Study on bisphosphonate-related osteonecrosis of the jaw (BRONJ): case report and literature review

Yeo-Gab Kim; Baek-Soo Lee; Yong-Dae Kwon; Joon-Ho Suh; Sang-Mi Jeen

doi:10.5125/jkaoms.2010.36.4.291

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Kim, Lee, Kwon, Suh, and Jeen: Study on bisphosphonate-related osteonecrosis of the jaw (BRONJ): case report and literature review

Original Article

J Korean Assoc Oral Maxillofac Surg 2010;36(4):291-301.

Published online: 10 January 2010

DOI: https://doi.org/10.5125/jkaoms.2010.36.4.291

Study on bisphosphonate-related osteonecrosis of the jaw (BRONJ): case report and literature review

Yeo-Gab Kim¹, Baek-Soo Lee¹, Yong-Dae Kwon¹, Joon-Ho Suh¹, Sang-Mi Jeen²

¹Department of Oral and Maxillofacial Surgery, School of Dentistry, Seoul, Korea

²School of Dentistry, Kyung Hee University, Seoul, Korea

Yeo-Gab Kim 1 Hoegidong, Dongdaemungu, Seoul, 130-701, Korea Department of Oral and Maxillofacial Surgery, Kyung-Hee University Tel: +82-2-958-9440 E-mail: kyukab@khu.ac.kr

Received 6 May 2010 Revised 15 July 2010 Accepted 27 July 2010

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a side effect of Bisphosphonates (BPs) use. These days, oral bisphosphonates are normally prescribed to treat osteoporosis. Intravenous BPs are used extensively to treat osteolytic bone lesions related to multiplemyeloma and bone metastasis of solid cancers, breast cancer or prostate cancer. As the prescription of BPs is universalized and the number of people treated with BPs is increasing, an accurate understanding and proper management of BRONJ are required. The aim of this study was to improve the clinicians’ understanding of BRONJ by reviewing the literature. To achieve this, this paper introduces case reports as well as the current concept of BRONJ based on the 2009 updates by American Association of Oral and Maxillofacial (AAOMS) including the definition, epidemiology, etiology, diagnosis, treatment and prevention of BRONJ.

Keywords: Bisphosphonate, Osteonecrosis, Osteoporosis, Jaw diseases

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Fig. 1.

A. Delayed healing of the extraction wounds with exposure of alveolar bone and pus discharge of the maxillary right first premolar. B. Maxillary left second premolar and second molar.

Fig. 2.

Radiolucent status with ill-defined border of the lesion area is observed in the panoramic view of the initial examination.

Fig. 3.

Bilateral maxillary sinus area haziness is shown in the water's view of the initial examination.

Fig. 4.

Bone destruction status is observed in the maxillary left and right lesion area, sequestrum formation can be identified in the maxillary right lesion area, and reactive osteophytic status is shown in the sinus floor area in the lesion area of the maxillary left side in the dental computed tomography (CT) image of the initial examination.

Fig. 5.

After 3 months from the initial visit, the inflammatory state has been clinically relieved and according to the panoramic view taken for preoperative examination purpose, significant bone formation and sequestrum (maxillary left molar and premolar area) formation can be identified.

Fig. 6.

A. Left Maxillary Lesion, B. The Sequestrum was removed, and the tissue removed was further examined through biopsy for a confirmed diagnosis.

Fig. 7.

Four weeks after surgery, according to the radiographic image the irregularity of the maxillary left and right surgery area has decreased and, due to new bone formation, was merging with the adjacent bone.

Fig. 8.

Six weeks after surgery, the surgery area of the maxillary left and right side is healing progressively.

Fig. 9.

Ten weeks after surgery, according to radiographic image, the bone of the surgery area in the maxillary left and right side is maturing into similar configuration as the adjacent bone.

Fig. 10.

Nitrogen-containing bisphosphonates inhibit farnesyl diphosphate (FPP) synthase, an enzyme in mevalonate pathway. FPP synthase is responsible for isoprenylation of small GTPases that promote an array of activities in the osteoclasts that control bone resorption. Without this activity, bone resorption is slowed. (HMG: 3-hydroxy-3-methylglutaryl)

Fig. 11.

Bisphosphonates used most frequently in the clinic today have a characteristic structure. All have a hydroxyl group on the carbon atom that confers high affinity for calcium and the skeleton. They vary only at the R-group, which always contains a nitrogen atom that is in either an alkyl or a heterocyclic structure.

Table 1.

Amino bisphosphonate drugs^12,13

Drug name	Active ingredients	Dosage form: route	FDA approval	Relative potency¹
Fosamax	Alendronate sodium	Tablet: oral	1995	1,000
Actonel	Risedronate sodium	Tablet: oral	1998	5,000
Boniva	Ibandronate sodium	Tablet / injectable:	2003	10,000
Boniva		oral / IV injection	2006
Aredia	Pamidronate disodium	Injectable: IV infusion	1991	100
Zometa	Zoledronic acid	Injectable: IV infusion	2001	100,000
Reclast	Zoledronic acid	Injectable: IV infusion	2007	100,000

¹ relative to etidronate, a non-nitrogen-containing bisphosphonate with relative potency of 1, FDA: the Food and Drug Administration)

Table 2.

Clinical stages of BRONJ patient¹²

Stage	Description
At risk	treated with BPs by oral oculation or injection including IV
	no symptom
	no clinical definite bone exposure or osteonecrosis is observed
Stage 0	no bone exposure or osteonecrosis is observed
	complain of non-specific symptom
	clinically or radiographically BRONJ is suspicious
Stage 1	osteonecrosis is observed
Stage 1	no evidence of symptom or infection
Stage 2	regardless of pus drainage, pain, erythema, inflammatory reaction shows
Stage 2	osteonecrosis is observed with infection
Stage 3	with symptom of stage 2 lesions, accompanies one or more of following:
	− exposured site of bone necrosis encompass alveolar bone and causes pathological fracture
	− forms extra-oral fistula
	− forms oral/ nasal fistula or communication
	− osteolysis extending to the inferior border of mandible

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