Bisphosphonate-related osteonecrosis of the jaw in metastatic breast cancer patients: a review of 25 cases

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Abstract

Background

Intravenous bisphosphonates have been used in metastatic breast cancer patients to reduce pathologic bone fracture and bone pain. However, necrosis of the jaw has been reported in those who received intravenous bisphosphonates. Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is caused by dental extraction, dental implant surgery, and denture wearing; however, it occurs spontaneously. The purpose of this study was to report BRONJ in metastatic breast cancer patients.

Methods

Consecutive 25 female patients were referred from the Department of Oncology from 2008 to 2014 for jaw bone discomfort. Staging of breast cancer, history of bisphosphonate infusion, etiology of BRONJ, and treatment results were reviewed. Average age of the patients was 55.4 years old (38–74). Twelve maxillae and 16 mandibles were involved. Conservative treatments such as irrigation, antibiotic medication, analgesics, and oral gargle were applied for all patients for the initial treatment. Patients who had sequestrum underwent debridement and primary closure.

Results

The etiologies of BRONJ were dental extraction (19 cases), dental implant (2 cases), and endodontic treatment (1 case). However, three patients did not have any risk factors to cause BRONJ. Three patients died of progression of metastasis during follow-up periods. Surgical debridement was performed in 21 patients with success in 18 patients. Three patients showed recurred bone exposure and infection after operation.

Conclusions

Prevention of the BRONJ is critical in metastatic breast cancer patients. Conservative treatment to reduce pain, discomfort, and infection is recommended for the initial therapy. However, if there is a sequestrum, surgical debridement and primary closure is the key to treat the BRONJ.

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Most cited references 31

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Bisphosphonates: mechanisms of action.

H Fleisch, G Rodan (1996)

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Osteonecrosis of the jaws associated with the use of bisphosphonates: a review of 63 cases.

T. Rosenberg, Bhoomi Mehrotra, L. Ruggiero … (2004)

Bisphosphonates are widely used in the management of metastatic disease to the bone and in the treatment of osteoporosis. We were struck in the past 3 years with a cluster of patients with necrotic lesions in the jaw who shared 1 common clinical feature, that they had all received chronic bisphosphonate therapy. The necrosis that was detected was otherwise typical of osteoradionecrosis, an entity that we rarely encountered at our center, with less than 2 patients presenting with a similar manifestation per year. We performed a retrospective chart review of patients who presented to our Oral Surgery service between February 2001 and November 2003 with the diagnosis of refractory osteomyelitis and a history of chronic bisphosphonate therapy. Sixty-three patients have been identified with such a diagnosis. Fifty-six patients had received intravenous bisphosphonates for at least 1 year and 7 patients were on chronic oral bisphosphonate therapy. The typical presenting lesions were either a nonhealing extraction socket or an exposed jawbone; both were refractory to conservative debridement and antibiotic therapy. Biopsy of these lesions showed no evidence of metastatic disease. The majority of these patients required surgical procedures to remove the involved bone. In view of the current trend of increasing and widespread use of chronic bisphosphonate therapy, our observation of an associated risk of osteonecrosis of the jaw should alert practitioners to monitor for this previously unrecognized potential complication. An early diagnosis might prevent or reduce the morbidity resulting from advanced destructive lesions of the jaw bone.

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Bisphosphonates promote apoptosis in murine osteoclasts in vitro and in vivo.

Alexandre A. Sasaki, Michael D. Hughes, G D Mundy … (1995)

Bisphosphonates inhibit bone resorption and are therapeutically effective in diseases of increased bone turnover, such as Paget's disease and hypercalcemia of malignancy. The mechanisms by which they act remain unclear. Proposed mechanisms include inhibition of osteoclast formation from precursors and inhibitory or toxic effect on mature osteoclasts. We have developed a new in vitro model to study osteoclast survival and in this paper present in vitro and in vivo evidence that may explain both the observed reduction in osteoclast numbers and in bone resorption by mature osteoclasts, namely that bisphosphonates induce programmed cell death (apoptosis). Three bisphosphonates (risedronate, pamidronate, and clodronate) caused a 4- to 24-fold increase in the proportion of osteoclasts showing the characteristic morphology of apoptosis in vitro. This observation was confirmed in vivo in normal mice, in mice with increased bone resorption, and in nude mice with osteolytic cancer metastases, with similar-fold increases to those observed in vitro. Of the three compounds, risedronate, the most potent inhibitor of bone resorption in vivo, was the strongest inducer of osteoclast apoptosis in vitro. Osteoclast apoptosis may therefore be a major mechanism whereby bisphosphonates reduce osteoclast numbers and activity, and induction of apoptosis could be a therapeutic goal for new antiosteoclast drugs.

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Author and article information

Contributors

Hong-Joon Kim: smilehjk1109@naver.com

Tae-Jun Park: artdent7@naver.com

Kang-Min Ahn: 82-2-3010-5901 , ahnkangmin@hanmail.net

Journal

Journal ID (nlm-ta): Maxillofac Plast Reconstr Surg

Journal ID (iso-abbrev): Maxillofac Plast Reconstr Surg

Title: Maxillofacial Plastic and Reconstructive Surgery

Publisher: Springer Berlin Heidelberg (Berlin/Heidelberg )

ISSN (Print): 2288-8101

ISSN (Electronic): 2288-8586

Publication date (Electronic): 1 February 2016

Publication date PMC-release: 1 February 2016

Publication date Collection: December 2016

Volume: 38

Issue: 1

Electronic Location Identifier: 6

Affiliations

Department of Oral and Maxillofacial Surgery, College of Medicine, University of Ulsan, Seoul Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 138-736 South Korea

Article

Publisher ID: 52

DOI: 10.1186/s40902-016-0052-6

PMC ID: 4735266

PubMed ID: 26870717

SO-VID: 2662dcec-4840-46d1-a5cd-ce35e8cd0a60

License:

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

History

Date received : 1 November 2015

Date accepted : 21 January 2016

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Keywords: bisphosphonate,breast cancer,bisphosphonate-related osteonecrosis of the jaw (bronj),extraction,dental implant

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Keywords: bisphosphonate, breast cancer, bisphosphonate-related osteonecrosis of the jaw (bronj), extraction, dental implant

Bisphosphonate-related osteonecrosis of the jaw in metastatic breast cancer patients: a review of 25 cases

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Karger: Oncology

Most cited references 31

Bisphosphonates: mechanisms of action.

Osteonecrosis of the jaws associated with the use of bisphosphonates: a review of 63 cases.

Bisphosphonates promote apoptosis in murine osteoclasts in vitro and in vivo.

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