Bisphosphonates Cause Osteonecrosis of the Jaw-Like Disease in Mice

Bi, Yanming; Gao, Yamei; Ehirchiou, Driss; Cao, Chunzhang; Kikuiri, Takashi; Le, Anh D.; Shi, Songtao; Zhang, Li

doi:10.2353/ajpath.2010.090592

Cited by 151 publications

(204 citation statements)

References 28 publications

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“…Intralesional injections of triamcinolone acetonide have also been prescribed in view of its anti-inflammatory and antiangiogenic properties. The combined treatment (pharmacological and surgical) is advantageous for large aggressive lesions insofar as it reduces their size, minimizing functional and physical imperfections (4,8,10,21,23,25,26,29) . The anti-angiogenic therapy in combination with curettage has proven to be a useful approach to the treatment of aggressive CGCL (25) .…”

Section: Central Giant Cell Lesionsmentioning

confidence: 99%

Peripheral and central giant cell lesions: etiology, origin of giant cells, diagnosis and treatment

Vasconcelos

Vasconcelos²,

Queiroz

2013

J. Bras. Patol. Med. Lab.

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Introduction and objective: The peripheral and central giant cell lesions (PGCL and CGCL) are a group of pathological entities with similar histopathological features and whose origin has not been fully elucidated. The former is reactive and the latter exhibits a nonneoplastic proliferative behavior. This article aims to review the literature on peripheral giant cell lesions (PGCL) and central giant cell lesions (CGCL) by discussing the most important aspects pertaining to each of them. Results: These lesions are found in different locations and show diverse clinical signs despite having the same histopathological features. The treatment consists in the surgical resection by different techniques depending on the type of the lesion and clinical conditions. In the case of CGCL, drug therapy may also be employed. Conclusion: Although there is no consensus in the literature, it is essential to know the etiology of these lesions as well as the exact origin of the giant cells. Due to their singular biological behavior, it is of utmost importance to establish a differential diagnosis between the two lesions and other processes that have similar clinical, radiological and histological characteristics, inasmuch as this procedure is essential to provide a suitable treatment and establish a prognosis.

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Section: Central Giant Cell Lesionsmentioning

confidence: 99%

Peripheral and central giant cell lesions: etiology, origin of giant cells, diagnosis and treatment

Vasconcelos

Vasconcelos²,

Queiroz

2013

J. Bras. Patol. Med. Lab.

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“…ZOL inhibits angiogenesis and cell migration in the oral epithelium 8,20) while DEX inhibits angiogenesis and type I collagen formation 9) and has an immunosuppressive effect 10 ) . The combined pharmacologic actions of ZOL and DEX may contribute to delayed healing.…”

Section: Discussionmentioning

confidence: 99%

“…Other factors contributing to an increased incidence of BRONJ include steroidassociated immunosuppression and suppression of collagen production 9) . Many studies evaluating the incidence of BRONJ have been based on tooth extraction with administration of both ZOL and steroids 3,[10][11][12] . However, the relationship between jawbone changes and changes in osteoclast and osteoblast activity induced by ZOL and steroids under invasive and non-invasive conditions has not been studied in detail.…”

Section: Introductionmentioning

confidence: 99%

Jawbone Changes in Sodium Zoledronic Acid- and Dexamethasone-Treated Rats

Tezuka

Tanaka

2016

J. Hard Tissue Biology.

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Previous studies have evaluated bisphosphonate-related osteonecrosis of the jaw (ONJ) after tooth extraction with concurrent administration of bisphosphonate zoledronic acid (ZOL) and steroids. However, details of jawbone changes after administration of ZOL and steroids without tooth extraction remain unclear. In this study, we administered ZOL and dexamethasone (DEX) in rats and compared changes in the jawbone with and without tooth extraction. The right maxillary first molar (M 1 ) was extracted from 8-week-old rats treated with ZOL, ZOL+DEX or DEX. The right maxillary M 1 region as the extraction sample and the left maxillary M 1 region as the non-extraction sample were compared with macroscopic, radiological, histologic and immunohistochemical examinations. In the extraction samples, we detected incomplete mucosal closure macroscopically and found ONJ on histological examination. In addition, immunohistochemical and threedimensional analysis of trabecular bone structure showed inhibition of remodeling and angiogenesis in the extraction samples. In the non-extraction samples, we observed inhibition of remodeling, reduced activity of osteoclasts and osteoblasts and suppression of angiogenesis. These findings demonstrate that ONJ can develop under the mucosa with ZOL and DEX treatment, even without invasive procedures. The data suggest that ZOL and DEX can induce ONJ in rats under both invasive and noninvasive conditions because ZOL suppresses osteoclast activity and DEX inhibits remodeling by suppressing osteoblast activity. The results also suggest that surgical stress, such as tooth extraction or bacterial infection, might lead to more severe bisphosphonaterelated ONJ.

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“…In order to generate evidence that may help in establishing these protocols, this study observed the behavior of periapical lesions in rats treated with BP. Other studies have also used animal models to simulate what occurs in patients using BP (13,(15)(16)(17)(18)(19). Most of these researches used tooth extractions and high doses of BP to simulate clinical, radiographic and histologic features of BRONJ (14).…”

Section: G8mentioning

confidence: 99%

Effects of Zoledronic Acid in Experimental Periapical Lesions in Rats: An Imaging and Histological Analysis

et al. 2017

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The aim of this study was to assess the imaging and histological features of experimental periapical lesions, including the adjacent alveolar bone, in rats under zoledronic acid treatment. The study used 40 male Wistar rats distributed into 8 groups of 5 animals each: G1: induction of periapical lesion (PL) and weekly intraperitoneal administration (WIPA) of saline solution (0.9% NaCl) for 4 weeks; G2: PL induction and WIPA of zoledronic acid (0.15 mg/kg/week) for 4 weeks; G3: PL induction and WIPA of saline solution for 8 weeks; G4: PL induction and WIPA of zoledronic acid for 8 weeks; G5:WIPA of saline solution for 4 weeks and subsequent PL induction; G6: WIPA of zoledronic acid for 4 weeks and subsequent PL induction; G7: WIPA of saline solution for 8 weeks and subsequent PL induction; G8: WIPA of zoledronic acid for 8 weeks and subsequent PL induction. The administration of zoledronic acid or saline solution continued after PL induction until the euthanasia. Thus, cone beam computed tomography and histological analysis were performed. Statistical analyzes were performed by ANOVA and Kruskal-Wallis test. Groups treated with zoledronic acid showed significantly smaller size of PL than the groups treated with 0.9% NaCl (p<0.05). PLs were formed by chronic inflammation ranging from mild to moderate, with no difference between groups. In all specimens, no mandibular necrosis was observed. In conclusion, the presence of PLs apparently does not represent an important risk factor for the development of bisphosphonate-related osteonecrosis of the jaws.

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Bisphosphonates Cause Osteonecrosis of the Jaw-Like Disease in Mice

Cited by 151 publications

References 28 publications

Peripheral and central giant cell lesions: etiology, origin of giant cells, diagnosis and treatment

Peripheral and central giant cell lesions: etiology, origin of giant cells, diagnosis and treatment

Jawbone Changes in Sodium Zoledronic Acid- and Dexamethasone-Treated Rats

Effects of Zoledronic Acid in Experimental Periapical Lesions in Rats: An Imaging and Histological Analysis

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