OSTEORADIONECROSIS.pptx

1. DR. P. KISHORE
SURGICAL ONCOLOGY RESIDENT
GOVT. ROYAPETTAH HOSPITAL
CHENNAI-14
OSTEORADIONECROSIS

2. MARX
REGUAD
EWING MARX AND
JOHNSON
1926 1983 1987
Over 20
years
Radiation osteitis
First evidence of
osteoradionecrosis
related to radiotherapy
1922
ORN – area >1cm of
exposed bone in
irradiated field – fails
to heal for 6 months
Modified the definition as “the
exposure of non viable bone
which fails to heal without
intervention.”
HISTORY
Prof S.Subbiah et al

3. DEFINITION
 Osteoradionecrosis is defined as “exposed irradiated bone that fails to heal over a period
of 3 months at any time after radiotherapy without the evidence of persistent or
recurrent tumor”.
Prof S.Subbiah et al

4. CLINICAL DIAGNOSTIC CRITERIA
 The affected site should be within the radiation field.
 Mucosal breakdown or failure to heal should occur resulting in exposure of bone.
 The overlying bone is dead or necrotic.
 The bone exposure persists for a minimum of 3 months.
 There should be an absence of recurrent tumor on the affected side.
 Cellulitis, fistulation or pathological fracture need not to be present to be considered as ORN.
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5. INCIDENCE
 Upto 56% in the literature but reduced to 4-8% in the modern era because of evolution in
radiation modalities.
 3 fold higher in men.
 Common in age more than 50 years.
 Mandible more than maxilla (24:1)
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6. WHY BONE THAN SOFT TISSUE ?
 Because of its mineral composition, bone has density 1.6 to 1.8 times greater
than soft tissues, bone absorbs more energy and is more susceptible.
 Most oral tumors are peri mandibular.
 Maxilla has more extensive blood supply ( less chance of hypoxic necrosis ) .
 Posterior mandible more common because of its high bone density resulting
in increased absorption of radiation dose.
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7. TIME LAPSE TO ORN
 Can occur at any time, even beyond 10 years following RT.
 Most frequently (70-94%) in the first few years after completion of RT.
 The median latency period is 12-24 months
 Early onset within 24 months is related to radiation doses higher than 60Gy.
 Late onset is related to trauma in a chronically hypoxic tissue environment.
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8. ETIOLOGY
 Precipitating factors :
o Approximately , one third of ORN occur spontaneously (at radiation doses above 70Gy without
preceding dental trauma ).
RADIATION
TRAUMA
INFECTION
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9. RADIATION :
 TOTAL DOSE OF RADIATION AND TIME FACTORS :
Doses of < 67.5 Gy delivered in < 6.5weeks resulted in no cases of ORN as compared to a 50
% incidence with higher doses delivered in < 6.5 weeks.
 ENERGY SOURCE :
1.Brachytherapy sources deposit a higher dose within a short period of time resulting in
higher risk.
2. High energy photons have a higher exit beam dose - increase the risk of ORN.
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10. TRAUMA :
Usually by tooth removal (88%), trauma places a greater energy, oxygen and other metabolic demands on tissues,
unable to meet them in the presence of hypoxia.
SURGICAL PROCEDURE :
Surgery to jaw after irradiation increases the risk since vascularisation of tissues is impaired.
TOBACCO AND ALCOHOL :
These strong tissue irritants significantly contributes to the breakdown of mucosa and exposure of bone.
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11. RISK PREDICTION
TUMOR RELATED
FACTORS
• Primary tumour site
• Size
• Stage
• Proximity to the
bone
TREATMENT
RELATED FACTORS
• Total RT dose
• RT technique
• Volume of
irradiated mandible
• Dose fractionization
• Re- irradiation
PATIENT RELATED
FACTORS
• Tobacco and
alcohol use
• Oral hygiene
• Dental caries
• Periodontal disease
• Dental extraction
before or after RT
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12. PATHOPHYSIOLOGY
MEYER’S INFECTION THEORY
Secondary infection due to local injury to the devitalized bone - “radiation induced
osteomyelitis” – explained the role of antibiotics in ORN.
Also store et al using DNA hybridization demonstrated that bacteria plays an role in
ORN. Teeth represent the port of entry for micro organisms. He demonstrated the existence of a
diverse microbiota in the medullary parts of the mandible by electron microscopy and DNA –
DNA hybridization assay.
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13. MARX THEORY OF ENDARTERITIS
Radiation induced endarteritis resulting “hypoxia, hypo vascularity and hypocellularity” (3H’S of ORN)
ORN) – formed the corner stone of hyperbaric oxygen therapy (HBO).
FIBRO ATROPHIC THEORY
Activation and dysregulation of fibroblastic activity leads to atrophic tissue within a previously
irradiated area – this formed development of new therapeutic regimen including Pentoxifylline and
Tocopherol.
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14. MICROBIOLOGY
 Cultures streptococci , candida spp., and gram negative organisms.
 When skin is affected staphylococcus aureus and epidermidis.
 No organisms are found deep in bone .
 Radiation predisposes to actinomycotic infection – bone tissue alteration acts as favourable
environment.
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15. CLINICAL PRESENTATION
 Early stages - asymptomatic.
 Pain with or without swelling - common presentation
 Tooth mobility or spontaneous tooth exfoliation.
 Trismus
 sensory neurological symptoms such as dysesthesia or anesthesia in the distribution of inferior alveolar
nerve in late stages.
 Secondary infection resulting in chronic pus drainage, draining extra oral fistulae or even pathological
fracture.
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16. Prof S.Subbiah et al

17. CLASSIFICATION
 Several classification has been made based on
response to hyperbaric oxygen therapy, clinical
– radiological findings, duration of bone
exposure and treatment required
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18. Prof S.Subbiah et al

19. Notani et al .- Based on clinical findings
• ORN confined to alveolar bone
Stage 1
• ORN limited to alveolar bone and / or mandible
above the level of inferior alveolar canal
Stage 2
• ORN involving the mandible below the level of the
inferior alveolar canal and / or skin fistula and / or
pathological fracture
Stage 3
Prof S.Subbiah et al

20. Marx.- Based on response to HBO therapy
• Exposed alveolar bone without pathological
fracture, which responds to HBO therapy
Stage 1
• Disease does not respond to HBO therapy
and requires sequestrectomy/saucerisation
Stage 2
• Full thickness bone damage or pathological
fracture, requires complete resection
Stage 3
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21. RADIOLOGICAL
CHANGES
 Computed tomography ( imaging modality
of choice )
 OTHERS : Orthopantomogram , MRI, Bone
scintigraphy
 CT – EARLY CHANGES : well defined area of
bone resorption within the outer cortical
plate of mandible
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22.  LATE CHANGES : lytic or sclerotic or mixed. In
rare cases, stimulated periosteal bone
formation.
 Irregular widening of periodontal membrane
space.
 Can present as radiolucent areas surrounding
the tooth extraction sockets that remain visible
more than 12 months.
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23.  ORTHOPANTOMOGRAM (OPT) –undefined radiolucency, without sclerotic demarcation, which surrounds
necrotic zone.
 In order to visible in an OPT, a substantial alteration in mineral content and extensive involvement of
bone is required and this only happens in later stages.
Prof S.Subbiah et al

24.  MRI : With gadolinium administration, an abnormal marrow signal, cortical
destruction and mild irregular enhancement is demonstrated.
 BONE SCAN : Using 99mTc- marked diphosphonates ( 99mTc-MDP ), allows highly
sensitive depiction of mandibular lesions as a result of their altered phosphate
metabolism.
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25. HISTOLOGY
 Obliteration of lumen vessels and sclerotic
changes in their walls
 Reduced vascularity, fibrosis and bone
trabeculae are reduced in width
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26. DIFFERENTIAL
DIAGNOSIS
 Bone resorption simulated by high dose
radiation ( differentiated by absence of
exposed bone ) .
 Chronic osteomyelitis ( no history of
radiotherapy ) .
 Bisphosphonates induced osteonecrosis .
 Recurrence of tumor
Prof S.Subbiah et al

27. TREATMEN
T
 Prevention
 Conservative management
 Surgical management
 Hyperbaric oxygen therapy (HBO)
 Pentoxifylline and tocopherol (PENTO treatment)
 Ultrasound therapy
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28. PREVENTION
 RADIOTHERAPY :
1.Regimes such as hyperfractionation, improve local control but with increased local complication.
2.3D conformational radiotherapy and IMRT - maximize delivery to treatment areas and reduce the incidence
and severity of ORN.
 PRE IRRADIATION CARE :
Extraction of periodontally compromised tooth in atraumatic approach with primary closure and usually a
healing time of 10 to 14 days between extraction and commencement of RT is followed.
 DURING RADIOTHERAPY :
Mouth rinse with 0.2% chlorhexidine.
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29.  POST IRRADIATION CARE :
1.Dentures should not be used for one year
2. Good oral hygiene
3.Use of salivary substitutes to avoid dry mouth
4. Fluoride therapy ( in the form of dentifrice toothpaste )
5. Atraumatic tooth extraction –
No flap approach
Local anaesthetic without adrenaline should be used.
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30. CONSERVATIVE MANAGEMENT
FOR WHOM ? – asymptomatic or mildly symptomatic ( Notani I or II )
 Strict oral hygiene, saline irrigation, chlorhexidine mouth rinses.
 Antibiotics – penicillin derivatives plus metronidazole or clindamycin.
 Pulsating irrigation devices can be used – high pressure avoided as it might force the debris deeply into the tissues.
 Exposed bone mechanically debrided and smoothened and covered with pack saturarted with zinc peroxide and neomycin.
 Gentle removal of sequestra.
Success rate – 80 to 90%
Advantage – integrity of inferior border of mandible is maintained.
Prof S.Subbiah et al

31. SURGICAL MANAGEMENT
WHEN ? –
 Conservative management is unsuccessful
 Progressive ORN ( Notani III ) leading to pathological fractures and draining fistula
WHAT are the CHOICES ?
 Segmental mandibulectomy
 Hemi mandibulectomy
 Osteo cutaneous free flap reconstruction ( FIBULA – the work horse in reconstruction for
mandibular ORN )
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32. CASE SCENARIO 1
 64 YEAR OLD MALE, A KNOWN CASE OF
CARCINOMA RIGHT POSTERIOR ONE THIRD
TONGUE WHO UNDERWENT DEFINITIVE
CHEMORADIATION WITH 70GY ON 16-6-
2021.
 PRSENTED WITH COMPLAINTS OF PAIN
OVER RIGHT MANDIBLE ON 5-4-2023.
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33.  ORAL CAVITY
EXAMINATION – GRADE III
TRISMUS PRESENT,
FRACTURED RIGHT HEMI
MANDIBLE PRESENT
COVERED WITH SLOUGH.
 PROCEDURE DONE :
RIGHT HEMI
MANDIBULECTOMY
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34. CASE SCENARIO 2 :
 56 YEAR OLD MALE, A KNOWN CASE OF
CARCINOMA FLOOR OF MOUTH WHO
UNDERWENT WLE + MARGINAL
MANDIBULECTOMY + B/L SOHND + ALT
FREE FLAP + ADJUVANT 66GY RT ON 16-04-
2021
 PRESENTED WITH C/O EXPOSURE OF BONY
CHIP ON 13-5-2023
 ORAL CAVITY EXAMINATION – EXPOSURE
OF BONE IN ANTERIOR GINGIVAL ASPECT
1X1CM
 PROCEDURE DONE – SEQUESTRECTOMY
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35. HYPERBARIC OXYGEN THERAPY
100% oxygen inhalation therapy at a pressure greater than that of 1 atm, usually about 2.4 absolute
atmospheres.
Mechanism –
 Partial reversal of 3 – H tissue
 Elevates the PaO2 - through dissolution of oxygen into blood irrespective of the haemoglobin.
 Has angiogenic and fibroblastic effects based on availability of molecular O2.
 Inhibits inflammation through direct bactericidal effects on anaerobes .
 Enhances phagocytic killing by WBC.
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36. THERAPY
ELECTIVE SURGERY PROTOCOL : PROPHYLACTIC PERIOPERATIVE HYPERBARIC OXYGEN.
 20 sessions prior to elective surgery followed by 10 sessions after surgery
 100 % oxygen at 2.4 atmospheric pressure for 90 minutes/day for 5 days a week.
 Single person chambers 120 treatment minutes
 Elective surgery protocol is used in all elective surgery in radiated tissue which may range from
tooth extraction to bone grafting.
 Studies have shown reduction from 30% to 5% in incidence of ORN
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37. 2. MULTI PERSON CHAMBER
1. SINGLE PERSON CHAMBER
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38. CONTRAINDICATIONS
ABSOLUTE :
 Optic neuritis ( exacerbation occurs )
 Immunosuppressive disorders(reports of
viral encephalitis )
RELATIVE :
 COPD
 claustrophobia
Prof S.Subbiah et al

39. HBO therapy is relatively safe if pressures within the chamber are kept below three times
normal atmospheric pressure (3atm) and if sessions lasts no longer than 2 hours.
COMPLICATIONS
•MINOR COMPLICATIONS
1. Light headedness.
2. Headache and fatigue.
3. Claustrophobia ( in monoplace
chambers).
MAJOR COMPLICATIONS
1. Ruptured middle ear and bleeding
2. Mucous plugs in patients with
congested sinus ,asthma and COPD
3. Myopia
4. Lung damage and pulmonary edema
5. Convulsions ( oxygen related CNS
toxicity )
Prof S.Subbiah et al

40.  Based on systemic review ,there was no conclusive evidence to support the routine use of HBO for
prevention and management of ORN.
 HBO may be considered for use as adjuvant therapy on individual basis who failed response to
conservative management and subsequent surgical resection.
 More recent papers and a prospective randomized controlled study by Annane et al. showed no
benefit of HBO over placebo.
Prof S.Subbiah et al

41. PENTO AND PENTOCLO
 BASIS - Pathogenesis of ORN as a “radiation-induced fibro atrophic process”.
 More advanced or refractory cases may benefit from addition of pentoxifylline and tocopherol (
PENTO )
 Pentoxifylline – improves blood flow to the affected bone .
 Tocopherol ( Vitamin E ) – boosts immune system, prevents blood clots and scavenges free radicals
and protects cell membranes against lipid peroxidation.
 PENTO + CLODRONATE ( PENTOCLO )
 CLODRONATE – a bisphosphonate – reduces the bone resorption.
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42.  PENTO treatment achieved a complete disease control in a significant number of patients in all studies.
 When there is no clinical improvement noted in 3 months of PENTO treatment, CLODRONATE is added as a potentiator.
 However, there is no standardized pharmacological dosage for administering the PENTO therapy.
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43. ULTRASOUND THERAPY
 Promotes neovascularity and neocellularity of ischemic tissues.
 Using 1 watt/ cm 2 , 3 MHz pulse, 1:4; 15 minutes a day for 60 days combined with metronidazole
and local debridement induces neovascularity and cellularity.
 Used in early stages of ORN as a part of conservative management.
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44. Take home message…
 Doses of < 67.5 Gy delivered in < 6.5weeks avoids ORN.
 Mandible more common than maxilla with median latency period is 12-24 months.
 Conservative management in early stages with success rate of 80 – 90 %
 Surgery is the treatment of choice when conservative management fails and in late stages.
 The effectiveness of HBO therapy is unsatisfactory.
Prof S.Subbiah et al

45. THANK YOU