Vol.2, No.9, 535-537 (2013) Case Reports in Clinical Medicine
http://dx.doi.org/10.4236/crcm.2013.29139
Osteonecrosis of the jaw in a patient taking
once-yearly infusion of zoledronic acid for
osteopenia
Takako Imai Tanaka*, Charles Donald Taylor
1Department of Biomedical and Diagnostic Sciences, University of Detroit Mercy School of Dentistry, Detroit, USA;
*Corresponding Author: [e-mail]
2Department of Patient Management, University of Detroit Mercy School of Dentistry, Detroit, USA;
Received 14 September 2013; revised 10 October 2013; accepted 7 November 2013
Copyright © 2013 Takako Imai Tanaka, Charles Donald Taylor. This is an open access article distributed under the Creative Com-
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SCIRP as a guardian.
ABSTRACT
Osteonecrosis of the jaw (ONJ) is an adverse
effect of nitrogen-containing bisphosphonates.
Advancing age, intravenous administration of
zoledronic acid (ZOL), history of dento-alveolar
surgery, and concomitant systemic diseases
such as diabetes are known as risk factors for
developing ONJ. However, despite numerous
studies, the exact pathophysiology remains un-
clear and management strategies are largely an-
ecdotal. Once-year l y intravenously administered
5 mg ZOL was approved by the US Food and
Drug Administration in 2007 for the treatment of
osteoporosis and its efficacy with 3 year-regi-
men had been recently proven in preventing
new clinical fracture. Although occurrences of
ONJ have been repor ted to be rare with this drug
administration, available data is very limited and
long-term outcomes are lacking. We present a
case of ONJ identified in an osteopenic patient
with an intermittent but long standing sore
mouth related to exposed mandibular bone.
Once-yearly infusion of zoledronic acid used in
the treatment of osteopenia may contribute to
the spontaneous development of ONJ, espe-
cially in those presenting with multiple comor-
bidity factors. This report suggests the impor-
tance of health care professionals keeping
abreast of new developments in this area and
providing appropriate information to their pa-
tients.
Keyw ords: Osteopenia; Osteoporosis;
Bisphosphonates; Osteonecrosis; Letrozole;
Once-Ye arly Zoledro nic Acid; ONJ; ARON J; BRONJ
1. INTRODUCTION
Osteonecrosis of the jaw (ONJ) was first reported as
non-healing tooth extraction sites in cancer patients tak-
ing nitrogen-con taining bispho sphonates (NBPs) in 2003
[1]. Emerging cases of ONJ related to a wider variety of
medication use in osteoporosis such as Denosmub have
led to the introduction of new terminology “antiresorp-
tive agent-induced ONJ, “ARONJ” to replace bisphospho-
nate-related ONJ, “BRONJ”. Incidence of ARONJ is
estimated as small as 0.1% based on current available
evidence [2]. The risk factors for developing ARONJ
include advancing age, intravenous administration of
NBPs (especially zoledronic acid: ZOL), history of den-
toalveolar surgery, and concomitant systemic diseases
such as diabetes. Despite numerous studies, the exact
pathophysiology remains unclear and management strate-
gies are largely anecdotal.
Once-yearly intravenously administered 5 mg ZOL
was approved by the US Food and Drug Administration
in August 2007 for the treatment of osteoporosis. Its ef-
ficacy with 3 year-regimen has been proven signif icant in
preventing new clinical fracture [3]. Although occur-
rences of ONJ have been reported to be rare [4], avail-
able data are very limited and long-term outcomes are
lacking.
We present a case of ONJ identified in the United
States, where a patient suffered an intermittent but long
standing sore mouth related to exposed mandibular bone.

T. I. Tanaka, C. D. Taylor / Case Reports in Clinical Medicine 2 (201 3) 535-537
536
2. CASE SUMMARY
A 66-year-old female presented with sore mouth of-
duration of three weeks and exposed mandibular bone.
The patient denied any history of obvious trauma to the
affected area. Her medical history was significant for
diabetes mellitus type1, hypertension, hypothyroidism,
breast cancer, depression, osteoarthritis and osteopenia.
She was taking aspirin, insulin, levo thyroxine, buprop ion,
losartan, letrozole, atorvastatin and vitamin B12. Her
breast cancer was treated by lumpectomy followed by
chemotherapy. She denied history of breast cancer-re-
lated bisphosphonate therapy, however she was treated
with once-yearly infusion of 5 mg ZOL for osteopenia
the last two consecutive years.
Intraoral examination revealed 8 × 5 mm oval shaped
ulcer with exposed bone and significant erythematous
surround on the left posterior mandibular torus (Figures
1 and 2). There were no abnormal extraoral manifesta-
tions or radiographic findings noted. Based on clinical
diagnosis of BRONJ and because the pain was occa-
sional, management was palliative and no surgical inter-
vention was rendered. The use of antibacterial oral rinse
(0.12% chlorohexidine gluconate) along with maintain-
ing good oral hygiene and diabetes control (Patient re-
ports consistent hemoglobin A1C of 9%.) was advised
for the patient. At the 2 weeks re-evaluation, the oral
lesion was still present but pain-free. We recommended
periodic follow-up at our clinic in addition to notifying
her physicia n r e gar di n g her B R ONJ.
One month later, our patient presented to the emer-
gency clinic complaining of recurring severe pain and
difficulty speaking associated with a tongue lesion. In-
traorally, a mobile sequestra in the same area of the man-
dible and a traumatic ulceration on the adjacent tongue
were noted. Healing mucosa and mild bleeding were
visible underling the sequ estra. At this time the sequestra
Figure 1. Occlusal view of the mandible showing exposed
necrotic bone on the left posterior lingual tori.
Figure 2. Mirror image showing exposed bone with
inflammation in the surrounding ar ea.
was removed under local anesthesia and the patient was
instructed to continue using antibacterial oral rinse and
follow-up. Complete healing of both lesions was ob-
served in 3 weeks. The patient remains without signs and
symptoms of recurrence at 12 months.
3. DISCUSSION
Clinical manifestations in our patient were typical for
BRONJ. Dentoalveolar surgery such as tooth extraction
is a common precipitating factor, yet, as seen in our case,
up to 30% of BRONJ cases can occur spontaneously
without known h istory of trauma to the affected area [5].
The mandible is affected more often than the maxilla,
especially in the area of posterior torus covered by thin
mucosa. Pain, swelling and fistula formation arecommon
manifestations noted at the time of diagnosis. Jaw frac-
ture may occur in severe cases. Radiographic finding
such as diffused osteolytic lesions may not show unless
in an advanced case, however, it is difficult todifferenti-
ate from other chronic conditions such as osteomyelitis
or osteoradionecrosis [6].
Our patient had multiple other known risk factors for
developing ONJ: advancing age (older than 65 years), a
history of malignancy, diabetes and chemotherapy [7,8].
IV administration of high potent NBPs particularly ZOL
used in cancer patients is a major contributing factor for
ONJ, however, our patient had no history of using such
agents in that treatment regimen. Systemic conditions
such as DM or chronic use of chemotherapeutic agents
can decrease the inflammatory response and, as a result,
increa se th e risk of ON J. Th e negative impact of diabetes
on oral health is well-established. Delayed healing and
susceptible infectio n in patients with uncontrolled diab e-
tes are always of concern for oral health care providers.
The higher incidence of DM in patients with BRONJ
compared with patients without BRONJ, potentially due
to a compromised microvasculature and endothelial cell
dysfunction, has been reported [9]. In our case, the pa-
tient’s A1C was consistently around 9.0% during our

T. I. Tanaka, C. D. Taylor / Case Reports in Clinical Medicine 2 (201 3) 535-537 537
observation. We believe that prolonged bone exposure
was related to her diabetes condition.
It is noteworthy that our patient is taking Letrozole.
Letrozole is an aromatase inhibitor used inthe treatment
of hormonally-responsive breast cancer following sur-
gery. Letrozole has antiandrogen effects and is a poten-
tial inhibitor of epithelial growth factor [10]. Although
the exact etiology of BRONJ remains unclear, over sup-
pression of bone turnover, inhibited angiogenesis and
direct damage to oral mucosa have been considered to
play important roles particularly with ZOL [11]. Letroni-
dazole could further compromise the vasculature and
oxygen perfusion in the jaw bone exacerbating the ad-
verse effects of ZOL.
Due to unpredictable healing outcomes in patients who
developed BRONJ, the treatment is generally conserva-
tive. Invasive treatment such as surgical local debride-
ment of the affected area is usually reserved for severe
cases. Depending on the extent of infection, systemic
antibiotics such as penicillin VK or amoxicillin and/or
topical antibacterial oral suspension may be prescribed.
Infection was localized in our patient case, therefore, the
management was focused on maintenance of optimal oral
hygiene and control of her diabetes. The concept of drug
holidays in an attempt to reduce the risk of ONJ for pa-
tients planned for dento-alveolar surgery is controver-
sial [8,12]. Our patient had the third infusion of 5 mg
ZOL three months after complete healing of her oral le-
sions. The comprehensive dental treatment plan was
modified as a precautionary measure.
4. CONCLUSION
BRONJ as a disease process has multiple contributing
risk factors. Although reported to be low, the incidence
of BRONJ in osteopenic patients taking the once-yearly
infusion of 5 mg ZOL may be higher than previously
thought, especially in those with multiple comorbidities.
Coordinated efforts between physician and oral health
care provider related to the risks and benefits of continu-
ing antiresorptive therapy are imperative. All health care
providers are encouraged to keep abreast of new devel-
opments in this field, assess the risk carefully and inform
patients appropriately.
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