An experimental study of bisphosphonate-induced jaws osteonecrosis in Sprague-Dawley rats

López‐Jornet, Pía; Camacho-Alonso, Fabio; Molina‐Miñano, Francisco; Gómez-García, Francisco; Vicente-Ortega, Vicente

doi:10.1111/j.1600-0714.2010.00927.x

Cited by 46 publications

(35 citation statements)

References 27 publications

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“…By extracting only the second maxillary molar we were able to produce BRONJ in the experimental group (See Fig. 3) (17,15,20-22), while previous studies had extracted all hemimandible molars to obtain the same result (20,22). …”

Section: Discussionmentioning

confidence: 83%

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Dental extraction following zoledronate, induces osteonecrosis in rat´s jaw

Vidal-Gutiérrez

Jf²,

La³

2017

Med Oral

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BackgroundBisphosphonate-Related Osteonecrosis of the Jaw (BRONJ) is clinically characterized by the presence of exposed bone in the oral cavity that persists for more than eight weeks. Previous attempts to establish an animal model have not sufficiently considered disease features. Our aim was to establish an inexpensive and replicable animal model that develops BRONJ in a short time.Material and MethodsThirty-two male Wistar rats were randomly divided into two groups: control and experimental. In the experimental group, we administered 0.06mg/kg intraperitoneal dose of zoledronic acid (ZA) 7 and 14 days prior to maxillary second molar extraction. At two, four and six weeks after tooth extraction, the animals were euthanized, and we dissected the maxilla following histological procedures. We stained serial slides with hematoxylin and eosin and Masson’s trichrome. The samples were harvested for macroscopic, radiologic and histological evaluation of bone changes.ResultsAt two weeks postextraction, we observed exposed necrotic bone in dental socket areas in experimental groups. Radiological analysis revealed osteolytic lesions accompanied by extensive destruction and sequestrum formation in the same group. Histological examination confirmed the absence of necrotic bone in control groups in contrast with the experimental groups. The percentage of empty lacunae and the number of osteoclasts and the necrotic bone area were significantly increased (p<0.05) in the experimental groups.ConclusionsThe animal model using ZA administration to prior dental extraction successfully mimicked human BRONJ lesions. Also, the model was easily replicated, inexpensive and showed different features than other previous BRONJ models. Key words:Bisphosphonates, osteonecrosis, dental extractions, animal model, BRONJ.

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Section: Discussionmentioning

confidence: 83%

“…We also observed that the experimental group exhibit evident delayed reepithelialization at the fourth week, in contrast with other BRONJ models which showed the same condition but during a longer period of time. (2,9,22,23)…”

Section: Discussionmentioning

confidence: 99%

Dental extraction following zoledronate, induces osteonecrosis in rat´s jaw

Vidal-Gutiérrez

Jf²,

La³

2017

Med Oral

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“…The prevalence of BRONJ in patients receiving long-term oral BP therapy was reported to be approximately 0.1% [11]. Recently, BRONJ-like models have been established in various animals [25,26,[42][43][44]. The administration of BPs combined with dexamethasone induced BRONJ-like models with exposed bone in some studies [25,43,44], is clinically relevant because most cancer patients receive multiple immunosuppressive drugs, including dexamethasone and chemotherapeutic agents [45].…”

Section: Discussionmentioning

confidence: 96%

Multipotent mesenchymal stromal cell sheet therapy for bisphosphonate-related osteonecrosis of the jaw in a rat model

et al. 2016

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Bisphosphonates are frequently used to treat osteoporosis, bone metastasis of various cancers, and other diseases. However, bisphosphonate related-osteonecrosis of the jaw (BRONJ) is an intractable disease because it often recurs after surgery or is exacerbated following conservative treatment. Therefore, an alternative approach for treating BRONJ is needed. In this study, we developed a bone marrow-derived multipotent mesenchymal stromal cell (MSC) sheet to treat BRONJ and investigated the effect of MSC sheet transplantation in a rat model of BRONJ-like disease. The MSC sheet transplantation group showed wound healing in most cases, while only minimal healing was observed in the control group and MSC intravenous injection group. Our results suggest that the MSC sheet is a promising alternative approach for the treatment of BRONJ.

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“…This variability has been hypothesized to be due to the type, route of administration, and dose regimen of BP delivery, in combination with the lack of well-defined outcome measures that define the presence of ONJ in rodents [30]. It is noteworthy, that studies consistently reporting ONJ-like features in mice or rat extraction models include in their experimental design systemic risk factors such as steroid or chemotherapy treatment, vitamin D deficiency, or diabetes all of which alter soft tissue and/or bone homeostasis and compound wound healing [6–8, 10, 12, 37–39]. …”

Section: Discussionmentioning

confidence: 99%

Osteonecrosis of the jaws (ONJ) in mice after extraction of teeth with periradicular disease

Soundia

Hadaya

Esfandi

et al. 2016

Bone

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Osteonecrosis of the jaws (ONJ) is a complication of antiresorptive medications, such as denosumab or bisphosphonates, prescribed to patients with bone malignancy or osteoporosis. The most common instigating local factor in ONJ pathogenesis is tooth extraction. However, in adults the great majority of teeth are extracted due to dental disease. Here, we have investigated alveolar bone healing after extraction of healthy teeth or teeth with naturally occurring periradicular disease in mice treated with high dose zoledronic acid (ZA), a potent bisphosphonate, or OPG-Fc, a RANKL inhibitor. C57BL/6 mice were treated for eight weeks and in vivo micro-CT was performed to identify spontaneously occurring periradicular lesions around the roots of maxillary molars. Then, extractions of molars with and without dental disease were performed in all groups. Four weeks later, animals were euthanized and maxillae were dissected and analyzed. Clinically, all vehicle animals with extraction of healthy or diseased teeth, and most OPG-Fc or ZA animals with extraction of healthy teeth showed normal mucosal healing. On the contrary, most animals with OPG-Fc or ZA treatment and extraction of diseased teeth demonstrated impaired healing with visible mucosal defects. Radiographically, bone socket healing was significantly compromised in OPG-Fc and ZA-treated mice with periradicular disease in comparison to other groups. Histologically, all vehicle animals showed normal mucosal healing and socket remodeling. OPG-Fc and ZA animals with extraction of healthy teeth showed normal mucosal healing, woven bone formation in the socket, and decreased remodeling of the original socket confines. OPG-Fc and ZA animals with extraction of diseased teeth showed mucosal defects, persistent prominent inflammatory infiltrate, bone exposure and areas of osteonecrosis. These findings support that dental disease is critical in the pathogenesis of ONJ, not only as the instigating cause for tooth extraction, but also as a compounding factor in ONJ development and pathophysiology.

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An experimental study of bisphosphonate-induced jaws osteonecrosis in Sprague-Dawley rats

Abstract: The administration of pamidronate and dexamethasone in rats subjected to molar extraction increases the risk of osteonecrosis.

Cited by 46 publications

References 27 publications

Dental extraction following zoledronate, induces osteonecrosis in rat´s jaw

Dental extraction following zoledronate, induces osteonecrosis in rat´s jaw

Multipotent mesenchymal stromal cell sheet therapy for bisphosphonate-related osteonecrosis of the jaw in a rat model

Osteonecrosis of the jaws (ONJ) in mice after extraction of teeth with periradicular disease

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