Mandible Osteoradionecrosis

Article Author:
Levi Zehr
Article Editor:
Jeffrey Cooper
Updated:
2/28/2019 9:46:55 PM
PubMed Link:
Mandible Osteoradionecrosis

Introduction

Osteoradionecrosis (ORN) of the mandible is a severe iatrogenic disease of nonvital bone caused by radiation therapy of oral and oropharyngeal cancers. It is a state of injured bone tissue with inadequate healing or remodeling response of at least three to six months. The wound can result from radiotherapy combined with mechanical insult or radiotherapy exposure alone. ORN is separate from primary bone infection or secondary malignancy.[1][2][3][4]

Etiology

Radiation is a useful tool in the treatment of various cancers by damaging DNA and preventing cells from completing mitosis. Radiotherapy indiscriminately damages cells whether they are malignant or normal. Radiotherapy can cause a progressive endarteritis and subsequent reduction of tissue perfusion in areas exposed to radiation. The loss of cellularity along with impaired tissue repair mechanisms limit successful healing of the bone leaving a chronic non-healing wound.

Epidemiology

Since the 1970s the incidence of ORN caused by radiation is around 3%. ORN presents an average of two to four years after completion of radiation treatments. Most notably, the incidence is affected by radiation dose and also mechanical injury anytime, indefinitely, beyond radiotherapy initiation. ORN can occur years after radiotherapy both spontaneously or induced by an insult. Mechanical insults such as dental extractions and poorly fitting dentures less than two weeks before and anytime after radiotherapy can increase the risk of developing ORN.

Pathophysiology

ORN results from a sequence of injury events beginning with radiation exposure and often followed by surgical manipulation of the tissue. The irradiated mandible and surrounding tissues develop hyperemia, inflammation, and obliterative endarteritis. The small vessels thrombose causing hypovascular-hypocellular-hypoxic tissue which undergoes tissue breakdown. The rate of cell death and collagen lysis exceeds the homeostasis of cell replacement and collagen synthesis. The inability to repair leads to further inadequate vasculature and oxygen delivery. The overall result is a chronic, aseptic, non-healing wound.[5][6]

Toxicokinetics

The most recent studies find ORN is rarely reported at total radiation dose less than 6000 rads in six weeks. The next two dose ranges and their ORN incidences are 6000-7000 (1.8%) and  > 7000 (9%) rads in seven weeks.

History and Physical

Symptoms include mouth pain, jaw swelling, foul smelling breath, mouth sores, and difficulty opening jaw. Determine history of dental procedures or mouth trauma and then correlate to when radiotherapy was done. Signs of exposed bone, pathologic fractures, malocclusion, trismus, mucosal ulcers, and oral-cutaneous fistulas may be seen.

Evaluation

The evaluation should include:

  • Review radiotherapy and dental record

  • Biopsy of wound

  • Panographic Radiographs

  • CT of mandible

  • Stage the disease

Rule out recurrence/persistence of primary malignancy or new secondary malignancy by getting a biopsy of the wound.[7][8][9][10]

Imaging studies aid diagnosis and quantifies the extent of disease.

CT findings:

  • Cortical bone disruption with mixed lysis and sclerosis can be seen. Pathologic fractures can also be seen.

Panographic radiograph findings:

  • Plain radiographs are useful for screening but can underestimate the extent of lesions.

  • Lytic areas, with ill-defined, non-sclerotic borders can be seen.

Gather record of radiotherapy and review treatment method, radiation portal, and total dose.

Marx Staging of ORN is most common staging system in use. It is based on response to hyperbaric oxygen therapy (HBO).

  • Stage 1

    • Exposed alveolar bone without pathologic fracture, which responds to hyperbaric oxygen therapy and minor bony debridement

  • Stage 2

    • The disease does not respond to 30 daily HBO treatments with minor bony debridement, or it requires major bony debridement initially. They are then considered Stage 2 and receive more radical surgical debridement plus ten postoperative HBO treatments.

  • Stage 3

    • Failed treatment in stage 1 or 2 or initially present with signs below:

      • Pathologic fracture

      • Orocutaneous fistulae

      • Evidence of lytic involvement of inferior mandibular border

    • Treatment involves mandibular segmental resection of all necrotic bone and 30 preoperative and ten postoperative HBO treatments.

Treatment / Management

Prevention of ORN is extremely important. The approach to ORN treatment is separated into two phases: pre-radiotherapy prevention and ORN rehabilitation. ORN can be managed dentally, medically, surgically, and with hyperbaric oxygen.[11][12][13]

The pre-radiotherapy phase of a patient who will be undergoing radiotherapy of the oral cavity includes pretreatment dental evaluation and management by a dentist experienced with head and neck cancers. The pretreatment evaluation should include full mouth radiographs, dental and periodontal diagnosis, and extraction of teeth with poor prognosis. Tooth extraction should ideally occur at least two weeks before radiotherapy. Optimal dental health is necessary for lowest risk of ORN. Dental prophylaxis and management should occur before during and after radiotherapy. Medical treatment plays a small role in prevention and management of ORN. Maintaining adequate nutrition and saline irrigation helps to manage oral mucositis. Antibiotics are only necessary when a definitive secondary infection is also present. Pentoxifylline, an anti-inflammatory and vasodilator, has been useful for treating soft-tissue involvement.

Treating diagnosed ORN requires surgical intervention. The non-viable bone will need to be removed. For planned surgery or tooth extraction in a tissue area that has already received greater than 60 Gy, HBO should be utilized prophylactically. The role of HBO is to promote angiogenesis in hypoxic tissues thus promoting optimal reparative conditions.The standard HBO protocol includes 30 preoperative and ten postoperative treatments. The treatments occur at 2-2.5 atmospheres for 90–120 minutes done one treatment per day, five days per week. Removal of non-viable bone and replacement with a free flap graft using microvascular techniques allows the mandible to regain function.

Pearls and Other Issues

Unavoidable post-radiotherapy extractions require careful planning and management. ORN risk similar to pre-radiotherapy extractions can be accomplished with HBO before and after extraction. The protocol is 20 pre-extraction treatments and ten post-extraction treatments to 2.4 atmospheres for 90 minutes, one treatment per day, five days per week.

Bisphosphate-related osteonecrosis of the jaw (BRONJ) is a separate disease sharing some similarities to ORN of the mandible. The etiology of BRONJ is due to bisphosphate usage often combined with trauma to dentoalveolar tissues. Both diseases result in a chronic, poorly healing the wound of the bone. Differentiating the two relies on the clinical history and imaging. ORN has a history of radiation exposure and has osteolytic lesions on CT imaging. BRONJ has a history of bisphosphate usage and more likely to have osteosclerotic lesions on CT imaging. Differentiating the two is important as the treatment approach is distinctly oppositional. BRONJ is more likely to respond to medical treatment without the need for surgical interventions. As discussed, ORN is primarily treated surgically.

Enhancing Healthcare Team Outcomes

The diagnosis and management of ORN is with a multidisciplinary team that includes a dentist, oral maxilofacial surgeon, pharmacist, hyperbaric medicine specialist and a dental nurse. 

Prevention of ORN is extremely important. The approach to ORN treatment is separated into two phases: pre-radiotherapy prevention and ORN rehabilitation. ORN can be managed dentally, medically, surgically, and with hyperbaric oxygen.

The pre-radiotherapy phase of a patient who will be undergoing radiotherapy of the oral cavity includes pretreatment dental evaluation and management by a dentist experienced with head and neck cancers. The pretreatment evaluation should include full mouth radiographs, dental and periodontal diagnosis, and extraction of teeth with poor prognosis. Medical treatment plays a small role in prevention and management of ORN. Maintaining adequate nutrition and saline irrigation helps to manage oral mucositis. 

Treating diagnosed ORN requires surgical intervention. The non-viable bone will need to be removed. For planned surgery or tooth extraction in a tissue area that has already received greater than 60 Gy, HBO should be utilized prophylactically. The role of HBO is to promote angiogenesis in hypoxic tissues thus promoting optimal reparative conditions.

The prognosis of patients with ORN is guarded.[14] (Level V)


References

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