Further development of the MRONJ minipig large animal model

Otto, Sven; Pautke, Christoph; Jurado, Olga Martin; Nehrbass, Dirk; Stoddart, Martin J.; Ehrenfeld, Michael; Zeiter, Stephan

doi:10.1016/j.jcms.2017.07.002

Cited by 38 publications

(45 citation statements)

References 41 publications

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“…A case–control study reported that the likelihood of developing osteonecrosis was almost double in patients with a history of suppuration compared to those with a history of dental extractions (Barasch et al, ). Animal studies supported the clinical findings and showed that frank, exposed, and necrotic bone can appear on the areas of dental/periodontal infection in the absence of dental extraction (Otto et al, ). Induced dental infection was implicated on the initiation of the osteonecrosis process before extraction in rats (Bolette et al, ).…”

Section: Introductionmentioning

confidence: 82%

Alveolar bone histological necrosis observed prior to extractions in patients, who received bone‐targeting agents

et al. 2020

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Objective We reported the alveolar bone histology prior to dental extractions in cancer patients, who received bone‐targeting agents (BTA). Subjects and Methods Fifty‐four patients were included. Patients underwent extractions, and bone biopsies were taken. Results Extractions were performed due to pain, swelling, purulence, fistula, and numbness, not responding to treatment, in 40 patients (group A); extractions due to asymptomatic, non‐restorable teeth, were performed in 14 patients (group B). Complete alveolar jaw bone histological necrosis was observed in 28 of 40 (70%) patients of group A and none of group B (p < .001). The development of clinical osteonecrosis (MRON) was assessed in 44 patients; 10 patients, who were also treated with Low Level Laser Treatments‐LLLT, were excluded from this analysis, as the alternative therapies were a confounding factor. Twelve patients, with alveolar bone histological necrosis prior to extraction, developed medication‐related osteonecrosis of the jaw (MRONJ) compared with two patients with vital or mixed vital/non‐vital bone (p < .0007). BTAs >1 year and concurrent targeted therapy were also significantly associated with MRONJ (p = .016 and p = .050). Conclusion Pain, swelling, purulence, fistula, and numbness were significantly associated with complete bone histological necrosis prior to extractions and increased MRONJ development. Research is justified to explore whether histological necrosis represents an early stage of osteonecrosis.

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Section: Introductionmentioning

confidence: 82%

Alveolar bone histological necrosis observed prior to extractions in patients, who received bone‐targeting agents

et al. 2020

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“…However, the transferability of those results to humans is limited and no prediction with regard to the regeneration of challenging human extensive bone defects is possible. In contrast to small animal models, the minipig model used in this study resembles human physiology, bone regeneration rates and human anatomy, especially with regard to the shape and the dimensions of the mandibular bone [47][48][49] . Thus, it is possible to create a large size defect simulating a human critical size defect of the mandible.…”

Section: Discussionmentioning

confidence: 99%

Bone regeneration of minipig mandibular defect by adipose derived mesenchymal stem cells seeded tri-calcium phosphate- poly(D,L-lactide-co-glycolide) scaffolds

Probst

Fliefel

Burian

et al. 2020

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Reconstruction of bone defects represents a serious issue for orthopaedic and maxillofacial surgeons, especially in extensive bone loss. Adipose-derived mesenchymal stem cells (ADScs) with tri-calcium phosphates (tcp) are widely used for bone regeneration facilitating the formation of bone extracellular matrix to promote reparative osteogenesis. The present study assessed the potential of cell-scaffold constructs for the regeneration of extensive mandibular bone defects in a minipig model. Sixteen skeletally mature miniature pigs were divided into two groups: Control group and scaffolds seeded with osteogenic differentiated pADSCs (n = 8/group). TCP-PLGA scaffolds with or without cells were integrated in the mandibular critical size defects and fixed by titanium osteosynthesis plates. After 12 weeks, ADSCs seeded scaffolds (n = 7) demonstrated significantly higher bone volume (34.8% ± 4.80%) than scaffolds implanted without cells (n = 6, 22.4% ± 9.85%) in the micro-CT (p < 0.05). Moreover, an increased amount of osteocalcin deposition was found in the test group in comparison to the control group (27.98 ± 2.81% vs 17.10 ± 3.57%, p < 0.001). In conclusion, ADSCs seeding on ceramic/polymer scaffolds improves bone regeneration in large mandibular defects. However, further improvement with regard to the osteogenic capacity is necessary to transfer this concept into clinical use. Maxillofacial bone defects, which occur due to trauma, craniofacial deformities, tumour or infection can lead to facial deformities and severe maxillofacial dysfunctions provoking a dramatic decrease in the quality of life of the patients 1,2. The reconstruction of large bone defects poses many challenges in oral and maxillofacial surgery. Although autologous bone grafts are considered the gold standard in bone defect repair, there are some concerns related to the limited supply and donor site morbidity 3. Several alternatives as allografts, xenografts or synthetic bone substitutes have been brought by researchers and clinicians to restore the function and architecture of the defective bone but still cannot solve the problem due to various limitations. The search of new treatment alternatives has emerged enormously in the past few

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“…Recent studies have reported the presence of histologically proven alveolar necrotic bone associated with dental/periodontal infection at the time of the extraction of teeth (Nicolatou‐Galitis et al, ; Nicolatou‐Galitis, Schiødt, et al, ). Similarly, animal studies have reported that MRONJ can develop to areas of periodontal infection in the absence of dental extraction surgery (Nowicki et al, ; Otto et al, ). Although evidence remains not robust and further well‐designed clinical trials are needed, the Group suggested that patients on anti‐resorptive therapy should not be declined dental extractions for the treatment of recurrent dental/periodontal infections that cannot be resolved or have failed to resolve with restorative treatment, as the persistence of the infection per se represents a notable risk factor for MRONJ development.…”

Section: Controversies On Risk Factorsmentioning

confidence: 95%

Workshop of European task force on medication‐related osteonecrosis of the jaw—Current challenges

et al. 2019

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Further development of the MRONJ minipig large animal model

Cited by 38 publications

References 41 publications

Alveolar bone histological necrosis observed prior to extractions in patients, who received bone‐targeting agents

Alveolar bone histological necrosis observed prior to extractions in patients, who received bone‐targeting agents

Bone regeneration of minipig mandibular defect by adipose derived mesenchymal stem cells seeded tri-calcium phosphate- poly(D,L-lactide-co-glycolide) scaffolds

Workshop of European task force on medication‐related osteonecrosis of the jaw—Current challenges

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