OSTEORADIONECROSIS

ABEL ABRAHAM
III MDS
TABLE OF CONTENTS

 INTRODUCTION
 DEFINITION
 THEORIES OF PATHOGENESIS
 CURRENT CONCEPT
 CLASSIFICATION SYSTEMS
 RISK FACTORS
 CLINICAL FINDINGS
 RADIOGRAPHIC FINDINGS
 CONSERVATIVE MANAGEMENT
 SURGICAL MANAGEMENT
 CONCLUSION
INTRODUCTION

 Malignancies of the maxillofacial region continue to plague our patients and often occupy
a large portion of our practices
 Radiation therapy plays a valuable role in treatment of maxillofacial malignancies, but it
also has well-known and very real complications.
 The most dreaded complication of radiation therapy to the jaws is the development of
osteoradionecrosis (ORN).
 In 1922, Regaud published what was arguably the first report about osteoradionecrosis
(ORN) of the jaws after radiotherapy.
 During the past 80 years, this condition has persisted as a consequence of radiotherapy for
head and neck cancer in an appreciable minority of patients
DEFINITION

 Ewing was the first to use the term ‘radiation osteitis’

 In 1974, Guttenberg proposed the term ‘septic ORN of the mandible’ to describe the stage
of necrosis when irradiated bone becomes superficially infected
 In 1983, Marx defined ORN as ‘an area >1 cm of exposed bone in a field of irradiation
that failed to show any evidence of healing for at least 6 months’
 In 1987, Marx and Johnson suggested the definition of ORN as: ‘The exposure of
nonviable bone which fails to heal without intervention
 According to the literature published in the last 15 years, ORN of the jaws is defined as
exposed irradiated bone that fails to heal over a period of 3 months without evidence of
persisting or recurrent tumour with no history of bisphosphonate use.
THEORIES OF PATHOPHYSIOLOGY

 Watson and Scarborough reported three crucial factors: ; exposure to radiotherapy above a
critical dose; local injury; and infection
 Meyer suggested that injury provided the opening for invasion of oral microbiological
flora into the underlying irradiated bone
 Marx proposed the hypoxic-hypocellular-hypovascular theory
 Marx concluded, “ORN is not a primary infection of irradiated bone, but a complex
metabolic and homeostatic deficiency of tissue that is created by radiation-induced
cellular injury; micro-organisms play only a contaminating role in ORN; and trauma may
or may not be an initiating factor”
CONTEMPORARY UNDERSTANDING

 Radiation-induced fibrosis was introduced in 2004

 The histopathological phases of the development of ORN closely reflect those seen in
chronic healing of traumatic wounds
 Three distinct phases are seen
 The initial prefibrotic phase
 The constitutive organised phase
 The late fibroatrophic phase
CLASSIFICATION SYSTEMS
RISK FACTORS
CLINICAL FINDINGS

 Ulceration or necrosis of the mucosa with exposure of necrotic bone for longer
than 3 months,
 Suppuration in the area
 Neurological symptoms, such as pain, dysaesthesia or anaesthesia, as well as
fetor oris, dysgeusia and food impaction in the area
 Exposure of rough and irregular bone can result in physical irritation of
adjacent tissues.
 Progression of ORN may lead to pathological fractures,
intra-oral or extra-oral fistulae and local or systemic
infection.
 Difficulties in mouth opening, mastication and speech
frequently arise
 In patients treated with external beam radiation therapy
(EBRT), osseous alterations usually appear in the body of
the mandible (premolar and molar regions)
 In those managed with brachytherapy, the lingual or buccal
surfaces are affected
 The diagnosis of septic ORN appears to be easier.
 Marked pain is the primary symptom.
 Intra- or extra-oral draining fistulae, ulcerations of the mucous membrane
 Exposed devitalised bone
 Haemorrhage, cellulitis or pathological fractures.
 A biopsy is mandatory for final diagnosis in order to exclude metastatic cancer
RADIOLOGICAL FINDINGS

 OPG - mandibular ORN usually appears as

inhomogeneous lytic areas, interspersed with zones of
increased radiodensity, sometimes associated with a
pathologic fracture, and radiopaque sequestra may be
seen
 CT - Can help distinguish between bone
destruction related to ORN and that
associated with tumor recurrence. Also,
interruptions in the cortical margins of the
mandible are nearly always seen, and bone
fragmentation is often present
 MRI shows altered bone marrow signal intensities in the mandibular parts involved by
ORN. These areas show abnormal, homogeneous, low-marrow signal intensity on T1-
weighted images; increased signal intensity on T2-weighted images .
 On both MRI and CT scanning, the occurrence of abnormal findings distant or
contralateral to the site of the primary tumor, and a long interval (>2 years) between
primary tumor treatment and onset of symptoms suggest the diagnosis of ORN
 Radionuclide bone scanning with technetium methylene diphosphonate can identify
osteoblastic activity, and can detect bony changes earlier than conventional radiography
PREVENTION

 Criteria for the extraction of teeth before radiation therapy include moderate to advanced
periodontal disease (pocket-depth of more than 5 mm);
 extensive periapical lesions of the roots;
 extensive tooth decay;
 partially impacted or incompletely erupted teeth; and
 residual root tips not fully covered by bone or showing radiolucency
 Extractions should be performed atraumatically with careful tissue handling, with
alveolotomy and primary wound closure when possible.
 An interval of 2 to 3 weeks’ healing time between tooth extraction and the onset of
radiation therapy is recommended
Role of Intensity-Modulated Radiation
Therapy

 IMRT allows for higher doses of radiation to be targeted at the tumor and minimizes
collateral damage to the adjacent normal tissue.
 Decreasing radiation exposure to the mandible has the potential to decrease ORN.
 Ahmed et al showed that IMRT decreased the total maximum radiation dose to the
mandible and also decreased the volume of the mandible that was exposed to higher doses
of 50, 55, and 60 Gy
CONSERVATIVE MANAGEMENT

 Avoidance of irritants such as tobacco, alcohol, and ill-fitting dentures

 Weekly physician visits that involve local debridement with antiseptic solutions including
chlorhexidine, sodium iodide, and peroxide.
 Systemic antibiotics are saved for episodes of acute infection.
 Fixation plates and screws are removed if they appear to be a contributing factor.
 Analgesics and anti-inflammatories are prescribed when necessary.
 Reduction of local irritants such as alcohol or tobacco.
Hyperbaric Oxygen

 During HBOT, patients breathe 100% oxygen at increased pressures (2–3 atm).
 This results in the increase of the tissue oxygen pressure
 Leads to augmented endothelial cell and fibroblast proliferation.
 In the long term it stimulates collagen synthesis, matrix deposition, angiogenesis, and
epithelialization which, in turn, promotes wound healing
Current protocol:
 20 to 30 dives at 2.0 to 2.5 atmospheres for 90 to 120 minutes at each session, once a day
for 5 days. If a dental extraction or surgical procedure is performed, the patient takes an
additional 10 dives.
Complications include:
 Eustachian tube dysfunction, middle ear barotrauma, seizure, and decompression
sickness. The main contraindications are optic neuritis and pulmonary disease
ULTRASOUND

 Ultrasound increases angiogenesis and stimulates collagen and bone production.

 Harris proposed a protocol of 40 to 50 10-minute sessions until healing is complete.
 Ultrasound can also be used as prophylaxis prior to postradiation dental extractions
Pentoxifylline-Tocopherol Combination

 Targets radiation-induced bone fibrosis and stimulates osteogenesis via the antioxidant
pathway.
 Pentoxifylline is a methlyxanthine derivative that exerts an anti–TNF-a effect,
vasodilates, and inhibits inflammatory reactions.
 Tocopherol (vitamin E) scavenges the ROS generated during oxidative stress.
 These two drugs work synergistically as potent antifibrotic agents.
SURGICAL MANAGEMENT

Indications for surgery in ORN include:

 Stage III disease,
 Involvement of the inferior borders of the mandible,
 Pathologic fracture, and
 Failed conservative management.
 Surgery involves resection of all involved necrotic bone and soft tissue, and primary
reconstruction.
 Resection is continued until the presence of healthy bleeding bone at the margin is
identified.
 The majority of the intraoral mucosa can be preserved.
 Tetracycline bone fluorescence has also been proposed as a guide to pinpoint the margins
of resection in ORN
 After resection, reconstruction options include osseous or osteocutaneous microvascular
free tissue transfer from a variety of sites including the fibula, scapula, and iliac crest.
 Based on the peroneal vessels, the fibula free flap has up to
25 cm of vascularized bone
 The periosteal blood supply is abundant and there is little variation in
bone shape along the length of the graft, permitting multiple
osteotomies to be performed as little as 1 cm apart, and allowing
great flexibility in contouring the graft to simulate the shape of the
mandible
 Regardless of which donor site is used, the goals of mandible
reconstruction are to reestablish the form of the lower third of the
face and restore the patient’s ability to eat, speak, and maintain a
patent airway
CONCLUSION

 ORN can be a devastating complication of radiation therapy after treatment of head and
neck cancer. While predisposing factors are clearly evident, there is an ongoing debate on
how best to define and classify this disease process. There is also controversy regarding
the best protocol for treatment, particularly the use of HBOT.
 Radical resection and immediate well-vascularized tissue flap reconstruction seem to be
reliable and successful methods for a patient whose ORN does not respond to
conservative nonoperative treatment.
 Preventing ORN occurrence is time consuming and demands teamwork, and the oral and
maxillofacial surgeon should minimize trauma to the jaws as much as possible, especially
for patients who need to receive postsurgical radiotherapy.
REFERENCES
 Shaw, R. J., & Dhanda, J. (2011). Hyperbaric oxygen in the management of late radiation injury to the head and neck. Part I: treatment. British
Journal of Oral and Maxillofacial Surgery, 49(1), 2–8. doi:10.1016/j.bjoms.2009.10.036 
 Rommel N, Kesting MR, Rohleder NH, Wolff KD, Weitz J. Surgical management of severe osteoradionecrosis of the mandibular bone by
using double free flap reconstruction. J Craniomaxillofac Surg. 2018 Jan;46(1):148-154. doi: 10.1016/j.jcms.2017.09.025. Epub 2017 Nov 2.
PMID: 29174551.
 Dai, T., Tian, Z., Wang, Z., Qiu, W., Zhang, Z., & He, Y. (2015). Surgical Management of Osteoradionecrosis of the Jaws. The Journal of
Craniofacial Surgery, 26(2), e175–e179. doi:10.1097/scs.0000000000001445 
 O’Dell, K., & Sinha, U. (2011). Osteoradionecrosis. Oral and Maxillofacial Surgery Clinics of North America, 23(3), 455–464.
doi:10.1016/j.coms.2011.04.011 
 Nadella KR, Kodali RM, Guttikonda LK, Jonnalagadda A. Osteoradionecrosis of the Jaws: Clinico-Therapeutic Management: A Literature
Review and Update. J Maxillofac Oral Surg. 2015;14(4):891-901. doi:10.1007/s12663-015-0762-9
 Frederik K L Spijkervet, Michael T Brennan, Douglas E Peterson, Max J H Witjes, Arjan Vissink, Research Frontiers in Oral Toxicities of
Cancer Therapies: Osteoradionecrosis of the Jaws, JNCI Monographs, Volume 2019, Issue 53, August 2019, lgz006, 
https://doi.org/10.1093/jncimonographs/lgz006
 Chronopoulos A, Zarra T, Ehrenfeld M, Otto S. Osteoradionecrosis of the jaws: definition, epidemiology, staging and clinical and radiological
findings. A concise review. International dental journal. 2018 Feb 1;68(1):22-30.
 Thorn JJ, Hansen HS, Specht L, Bastholt L. Osteoradionecrosis of the jaws: clinical characteristics and relation to the field of irradiation.
Journal of oral and maxillofacial surgery. 2000 Oct 1;58(10):1088-93.
 Glick, M. (2015). Burket's oral medicine. PMPH USA.
 Fonseca, R. J. (2017). Oral and Maxillofacial Surgery-E-Book: 3-Volume Set. Elsevier Health Sciences.

THANK YOU