Absence of medication-related jaw osteonecrosis after treatment with strontium ranelate in ovariectomized rats.

This study aimed to evaluate the potential of strontium ranelate (SR) in medication-related jaw osteonecrosis (MRONJ) after tooth extraction in ovariectomized rats. Thirty ovariectomized rats were divided into three groups (n = 10): bisphophonate (BP) group (zoledronic acid; 0.4 mg/kg/week), SR group (625 mg/kg/day), and control group (saline solution). The lower first molars were extracted after 60 days of drug therapy. Drug administration was continued for another 30 days after tooth extraction. The mandibles were subjected to clinical, histological, radiographic, and microtomographic evaluations. Only the BP group showed clinical changes, characterized by the presence of 70% (n = 7) and 20% (n = 2) of ulcers and extraoral fistulas. Radiographic evaluation demonstrated bone sequestration only in the BP group (n = 7, 70%). Microtomographic analysis revealed increased bone porosity after ovariectomy, particularly in the the control group (p < 0.05). The BP group showed a higher bone surface density, bone volume, and trabecular number than SR and control groups, but with less trabecular separation (p < 0.05). All the animals in the BP group demonstrated histological osteonecrosis. There was no evidence of osteonecrosis in the control and SR groups, which was characterized by the absence of empty osteocyte gaps and associated with the gradual healing of the extraction area. Also, an increased number of blood vessels and a reduced number of osteoclasts were observed in the SR group (p < 0.05). Therefore, SR treatment increased angiogenesis and osteoclastogenesis in the healing socket and was not associated with MRONJ development after tooth extraction in ovariectomized rats.

Effect of pentoxifylline and α-tocopherol on medication-related osteonecrosis of the jaw in rats: Before and after dental extraction.

OBJECTIVE: Evaluate the effect of pentoxifylline and α-tocopherol administration in the prevention or treatment of medication-related jaw osteonecrosis (MRONJ). METHODOLOGY: Sixty Wistar rats were divided into three prevention (C-prev, BP-prev and BP/PT-prev) and three treatment groups (C-treat, BP-treat and BP/PT-treat), n = 10. The animals in the BP-prev, BP/PT-prev, BP-treat and BP/PT-treat groups received zoledronic acid (0.1 mg/kg) for 12 weeks, while the animals in the C-prev and C-treat groups received saline solution. At week 6, all animals underwent tooth extraction. Between week 5 and week 12, the BP/PT-prev group was treated with pentoxifylline (50 mg/kg/day) and α-tocopherol (80 mg/kg/day), with euthanasia at the end of week 12. The BP/PT-treat group received the same drug protocol, but it was performed between week 12 and week 16, with euthanasia at the end of week 16. Afterwards, the presence of osteonecrosis was evaluated by clinical analysis, radiographic and histological. RESULTS: BP/PT-treat group showed a reduction in the histological incidence of osteonecrosis by 50%, decrease the percentage of empty osteocyte gaps and the necrotic area, decrease the presence of bone sequestration and increase the number of osteocytes and alveolar blood flow (p < 0.05). However, BP/PT-prev group showed only a reduction in the necrotic area percentage when compared to BP-prev (p < 0.05). CONCLUSIONS: Pentoxifylline and α-tocopherol administration before tooth extraction was not effective in preventing MRONJ. However, this drug protocol was able to reduce MRONJ manifestation when administrate after discontinuation of bisphosphonate, thus it can be considered as a viable strategy for the treatment of this pathological condition.

Absence of medication-related jaw osteonecrosis after treatment with strontium ranelate in ovariectomized rats

Abstract This study aimed to evaluate the potential of strontium ranelate (SR) in medication-related jaw osteonecrosis (MRONJ) after tooth extraction in ovariectomized rats. Thirty ovariectomized rats were divided into three groups (n = 10): bisphophonate (BP) group (zoledronic acid; 0.4 mg/kg/week), SR group (625 mg/kg/day), and control group (saline solution). The lower first molars were extracted after 60 days of drug therapy. Drug administration was continued for another 30 days after tooth extraction. The mandibles were subjected to clinical, histological, radiographic, and microtomographic evaluations. Only the BP group showed clinical changes, characterized by the presence of 70% (n = 7) and 20% (n = 2) of ulcers and extraoral fistulas. Radiographic evaluation demonstrated bone sequestration only in the BP group (n = 7, 70%). Microtomographic analysis revealed increased bone porosity after ovariectomy, particularly in the the control group (p < 0.05). The BP group showed a higher bone surface density, bone volume, and trabecular number than SR and control groups, but with less trabecular separation (p < 0.05). All the animals in the BP group demonstrated histological osteonecrosis. There was no evidence of osteonecrosis in the control and SR groups, which was characterized by the absence of empty osteocyte gaps and associated with the gradual healing of the extraction area. Also, an increased number of blood vessels and a reduced number of osteoclasts were observed in the SR group (p < 0.05). Therefore, SR treatment increased angiogenesis and osteoclastogenesis in the healing socket and was not associated with MRONJ development after tooth extraction in ovariectomized rats.

Histological Comparison between Biphasic Calcium Phosphate and Deproteinized Bovine Bone on Critical-Size Bone Defects.

The limited options for bone repair have led to an extensive research of the field and the development of alloplastic and xenogeneic grafts. The purpose of this study was to evaluate bone repair with two bone substitutes: deproteinized bovine bone (DBB) and biphasic calcium phosphate ceramic (BCP) in critical-size defect. A total of 8-mm defects were made in the parietal bones of rabbits (n=12). The animals were divided into three experimental groups: sham (defect filled with a blood clot), DBB (defect filled with DBB), and BCP (defect filled with BCP). After the experimental periods of 15 and 45 days, the animals were euthanized and submitted to histomorphometric analysis. The total defect area, mineralized tissue area, biomaterial area, and soft tissue area were evaluated. A greater amount of immature bone tissue and biomaterial particles were observed in the BCP group compared to DBB and sham at 45 days (p<0.05). There was no difference in the qualitative pattern of bone deposition between DBB and BCP. However, the sham group did not show osteoid islands along with the defect, presenting a greater amount of collagen fibers as well in relation to the DBB and BCP groups. There was a greater number of inflammatory cells in the DBB at 45 days compared to BCP and sham groups. In conclusion, BCP and DBB are options for optimizing the use of bone grafts for maxillofacial rehabilitation. Bone defects treated with BCP showed greater deposition of bone tissue at 45 days.

Histological comparison between biphasic calcium phosphate and deproteinized bovine bone on critical-size bone defects

Abstract The limited options for bone repair have led to an extensive research of the field and the development of alloplastic and xenogeneic grafts. The purpose of this study was to evaluate bone repair with two bone substitutes: deproteinized bovine bone (DBB) and biphasic calcium phosphate ceramic (BCP) in critical-size defect. A total of 8-mm defects were made in the parietal bones of rabbits (n=12). The animals were divided into three experimental groups: sham (defect filled with a blood clot), DBB (defect filled with DBB), and BCP (defect filled with BCP). After the experimental periods of 15 and 45 days, the animals were euthanized and submitted to histomorphometric analysis. The total defect area, mineralized tissue area, biomaterial area, and soft tissue area were evaluated. A greater amount of immature bone tissue and biomaterial particles were observed in the BCP group compared to DBB and sham at 45 days (p<0.05). There was no difference in the qualitative pattern of bone deposition between DBB and BCP. However, the sham group did not show osteoid islands along with the defect, presenting a greater amount of collagen fibers as well in relation to the DBB and BCP groups. There was a greater number of inflammatory cells in the DBB at 45 days compared to BCP and sham groups. In conclusion, BCP and DBB are options for optimizing the use of bone grafts for maxillofacial rehabilitation. Bone defects treated with BCP showed greater deposition of bone tissue at 45 days.

Resumo As opções limitadas para reparo ósseo levaram ao desenvolvimento de abrangente pesquisa na área de enxertos aloplásticos e xenogênicos. O objetivo deste estudo foi avaliar o reparo ósseo com dois substitutos ósseos: osso bovino desproteinizado (DBB) e cerâmica fosfática de cálcio bifásica (BCP) em defeito de tamanho crítico. Material e métodos: defeitos críticos de 8 mm foram feitos nos ossos parietais de coelhos (n=12). Os animais foram divididos em três grupos experimentais: sham (defeito preenchido com coágulo sanguíneo), DBB (defeito preenchido com DBB) e BCP (defeito preenchido com BCP). Após os períodos experimentais de 15 e 45 dias, os animais foram sacrificados e submetidos à análise histomorfométrica. Foram avaliadas a área total de defeitos, área de tecidos mineralizados, área de biomateriais e área de tecidos moles. Resultados: maior quantidade de tecido ósseo imaturo e de partículas de biomaterial foram observados no grupo BCP em comparação aos grupos DBB e sham aos 45 dias (p<0,05). Não houve diferença no padrão qualitativo de deposição óssea entre DBB e BCP. Ainda, o grupo sham não apresentou ilhas osteóides ao longo do defeito, apresentando maior quantidade de fibras colágenas em relação aos grupos DBB e BCP. Houve maior quantidade de células inflamatórias no DBB aos 45 dias em comparação aos grupos BCP e sham. Conclusões: BCP e DBB são opções para otimizar o uso de enxertos ósseos na reabilitação de pacientes. Defeitos ósseos tratados com BCP mostraram maior deposição de tecido ósseo aos 45 dias.

Caloric restriction prevents alveolar bone loss in the experimental periodontitis in obese rats.

AIMS: It has been shown that periodontitis, can be modified by systemic changes, including behavioral factors, such as diet. Caloric restriction is one of the dietary therapeutic strategies indicated for obesity. It is associated with several benefits, among them, modulation of the inflammatory response. The aim of this study was to verify whether caloric restriction in obese rats changes the progression of experimental ligature-induced periodontitis. MATERIALS AND METHODS: Forty-eight Wistar rats were used for 24 weeks and initially fed with cafeteria diet during 12 weeks. The animals were divided into four groups according to the caloric restriction and experimental periodontitis. The cotton thread was placed around the mandibular first molars, for 15 days, before the end of the experiment. Rats submitted to caloric restriction received, from the 13th week of the experimental protocol, 70% of the food intake compared to the ad libitum animals of other study of the our research group. Alveolar bone loss was assessed using macroscopic morphometric analysis. Analyzes of clinical periodontal measures, biometrics, serum biomarkers and biochemical parameters were performed. KEY FINDINGS: Caloric restriction decreased the alveolar bone loss in the periodontitis group when compared to the group that received a cafeteria diet with periodontitis. Moreover, the results demonstrate the improvement in the glycemic profile, without prejudice to bone tissue biomarkers. SIGNIFICANCE: Based on the results, caloric restriction reduces the progression of alveolar bone loss in rats with experimental periodontitis, in addition to presenting benefits in biometric data, decreasing both glycemic profile and clinical periodontal measures.