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American Journal of Otolaryngology–Head and Neck Medicine and Surgery 28 (2007) 158 – 163
www.elsevier.com/locate/amjoto

Osteonecrosis of the jaws due to bisphosphonate use.
A review of 60 cases and treatment proposals
Christos Magopoulos, DDSa,4, Georgios Karakinaris, DDSa, Zisis Telioudis, DDSb,
Konstantinos Vahtsevanos, MD, DDSb, Ioannis Dimitrakopoulos, MD, DDSa,
KonstantinosAntoniadis, MD, DDSa, Sideris Delaroudis, MDc
a

Department of Oral and Maxillofacial Surgery, Aristotle University, Thessaloniki, Greece
b
dTheagenioT Cancer Istitute, Thessaloniki, Greece
c
Department of Endocrinology, Military Hospital, Thessaloniki, Greece
Received 15 May 2006

Abstract

Purpose: Bisphosphonates are compounds used in the treatment of various metabolic and malignant
bonediseases. In the last two and a half years, there has been a striking increased referral of patients
with exposed necrotic jawbone, mostly after several teeth extractions. The only clinical feature
common in all patients was the use of bisphosphonates in the treatment of bone diseases.
Patients and methods: We performed a retrospective multicentric study of 60 patients with necrotic
bonelesions of the jaws of various extent from July 2003 to October 2005. The necrotic bone
involved the maxilla (37%), the mandible (50%), or both (13%). The bisphosphonate administered
was mostly zoledronate. The management of the patients included cessation of bisphosphonate
therapy for more than 6 months, long-term antibiotics, hyperbaric oxygen administration in some
cases, and various surgicalrestorative procedures.
Results: The implementation of the treatment protocol in 7 patients so far lead to high cure rates,
whereas surgical restoration of the defect without previous cessation of bisphosphonate therapy had
discouraging results.
Conclusions: Clinicians and dentists should have in mind this new complication of bisphosphonate
administration to identify and treat osteonecrosis ofthe jaws.
D 2007 Elsevier Inc. All rights reserved.

1. Introduction
Bisphosphonates have been developed over the past
3 decades and have been used in the treatment of many
skeletal disorders, such as bone metastases, osteoporosis,
Paget disease, hypercalcemia of malignancy, and bone pain.
Those that contain nitrogen and are the most potent ones are
the N-BPs and are represented byaledronate, ibandronate,
incadronate, olpadronate, pamidronate, risedronate, and
zoledronate, whereas the non–N-BPs are mainly clodronate,
etidronate, and tiludronate [1,2].

4 Corresponding author. Glinou 4-Pilea, 54352 Thessaloniki, Greece.
Tel.: +30 2310949711; fax: +30 2310995362.
E-mail address: mago@med.auth.gr (C. Magopoulos).
0196-0709/$ – see front matter D 2007 Elsevier Inc. All rightsreserved.
doi:10.1016/j.amjoto.2006.08.004

The main pharmacological effect of bisphosphonates is
the inhibition of bone resorption caused by osteoclasts
decreased function, whereas other effects, like inhibition of
calcification in the treatment of hypercalcemia of malignancy and reduction of joint inflammatory reaction in the
treatment of arthritis, are of secondary magnitude.
In thelast 2 years, there has been an increased referral of
patients with exposed necrotic jaw bone, diagnosed elsewhere as chronic refractory osteomyelitis of jaws mostly
after teeth extractions. Most of the patients had a natural
history of malignancy, and the only thing in common was the
long-term intravenous administration of bisphosphonates.
In this article, we present the clinical evaluation ofthis
recently described complication of the use of bisphosphonates previously called drug-induced avascular osteonecrosis or bisphosphonate-induced exposed bone of the

C. Magopoulos et al. / American Journal of Otolaryngology–Head and Neck Medicine and Surgery 28 (2007) 158–163

159

Table 1
Patient data
Patient no.

Diagnosis

Bisphosphonates

Osteonecrosis

Management...
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