Osteoradionecrosis

Article Author:
William Gossman
Article Author (Archived):
Mary Hanley
Article Editor:
Jeffrey Cooper
Updated:
6/4/2019 9:16:04 PM
PubMed Link:
Osteoradionecrosis

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 complication, but the rest can go on to be chronic and result in osteomyelitis and even fractures of the mandible. These patients may develop soft tissue necrosis as a further complication.[1][2]

Hyperbaric oxygen treatment has become a mainstay of a multidisciplinary team approach to treating osteoradionecrosis. The team must consist of oral maxillofacial surgeons, dentists, undersea and hyperbaric medicine specialists, infectious disease specialists, and radiation oncologists. Unless hyperbaric treatments are given adjunctively with surgical debridement and appropriate culture-directed antibiotic therapy, the results will not be as effective and long-lasting.

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

Stage I osteoradionecrosis: Patients with exposed bone which 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 osteoradionecrosis: 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 osteoradionecrosis: 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, or 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.[3]

Etiology

Osteoradionecrosis of the jaw (ORN) is a late effect of radiation therapy. Previously irradiated head and neck tissues become hypovascular and hypoxic. The mandible, if in the irradiated field, develops an 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 can occur years to decades after radiation is concluded.[4][5]

Epidemiology

Osteoradionecrosis occurs in approximately 9% of patients who receive more than 7000 cGy of ionizing radiation to treat a head or neck malignancy. Two percent 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 a potential precipitant of osteoradionecrosis or the jaw. 

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, hypoxia and can cause an avascular necrosis picture in bone. Patients may develop areas of exposed bone in the mouth and resultant loss of teeth and supporting structures and chronic infections which can lead to osteomyelitis and soft tissue orocutaneous fistulae.[6]

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, CT, MRI should be reviewed. There are no lab studies that are diagnostic for ORN per se other than biopsy. Sedimentation rate and C-reactive protein (CRP) may be elevated in osteomyelitis.

Treatment / Management

Treatment of osteoradionecrosis requires a multidisciplinary 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.[7]

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 afforded by hyperbaric oxygen treatment. 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 irradiated fields.

Further prevention of osteoradionecrosis is that 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 a multidisciplinary team that includes oncology nurses. 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.

The outcomes for patients with osteoradionecrosis are guarded. Surgery is often debilitating and associated with its own complications. While HBO treatment may help heal some wounds, others may go on to develop chronic osteomyelitis or cutaneous fistulas, leading to a poor quality of life.[8]


References

[1] Bettoni J,Olivetto M,Duisit J,Caula A,Bitar G,Lengele B,Testelin S,Dakpé S,Devauchelle B, Treatment of mandibular osteoradionecrosis by periosteal free flaps. The British journal of oral     [PubMed PMID: 31104917]
[2] Elakkad A,Romero-Sanchez GT,Forghani R,Ginsberg LE, Styloid Process Osteoradionecrosis: Report of 3 Cases. Journal of computer assisted tomography. 2019 May/Jun;     [PubMed PMID: 31082954]
[3] Bianco E,Maddalone M,Porcaro G,Amosso E,Baldoni M, Treatment of Osteoradionecrosis of the Jaw with Ozone in the Form of Oil-based Gel: 1-year follow-up. The journal of contemporary dental practice. 2019 Feb 1;     [PubMed PMID: 31058646]
[4] Bettoni J,Olivetto M,Bouaoud J,Devauchelle B, Technical note on the harvest of periosteal forearm composite free flaps in the treatment of early mandibular osteoradionecrotic injury. Journal of stomatology, oral and maxillofacial surgery. 2019 Apr 26;     [PubMed PMID: 31035022]
[5] Siegmund BJ,Rustemeyer J, Case report: chronic inflammatory ulcer and osteoradionecrosis of the skull following radiotherapy in early childhood. Oral and maxillofacial surgery. 2019 Apr 23;     [PubMed PMID: 31011848]
[6] West JL,Frenkel MB,Renfrow JJ,Wilson JA, Craniocervical Osteoradionecrosis Treated with Neoadjuvant and Adjuvant Hyperbaric Oxygen in Combination with Posterior Spinal Fusion. World neurosurgery. 2019 Mar 8;     [PubMed PMID: 30858001]
[7] Park MS,Eo MY,Myoung H,Kim SM,Lee JH, Early diagnosis of jaw osteomyelitis by easy digitalized panoramic analysis. Maxillofacial plastic and reconstructive surgery. 2019 Dec;     [PubMed PMID: 30800645]
[8] Kolokythas A,Rasmussen JT,Reardon J,Feng C, Management of osteoradionecrosis of the jaws with pentoxifylline-tocopherol: a systematic review of the literature and meta-analysis. International journal of oral and maxillofacial surgery. 2019 Feb;     [PubMed PMID: 30205911]