# Osteoradionecrosis of the Jaw

## Introduction

Osteoradionecrosis (ORN) is a serious complication of radiation therapy to the head and neck, defined as exposed irradiated bone that fails to heal over a period of three months without evidence of residual or recurrent tumor. The mandible is the most commonly affected site due to its limited blood supply and dense cortical structure. The OMFS surgeon is central to both prevention and management.

## Pathophysiology

### Historical Models

Marx's "Three H" theory proposed that hypoxia, hypocellularity, and hypovascularity of irradiated bone lead to tissue breakdown, though this model has been challenged by more recent research. The radiation-induced fibroatrophic theory of Delanian and Lefaix is a more contemporary model describing three phases: a pre-fibrotic phase characterized by endothelial damage, inflammation, and free radical production; a constitutive organized phase involving abnormal fibroblast activity and progressive fibrosis; and a late fibroatrophic phase in which tissue remodeling fails, leaving fragile atrophic tissue susceptible to breakdown.

### Key Factors

A radiation dose exceeding 60 Gy to the mandible significantly increases risk. Intensity-modulated radiation therapy (IMRT) reduces dose to non-target bone and has helped lower the incidence. Radiation disrupts the periosteal and endosteal blood supply, reduces osteocyte and osteoblast populations, and impairs collagen synthesis and angiogenesis.

## Risk Factors

The radiation dose is the strongest risk factor, with doses greater than 60 Gy carrying the highest risk. Additional risk factors include tumor proximity to bone with mandibular involvement in the radiation field, dentoalveolar surgery after radiation (especially extractions), poor oral hygiene and periodontal disease, tobacco and alcohol use, concurrent chemotherapy, and poorly fitting prostheses. The posterior mandible is the most vulnerable anatomic location because it lies in a watershed vascular zone.

## Clinical Presentation

ORN presents as exposed non-vital bone in the mandible or maxilla, often accompanied by pain that may be severe. Trismus from fibrosis of the muscles of mastication is common. Purulent drainage and fistula formation (intraoral or extraoral) may develop, and pathologic fracture occurs in advanced cases. Patients may experience difficulty eating, weight loss, and significantly reduced quality of life. ORN may occur spontaneously or be triggered by trauma such as dental extraction or biopsy.

![Clinical photograph of exposed necrotic bone in the posterior mandible in a patient with osteoradionecrosis](/images/residency/omfs/orn-clinical.jpg)

## Classification (Notani Classification)

| Grade | Extent | Features |
|---|---|---|
| I | Confined to alveolar bone | Localized exposure |
| II | Extends to mandible above IAN canal | Deeper bone involvement |
| III | Full thickness of mandible | Pathologic fracture, skin fistula possible |

Grade I ORN is confined to the alveolar bone. Grade II extends to the mandible above the level of the inferior alveolar canal. Grade III extends through the full thickness of the mandible and may involve pathologic fracture or skin fistula.

## Prevention

### Pre-Radiation Dental Assessment

A comprehensive dental evaluation should be completed before initiation of radiation therapy. Non-restorable teeth and teeth with poor prognosis are extracted with a minimum of 14 to 21 days of healing time allowed before radiation begins. Periodontal treatment and caries control are completed. Custom fluoride trays are fabricated for lifelong daily fluoride application. Patients are educated on oral hygiene and the long-term risk of ORN.

### Post-Radiation Precautions

Extractions should be avoided if possible, with endodontic therapy preferred. When extraction is necessary, atraumatic technique with primary closure and perioperative antibiotics is employed. Elective surgery in heavily irradiated fields should be avoided. The role of hyperbaric oxygen (HBO) for pre-extraction prophylaxis remains controversial, as the HOPON trial showed no benefit.

## Management

### Conservative (Non-Surgical)

Conservative management includes antimicrobial mouth rinses (chlorhexidine), systemic antibiotics for secondary infection, and the PENTOCLO protocol consisting of pentoxifylline (400 mg three times daily) and tocopherol (vitamin E, 1000 IU daily). The PENTOCLO protocol promotes antifibrotic and antioxidant effects, and clodronate may be added in the full protocol. Response may take 6 to 12 months, but the regimen has been shown to reduce bone exposure in many cases. Superficial sequestrectomy of loose, devitalized bone is performed as needed. Nutritional support and pain management are integral components of care.

### Surgical

Surgery is indicated for Grade II/III ORN refractory to conservative management. Sequestrectomy and debridement with primary closure are appropriate for limited disease. Advanced ORN requires segmental mandibulectomy with free tissue transfer, and the fibula free flap is the gold standard for mandibular reconstruction, providing well-vascularized bone and soft tissue to the irradiated field and enabling future dental rehabilitation with implants. Hyperbaric oxygen therapy using the Marx protocol (20-30 dives pre-surgery, 10 post-surgery) may be considered, though its efficacy has been debated following the HOPON trial.

![Panoramic radiograph showing pathologic fracture of the mandibular body secondary to osteoradionecrosis](/images/residency/omfs/orn-pathologic-fracture.jpg)

## Hyperbaric Oxygen Therapy

The proposed mechanism of HBO is increased tissue oxygen tension, which stimulates angiogenesis and fibroblast proliferation. The Marx protocol consists of 20 pre-operative dives at 2.4 ATA for 90 minutes, followed by surgery, then 10 post-operative dives. The HOPON trial (2004), a randomized controlled trial, found no benefit of HBO for preventing ORN after extractions in irradiated patients. Current consensus holds that HBO may be considered as an adjunct but should not delay definitive surgical management. Cost and availability remain significant barriers.

![Intraoperative photograph showing segmental mandibulectomy and reconstruction with vascularized fibula free flap for advanced ORN](/images/residency/omfs/orn-fibula-reconstruction.jpg)

## Clinical Pearls

Prevention through pre-radiation dental optimization is the most effective strategy against ORN. The PENTOCLO protocol (pentoxifylline and tocopherol) is a first-line conservative treatment with growing evidence of efficacy. Pathologic fracture and extraoral fistula indicate advanced disease requiring surgical resection and free flap reconstruction. HBO remains controversial and should not delay definitive surgery in advanced cases. Close coordination with radiation oncology to minimize mandibular radiation dose using IMRT is essential.

## References

1. Marx RE. Osteoradionecrosis: a new concept of its pathophysiology. *J Oral Maxillofac Surg*. 1983;41(5):283-288.
2. Delanian S, Lefaix JL. The radiation-induced fibroatrophic process: therapeutic perspective via the antioxidant pathway. *Radiother Oncol*. 2004;73(2):119-131.
3. Annane D, Depondt J, Aubert P, et al. Hyperbaric oxygen therapy for radionecrosis of the jaw: a randomized, placebo-controlled, double-blind trial from the ORN96 study group. *J Clin Oncol*. 2004;22(24):4893-4900.
4. Rice N, Polyzois I, Ekanayake K, et al. The management of osteoradionecrosis of the jaws — a review. *Surgeon*. 2015;13(2):101-109.