REVIEW

CURRENT
OPINION Reconstruction of the mandible
for osteoradionecrosis
Kareem Haroun and Orly M. Coblens

Purpose of review
To describe current standard of care for osteoradionecrosis (ORN) of the mandible and report possible
future trends.
Recent findings
Cutting guides may be used to reduce surgical time and possibly improve outcomes. There has also been
recent investigation into the use of pentoxifylline and tocopherol or pentoxifylline, tocopherol and
clodronate (a well known conservative medial regime) as a prevention for development of ORN after
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dental extractions and the first randomized controlled study is upcoming. Augmented reality has shown
promise as a comparable and inexpensive possible alternative to cutting guides.
Summary
Current standard of care involves conservative/supportive therapy with antioxidants, antibiotics, steroids,
and pain control for low-grade ORN with surgery reserved for high-grade/progressive ORN with refractory
to conservative therapy and with significant oral dysfunction.
Keywords
hyperbaric oxygen, mandibular osteoradionecrosis, mandibular reconstruction, pentoxifylline and tocopherol or
pentoxifylline, tocopherol and clodronate

INTRODUCTION/BACKGROUND spaces [7], which, in turn, cause bone hypovascula-

Mandibular osteoradionecrosis (MORN) is a signifi-
cant long-term sequela of the treatment of head and
neck cancers by radiation therapy and may occur
months to years after treatment [1–4]. Generally,
MORN is defined as an area of exposed bone follow-
ing radiation therapy resulting from necrosis of the
bone and/or surrounding tissue that persists for
greater than 3–6 months [5]. The mandible is
thought to be most commonly involved due to its
relatively tenuous blood supply. The current theory
is that the blood supply is further reduced by a
radiation-induced fibroatrophic process [6] result-
ing in a hypoxic, hypocellular, and hypovascular
environment [2]. Delanian and Lefaix suggested
that trabecular bone is devitalized by radiation-
induced endothelial damage, either directly or indi-
rect via several harmful events triggered by reactive
oxygen species: constant release of cytokines fibro-
blasts, excessive myofibroblast proliferation, and
release of abnormal extracellular matrix compo-
nents, which may not be removed because of defec-
tive retroregulation [6]. Such an imbalance between
tissue synthesis and degradation generates progres-
sive hyalinization and fibrosis of the medullary
rization and development of radiation-induced
fibrotic scar tissue [6].
ORN has long been classified by a system first
described by Epstein et al. in 1987 but other systems
have since been published [8–10] (Fig. 1).
Marx and Johnson found the following physical
diagnostic signs to correlate with increased degrees of
radiation tissue injuries: induration of tissue, muco-
sal radiation telangiectasia, loss of facial hair growth,
cutaneous atrophy, cutaneous flaking and keratini-
zation, profound xerostomia, and taste loss [11].
Several studies have examined latency period
(time to presentation post radiation therapy) and
found that the median latency is typically less than
2 years [12– – 14]. Reported incidence of ORN
Department of Otolaryngology – Head and Neck Surgery, University of
Texas Medical Branch, Galveston, Texas, USA
Correspondence to Orly M. Coblens, MD, Assistant Professor, Depart-
ment of Otolaryngology – Head and Neck Surgery, University of Texas
Medical Branch, Galveston, Texas, USA. Tel: +1 409 772 2701;
e-mail: orcoblen@utmb.edu
Curr Opin Otolaryngol Head Neck Surg 2019, 27:401–406
DOI:10.1097/MOO.0000000000000571

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Head and neck reconstruction
KEY POINTS
 There are multiple treatment modalities available to
treat ORN and it must be appropriately staged for
optimal therapy.
 Multidisciplinary management is key to
optimally treatment.
 Mandibulectomy with osteocutaneous flap
reconstruction is ideal in surgical management of
advanced ORN and may be curative.
 New technologies such as three-dimensional printed
materials and augmented reality are emerging that
show promise in improving surgical outcome.
postradiation therapy has decreased over time from
as high as 25% in 1940 [15] to 4–8% in studies
published in the past 5 years [14,16–18]. This con-
sistent decline in the incidence of MORN is attrib-
uted to the advances in radiation therapy technique
including decreased dosing, improved targeting,
and novel technologies as well as possible improve-
ment in recognizing and mitigating risk factors [19].
Risk factors associated with the development of
MORN include tumor-related factors (tumor loca-
tion, size, stage, presence of bone invasion), treat-
ment-related factors (total radiation therapy dose,
radiation therapy technique, volume of mandible
irradiated), and patient-related factors (tobacco/
alcohol use, oral hygiene, dental extractions,
comorbidities) [12,14,16–18,20–26,28] (Fig. 2).
TREATMENT OPTIONS
Therapies include hyperbaric oxygen, antioxidant,
therapy, and surgical repair.
HYPERBARIC OXYGEN
Hyperbaric oxygen (HBO) has been described in
treatment of ORN as early at 1973 [30].
FIGURE 1. Epstein classification system for osteoradionecrosis
[8].
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Although there is no current evidence that HBO
cures mild or moderate ORN [31,32], it has been
shown in some studies to be useful for preventing
late onset radiation-induced tissue damage by
improving mucosal healing, restoring bone conti-
nuity, and decreasing wound dehiscence [33]. There
have also been studies that demonstrated improve-
ment or stabilization of ORN-related symptoms,
such as xerostomia, pain, erythema, and edema
[34,35]. Annane et al. [32] conducted a multicenter
randomized, double-blinded, placebo-controlled
trial in 2004 showing no benefit of HBO treatment
in patients for ORN of the jaw. Questionable effec-
tiveness and the great cost and difficulty of admin-
istration has led to HBO therapy falling out of favor
and the use of antioxidant therapy has become
more popular.
ANTIOXIDANT THERAPY (E.G.,
PENTOXIFYLLINE)
Antioxidant therapy was first described by Delanian
and Lefaix in 2002 and its pathophysiology was
further examined in a subsequent study in 2004
[6,36]. Although this process was traditionally con-
sidered irreversible, they postulated that the process
could be reversed by antioxidant therapy with pen-
toxifylline, tocopherol, and clodronate [6].
A systematic review by Martos-Fernandez et al.
found the best healing and clinical improvement
rates associated with pentoxifylline and tocopherol
(PVe) or PVe and clodronate (PENTOCLO) treat-
ment were obtained in mild and moderate ORN,
corresponding to stages I and II of the Epstein [8],
Robard [27], Lyons [37], and Notani [38] classifica-
tions. In more advanced stages (stages III and IV) or
in cases that are refractory to conservative manage-
ment, surgical treatment (mandibular resection
with reconstruction) is the only therapeutic option
&
available [29 ,39,40]. Treatment for more than
18 months but less than 3 years has been shown
&
to be most effective [29 ].
Patel et al. retrospectively analyzed data on 390
dental extractions in 82 patients who had under-
gone head and neck radiation therapy. Patients were
given PVe for an average of 11 weeks before surgery
and for an average of 13.6 weeks after surgery. The
incidence of ORN was found to be 1.2%, whereas the
historical benchmark was 7%, demonstrating PEN-
TOCLO may be useful as prophylactic therapy [41].
The first randomized trial to examine efficacy of
antioxidant therapy was proposed in 2019 with
PENTOCLO protocol is as follows: ‘400-mg pentox-
ifylline BID and 1000-IU vitamin E qAM Monday to
Friday taken orally. If the patient deteriorates then
add clodronate 1600 mg daily Monday to Friday.
Volume 27  Number 5  October 2019
 Reconstruction of the mandible for osteoradionecrosis Haroun and Coblens

FIGURE 2. Risk factors associated with development osteoradionecrosis adapted from Martos-Fernandez et al. [29 ]. &

This is done for a minimum of 6 months but up to fracture or discontinuity are equally vital in appro-
18 months if the patient has stable ORN and is not priately supporting the overlying soft-tissue struc-
deteriorating further.’ There are additional recom- tures to restore jaw motion [43].
mendations should the patient experience pain or
&
infection [42 ].
Myocutaneous/fasciocutaneous free flap and
mandibular reconstruction plate
SURGICAL OPTIONS Li et al. conducted a cohort study in which 116
In mandibular reconstruction, achieving adequate patients underwent latissimus dorsi free flap and
bone height and width as well as repairing any plate reconstruction following advanced

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Head and neck reconstruction
FIGURE 3. Osteoradionecrosis of right mandible repaired with fibular free flap (a) draining fistula secondary to
osteoradionecrosis (b) view of fractured mandible. (c) Reconstruction bar in place prior to fibular free flap anastomosis (d) free
flap with monitoring skin paddle in place.
oromandibular tumor resection with flap survival
rate of 99.1%. Despite favorable results, the use of
latissimus dorsi along with serratus anterior and
upper arm (humerus) flaps is becoming increasingly
less common, largely due to the limited available
bone to repair mandible defects, and the short pedi-
cle available, which make the flaps difficult to anas-
tomose [44] (Fig. 3).
Osteocutaneous free flap reconstruction
Four osteocutaneous flaps are commonly used for
mandible reconstruction: fibula flap, iliac crest flap,
scapula flap, and the radial flap.
In a systematic review, Lee et al. found the fibula
free flap was by far the most common free flap tissue
used (n ¼ 215) and, from the free flap failure data
reported, had a good success rate (95.3%) [45]. The
use of fibula free flap in the mandible was first
described by Hidalgo et al. [46] and is now consid-
ered as the workhorse for mandible reconstruction
[47–49]. Advantages of the fibula include its quality
of bone (cortical thickness) and length of bone
available (up to 25–30 cm), which permits multiple
osteotomies even whilst the pedicle is still attached
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and allows for potential dental implants [50,51]. The
dominant arterial supply is from the peroneal artery
and venous drainage via the two venae comitantes,
which have an average caliber of 1.5 and 3 mm,
respectively. These vessel diameters closely match
that of most recipient vessels within the head and
neck. The vascular pedicle is up to 15 cm in length.
Closely matched diameters and long pedicle length
facilitate anastomoses, particularly after tough dis-
section in an irradiated field [52]. Patients with signs
of lower limb vascular insufficiency or a history of
lower limb fracture are deemed unsuitable for the
fibula flap [47–49].
The iliac crest flap may be considered when
there is a contraindication to the fibula flap. The
iliac crest flap had a success rate of 76.6%, with
venous thrombosis as the most common cause of
failure [53]. Advantages include sufficient bone for
dental implants and minimal osteotomy as the
boney portion resembles the anatomic structure
of the mandible. The major drawback is that the
supplying perforators of the deep circumflex iliac
artery can tear easily as they pass through the layers
of the abdominal wall resulting in loss of the skin
paddle [54].
Volume 27  Number 5  October 2019
 Reconstruction of the mandible for osteoradionecrosis Haroun and Coblens
The scapula and parascapular flap may be con-
sidered for repairing complex facial defects as it has
abundant soft-tissue and two discrete skin paddles
which can make it a chimeric flap. Anterior man-
dibular defects may be repaired utilizing the scapu-
lar tip alone which is based on the angular branch.
Its bone is thin and bi-cortical allowing greenstick
osteotomies and making it a uniquely similar graft
for maxillary defect repairs as well [55]. A recent
retrospective institutional study (n ¼ 130) found
success rate of 96% and complication rate of 2.3%
[56]. Limitations include its limited length, thin
bone and the need for patient repositioning during
the surgery for harvest, prolonging operating room
time as harvest cannot be completed simultaneously
with the resection [57].
The radial forearm osteocutaneous free flap
offers robust blood supply to a limited bone flap,
but a large and pliable skin segment. Flap bulk can
be increased and sensory function preserved with
use of the brachioradialis muscle and its associated
nerve [58]. One third of the cross-sectional area of
the radius’ cortical bone can be taken without
increasing the risk of mechanical stress fracture.
Up to 10-cm length of bone is available but must
be carefully plated due to limited size [59,60]. Of 31
radial forearm free flaps in a recent systematic
review, no flap failures were reported. However, it
is unclear whether those undertaken in the studies
included osteotomy or if they were fasciocutaneous
flaps only [45].
Applications of new technology
Maintaining orthognathic integrity is critical in
shorting healing time and improving postoperative
function. Hirsch et al. have described the use of
three-dimensional modeling and three-dimensional
printed cutting guides as early as 2009 using fibular
free flap in mandibular reconstruction [61]. Further
studies have demonstrated that these precut guides
reduce ischemia time, reduce bone gaps resulting in
improved healing, and reduce operative time
among young surgeons [62–65]. It is controversial
whether they improve post operative position or
function of the temporomandibular joint [62].
Use of these guides in the scapular free flap is diffi-
cult given significant overlying soft tissue. However,
Kass et al. [66] have had recent success by utilizing
stabilizing flanges and bracket design. Augmented
reality is the latest technology applied to mandibu-
&&
lar reconstruction. Pietruski et al. [67 ] demon-
strated similar accuracy of assisted harvesting and
contouring of the fibula free flap as the cutting
guides in a proof of concept study using 126
simulated osteotomies.
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Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.
DISCUSSION
No randomized controlled trials exist describing
optimal treatment protocol of ORN. As described
above, current standard of care involves conserva-
tive/supportive therapy with antioxidants, antibiot-
ics, steroids, and pain control for low-grade ORN
with surgery reserved for high-grade/progressive
ORN with refractory to conservative therapy and
with significant oral dysfunction. Osteocutaneous
flaps may be utilized for reconstruction with flap
selection based on patient needs and health
status. Application of new technologies may
improve outcomes.
Acknowledgements
None.
Financial support and sponsorship
None.
Conflicts of interest
There are no conflicts of interest.
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Volume 27  Number 5  October 2019