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Page 2 of 10 Mayland et al. Plast Aesthet Res 2021;8:62 https://dx.doi.org/10.20517/2347-9264.2021.38

The mean duration from completion of radiation therapy to the development of head and neck ORN is
[3]
estimated at 22-47 months . Dental extractions are commonly found to be a precipitating factor, with some
[4,5]
studies noting a recent dental extraction in 50%-60% of cases . The incidence of head and neck ORN
[3,6]
throughout the literature ranges from 3%-15% . While ORN can occur in multiple head and neck subsites,
the mandible is the most common location . The treatment of ORN is dependent on the severity of
[7]
symptoms. The following narrative focuses on patients with advanced head and neck ORN with an
emphasis on refractory cases requiring a free flap reconstruction.

CLINICAL PRESENTATION
Patients with advanced ORN commonly present with pain and exposed bone [Figure 1]. Patients with
malignancy can also present with pain; therefore, an underlying malignancy should be ruled out prior to the
start of ORN treatment. As ORN progresses, the bone may experience loss of density and strength, resulting
in a pathologic fracture and/or orocutaneous fistula.

On panorex, early stages of ORN may present with findings of sclerotic bone or a poorly defined
[8]
radiolucent lesion. Panorex may also show findings of cortication loss following dental extraction .
Common computed tomography (CT) findings of ORN include cortical defect or lucency, disorganized
bony architecture, intraosseous air, and ultimately pathologic fracture . When considering surgical
[9]
intervention, CT imaging with 1mm cuts of the maxillofacial skeleton is recommended .
[10]

NON-SURGICAL MANAGEMENT
ORN treatment typically begins conservatively, with free flap reconstruction being reserved for refractory
and advanced cases . Conservative therapy for the early-stage disease includes optimizing oral hygiene,
[11]
[12]
eliminating dental disease, and the use of systemic antibiotics . While often non-curative, these
conservative interventions can provide symptomatic relief and slow progression. Antibiotics are commonly
administered for acute infections or in the setting of chronically draining orocutaneous fistulas [Table 1].

Hyperbaric oxygen (HBO) therapy was introduced as a possible treatment for ORN in 1983 by Marx .
[13]
HBO therapy works by increasing local tissue oxygen concentrations, thereby promoting tissue
epithelialization and bone regeneration. HBO therapy is sometimes used prophylactically in patients
requiring dental extractions after radiation to potentially prevent ORN development. However, a
randomized controlled trial of previously radiated patients requiring dental extraction found HBO therapy
before dental trauma did not prevent ORN complications . Currently, there are limited data
[14]
demonstrating efficacy for the use of HBO therapy in the treatment of ORN [Table 2] [15-17] .

PENTOCLO is an antioxidant therapy that consists of pentoxifylline, tocopherol, and clodronate. Previous
publications suggest improved wound healing when patients with ORN were administered
PENTOCLO [18,19] . Pentoxifylline is thought to improve microcirculation, while tocopherol (vitamin E) acts
as an antioxidant. Clodranate is a first-generation bisphosphonate that reduces osteoclast activity and
stimulates osteoblasts. A retrospective study found that patients who received pentoxifylline and tocopherol
after radiation had a lower incidence of ORN . Dissard et al. also found that administration of the
[20]
[21]
PENTOCLO regimen daily had a low side effect profile with high rates of symptom improvement when
given antibiotics and steroids.

SURGICAL MANAGEMENT
ORN has significant quality of life (QOL) implications, including pain, infection, draining fistulas, and/or
pathologic fractures. The decision to proceed with more invasive treatments is typically dictated by the