Introduction

Treatment of malignancies with ionizing radiation has saved countless lives in the past 50 years. However, a small percentage of patients treated with radiation for head and neck cancers will develop osteoradionecrosis (ORN) of the jaw. Patients treated with more than 6000 centigrays (cGy) of radiation have an approximately 9% incidence of developing mandibular osteoradionecrosis. A newer radiation technique called intensity-modulated radiation therapy (IMRT) has been reported to have a lower incidence of mandibular osteoradionecrosis.  Some of these patients will develop exposed intraoral mandibular bone. Many of these patients will go on to heal spontaneously and without complications, but some will develop osteomyelitis and even fractures of the mandible leading to eventual soft tissue necrosis.[1][2]

Hyperbaric oxygen treatment has become a mainstay treatment for osteoradionecrosis. An interprofessional team consisting of oral maxillofacial surgeons, dentists, undersea and hyperbaric medicine specialists, infectious disease specialists, and radiation oncologists can optimize treatment for patients who develop osteoradionecrosis as a complication of radiation treatment. Hyperbaric treatments should be given adjunctively with surgical debridement and appropriate culture-directed antibiotic therapy to provide the most optimal outcome.

Etiology

Osteoradionecrosis of the jaw (ORN) is a late effect of radiation therapy. Previously irradiated head and neck tissues become hypovascular and hypoxic. If in the irradiated field, the mandible may develop aseptic, avascular necrosis which can lead to infection, tooth loss, and even pathological fracture of the jaw. Osteoradionecrosis is rarely seen in patients who received less than 6000 centiGrays (cGy) of radiation and may occur years or even decades after radiation is concluded.[3][4]

Epidemiology

Osteoradionecrosis occurs in approximately nine percent (9%) of patients who receive more than 7000 cGy of ionizing radiation to treat a head or neck malignancy, two percent (2%) of patients receiving 6000 cGy to 7000 cGy, and almost no patients who receive less than 6000 cGy. Tooth extraction in a previously irradiated field is also a potential precipitant of osteoradionecrosis in the mandible.

Patients affected by osteoradionecrosis are typically older than 55 years of age.[5][6][7] It is also found that up to one-fifth of patients with aggressive osteoradionecrosis that does not respond to aggressive treatment have bone damage caused by recurrent malignancy or a tumor secondary to original radiation treatment.[8][6]

Pathophysiology

Osteoradionecrosis occurs in patients who have been previously exposed to ionizing radiation to treat head and neck cancers. The radiation leaves the bony and soft tissues with poor vascularity, resulting in a picture of avascular necrosis in the mandible. Patients may develop areas of exposed bone in the mouth and resultant loss of teeth and supporting structures. The resulting chronic infections can lead to osteomyelitis and soft tissue orocutaneous fistulae.[9]

Histopathology

There is a chronic inflammatory phase followed by fibrosis. The final phase is a fibro-atrophic phase with dense hyalinization and fibrosis with loss of marrow cells. There can be osteomyelitis, reactive squamous mucosa, necrotic or sclerotic bone, marrow fibrosis, and marrow necrosis overlying the above.

History and Physical

A thorough exam of the oral cavity using a dental mirror and tongue depressor is indicated. The condition of the teeth should be noted as well as any that are already missing or are going to need extraction. The tongue and gingiva should be inspected. Any exposed bone should be measured and documented. Any draining sinuses or fistulae should be documented. Palpation of the cervical, posterior auricular, and axillary lymph nodes should be done and results documented. The timing and dose of radiation should be requested from the radiation oncologist. Any chemotherapy given should be documented as well as start and completion dates noted. The presence of xerostomia, dysphagia, dysphonia and ageusia should be noted.

Evaluation

Imaging such as radiographs, panorax images, computed tomography (CT), magnetic resonance imaging (MRI) should be reviewed. There are no lab studies that are diagnostic for osteoradionecrosis (ORN) of the jaw per se other than biopsy. Sedimentation rate and C-reactive protein (CRP) may be elevated in osteomyelitis.

Treatment / Management

Treatment of osteoradionecrosis requires an interprofessional approach. Patients should be managed by surgery, infectious disease, radiology, and hyperbaric medicine specialists. None of these treatments can exist in a vacuum and if attempted separately, will likely not be successful. Patients should be staged and treated with surgical intervention and perioperative hyperbaric treatments as noted based on the stage of the osteoradionecrosis. All necrotic bone must be removed.[10] More advanced cases may benefit from the addition of pentoxifylline and tocopherol (PENTO treatment).[11]

Osteoradionecrosis is the result of an avascular, aseptic necrosis. Much of the pioneering studies on hyperbaric oxygen for osteoradionecrosis were done by Robert Marx, DDS who developed a staging system and treatment protocols for osteoradionecrosis. Marx's scale classifies mandibular necrosis and is used to describe the severity of the osteoradionecrosis.

Scale of Osteoradionecrosis

Stage I: Patients with exposed bone that has been chronically present or which developed rapidly. Patients are treated with 30 hyperbaric treatments preoperatively followed by bony debridement. Postoperatively they are given an additional ten treatments.

Stage II: These are patients who do not respond favorably to 30 pre-operative treatments, or when a more major operative debridement is required. Surgery for stage II osteoradionecrosis patients must be focused on preserving the integrity of the mandible. If mandibular resection is anticipated, patients are advanced to Stage III.

Stage III: Along with patients who have progressed from stages I and II, patients with stage III osteoradionecrosis have serious and potentially grave prognostic findings such as pathologic fracture, percutaneous fistulae, and lytic lesions that extend to the inferior border of the mandible. For patients with stage III osteoradionecrosis, mandibular resection is planned as part of the surgical treatment. It is critical that all necrotic bone be debrided and removed in stage III patients. Stage III osteoradionecrosis patients receive 30 treatments preoperatively followed by ten hyperbaric oxygen treatments postoperatively.[12][13][14][12]

Differential Diagnosis

In the evaluation of osteoradionecrosis, providers must consider wide differential diagnoses.

• Providers should consider a potential recurrence of the original malignancy or a radiation-induced secondary tumor.
• Osteomyelitis is a concomitant condition that must be treated with antibiotics.
• Bisphosphonate related osteonecrosis of the jaw must also be excluded, as osteonecrosis of the jaw is a well-known complication of the medication's use. A careful medical history will help to rule out this diagnosis.

Prognosis

Patients originally treated with antibiotics, hyperbaric oxygen therapy, and surgical debridement generally experienced a favorable clinical outcome. Those with advanced osteoradionecrosis of the jaw who do not respond to conventional treatment methods could be treated with pentoxifylline and tocopherol therapy, with reports indicating a 60% incidence of full recovery or significant improvement.[11]

Complications

Osteoradionecrosis often results in the following complications:

• Ulceration and necrosis of the mucosa with exposed bone, inevitably leading to infection and necrotic bone.
• Exposed bone often leads to irritation of surrounding oral soft tissues.
• Pathologic fractures can form in the weakened bone.
• Fistulae are a sign of spreading local infection, and can ultimately lead to systemic infection and even sepsis if not appropriately managed.[15]

Deterrence and Patient Education

While the incidence of osteoradionecrosis has decreased over the years, it is still a known complication of radiation treatment to the head and neck, and should be discussed with patients prior to any radiation treatment as a potential complication. Minimizing radiation treatment can help to prevent the incidence of this complication, and prompt evaluation can expedite appropriate treatment, minimizing complications.

Pearls and Other Issues

The addition of hyperbaric oxygen treatment improves the tissue response to surgical wounding and improves the patient's chances of healing after surgical resection or reconstruction of the mandible. Perioperative prophylactic hyperbaric oxygen treatment is recommended for patients with previous head and neck irradiation who are undergoing dental extractions or complete exodontia procedures again to increase the blood flow, oxygenation, and penetration of bone by antibiotics. Studies have shown a reduction from 30% to 5% incidence of osteoradionecrosis with the use of prophylactic hyperbaric oxygen treatment. Dentists are encouraged to refer patients at risk to hyperbaric medicine for consultation before tooth extraction in previously irradiated fields. Before beginning radiation therapy all patients should undergo a thorough dental evaluation. Prophylactic extraction before radiotherapy can preclude osteoradionecrosis issues later.

Enhancing Healthcare Team Outcomes

The management of osteoradionecrosis is best done with an interprofessional team that includes providers, pharmacists, and nurses across the fields of oral surgery, infectious disease, radiology, and hyperbaric medicine. None of these treatments can exist in a vacuum and if attempted separately, will likely not be successful. Patients should be staged and treated with perioperative hyperbaric treatments and antibiotic therapy, with surgery as needed based on the stage of the osteoradionecrosis. All necrotic bone must be surgically removed.