Pathophysiology The pathogenesis of ORN is multifactorial, involving a complex interplay of radiation-induced hypoxia, hypovascularity, hypocellularity, and tissue breakdown: a. Radiation Injury Radiation therapy leads to permanent damage to the vasculature of the bone and surrounding soft tissues. Endothelial cell damage results in fibrosis, thrombosis, and eventual obliteration of small blood vessels, reducing tissue perfusion. b. Hypoxia and Hypocellularity The irradiated bone becomes hypoxic and hypocellular. Fibroblasts are replaced with non-functional fibrocytes, leading to poor collagen production and defective repair mechanisms. c. Bone Necrosis Due to poor vascularity and cellularity, the bone fails to remodel or repair minor injuries. Secondary infection often sets in, further aggravating tissue destruction and leading to chronic necrosis and sequestration. d. Modern Theory Marx (1983) proposed the “hypoxic-hypocellular-hypovascular” theory, which remains widely accepted. Later, the concept of Radiation-Induced Fibroatrophic (RIF) process further elaborated on the fibroatrophic changes in soft tissues, emphasizing the progressive and irreversible nature of radiation damage. 4. Risk Factors Several risk factors contribute to the development of ORN: a. Radiation Dose and Field Doses >60 Gy are significantly associated with increased ORN risk. Larger radiation fields and inclusion of the mandible increase the risk. b. Dental Extractions Tooth extractions after radiation, especially within irradiated bone, are a major precipitating factor. c. Poor Oral Hygiene Poor oral health predisposes to infection, periodontal disease, and trauma, contributing to ORN. d. Smoking and Alcohol

1. OSTEORADIONECROSIS
Dr Maroti
FHNO Fellow

2. Contents
➔ Introduction
➔ Other terminologies
➔ Definition
➔ Epidemiology
➔ Risk Factors
➔ Pathophysiology
➔ Clinical features
➔ Staging
➔ Radiological findings
➔ Prevention
➔ Non surgical management
➔ Surgical management

3. complication of radiotherapy in head and neck cancer.
first described by Regaud in 1922

4. Other terminologies
avascular bone necrosis

5. Definations
1983, Marx defined 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’.
In 1987, Marx and Johnson3 suggested the definition of ORN as: ‘The exposure of nonviable bone
which fails to heal without intervention’.
Epstein et al. defined ORN as ‘an ulceration or necrosis of the mucous membrane, with exposure of
necrotic bone for more than 3 months’.
Widmark et al. described ORN as ‘a non-healing mucosal or cutaneous ulcer with denuded bone,
lasting for more than 3 months’
In 1997, Wong et al. defined 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’.

6. ORN of the jaws is defined as exposed irradiated bone that fails to heal over
a period of 3 months without evidence of persisting or recurrent tumour

7. Epidemiology
0.4% to 56%
usually affects patients over 55 years of age
Mandible>>>Maxilla
mandible vascular supply is only
one-sixth that of the maxilla

8. Risk factors
the documented incidence of ORN after extractions is about 5%
three times higher in dentate than in edentulous patients
>50 Gy (ASCO guidelines)

9. Pathophysiology

10. ❖ animals were divided into three groups of 4,500, 5,500, and 7,500 r for
the first irradiation.
❖ The severity and extent of the necrosis were also in direct relationship to
the time of onset, which was related to the irradiation dose.
1963

11. classic triad of osteoradionecrosis as radiation, trauma, and infection.
trauma to be a portal of entry for oral bacterial flora into the underlying bone
He did not, however, demonstrate through cultures or tissue sections such a
spread of osteomyelitis and microorganisms throughout the bone;
Radiation
Trauma
Infection
1970

12. Osteoradionecrosis is not a primary infection of irradiated bone. It is a
complex metabolic and tissue homeostatic deficiency created by radiation-
induced cellular injury.
Micro-organism plays minor role in ORN
Direct role of trauma is que
Spontaneous orn is valid thing
three H” principle of irradiated tissue- hypovascular, hypocellular, and hypoxic
tissue
1983

14. osteoradionecrosis of the mandible is an ischemic necrosis caused by radiation-induced obliteration of
the inferior alveolar artery and branches of this artery, whereas revascularization from branches of the
facial artery is disturbed by radiation-induced vascular disease and periosteal damage.
1990

15. a radiation-induced fibroatrophic mechanism, including free radical
formation, endothelial dysfunction, inflammation, microvascular thrombosis,
fibrosis and remodeling, and finally bone and tissue necrosis.
late fibroatrophic phase
03
● an attempt to remodel the tissue with
formation of fragile healed tissues
that are at an increased risk of
reactivated inflammation when the
tissue sustains local injury, which
could possibly lead to tissue necrosis
organized phase
02 ● abnormal fibroblastic activity, and the
extracellular matrix loses organization
initial prefibrotic phase
01
● endothelial cells are mainly observed,
with an accompanying acute
inflammatory response
2004

17. bacteria, particularly anaerobes, may play a more fundamental role in the
pathophysiology of osteoradionecrosis
teeth present in the field of irradiation might represent the port of entry for
microorganisms.
Porphyromonas gingivalis was the most predominant organism, followed by
Fusobacterium nucleatum
2005

18. Clinical findings
1. ulceration or necrosis of the mucosa with exposure of necrotic bone for
longer than 3 months, pain, trismus and suppuration in the area
2. Neurological symptoms, such as pain, dysaesthesia or anaesthesia, as
well as fetor oris, dysgeusia and food impaction in the area
3. Progression of ORN may lead to pathological fractures, intra-oral or
extra-oral fistulae and local or systemic infection
4. intra- or extra-oral draining fistulae
5. A biopsy is mandatory for final diagnosis in order to exclude metastatic

19. ORN of the jaw should be operationally characterized
as:
radiographic lytic or mixed sclerotic lesion of bone
and/or
visibly exposed bone
and/or
bone probed through a periodontal pocket or fistula

22. Clinical diagnostic criteria

24. Staging
based on
1. response to hyperbaric oxygen (HBO) therapy,
2. degree of bone damage,
3. clinical–radiological findings,
4. duration of bone exposure and
5. treatment required

28. Which staging system should be used?

29. Radiological findings
Orthopantomography (OPT), cone-beam computed tomography (CBCT), and
computed tomography (CT) are the frequently used
recommended additional imaging techniques include bone scintigraphy,
single-photon emission computed tomography (SPECT), and positron
emission tomography (PET)

30. Orthopantomogram
most frequently used

31. CT
cortical destruction that is ill-defined resulting in a mixed sclerotic-lucent
pattern sequestration, especially of the buccal bone an absence of soft tissue
mass is an important feature to differentiate it from neoplastic recurrence
but the presence of soft tissue does not exclude osteoradionecrosis
. Any abnormal growth in the surrounding soft tissue should be considered a
second primary cancer or a tumor recurrence to rule out the possibility

32. Magnetic Resonance Imaging (MRI)
MRI can demonstrate altered bone marrow in the ORNJ region with aberrant,
homogeneous, low marrow signal intensity on T1-weighted images and
elevated signal intensity on T2-weighted images

33. Bone Scintigraphy, Single Photon Emission Computed Tomography (Spect), and Positron Emission Tomography (PET)
sensitivity of up to 100% in the diagnosis of ORNJ

34. Prevention
PRE-RT
❏ prophylactic oral care prior to, during, and after the completion of radiation
therapy.
❏ recommends a 2- week period of healing, if oncologically safe, should be
provided between date of dental extraction and start of RT. situations where
a patient does not have one to 2 weeks of healing available and presents
with hopeless teeth within the planned radiation field, the Panel
recommends removal.
❏ Radiation Dosimetry- radiation dose to the jaw of 50 Gy is at higher risk of
developing ORN

35. POST RT
❏ Dental extractions and implant placement in areas that received 50 Gy
≥
should be avoided
❏ noninvasive alternatives to dental extraction for problematic teeth in
areas at high risk for ORN
❏ Patients requiring dental extraction in a high-risk region due to recurrent
infection that cannot be alleviated without extraction should be
monitored closely for healing with frequent irrigation of the surgical site
❏ limited benefit of perioperative HBO for prevention of ORN

36. patients who required multiple dental extractions

37. NONSURGICAL MANAGEMENT OF ORN
1. Pentoxifylline and PENTOCLO
Evidence remains limited for pentoxifylline and PENTOCLO. With respect to mild to moderate
grades of ORN, PENTOCLO may be a useful tool in managing ORN without surgery.
Pentoxifylline- a methylxanthine derivative that exerts an anti-TNF_ effect, increases
erythrocyte flexibility, dilates blood vessels, inhibits inflammatory reactions in vivo, inhibits
proliferation of human dermal fibroblasts and the production of extracellular matrix and
increases collagenase activity in vitro
Vit-E- tocopherol (vitamin E), which scavenges the reactive oxygen species that were generated
during oxidative stress by protecting cell membranes against peroxidation of lipids, partial
inhibition of TGF-_1, and expression of procollagen genes, so reducing fibrosis.

38. 2. HBO
revascularize irradiated tissues and to improve the fibroblastic cellular
density
current literature is inconclusive regarding the effect of HBO, combined with
surgery or alone.

39. Wilfred-Hall Protocol

40. Surgical Management
➔ Sequestrectomy
➔ Resection

43. Treatment of Mandibular Osteoradionecrosis by Cancellous Bone Grafting
Distraction Osteogenesis

44. Conclusion
● ORN is still a serious complication resulting from radiotherapy
● overall incidence of 11.8 % before 1968 and 5.4 % thereafter.
● clinical management of ORN is difficult and normally comprises medical
care, the avoidance of toxic habits, improvement of dental hygiene, the
control of infections with antibiotics and antiseptics and removal of the
necrotic tissue with more aggressive surgery once complications have
appeared (pathological fractures)
● Effective management of any disease process initially requires diagnosis
before treatment.