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CLINICAL REVIEW David W. Eisele, MD, Section Editor
Resection and microvascular reconstruction of bisphosphonate-related osteonecrosis
of the jaw: The role of microvascular reconstruction
Tiago Neto, MD,
1
*Ricardo Horta, MD,
2,3
Rui Balhau, MD,
1
L
ıgia Coelho, MD,
1
Pedro Silva, MD,
2
In^
es Correia-S
a, MD,
2,3
Alvaro Silva, MD
2
1Maxillofacial Surgery Unit, Department of Plastic, Reconstructive, Aesthetic Surgery, Maxillofacial Surgery, and Burn Unit, Hospital S~
ao Jo~
ao, Porto, Portugal, 2Department of
Plastic, Reconstructive, Aesthetic Surgery, Maxillofacial Surgery, and Burn Unit, Hospital S~
ao Jo~
ao, Porto, Portugal, 3Faculty of Medicine, University of Porto, Porto, Portugal.
Accepted 17 December 2015
Published online 00 Month 2016 in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/hed.24395
ABSTRACT: Background. Current treatment guidelines caution against
osseous reconstruction using free flap tissue to treat bisphosphonate-
related osteonecrosis of the jaw (BRONJ). The primary rationale for this
stance is the theoretical risk of nonunion and recurrence of disease
within the reconstruction. Emerging evidence suggests that these theo-
retical risks may be overestimated. We performed a literature review of
this procedure for the treatment of advanced BRONJ. We also present a
new case report of resection and microvascular reconstruction in a 58-
year-old man with stage III BRONJ.
Methods. A MEDLINE search was performed to gather all reports of max-
illary and mandibular reconstruction using free tissue flap transfer for
BRONJ. Inclusion criteria were confirmed stage II or III BRONJ, free tis-
sue transfer and reconstruction, and reported complications. Articles
were excluded if they contained only local flap reconstruction, wound
closure without reconstruction, or osteoradionecrosis. Outcomes from
our case report were added to the analysis.
Results. We identified 10 articles that met criteria. Adding our case, we
identified 40 cases of free flap reconstruction. The rate of nonunion was
5% (2 of 40). Fistulas formed in 4 cases (10%). BRONJ recurred in 2
cases (5%).
Conclusion. Complication rates after free flap microvascular reconstruc-
tion in BRONJ seem acceptable. Nonunion is relatively rare and should
not be the sole reason to recommend against free flap reconstruction. A
randomized clinical trial would help clarify the role of this procedure in
refractory BRONJ; however, we believe that segmental resection and
microvascular reconstruction is a viable option in select cases of BRONJ.
V
C2016 Wiley Periodicals, Inc. Head Neck 00: 000–000, 2016
KEY WORDS: bisphosphonates, osteonecrosis, bisphosphonate-
related osteonecrosis of the jaw (BRONJ), fibula free flap reconstruc-
tion, medication-related osteonecrosis of the jaw
INTRODUCTION
Bisphosphonates inhibit normal and pathological bone
resorption by osteoclasts.
1
These drugs reduce osteoclast
binding to the bone, decrease the production of new osteo-
clasts, and stimulate osteoclast apoptosis.
2
Bisphosphonates
also have antiangiogenic properties.
3–5
This results in a
decreased bone turnover, with hypermineralization (target
of the therapeutic use) and bone hypovascularization. Com-
bination of a compact and avascular bone is believed to
result in osteonecrosis by a mechanism of ischemia and
secondary infection.
3,6–12
Since the 1990s, this class of drugs has been used to
treat diseases with increased bone resorption, such as
osteoporosis, Paget disease, and neoplastic diseases of
bone.
13
Pamidronate and zoledronate are the most potent
bisphosphonates and are roughly 5000 to 10,000 times
more potent than the least potent drug in the class,
etidronate.
In 2003, Marx et al
3
first reported a nonhealing necrosis
of the maxillofacial region in some patients taking
bisphosphonates. Although initially considered a new dis-
ease, bisphosphonate-related osteonecrosis of the jaw
(BRONJ) is similar to the historical entity “phossy jaw,” a
chemically induced osteonecrosis, observed by Lorinser, in
phosphate miners, more than a century ago.
14–17
“Phossy
jaw” was characterized by exposed bone that failed to heal
after tooth extraction and was associated with pain, foul
odor, and suppuration. In 2004, Ruggiero et al
18
published a
series of 63 cases and Novartis includes BRONJ as adverse
reactions of Aredia and Zometa. In 2005, Migliorati et al
19
published a series of 17 cases and the Food and Drug
Administration published a notice including BRONJ as an
adverse reaction to all the bisphosphonate class, including
oral forms. According to the American Association of Oral
and Maxillofacial Surgeons (AAOMS), the clinical defini-
tion of BRONJ requires the existence of exposed necrotic
bone in the mandible or maxilla for a period of 8 weeks,
current or previous treatment with bisphosphonates, and the
absence of history of radiotherapy to the jaw.
BRONJ affects the mandible and maxilla almost exclu-
sively, with the mandible 2 times more likely to be
affected than the maxilla, especially at the level of lingual
*Corresponding author: T. Neto, Maxillofacial Surgery Unit, Department of
Plastic, Reconstructive, Aesthetic Surgery, Maxillofacial Surgery, and Burn Unit,
Hospital S~
ao Jo~
ao, Av. 5 de Outubro, 46, 118frt, 8000-076, Faro, Portugal.
E-mail: tgneto@gmail.com
HEAD & NECK—DOI 10.1002/HED MONTH 2016 1
torus or mylohyoid line.
20,21
Although it is unclear why
the jaw is particularly vulnerable to this condition, puta-
tive reasons include high bone turnover because of micro-
trauma from mastication, high bone density of the jaw,
and the susceptibility to infection because of close prox-
imity to the oral cavity.
20,22
Currently, treatment decisions are based on the AAOMS
4-tier staging system (Table 1).
23–25
Stage 0 BRONJ is
diagnosed in patients without clinical evidence of necrotic
bone yet who have early nonspecific clinical or radio-
graphic findings consistent with the disease. Stage I is the
presence of exposed necrotic bone in a patient without
symptoms or infection. Stage II is distinguished from stage
I in that the patient is experiencing symptoms from the
lesion and there is evidence of infection. Stage III, the
most advanced stage, includes stage II patients with one or
more of the following: pathologic fracture, extraoral fistula,
or severe osteolysis extending to the inferior border of the
mandible, nasal floor, or maxillary sinus.
The therapeutic goals in BRONJ are preservation of the
quality of life and management and prevention of pain,
infection, and progression of lesions. Treatment recom-
mendations for patients with stage I disease includes anti-
biotic mouth rinse, clinical follow-up, and patient
education. Most patients with stage II disease are also
treated with medical interventions, whereas the surgical
debridement and resection may be considered for people
with intractable infection and pain.
23
Surgical debride-
ment combined with antibacterial mouth rinse, systemic
antibiotics, and pain management is the recommended
treatment approach for stage III disease. Surgical debride-
ment is not always effective, however. Both 2007 and
2009 guidelines conclude immediate reconstruction with a
reconstruction plate or obturator in patients with stage III
disease may follow resection.
23,24
This recommendation
was bolstered by reports of successful surgical resection
of stage II and III BRONJ.
26
The 2009 update discourages immediate reconstruction
with nonvascularized or vascularized bone considering it
“potentially problematic, because necrotic bone could be
present at the resection margins or develop at the recipi-
ent site.”
23
Nevertheless, numerous case series have
reported successful outcomes after combined resection
and microvascular reconstruction in BRONJ.
27
The 2014 update favors the term medication-related
osteonecrosis of the jaw instead of BRONJ to accommo-
date the growing number of osteonecrosis cases involving
the maxilla and mandible associated with other antire-
sorptive (denosumab) and antiangiogenic therapies.
25
Denosumab is an antiresorptive agent that exists as a fully
humanized antibody against receptor activator of nuclear
factor kappa B ligand and inhibits osteoclast function and
associated bone resorption. It is administered subcutane-
ously every 6 months to decrease the risk of vertebral,
nonvertebral, and hip fractures in osteoporotic patients
and administered monthly in metastatic bone disease from
solid tumors.
25,28,29
Denosumab is superior to zoledronic
acid in preventing complications for patients with bone
metastases. However, further studies are still needed to
assess longer-term safety and efficacy of denosumab.
29–33
We report a successful case of microvascular recon-
struction in a 58-year-old man with BRONJ who was
treated with intravenous zoledronic acid for bone metasta-
sis from squamous nonsmall cell lung carcinoma. We
TABLE 1. American Association of Oral and Maxillofacial Surgeons Staging and treatment strategies for medication-related osteonecrosis of the jaw.
Staging Definition Treatment Strategies*
Patient
at risk
No apparent necrotic bone in patients who have been treated with oral
or intravenous bisphosphonates
No treatment indicated
Patient education
Stage 0 No clinical evidence of necrotic bone but nonspecific clinical findings,
radiographic changes, and symptoms
Systemic management, including use of
pain medication and antibiotics
Stage I Exposed and necrotic bone or fistulas that probes to bone in patients
who are asymptomatic and have no evidence of infection
Antibacterial mouth rinse
Clinical follow-up on a quarterly basis
Patient education and review of indications
for continued bisphosphonate therapy
Stage II Exposed and necrotic bone or fistulas that probes to bone associated
with infections evidenced by pain and erythema in the region of
exposed bone with or without drainage
Symptomatic treatment with oral antibiotics
Oral antibacterial mouth rinse
Pain control
Debridement to relieve soft tissue irritation
and infection control
Stage III Exposed and necrotic bone or fistula that probes to bone in patients with
pain, infection, and 1 of the following: exposed and necrotic bone
extending beyond the region of alveolar bone (ie, inferior border and
ramus in mandible, maxillary sinus, and zygoma in maxilla) resulting
in pathologic fracture, extraoral fistula, oral antral or oral nasal com-
munication, or osteolysis extending to inferior border of the mandible
or sinus floor
Antibacterial mouth rinse
Antibiotic therapy and pain control
Surgical debridement or resection for
longer-term palliation or infection and pain
* Regardless of disease stage, mobile segments of bony sequestrum should be removed without exposing uninvolved bone. Extraction of symptomatic teeth within exposed necrotic bone should be
considered because it is unlikely that extraction will exacerbate the established necrotic process.
NETO ET AL.
2HEAD & NECK—DOI 10.1002/HED MONTH 2016
also performed a literature review of reported cases in
which reconstruction has been used to treat BRONJ. The
potential role for this surgical approach is discussed.
MATERIALS AND METHODS
Literature search parameters and process
In May 2015, we searched MEDLINE (PubMed) using
the following search terms: (“bisphosphonate-related
osteonecrosis” OR “bisphosphonate osteonecrosis” OR
“BRONJ” OR “bisphosphonate-related osteonecrosis of
the jaw”) AND (“surgery” OR “microsurgery” OR
“microvascular reconstruction” OR “microsurgical
reconstruction” OR “free flap” OR “free tissue” OR
“microvascular”), which yielded 352 results. Abstracts of
these results where read to identify all potentially relevant
articles. After abstract review, 95 full-length articles were
identified and retrieved for further scrutiny. Articles were
included if they contained: (1) clinically diagnosed stage
II or stage III BRONJ with radiological and/or histologi-
cal confirmation of the diagnosis; (2) free tissue transfer
and reconstruction; and (3) listing of complications.
Articles, or cases within individual articles, were
excluded if they contained only local flap reconstruction,
wound closure without reconstruction, or osteoradionecro-
sis as an etiology. Full-length articles meeting inclusion
criteria were manually reviewed to identify all reports of
maxillary and mandibular reconstruction using free tissue
flap transfer for the treatment of BRONJ (n510). Man-
ual searches of bibliographies did not reveal any addi-
tional studies meeting selection criteria at the end
introduce (see Figure 1).
CASE REPORT
A 54-year-old man with long-standing smoking history
and otherwise good physical and dental health was diag-
nosed with squamous nonsmall cell lung carcinoma with
metastasis to the left pelvis in 2007. At that time, he
underwent a thoracotomy and resection of the middle
mediastinum and left para-hilar mass. The pelvis metasta-
sis was treated with 2 courses of external radiotherapy
(30 Gy, 2.5 Gy/day, 12 fractions), according to a compu-
terized dosimetry plan. Given the metastasis to bone, the
man was also treated with bisphosphonate, zoledronic
acid, intravenously over a period of 3 years.
In 2011, the now 58-year-old man presented with jaw
pain and an oral lesion. The patient had no history of
recent tooth extraction or oral surgery. Physical examina-
tion revealed exposed bone at the level of the alveolar
ridge of the right body of the mandible along with a path-
ological fracture. Maxillofacial CT showed a complex
lytic lesion in the right body of the mandible with 42 3
11 mm bone sequester and pathologic fracture (see Figure
2). The man was diagnosed with stage III BRONJ,
according to the AAOMS staging criteria.
23
BRONJ was
initially unsuccessfully treated with antibiotics, antiseptic
mouth rinse, and limited surgical debridement. Because
of disease progression, the bisphosphonate was stopped
and weighted more aggressive surgical treatment.
We performed a mandibular resection and microvascu-
lar reconstruction using the following approach. Because
of unavailability of patient-specific reconstruction plate
and cutting guides for both the mandible and fibula, a
mandibular locking reconstruction plate was molded on
the jaw before osteotomy. Using a transcervical approach,
a right segmental resection from the symphysis to the
right angle of the mandible was performed along with 1-
cm margins of grossly healthy bone. The inferior alveolar
nerve was sacrificed. A fibula myoosseous free flap was
used to reconstruct the defect. The fibula flap was divided
in 2 segments to match the curvature of the natural man-
dible. Each segment was fixed with 3 locking screws to
the mandibular reconstruction plate. Microvascular anas-
tomosis was performed between the peroneal and the
facial vessels. No skin paddle was required because there
was no significant skin or mucosal defect. A watertight
closure was made with the oral mucosa over the recon-
structed mandible/fibula flap.
RESULTS
Literature review
No randomized controlled clinical trials have been per-
formed comparing free flap reconstruction after resection
in patients with BRONJ. All published studies to date
FIGURE 1. Flow of information during
the literature search.
RESECTION AND MICROVASCULAR RECONSTRUCTION OF THE JAW
HEAD & NECK—DOI 10.1002/HED MONTH 2016 3
have been case reports and case series (Table 2).
27,34–43
There have been 2 systematic reviews published on the
topic, the latter
27
included cases from and added to the
former.
44
Spinelli et al
43
documented results from an
additional 8 patients with BRONJ since the recent review
authored by Vercruysse et al.
27
Including the case we cur-
rently report, there have been 40 cases of stage III
BRONJ treated with free flap reconstruction in the pub-
lished literature. Two articles were included because they
met inclusion/exclusion criteria; however, the data were
not presented in a way to separate individual patient
outcomes.
35,40
Of the 40 cases of free flap reconstruction for BRONJ,
38 were successful (Table 1). All authors, with the excep-
tion of Seth et al,
42
reported on cases with at least 12
months of postoperative follow-up (36 cases with >12
months of follow-up). Radiographic imaging with CT, con-
ebeam, and/or orthopantomogram were obtained during
follow-up in 38 of 40 cases (95%). Flap failure occurred in
2 cases, 1 case from the fibula
45
and 1 case from the iliac
crest.
2
In both instances, a second flap was constructed
from additional tissue during a second procedure.
Fistulas formed in 4 cases (10%),
41,42
making it the
most common complication observed across studies.
BRONJ recurred in the contralateral jaw in 2 cases.
27,36
In
2 separate cases, BRONJ was detected in the reconstructed
tissue, both resulting in nonunion initially.
40,41
The first
casewasreportedbyNocinietal
40
in 2009 and occurred
because the resected margins were not free of disease. This
finding was not evident during surgery and was found dur-
ing histological evaluation of the resected tissue. In 2011,
Pautke et al
41
found bisphosphonate-related osteonecrosis
in the iliac crest tissue harvested for reconstruction. Histo-
logical preparations from grossly necrotic iliac bone
showed necrosis without osteocytes, bacterial colonization,
hypervascular tissue, and new trabecular bone formation.
The partially osteonecrotic flap was vital and the osteonec-
rosis resolved with additional stabilization.
In the selected case series for which data were available,
bisphosphonates were administered intravenously in 84%
TABLE 2. Reported cases of bisphosphonate-related osteonecrosis of the jaw treated with free tissue transfer.
Author
No. of
patients Age Sex Bisphosphonate Route Indication
Flap
source Complications
BRONJ
recurrence?
Engroff
36
2 64 F P IV Metastatic breast cancer Fibula None No
49 F Z IV Metastatic breast cancer Fibula Hematoma Contralateral
jaw
Ferrari
37
166M Z1P IV Multiple myeloma Fibula None No
M€
ucke
39
2 48 F Z IV Metastatic breast cancer Iliac crest None No
60 F Z IV Multiple myeloma Fibula None No
Nocini
40
761
(mean)
6F 5P 7IV 5 metastatic breast cancer Fibula 1 Ruptured
miniplate
1 Margin
(1nonunion)1M 2Z 1 metastatic prostate cancer
1 metastatic breast cancer
Seth
42
11 68 M Z IV Metastatic prostate cancer Fibula Infection No
56 F Z IV Metastatic breast cancer Fibula None No
50 F Z IV Metastatic breast cancer Fibula None No
72 F A PO Osteoporosis Fibula Fistula No
48 F Z IV Metastatic prostate cancer Fibula Fistula No
71 F I IV Multiple myeloma Fibula None No
67 F E PO Metastatic breast cancer Fibula None No
60 F A PO Osteoporosis Fibula None No
51 F Z IV Multiple myeloma Fibula None No
72 M I IV Metastatic breast cancer Fibula Fistula No
60 F Z IV Metastatic breast cancer Fibula None No
Bedogni
35
3 NR NR NR NR NR Fibula 1 flap failure No
Pautke
41
1 76 M Z IV Metastatic prostate cancer Iliac crest Fistula Margin
(1nonunion)
Ghazali
38
1 82 F A PO Osteoporosis Fibula None No
Vercruysse
27
3 54 F Z IV Multiple myeloma Iliac crest None No
70 F C PO Metastatic breast cancer Iliac crest None No
64 F Z IV Multiple myeloma Iliac crest 1 Flap Failure Contralateral
Spinelli
26
8 73 M Z IV Metastatic prostate cancer Fibula None No
77 F P IV Metastatic breast cancer Fibula None No
64 F Z 1P IV Multiple myeloma Fibula None No
53 F Z IV Metastatic breast cancer Fibula None No
62 M P IV Multiple myeloma Fibula None No
68 F Z 1P IV Metastatic breast cancer Fibula None No
57 M Z IV Multiple myeloma Fibula None No
64 F P IV Multiple myeloma Fibula None No
Neto (this
study)
1 54 M Z IV Metastatic lung cancer Fibula None No
Abbreviations: BRONJ, bisphosphonate-related osteonecrosis of the jaw; P, pamindronate; Z, zolindronate; A, alendronate; I, ibandronate; E, etidronate; NR, not reported; C, clodronate.
NETO ET AL.
4HEAD & NECK—DOI 10.1002/HED MONTH 2016
of cases. Zoledronate (52%; 20 of 39 cases) was the most
common bisphosphonate used, either alone or in combina-
tion with pamidronate, the second most commonly used
bisphosphonate (31%). Metastatic breast cancer was the
most common indication for bisphosphonates among pub-
lished cases (45%; 18 of 40), followed by multiple
myeloma (25%; 10 of 40), metastatic prostate cancer
(12.5%; 5 of 40), osteoporosis (7.5%; 3 of 40), and meta-
static lung cancer (2.5%; 1 of 40). The fibula was used for
jaw reconstruction in 88% (35 of 40) of reported cases,
whereas the rest were harvested from the iliac crest.
Surgical case
Postoperative orthopantomography revealed acceptable
positioning of the flap and reconstruction plate. Pathologi-
cal examination of the resected mandible revealed lesions
consistent with chronic osteomyelitis with significant bac-
terial and fungal overgrowth. The resection margins were
free of osteonecrosis. The report also noted osteosclerosis
in the grossly evident pathological fracture and the sam-
ple was free of malignancy (see Figure 3).
The patient experienced no postoperative complications,
including infection. The reconstructed flap had good vas-
cularity. Both the donor site and the reconstructed mandi-
ble healed without complication. The patient enjoyed a
complete resolution of symptoms and was without pain,
fistula, infection, or pathologic fracture during the 48
months of follow-up. The patient reports a high degree of
satisfaction both with the aesthetic and functional out-
comes of the surgery (Figures 4 and 5).
DISCUSSION
BRONJ is a risk for anyone receiving bisphosphonates
and patients should be warned of this potential outcome.
This risk is greater in patients who require intravenous
bisphosphonates,
46,47
people who smoke,
48
taking
bisphosphonates for greater than 1 year, and also taking
other medications that affect bone turnover, such as ste-
roids or chemotherapy for the primary oncologic
disease.
49,50
Bisphosphonates are potent inhibitors of normal and
pathological bone resorption by osteoclasts and are anti-
angiogenic.
3,5,6
Antiangiogenic medications used in chem-
otherapy, such as trastuzumab, may represent an
independent and agonistic risk factor for developing
BRONJ.
50
Other medications, such as methotrexate and
steroids that suppress the immune system, may also com-
plicate the management of BRONJ.
51
Treatment of BRONJ requires a multidisciplinary
approach, including dentistry, maxillofacial surgery, sto-
matology, rheumatology, oncology (in cases of malig-
nancy), and primary care.
52
The authors believe that
prevention is the best approach and that all patients
should be evaluated by a dentist before starting
bisphosphonate treatment with routine follow-up to help
promote good oral hygiene, prompt treatment of caries
and dental infections, avoid insufficient endodontic treat-
ment, and maintain removable dentures.
Published reports and guidelines by the AAOMS have
cautioned against the use of osseous tissue for the recon-
struction of maxillary and mandible reconstruction in
BRONJ.
23,53
Those who favor conservative medical and
surgical treatment cite several possible, yet mainly theo-
retical risks. These include diminished wound healing in
this patient population, nonunion at the flap border,
FIGURE 2. Preoperative imaging of a patient with stage III bisphosphonate-related osteonecrosis of the jaw (BRONJ). [Color figure can be viewed in
the online issue, which is available at wileyonlinelibrary.com]
FIGURE 3. Histological preparation of jaw showing chronic osteo-
myelitis and osteosclerosis. [Color figure can be viewed in the
online issue, which is available at wileyonlinelibrary.com]
RESECTION AND MICROVASCULAR RECONSTRUCTION OF THE JAW
HEAD & NECK—DOI 10.1002/HED MONTH 2016 5
transfer of malignant cells to the maxillofacial area, and a
“minimal benefit to the patient.”
45,54,55
Some authors have
stated that “aggressive” surgery, in this case resection and
reconstruction with a free flap, is inappropriate because of
the diminished life expectancy, poor general condition, and
concomitant medications, such as steroids or chemotherapy,
that can interfere with the postoperative result of patients
with advanced BRONJ and the overall success of conserva-
tive measures and minimal surgical procedures.
54
Diminished life expectancy is certainly a theoretical
concern given that most people who received intravenous
bisphosphonates in our and others’ reviews had metastatic
cancer to the bone or malignancy-related hypercalce-
mia.
49,56
Indeed, 1 patient in the Seth et al
42
series died 8
weeks after reconstruction surgery in consequence of
cancer-related complications. On the other hand, most
patients among published reports survived at least 12
months and many for at least several years after surgery
suggesting that health status alone should not be an abso-
lute contraindication to this procedure.
The authors of the 2009 position statement of the
AAOMS recommend reserving resection and immediate
reconstruction for patients with stage III disease. The
authors also note, however, that there have been accepta-
ble outcomes for patients with stage II and III disease. To
date, no fewer than 40 cases of free flap reconstruction in
patients with stage II or III BRONJ have been docu-
mented.
27,43,54
Since the most recent review of this litera-
ture, Spinelli et al
43
documented similarly excellent
results without complications in 8 patients with BRONJ.
The most feared complication of free osseous flap recon-
struction for BRONJ is nonunion.
43
We found only 2
instances of nonunion among 40 cases making it an infre-
quent complication.
27,36
Our results add to the growing body of literature dem-
onstrating good or excellent outcomes with microvascular
reconstruction using a free flap constructed from the fib-
ula bone. In the clinical case here reported, despite
advanced oncologic and osteonecrosis disease at diagno-
sis, the patient remains with good aesthetic and functional
results and no evidence of recurrence of both diseases 4
years after jaw reconstruction. Our patient was fully satis-
fied with the functional and aesthetic result of the proce-
dure and did not experience any significant
complications. We believe that such result would not be
possible with other reconstructive method. We think that
microsurgical reconstruction should be considered as an
option in advanced stages of BRONJ or medication-
related osteonecrosis of the jaw in the same way it is cur-
rently considered in advanced stages of head and neck
oncology. In light of these newer reports, we posit that
surgical resection and reconstruction is a reasonable and
effective treatment option for advanced (stages II and III)
BRONJ, with acceptable overall risks.
Although it was not a specific search criterion in our
literature review, we found no reported instances of
FIGURE 4. Postoperative imaging showing bony fusion and regrowth of the fibula flap/jaw with no recurrence of osteonecrosis. [Color figure can
be viewed in the online issue, which is available at wileyonlinelibrary.com]
FIGURE 5. Postoperative result.
[Color figure can be viewed in
the online issue, which is avail-
able at wileyonlinelibrary.com]
NETO ET AL.
6HEAD & NECK—DOI 10.1002/HED MONTH 2016
bisphosphonate-related osteonecrosis in tissue harvested
from the fibula in the 95 full-length articles reviewed. A
cursory search specifically looking for this outcome also
failed to reveal any cases of osteonecrosis subsequent to
fibula free flap. Because the precise pathophysiology of
BRONJ is not known, it remains unclear whether free
flap from the fibula would be less likely to develop recur-
rent BRONJ than tissue taken from the iliac crest. Like-
wise, metastatic disease to the fibula is rare, making the
seeding of malignant cells in the jaw exceedingly
unlikely.
57
Our results seem to indicate proportionally
fewer complications after fibula reconstructions than
those using iliac crest tissues; however, the relative safety
of iliac versus fibula bone transfers has not been directly
addressed.
Currently, virtual surgical planning, patient-specific
reconstruction plates, and cutting guides for both the mandi-
ble and fibula can improve surgical outcomes and minimize
operative time in free flap mandible reconstruction.
58–63
CONCLUSIONS
With the publication of 40 cases, complication rates after
microvascular reconstruction using a free flap in the treat-
ment of BRONJ seem acceptable. The fistula seems to be
the most common serious complication. Nonunion is rela-
tively rare and should not be the sole reason to recommend
against free flap reconstruction. A randomized clinical trial
would help clarify the role of this procedure in refractory
BRONJ. Most patients enjoy good to excellent functional
and aesthetic results after free flap reconstruction. Harvest-
ing the flap from the fibula may be superior to the iliac
crest, although this assertion requires further testing. We
believe segmental resection and microvascular reconstruc-
tion may be a valid option in select advanced cases of
BRONJ and that the treatment algorithm of these cases
may be redefined in the near future.
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