Osteonecrosis of the jaw in a patient taking once-yearly infusion of zoledronic acid for osteopenia

doi:10.4236/crcm.2013.29139

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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: [email protected]

2Department of Patient Management, University of Detroit Mercy School of Dentistry, Detroit, USA;

[email protected]

Received 14 September 2013; revised 10 October 2013; accepted 7 November 2013

mons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work

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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