Mandible Osteoradionecrosis


Article Author:
Levi Zehr


Article Editor:
Jeffrey Cooper


Editors In Chief:
Neha Amin
Manuj Agarwal


Managing Editors:
Avais Raja
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Khalid Alsayouri
Kyle Blair
Trevor Nezwek
Radia Jamil
Erin Hughes
Patrick Le
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Hassam Zulfiqar
Navid Mahabadi
Hussain Sajjad
Steve Bhimji
Muhammad Hashmi
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Sarosh Vaqar
Mark Pellegrini
James Hughes
Beata Beatty
Daniyal Ameen
Altif Muneeb
Beenish Sohail
Nazia Sadiq
Hajira Basit
Phillip Hynes
Komal Shaheen
Sandeep Sekhon


Updated:
2/28/2019 9:46:55 PM

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)


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Mandible Osteoradionecrosis - Questions

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Which of the following has NOT been reported to be a useful aid when determining the extent of resection necessary for a patient with osteoradionecrosis (ORN)?



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A 60-year-old male with a history of 40 pack years of smoking and chewing tobacco abuse was recently diagnosed with squamous cell carcinoma of the floor of the mouth. The lesion was previously treated with antibiotics and oral saline rinses without success prompting a biopsy and subsequent cancer diagnosis. FDG-PET/CT shows enhancement only in the primary lesion without regional lymph node enhancement. The planned treatment will include surgical resection with regional lymph node dissection for staging and probable radiation therapy (radiotherapy). What is the most important preventative measure to decrease the risk of osteoradionecrosis before radiotherapy is started?



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A 55-year-old male presents after a course of radiation therapy for squamous cell carcinoma of the tongue with a non-healing oral lesion and exposed bone. When gathering information, what is a highly influential factor for an increased incidence of osteoradionecrosis of the mandible?



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What is the mechanism of action for hyperbaric oxygen (HBO) therapy in the management of delayed radiation-induced tissue damage?



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What is the ideal treatment sequence for stage III osteoradionecrosis of the mandible according to the Marx Protocol using hyperbaric oxygen treatments (HBOT) and surgical resection?



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What is included in the initial treatment of stage III osteoradionecrosis of the mandible according to the Marx protocol?



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Mandible Osteoradionecrosis - References

References

Renda L,Tsai TY,Huang JJ,Ito R,Hsieh WC,Kao HK,Hung SY,Huang Y,Huang YC,Chang YL,Cheng MH,Chang KP, A nomogram to predict osteoradionecrosis in oral cancer after marginal mandibulectomy and radiotherapy. The Laryngoscope. 2019 Feb 20;     [PubMed]
Toledano-Serrabona J,Párraga-Manzol G,Sánchez-Garcés MÁ,Gay-Escoda C, Osteoradionecrosis of the jaws triggered by dental implants placement: A case report. Journal of clinical and experimental dentistry. 2019 Jan;     [PubMed]
Stranix JT,Stern CS,Rensberger M,Ganly I,Boyle JO,Allen RJ Jr,Disa JJ,Mehrara BJ,Garfein ES,Matros E, A Virtual Surgical Planning Algorithm for Delayed Maxillomandibular Reconstruction. Plastic and reconstructive surgery. 2019 Jan 21;     [PubMed]
Feng Z,Wang C,Li B,Kim K,Li J,Mao M,Qin L,Li H,Han Z, A pilot study of modified resection for anterior floor of the mouth squamous cell carcinoma without infiltration of the mandible. Journal of cranio-maxillo-facial surgery : official publication of the European Association for Cranio-Maxillo-Facial Surgery. 2019 Mar;     [PubMed]
Sharif KF,Baik FM,Yue LE,Qazi M,Brandwein-Weber M,Khorsandi AS,Urken ML, Osteoradionecrosis of the hyoid bone complicated by pharyngocutaneous fistula: A case report and literature review. American journal of otolaryngology. 2019 Mar - Apr;     [PubMed]
Dekker H,Bravenboer N,van Dijk D,Bloemena E,Rietveld DHF,Ten Bruggenkate CM,Schulten EAJM, The irradiated human mandible: A quantitative study on bone vascularity. Oral oncology. 2018 Dec;     [PubMed]
Liu Z,Cao Y,Ma C,Sun J,Zhang C,He Y, Nomogram model to predict postoperative relapse after mandibular osteoradionecrosis surgery. Journal of cranio-maxillo-facial surgery : official publication of the European Association for Cranio-Maxillo-Facial Surgery. 2018 Nov;     [PubMed]
van de Meent MM,Pichardo SEC,Rodrigues MF,Verbist BM,van Merkesteyn JPR, Radiographic characteristics of chronic diffuse sclerosing osteomyelitis/tendoperiostitis of the mandible: A comparison with chronic suppurative osteomyelitis and osteoradionecrosis. Journal of cranio-maxillo-facial surgery : official publication of the European Association for Cranio-Maxillo-Facial Surgery. 2018 Sep;     [PubMed]
Menapace DC,Van Abel KM,Jackson RS,Moore EJ, Primary vs Secondary Endosseous Implantation After Fibular Free Tissue Reconstruction of the Mandible for Osteoradionecrosis. JAMA facial plastic surgery. 2018 Sep 1;     [PubMed]
Raggio BS,Winters R, Modern management of osteoradionecrosis. Current opinion in otolaryngology     [PubMed]
Silvestre-Rangil J,Silvestre FJ, Clinico-therapeutic management of osteoradionecrosis: a literature review and update. Medicina oral, patologia oral y cirugia bucal. 2011 Nov 1;     [PubMed]
Chaine A,Pitak-Arnnop P,Hivelin M,Dhanuthai K,Bertrand JC,Bertolus C, Postoperative complications of fibular free flaps in mandibular reconstruction: an analysis of 25 consecutive cases. Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics. 2009 Oct;     [PubMed]
Teng MS,Futran ND, Osteoradionecrosis of the mandible. Current opinion in otolaryngology     [PubMed]
Löfstrand J,Nyberg M,Karlsson T,Thórarinsson A,Kjeller G,Lidén M,Fröjd V, Quality of Life after Free Fibula Flap Reconstruction of Segmental Mandibular Defects. Journal of reconstructive microsurgery. 2018 Feb;     [PubMed]
Shaw RJ,Butterworth CJ,Silcocks P,Tesfaye BT,Bickerstaffe M,Jackson R,Kanatas A,Nixon P,McCaul J,Praveen P,Lowe T,Blanco-Guzman M,Forner L,Brennan P,Fardy M,Parkin R,Smerdon G,Stephenson R,Cope T,Glover M, HOPON (Hyperbaric Oxygen for the Prevention of Osteoradionecrosis): a randomised controlled trial of hyperbaric oxygen to prevent osteoradionecrosis of the irradiated mandible after dentoalveolar surgery. International journal of radiation oncology, biology, physics. 2019 Mar 6;     [PubMed]

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