Bisphosphonate related osteonecrosis of the jaw: A minipig large animal model

Pautke, Christoph; Kreutzer, Kilian; Weitz, Jochen; Knödler, Martina; Münzel, Daniela; Wexel, Gabriele; Otto, Sven; Hapfelmeier, Alexander; Stürzenbaum, Stephen R.; Tischer, Thomas

doi:10.1016/j.bone.2012.04.020

Cited by 76 publications

(70 citation statements)

References 41 publications

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“…Considering the current discussion of MRONJ clinical stage classification a very interesting fact was observed in this study 21,22 . In a literature review of experimental models on MRONJ 15 , authors considered 10 small animal models [23][24][25][26][27][28][29][30][31][32] , and 5 large animal models 15,[33][34][35][36][37] . In all studies, when used as the extraction inducing factor, premolars and molars were used [23][24][25][26][27][28][29][30][31][32] .…”

Section: Discussionmentioning

confidence: 99%

Medication-related osteonecrosis of the jaw. Introduction of a new modified experimental model

Curra

Cardoso

Júnior³

et al. 2016

Acta Cir. Bras.

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PURPOSE:To evaluate a modified experimental model for medication-related osteonecrosis of the jaw (MRONJ) through the upper right central incisor extraction followed by intravenous bisphosphonate administration. METHODS:Forty five rats underwent the upper right central incisor tooth extraction were divided in 2 groups: Group I -experimental group, 30 rats received an intravenous administration protocol of zoledronic acid 35μg/kg into the tail vein every two weeks, totalizing four administrations, during eight weeks of administration, previously the extraction, and Group II -control group, 15 rats didn't received any medication before extraction. The groups were subdivided in postoperative periods: 14/28/42 days. Clinical analysis and microtomography were performed to verify the presence of osteonecrosis. In addition, descritive histological analysis of hematoxylineosin stained sections was performed to evaluate the presence of osteonecrosis or necrotic foci. RESULTS:Twelve (40%) rats, from experimental group, showed clinical signs of MRONJ (p=0.005), however, all samples showed imaginologic findings like osteolysis and loss of integrity of the cellular walls (p≤0.001). Microscopic evaluation revealed osteonecrosis areas with microbial colonies and inflammatory infiltrate (p≤0.001). In the control group, all animals presented the chronology of a normal wound healing. CONCLUSIONS:The presence of medication-related osteonecrosis of the jaw after maxillary central incisor extraction in rats. This new experimental model may be considered an option for the study of MRONJ.

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Section: Discussionmentioning

confidence: 99%

Medication-related osteonecrosis of the jaw. Introduction of a new modified experimental model

Curra

Cardoso

Júnior³

et al. 2016

Acta Cir. Bras.

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“…A large number of rodent models have been described and used (Sharma et al, 2013); however, a canine model (Allen and Burr, 2008;Burr and Allen, 2009) in which the amount of necrotic bone could only be evaluated histologically, and a minipig model showing MRONJ lesions (Pautke et al, 2012), are the only large animal models published to date (Allen, 2009). …”

Section: Introductionmentioning

confidence: 99%

Zoledronate induces osteonecrosis of the jaw in sheep

Voss

Stoddart

Ziebart³

et al. 2015

Journal of Cranio-Maxillofacial Surgery

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“…Ottewel et al (22) administered a dose of 0.1 mg/kg (100 µg/kg), and according to these authors, this is equivalent to a human dose of 4 mg/ kg of body weight. Sonis et al (13) used a dose of 7.5 µg/kg, whereas Pautke et al (19) used the dose of 0.05 mg/kg of zoledronic acid in minipigs. In this study, we used the dose of 0.15 mg/ kg/ week based on the dose of 0.6 mg/kg/28 days used by Maahs et al (23).…”

Section: G8mentioning

confidence: 99%

“…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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Bisphosphonate related osteonecrosis of the jaw: A minipig large animal model

Cited by 76 publications

References 41 publications

Medication-related osteonecrosis of the jaw. Introduction of a new modified experimental model

Medication-related osteonecrosis of the jaw. Introduction of a new modified experimental model

Zoledronate induces osteonecrosis of the jaw in sheep

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

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