OSTEORADIONECROSIS

Introduction Most serious complication of radiation therapy for cancer Probably the first evidence of ORN related to radiotherapy

was reported by Regaud in 1922 Its pathology was further described by Ewing in 1926, under

the name ‘radiation osteitis’ Meyer classified ORN as one special type of osteomyelitis. Titterington also related ORN to osteomyelitis, providing one

of its first definitions, and used the term ‘osteomyelitis of irradiated bone’

Marx defined it as ‘an area greater than 1 cm of exposed bone in a field of irradiation that had failed to show any evidence of healing for at least 6 months’. He also clarified that in ORN there is no intersticial infection, but only superficial contamination

1. The affected site should have been previously irradiated; 2. There should be absence of recurrent tumour on the

affected site; 3. Mucosal breakdown or failure to heal should occur,

resulting in bone exposure (except in cases of bones that lie within thick soft tissue integument’s, such as the pelvis or femur, or rarely in cases of a pathological fracture of the mandible after irradiation);

4. The overlying bone should be ‘dead’, usually due to a hypoxic necrosis;

5. Cellulitis, fistulation, or pathologic fracture need not be present to be considered ORN

Classification of bone exposures Bone exposure resulting from tumor necrosis where

tumor death results in a loss of soft tissue coverage. bone exposure at the site of tumor during or

within a week of radiotherapy Bone exposure as a consequence of tumor recurrence.

In all cases surgical resection was undertaken –tumor recurrence

Bone exposure resultant from oral surgical or dental interventions. Extractions sites. Persistent bone necrosis due to

denture irritation Bone exposure de novo.

no obvious source of trauma

DEFINITION An exposure of irradiated bone which fails to

heal with out intervention (Marx 1983) It is a chronic nonhealing wound caused by

hypoxia, hypocellularity, and hypovascularity of irradiated tissue. Marx and Johnson (1987)

Clinical definition by Van Merkesteyn (1995) Bone and soft tissue necrosis of 6 months

duration excluding radiation induced periodontal breakdown

INCIDENCE

Before 1960 orthovoltage -ORN ranging from 17%-37%

megavoltage therapy is bone sparing. Incidence ranges from upto 10%. By Reuther et al the incidence was found to be

8.2% in population of 830 individuals investigated for over a period of 30 years

Mandible is affected more commonly; because most oral tumors are peri mandibular. More extensive blood supply in maxilla

Int J Oral Maxillofac Surg. 2003 Jun;32(3):289-95

Osteoradionecrosis of the jaws as a side effect of radiotherapy of head and neck tumor patients--a report of a thirty year retrospective review

Reuther T, Schuster T, Mende U, Kubler A.

Retrospective 830 pts Incidence 8.2%3 fold higher in MenBody of mandibleExtraction -50%Presurgical earlier ORNCombined radio and chemo

Bedwinek et.al T3 AND T4 lesions - more prone

higher tissue destruction, larger treatment volume. No necrosis if 50-60Gy used

Low dosing brachytherapy higher ORN, secondary to decay profile of a combination of mix of alpha, beta and gamma particle spin off.

Etiology Radiation in excess of 50Gy- kills bone cells

– osteoblasts & fibroblasts leading to hypocellularity

Vessels -tunica intima endarteritis,

periarteritis hyalinization and fibrosis Progressive obliterative arteritis.—

hypovascularity Periosteal vessels and inferior alveolar artery involved

Hypoxia

angiogenesis and stem cell mitogenisis -platelet derived growth factors

third day -under macrophage Migrate - excess of 20 mm of Hg. Radiation shallow oxygen gradient

macrophage chemotaxis angiogenic and fibroblast growth

factors 3-H TISSUE

wound healing

Radiation beam

field effect greater -central beam tapers off -outward resemble a target center -most affected Healing -reduced or absent

Precipitating factors

Triad

Concept challenged by Gowgiel. Approximately one third of ORN occur spontaneously.

RADIATION

TRAUMA INFECTION

Modern concept - Marxbiochemical and cellular

pathology ORN is radiation induced,

nonhealing hypoxic wound rather than true osteomyelitis or irradiated bone

Microbiology Cultures streptococci, Candida spp., and

gram negative organisms. When skin is affected S. aureus and

S.epidermidis. No organisms are found deep in bone. Radiation predisposes to actinomycotic

infection; because is favorable environment for microorganism to flourish due to bone tissue alteration

CLINICAL FEATURES

Within two years Asymptomatic dehiscence of mucosa Glabrous skin As necrosis progresses site more

erythematous and severe, deep burning pain

Evidence of exposed bone

Tissue surrounding may be ulcerated from infection or recurrent tumor.

Trismus Fetid breath Elevated temperature Exposed bone with a grey to yellow color Intraoral and extra oral fistula Pathological fracture

Radiographic changes

Little-evident sequestra or involucra occur late radiolucent modeling -nonsclerotic Nuclear isotope technetium 99

methylene diphosphonate Bony algorithm high resolution CT

Histologically look like MICROANATOMIC DESERT Reduced vascularity, fibrosis

Diagnosis of osteoradionecrosis should focus primarily on ruling out recurrent or metastatic disease. Therefore is diagnosis of exclusion

MANAGEMENT

Protocol for preirradiation oral evaluation

Osteoradionecrosis of jaws Marciani RD, Ownby H E J Oral Maxillofac Surg 44; 218-223;

1986

Post irradiation care Dentures should not be used for one year Good oral hygiene maintenance Fluoride therapy Saliva substitute to prevent dry mouth Pulpitis- endodontic therapy Atraumatic extractions –no flap or linear

closure Local anesthetic without adrenaline should

be used Antibiotic should be administered

Management of osteoradionecrosis Aim - To control frank infection Antibiotics Penicllin plus metronidazole or clindamycin Supportive therapy with fluids Pulsating irrigation device can be used.

High pressure should not be used debris might be forced deeply into tissues

Exposed bone can be mechanically debrided and smoothed with round burs and covered with a pack saturated with zinc peroxide and neomycin

Conservative management of osteoradionecrosis

J K Wong, R E Wood, Mc Lean Triple O 1997; 84:16-21

local irrigation (saline solution, NaHCO3, or chlorhexidine), systemic antibiotics in acute infectious episodes, avoidance or irritants and oral hygiene instruction.

Simple management refers to the gentle removal of sequestra in sequestrating lesions

Had 48% success rates

Treatment of small areas with drilling multiple holes into vital bone is recommended by Hahn and Cargill (1967) to encourage sequestration.

Daland (1949) advised electro coagulation of exposed bone to expedite sequestration and drainage of subcutaneous abscesses to prevent sloughing of skin.

Treatment of osteonecrotic wounds

Rule out neoplastic disease Stabilize the patient medically

especially nutritional status Preoperative hyperbaric oxygen Debridement of necrotic mass Postoperative hyperbaric oxygen Soft tissue vascular flap support Bony reconstruction

Ultra sound therapy

Is non invasive and reportedly promotes neovascularity and neocellularity of ischemic tissues

Major healing of refractory mandible osteoradionecrosis after treatment combining pentoxifylline and tocopherol: a phase II trial.

Head Neck. 2005 Feb;27(2):114-23. Delanian S, Depondt J, Lefaix JL

Effective in reversing fibronecrotic process

Eighteen patients 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

at 6 months, with 84% healing

HYPER BARIC OXYGEN

THREAPY

DEFINITION

Short term -100% oxygen inhalation therapy at a pressure greater than that of sea level. The pressure is usually about 2.4 absolute atmospheres or ATA.

Greenwood and Gilchrist (1973) were the first to report beneficial effects of HBO on wound healing in post RT.

1975 – Mainous and Hart – 14 cases of refractory ORN of mandible treated with HBO and hemimandibulectomy

1981 Mansfield reported complete healing with HBO

1993 McKenzie reported resolution of ORN following HBO in 69% patients

USES

Decompression sicknessElective surgery to prevent

clinical radiation necrosis Treatment of

osteoradionecrosis Non healing diabetic ulcers

Mechanism

Partial reversal of 3-H tissue physical mechanism

dissolution of oxygen into blood 80-100 mm Hg range to 1000-1200 mm Hg HBO elevates the PAO2 irrespective of hemoglobin O2 gradients -radiated tissue from 50 to 250

mm Hg-macrophage activity

Angiogenic and fibroblastic effects- collagen synthesis crucially depends on the availability of molecular O2 that incorporates into a peptide chain to form hydroxyl propyl and hydroxyl lysyl residues.

HBO inhibits inflammation through direct bactericidal effects on anaerobes due to increased production of free radical and toxic products

HBO enhances phagocytic killing by WBC (Parl 1994)

Stage I 30 x (100% O2 for 90 mins at 2.4 ATA)

Examine exposed bone No surgery cutaneous fistula No antibiotics Rinsing only pathologic fracture

resorption of Inferior border of mandible

Response no response

10x (100% O2 for 90 mins at 2.4 ATA)Stage I responder

Stage II Stage III

Stage II

Surgery maintain inferior border

10x (100% O2 for 90 mins at 2.4 ATA)

Response no response

Stage II responder Healing with out exposed bone

stage III Excision of nonviable bone Fixation of mandibular segments 10x (100% O2 for 90 mins at 2.4 ATA)

Reconstruction after three months

No HBO Required

Protocol of hyperbaric oxygen for elective surgery.

20 sessions of hyperbaric oxygen prior to elective surgery, followed by 10 sessions after surgery

100% oxygen at 2.4 atmospheric pressure or ATA for 90 treatment minutes

single person chambers 120 treatment minutes

The elective surgery protocol is used in all elective surgery in radiated tissue, which may range from tooth extraction, to bone graft reconstruction to vascularized pedicled and free anatomic transfers

effects of hyperbaric oxygen are permanent,

Absolute contraindication

Optic neuritis – exacerbation of retinal inflammation and hyperemia

Immunosuppressive disorders- reports of viral encephalitis

Relative contraindication

Chronic obstructive pulmonary disease

Bullous lung change and significant CO2 retention

Claustrophobia. Acute respiratory infections Surgery induced Eustachian tube

dysfunction

Hyper baric oxygen in therapeutic management of osteoradionecrosis of facial bones

S Vudiniabola, P J Williamson, A N GossInt J Oral Maxillofac Surg 2000;

29:435-438

Have reviewed 17 cases of facial bone osteoradionecrosis treated according to Marx protocol plus or minus surgery

Dental extraction was the cause in 9 cases.

Three cases of temporal bone ORN were of spontaneous onset.

All were stage I responded well to HBO

FREE OMENTAL TRANSFER FOR ORN OF MANDIBLE

Int J Oral Maxillofac Surg 2000 :29:201-206 K.Wataru, K Makoto et.al

Omentum is an intra abdominal organ rich in vascular and lymphatic plexus.

McLEAN &BUNCKE first to use greater omentum

Moran and Panje use it for ORN of mandible.

4 cases treated with same no recurrence

Advantages

The natural mandibular contour and continuity can be preserved

Can be used regardless of size of defect

No need for bone grafting Short procedure compared to

osteocutaneous flaps

CONCLUSION

ORN is best defined as a slow healing radiation induced ischemic necrosis of bone with associated soft tissue necrosis of variable extent occurring in absence of local primary, tumor necrosis, recurrence or metastatic disease that may or may not

Be super infected And companied by fistulation End in pathologic fracture Resolve with out surgery HBO or both

THANK YOU