Osteonecrosis of the jaws due to bisphosphonate use. A review of 60 cases and treatment proposals

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Abstract

Purpose

Bisphosphonates are compounds used in the treatment of various metabolic and malignant bone diseases. 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 bone lesions 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 surgical restorative 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 of the jaws.

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 by aledronate, ibandronate, incadronate, olpadronate, pamidronate, risedronate, and zoledronate, whereas the non–N-BPs are mainly clodronate, etidronate, and tiludronate [1], [2].

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 the last 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 of this recently described complication of the use of bisphosphonates previously called drug-induced avascular osteonecrosis or bisphosphonate-induced exposed bone of the jaws [3]. We suggest a therapeutic protocol for these patients, and in the discussion that follows, we put under speculation the mechanism that leads to this complication.

Section snippets

Patients and methods

From July 2003 to October 2005, 60 patients referred to the Department of Oral and Maxillofacial Surgery of Aristotle University and ‘Theagenio’ Cancer Institute of Thessaloniki with the diagnosis of refractory osteomelitis of the jaws subsequent to their main oncological history of one of the following diseases: multiple myeloma (32 cases, 53.33%), breast cancer (18 cases, 30%), prostate cancer (5 cases, 8,33%), lung cancer (2 cases, 3.33%), neuroendocrine cancer (1 case, 1.67%), fibrous

Results

All the biopsy specimens taken from the area of necrotic bone including both soft and hard tissue were negative for malignancy, whereas culture results revealed normal oral flora with sporadic cases of Actinomyces israeli, Escherichia coli, and Bacteroides melaninogenicous.

For the first 7 patients, the implementation of protocols 1 and 2 resulted in complete wound healing (Fig. 1, Fig. 2, Fig. 3, Fig. 4, Fig. 5). In the next 18 patients, treatment following protocols 3, 4, and 5 lead to bone

Discussion

The high incidence of osteonecrosis—especially maxillary—in patients who are receiving bisphosphonates and have not previously received radiation therapy in the head and neck region is in contrast with the current knowledge. Marx et al [3], [4] first reported osteonecrotic lesions of the jaws similar to those of osteoradionecrosis, which they called drug-induced avascular osteonecrosis, implying that the destruction of the vascular complexity of the jaws mediated by the use of bisphosphonates

References (14)

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