Osteoradionecrosis of Jaws

Osteoradionecrosis of jaws
What is ORN?
 Osteoradionecrosis (ORN), also known as post radiation osteonecrosis (PRON).

 It was first described by Regaud 1920.
 MARX (1983) An area of exposed bone>1cm in a field of irradiation that has failed to
show any evidence of healing for atleast 6 months
 EPSTEIN (1987) An ulceration or necrosis of the mucous membrane(in the absence of
recurrence or metastatic disease )with exposure of necrotic bone for more than 3 month.
Pathophysiology of ORN
 Meyer in 1970 –
Triad of radiation, trauma, and infection
 Marx 1983 ......

• Osteoradionecrosis - cumulative tissue damage
• induced by radiation rather than trauma or bacterial invasion of bone.
• Three "H" principle
 Bras, et. Al (1990) radiation induced obliteration of the inferior alveolar artery was
consistently found in osteoradionecrosis of mandible and was felt to be a dominant factor
in the onset of the disease.
 Delanian & lefaix 2004 Radiation-induced Fibroatrophic (RIF) Theory

Key event in the progression of ORN is the activation and dysregulation of fibroblastic activity
that leads to atrophic tissue within a previously irradiated area. .
Radiation-induced Fibroatrophic (RIF)
Theory
 Prefibrotic phase in which changes in endothelial cells predominate, with the
acute inflammatory response.
 Constitutive organised phase in which abnormal fibroblastic activity

predominates, and there is disorganisation of the extracellular matrix .
 Late fibro-atrophic phase, attempted tissue remodelling occurs with the

formation of fragile healed tissues that carry a serious inherent risk of late
reactivated inflammation in the event of local injury .
Common sites of ORN
 Commonest site is mandible.

 Also reported in maxilla, temporal bone, sphenoid and base of skull.
Why in mandible ?
 Mandible - different dominant pattern of blood supply according to various anatomical
regions in the bone itself.
 The posterior segment of the mandible (condyle process and neck, coronoid, angle, and
upper ramus) - redundant blood supply from the surrounding musculature, either from
direct muscular attachments or through muscular perforators
 penetrating the periosteum.
 Because of this redundancy, the posterior segment is typically less susceptible to radiation
induced ischemia.
 The anterior segment of the mandible - no prominent nutrient vessel supply through the
muscular attachments.
 Injection studies in the mandible - primary nutrient source for the body, parasymphyseal,
and symphyseal regions is through an intramedullary source, the inferior alveolar artery.
 In a study by Bras, et. al., radiation induced obliteration of the inferior alveolar artery was
consistently found in osteoradionecrosis of mandible and was felt to be a dominant factor
in the onset of the disease.
Types of ORN
 SPONTANEOUS ORN (39%) – Degradative function exceeds new bone production.
 TRAUMA INDUCED ORN (61%) – Reparative capacity of bone is insufficient to

overcome an insult.
 Bone injury can occur through direct trauma –

1. Tooth extraction [84%],
2. Related cancer surgery or biopsy [12%],
3. Denture irritation [1%]) or
4. Secondary to overlying soft tissue necrosis.
Classification of ORN
Marx (1983)
 Type I – Develops shortly after radiation, Due to synergistic effects of surgical

trauma and radiation injury.
 Type II – Develops years after radiation and follows a trauma

Rarely occurs before 2 year after treatment
Due to progressive endarteritis and vascular effusion.
 Type III
Occurs spontaneously without a preceding a traumatic event. Usually
occurs between 6 months and 3 years after radiation. Due to immediate cellular
damage post radiation treatment.
Epstein ( 1987)
 Stage I – Resolved healed osteonecrosis

• (A) – No pathologic fracture
• (B) – Pathologic fracture
 Stage II – Chronic persistent and non-progressive osteonecrosis
 Stage III – Active progressive osteonecrosis
Notani (2004)
 grade I, ORN confined to alveolar bone;

 grade II, ORN limited to the alveolar bone and/or mandible above the level of inferior
alveolar canal.
 grade III, ORN involving the mandible below the level of inferior alveolar canal and ORN
with a skin fistula and/or pathologic fracture.
Incidence of ORN according to anatomic site of the tumor
Dental Factors
 Presence of carious and periodontally compromised teeth in the irradiated mandible –

Extraction.
 The current school of thought - grossly
carious, periodontally "hopeless," or those teeth deemed to have poor prognosis for
retention beyond twelve months should be removed prior to the initiation of radiation
therapy - this avoids dental manipulations in the post irradiation period.
Risk factors for ORN
Window period ?
 The post surgical healing time prior to starting radiation treatment -under debate.
 Marx and Johnson - compared the incidence of osteoradionecrosis in pre-treatment tooth
removal patients to the timing of the surgical insult.
 From their collected data, most of the osteoradionecrosis developed - in those patents in
which treatment was begun within the first two weeks post extraction.
 No cases of osteoradionecrosis, when the tissue was allowed to heal for 21 days or
more.
1.Marx RE, Johnson RP. Studies in the Radiobiology of Osteoradionecrosis and

Their Clinical Significance.
2.Oral Surgery Oral Medicine Oral Pathology. 64 (4): pg 384. 1987.
Clinically
• Pain
• Swelling
• Trismus
• Halitosis
• Exposed bone
• Pathologic fracture
• Oro-cutaneous fistula
Role of HBOT
MARX PROTOCOL
 Three treatment stages of advancing clinical severity.

 All patients who meet the definition of osteoradionecrosis (exposed bone present for six
months or longer with no healing), begin stage I treatment.
 If the disease does not resolve, Stage II treatment is begun.
 Three exceptions representing advanced disease: patients with pathologic fractures, fistulas
or radiographic evidence of osteolysis to the inferior border begin directly with stage III
treatment and usually require discontinuity resection.
Stage 1
 Perform 30 HBO dives (1 dive per day) to 2.4 atmospheres for 90 minutes in a multiplace
chamber or 2.0 ATA for 120 min in a monoplace chamber .
 Reassess the patient to evaluate decreased bone exposure, granulation tissue covering
exposed bone, resorption of nonviable bone, and absence of inflammation.
 For patients who respond favorably, continue treatment to a total of 40 dives.
 For patients who are not responsive, advance to stage II.
Stage 2
 Perform transoral sequestrectomy with primary wound closure followed by continued

HBO to a total of 40 dives.
 If wound dehiscence occurs, advance patients to stage III.
Stage 3
 Patients who present with orocutaneous fistula, pathologic fracture, or resorption to the
inferior border of the mandible advance to stage III immediately after the initial 30 dives.
 Perform transcutaneous mandibular resection, wound closure, and mandibular fixation
with an external fixator or maxillomandibular fixation, followed by an additional 10
postoperative HBO dives.
Stage 3 R
 Perform mandibular reconstruction 10 weeks after successful resolution of mandibular

ORN.
 Reconstruction of the mandible in these patients consisted of either autogenous particulate
bone and marrow within a custom-made stainless steel metal crib or autogenous particulate
bone and marrow within a freeze-dried allogenic bone framework .
 Complete 10 additional postoperative HBO dives.
Prevention of ORN
 Prior to radiation therapy- Dental consultation - To achieve optimal oral health.

 Sleeper (1950) and Meyer (1958) - recommendations before irradiation is started.
 The mouth should be made as clean as possible by scaling and irrigation.
 All infections of soft tissues should be eliminated.
 All infected and non-vital teeth should be extracted. All teeth in the line of irradiation,
good or bad, also should be extracted.
Prevention of ORN
 The patient should be thoroughly instructed in the maintenance of absolute hygienic care
of the mouth.
 Fluoride therapy should be used to prevent irradiation caries of any remaining teeth.
 No radiotherapy should be attempted for 7-10 days following extractions in the mandible
or for 3-6 days in the maxilla. If possible the radiation should start only 21 days after the
tooth extractions.
ORN after preradiation extraction and postradiation extraction
 Since 1986, the incidence of ORN after preradiation extraction (3.0 –3.2%; 23 of 711–756
patients) was approximately the same as the incidence of ORN after postradiation
extraction (3.1–3.5%; 16 of 461–508 patients) in pooled studies
 Osteoradionecrosis can also occur in edentulous patients or spontaneously, and
preradiation extractions cannot prevent these.
Michael J. Wahl, D.D.S. Osteoradionecrosis Prevention Myths

Int. J.Radiation Oncology Biol. Phys., Vol. 64, No. 3, pp. 661–669, 2006
Medical management
 Between June 1995 and January 2002, 18 patients were given a daily oral combination of
800 mg of PTX and 1000 IU of vitamin E for 6 to 24 months.
 In addition, the last eight patients who were the worst cases were given 1600 mg/day
clodronate 5 days a week.
 RESULTS: Sixteen (89%) of 18 patients achieved complete recovery. The remaining two
patients exhibited a 75% response at 6 months.
DELANIAN S, DEPONDT J, LEFAIX JL: MAJOR HEALING OF REFRACTORY MANDIBLE

OSTEORADIONECROSIS AFTER TREATMENT COMBINING PENTOXIFYLLINE AND
TOCOPHEROL: A PHASE II TRIAL. HEAD NECK 27:114, 2005
Pentoxyfylline
• Methylxanthine derivative
• Anti–tumor necrosis factor-α effect
• Increases erythrocyte flexibility
• Produces vasodilation
• Reduced fibroblast proliferation
• Increased collagenase activity
Tocopherol
• Organic compounds that act as vitamin E
• Antioxidant properties
• Partial inhibition of transforming growth factor-β1
• Vitamin K antagonistic properties
Clodronate
• 1st generation non- nitrogenous oral bisphosphonate
• Reduce osteoclast activity
• Decrease fibroblast and macrophage proliferation
 Martos-Fernández et al,
Pentoxifylline, tocopherol, and
clodronate for the treatment of
mandibular osteoradionecrosis: a
systematic review
 Oral Surgery, Oral Medicine, Oral

Pathology and Oral Radiology-
2018

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Osteoradionecrosis of jaws

 Osteoradionecrosis (ORN), also known as post radiation osteonecrosis (PRON).

 Marx 1983 ......

 Delanian & lefaix 2004 Radiation-induced Fibroatrophic (RIF) Theory

 Constitutive organised phase in which abnormal fibroblastic activity

 Late fibro-atrophic phase, attempted tissue remodelling occurs with the

 Commonest site is mandible.

 TRAUMA INDUCED ORN (61%) – Reparative capacity of bone is insufficient to

 Bone injury can occur through direct trauma –

 Type I – Develops shortly after radiation, Due to synergistic effects of surgical

 Type II – Develops years after radiation and follows a trauma

 Stage I – Resolved healed osteonecrosis

 grade I, ORN confined to alveolar bone;

 Presence of carious and periodontally compromised teeth in the irradiated mandible –

1.Marx RE, Johnson RP. Studies in the Radiobiology of Osteoradionecrosis and

 Three treatment stages of advancing clinical severity.

 Perform transoral sequestrectomy with primary wound closure followed by continued

 Perform mandibular reconstruction 10 weeks after successful resolution of mandibular

 Prior to radiation therapy- Dental consultation - To achieve optimal oral health.

Michael J. Wahl, D.D.S. Osteoradionecrosis Prevention Myths

DELANIAN S, DEPONDT J, LEFAIX JL: MAJOR HEALING OF REFRACTORY MANDIBLE

 Oral Surgery, Oral Medicine, Oral

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