Introducing a protocol to create bisphosphonate-related osteonecrosis of the jaw in rat animal model

Zandi, Mohammad; Dehghan, Arash; Malekzadeh, Hamid; Janbaz, Pejman; Ghadermazi, Khaled; Amini, Payam

doi:10.1016/j.jcms.2015.12.010

Cited by 31 publications

(27 citation statements)

References 40 publications

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“…Because of its convenience of administration (the intravenous route is typically selected to prevent gastrointestinal irritation), its long administration interval (often 4–5 mg, once a year for OP and once a month for oncology patients) and, most importantly, its strong anti‐bone resorption effect, ZA has become a new treatment choice. Moreover, ZA is more commonly used in creating BRONJ animal models (Çankaya et al, ; Stephen, Brynmor, Gregory, Mark, & Kenneth, ; Zandi, Dehghan, Malekzadeh, et al, ) than denosumab, because the latter is a human antibody and thus could not be used directly in animal experimentation.…”

Section: Discussionmentioning

confidence: 99%

“…In the study of Kikuiri et al (), 125 µg/kg ZA + 5 mg/kg DEX (intravenous) was used twice a week, and 33% of mice developed BRONJ lesions at 7 weeks after tooth extraction. Zandi, Dehghan, Malekzadeh, et al () showed that 83% of rats administered with 60 µg/kg ZA (intraperitoneal) weekly for 4 weeks before tooth extraction had BRONJ lesions at 4 weeks after tooth extraction. In another study, 200 µg/kg ZA + 5 mg/kg DEX (intraperitoneal) was used, and 66.6% of rats had osteonecrosis at 8 weeks after tooth extraction (Paulo Goberlânio de Barros et al, ).…”

Section: Discussionmentioning

confidence: 99%

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The effects of different doses of teriparatide on bisphosphonate‐related osteonecrosis of the jaw in mice

2020

Oral Diseases

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Objectives This study aimed to investigate the therapeutic effect of different doses of teriparatide (TPTD) on bisphosphonate‐related osteonecrosis of the jaw (BRONJ). Materials and Methods To establish the BRONJ model, 20 mice were randomly divided into two groups: a group that received tail vein administration of zoledronic acid with dexamethasone (ZA‐125 µg/kg, DEX 5 mg/kg) and a group that received saline weekly. The mice subsequently underwent bilateral maxillary first molar extraction. After 8 weeks of modelling administration, the maxilla samples were examined by micro‐computed tomography and histological staining (haematoxylin and eosin, Masson's trichrome and tartrate‐resistant acid phosphatase) and the cytokine level was measured (enzyme‐linked immunosorbent assay and Western blot). To determine the role of TPTD in BRONJ, the same protocol as previously described was applied in 100 mice (80 received ZA + DEX, and 20 received saline). After 8 weeks of modelling administration, 80 ZA + DEX mice were randomly divided into four groups: three groups with subcutaneous administration of TPTD (i.e. T1‐3, T2‐10 and T3‐30 µg kg−1 day−1) and one group with saline daily for the next 8 weeks. The other 20 saline mice continued to receive saline daily. Results In Part 1, the level of receptor activator of nuclear factor‐kappa Β ligand and the numbers of osteoclasts differed between the model and control groups. In Part 2, we found that TPTD had a positive effect on BRONJ in a mouse model based on clinical and histomorphological observations. Among the three treatment groups, the T1 and T2 groups significantly differed from the model group, whereas the T3 group showed no statistical differences. Conclusion Subcutaneous administration of TPTD has a beneficial effect on BRONJ in mice. Nevertheless, further studies are needed to determine whether the therapeutic effect on BRONJ is dose‐dependent.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The effects of different doses of teriparatide on bisphosphonate‐related osteonecrosis of the jaw in mice

2020

Oral Diseases

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“…To date, several ONJ animal models have been reported2223242526. For example, immune-deficient beige nu/nu Xid (III) mice exhibit ARONJ-like phenotypes following tooth extraction and treatment with the bisphosphonate zoledronate and the steroid dexamethasone27.…”

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confidence: 99%

Elevation of pro-inflammatory cytokine levels following anti-resorptive drug treatment is required for osteonecrosis development in infectious osteomyelitis

Morita

Iwasaki

Sato

et al. 2017

Sci Rep

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Various conditions, including bacterial infection, can promote osteonecrosis. For example, following invasive dental therapy with anti-bone resorptive agents, some patients develop osteonecrosis in the jaw; however, pathological mechanisms underlying these outcomes remain unknown. Here, we show that administration of anti-resorptive agents such as the bisphosphonate alendronate accelerates osteonecrosis promoted by infectious osteomyelitis. Potent suppression of bone turnover by these types of agents is considered critical for osteonecrosis development; however, using mouse models we found that acceleration of bone turnover by teriparatide injection did not prevent osteonecrosis but rather converted osteoclast progenitors to macrophages expressing inflammatory cytokines, which were required for osteonecrosis development. In fact, we demonstrate that TNFα-, IL-1α/β- or IL-6-deficient mice as well as wild-type mice administered a TNFα-inhibitor were significantly resistant to development of osteonecrosis accompanying infectious myelitis, even under bisphosphonate treatment. Our data provide new insight into mechanisms underlying osteonecrosis and suggest new ways to prevent it.

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“… 27 – 31 The tissues investigated were bone, oral mucosa, periodontium, and blood vessel supply. 23 , 24 , 32 – 43 The studies differed in the type of BP used as well as the route of application. 25 , 44 – 49 Only 2 studies analyzed non-N-BPs (clodronate at 20 mg/kg and etidronate at 5 mg/kg); the remaining 44 trials used N-BPs with zoledronate (0.01–0.6 mg/kg) being the most commonly used (30 studies), followed by alendronate (0.01–1 mg/kg) (14 studies), pamidronate (0.01–3 mg/kg) (5 studies), and ibandronate (0.003–0.3 mg/kg) and risedronate (0.1–1 mg/kg) (1 study each).…”

Section: Resultsmentioning

confidence: 99%

Pathogenesis of medication-related osteonecrosis of the jaw: a comparative study of in vivo and in vitro trials

et al. 2018

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ObjectiveThis study was performed to determine whether the results of prevailing in vivo and in vitro studies offer a reliable model for investigation of medication-related osteonecrosis of the jaw (MRONJ).MethodsEmbase, Medline, and the Cochrane Library were searched for articles published from September 2003 to June 2017 involving experimental approaches to the pathogenesis of MRONJ. In vivo and in vitro trials were analyzed with respect to the scientific question, study design, methodology, and results.ResultsOf 139 studies, 87, 46, and 6 conducted in vivo, in vitro, and both in vivo and in vitro experiments, respectively. Rats, mice, dogs, minipigs, sheep, and rabbits were the preferred animal models used. Osteoblasts, osteoclasts, fibroblasts, keratinocytes, macrophages, and human umbilical vein endothelial cells were the preferred cell types. Zoledronate, alendronate, ibandronate, and risedronate were the most frequent bisphosphonates used. MRONJ was most reliably induced in minipigs because of the close relationship with human bone physiology. In vitro studies showed that reduced viability, growth, and migration of cells in the bone and soft tissues were causative for MRONJ. Other than exposed jawbone after tooth extraction, no reliable cofactors were found.ConclusionThe minipig is the most suitable animal model for MRONJ.

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Introducing a protocol to create bisphosphonate-related osteonecrosis of the jaw in rat animal model

Cited by 31 publications

References 40 publications

The effects of different doses of teriparatide on bisphosphonate‐related osteonecrosis of the jaw in mice

The effects of different doses of teriparatide on bisphosphonate‐related osteonecrosis of the jaw in mice

Elevation of pro-inflammatory cytokine levels following anti-resorptive drug treatment is required for osteonecrosis development in infectious osteomyelitis

Pathogenesis of medication-related osteonecrosis of the jaw: a comparative study of in vivo and in vitro trials

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