Osteoradionecrosis of the Jaw

Osteoradionecrosis (ORN) of the jaw is a chronic, non-healing area of exposed, devitalised irradiated bone that persists for at least 3 months without recurrent tumour. It follows high dose head and neck radiotherapy for oral, oropharyngeal and nasopharyngeal cancer, with the mandible affected in over 90 percent of cases. Incidence is 5 to 15 percent in older series and 2 to 5 percent with intensity modulated radiotherapy.

The mechanism is hypoxia, hypovascularity and hypocellularity (the 3H model), with radiation induced fibroatrophy and impaired healing after injury. Mandibular dose above 60 Gy (over 70 Gy confers the highest risk), concurrent chemotherapy, smoking, alcohol, poor dental hygiene, dental extraction in irradiated bone (the commonest trigger), advanced tumour stage and oral mucosal ulceration increase the risk.

It can occur years after radiotherapy and persists for life. Staging used by many surgeons: stage 1 (exposed bone with no pathological fracture, responsive to conservative care), stage 2 (non-responsive stage 1, needs sequestrectomy), stage 3 (pathological fracture, orocutaneous fistula, or radiographic osteolysis to the inferior border).

• Exposed necrotic, yellow white bone in the irradiated jaw with a surrounding rim of inflamed, thin, atrophic mucosa.
• Pain (variable, can be severe), halitosis, bad taste, dysphagia, trismus.
• Purulent discharge, fistula (intraoral or cutaneous), tooth mobility, paraesthesia or anaesthesia of lip (inferior alveolar nerve).
• Pathological mandibular fracture, malocclusion, and weight loss.
• Red flags: orocutaneous fistula, fracture, uncontrolled infection, rapid progression, mass lesion suggesting recurrent tumour, systemic fever, and cervical spread.

• Clinical diagnosis: exposed bone for over 3 months in an irradiated field, no tumour on biopsy.
• Radiotherapy records (dose and field) to determine bone dose.
• Panoramic radiograph: moth eaten radiolucency, osteolysis, sequestra, cortical break, pathological fracture; cone beam CT or CT gives better delineation.
• MRI to assess marrow involvement and soft tissue; bone scintigraphy and PET-CT to exclude tumour recurrence.
• Biopsy: where suspicious for recurrence, takes a specimen for histology (necrotic bone with absent osteocytes, empty lacunae, fibrosis, bacterial colonies) and culture (Actinomyces and polymicrobial flora).
• Exclude recurrent carcinoma, osteomyelitis, MRONJ, odontogenic infection, dry socket, and osteosarcoma.

• Prevention: dental assessment with extraction of non-restorable teeth at least 14 to 21 days before radiotherapy; high fluoride toothpaste 5000 ppm twice daily, fluoride trays; oral hygiene; avoid post-radiotherapy extractions where possible; when extractions are necessary, use atraumatic technique with antibiotic cover and pentoxifylline 400 mg twice daily with tocopherol 1000 IU daily for 1 month before and 3 months after, or hyperbaric oxygen 20 sessions before and 10 after.
• Stage 1: conservative: chlorhexidine gluconate 0.2 percent mouthwash 10 mL twice daily, saline rinses, careful removal of loose sequestra, analgesia with paracetamol 1 g every 6 hours, and avoid denture trauma.
• Medical therapy for stage 1 to 2: pentoxifylline 400 mg orally twice daily (800 mg daily) with tocopherol (vitamin E) 1000 IU orally once daily and clodronate 1600 mg orally daily (800 mg twice daily, 5 days a week) for 6 to 12 months (the combination reduces fibrosis and promotes bone healing); monitor renal function and calcium; give pentoxifylline with food.
• Antibiotics for acute infection or exacerbation: amoxicillin 500 mg orally every 8 hours with metronidazole 400 mg every 8 hours for 7 to 14 days (clindamycin 300 mg every 6 hours if penicillin allergic); longer low dose courses in persistent cases.
• Hyperbaric oxygen 2.0 to 2.5 atmospheres for 90 minutes daily for 30 sessions before and 10 sessions after surgery, in selected stage 2 to 3 patients; benefit is debated and access is limited.
• Surgery: debridement and sequestrectomy for stage 2; segmental mandibulectomy with reconstruction (vascularised fibula free flap) for stage 3, with fracture, fistula and uncontrolled infection.
• Pain: paracetamol 1 g every 6 hours, gabapentin 300 mg at night titrated to 600 mg three times daily for neuropathic pain, and opioid when needed.
• Nutrition: dietician review, nasogastric or gastrostomy feeding in dysphagia or trismus; trismus physiotherapy.
• Follow up: monthly until stable, then 3-monthly; dental review every 3 months for life.
• Counselling: stop smoking and alcohol, tell all dentists about previous radiotherapy.