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1.
Biomed Res Int ; 2021: 6651318, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34055992

RESUMO

The study was aimed at investigating the effect of zoledronic acid on vascular morphometry in jawbones and long bones on a rat model. Twenty-four skeletal mature Sprague-Dawley female rats were administered oncologic dose of zoledronic acid (ZA) or normal saline for 4 weeks and then subjected to tooth extraction on the mandible and maxilla and a bone defect creation on the femur. After the surgical procedures, ZA or saline treatment was continued until sacrifice at week 2, week 4, and week 8 postoperatively. Vascular perfusion with MICROFIL was performed on all the animals. Micro-CT analysis demonstrated a tendency of decreased vessel density and vessel number in ZA-treated groups but no statistical difference. In conclusion, the neovessel formation is suppressed but not significantly by ZA treatment, indicating that angiogenesis inhibition may contribute to the development of MRONJ but does not play a key role.


Assuntos
Vasos Sanguíneos/anatomia & histologia , Arcada Osseodentária , Microtomografia por Raio-X , Ácido Zoledrônico/farmacologia , Ácido Zoledrônico/uso terapêutico , Animais , Vasos Sanguíneos/diagnóstico por imagem , Pesos e Medidas Corporais , Feminino , Fêmur/efeitos dos fármacos , Arcada Osseodentária/diagnóstico por imagem , Mandíbula/cirurgia , Maxila/cirurgia , Ratos , Ratos Sprague-Dawley , Extração Dentária
2.
Biomed Res Int ; 2021: 6689564, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33628807

RESUMO

This study is to investigate the effect of bisphosphonates on the osseointegration of dental implants in a rabbit model. Twenty female New Zealand White rabbits were equally assigned into control and experiment groups which received saline or zoledronic acid treatment 4 weeks prior to surgery. Titanium dental implant was placed on the calvarial bone. Zoledronic acid or saline treatment continued after surgery for 4 weeks (short-term subgroup) or 8 weeks (long-term subgroup) until sacrifice. Three different fluorochrome labeling solutions were administrated for assessing bone growth rates. Samples of the calvarial bone and mandible were subjected to microcomputed tomography (micro-CT), confocal microscope, and histology analysis. Zoledronic acid treatment significantly reduced bone growth rates in the calvarial bone, but had no significant influence in bone mineral density and trabecular microarchitecture. Significantly lower bone-to-implant contact ratios were found in zoledronic acid-treated animals compared to controls at week 4 but not at week 8. Oncologic dose zoledronic acid suppresses the bone growth rates of the calvarial bone; ZA may have an adverse effect on osseointegration of dental implant in short term, but this effect tends to diminish in long term.


Assuntos
Osseointegração/efeitos dos fármacos , Ácido Zoledrônico/farmacologia , Animais , Implantes Dentários , Feminino , Humanos , Coelhos , Microtomografia por Raio-X
3.
Biomed Res Int ; 2019: 1271492, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31662968

RESUMO

OBJECTIVES: This study aimed to assess the effect of zoledronic acid on an immunocompromised mice model with periapical disease. MATERIALS AND METHODS: Thirty C57BL/6N mice were randomly divided into three groups (N = 10). All animals were subjected to bilateral ovariectomy (OVX) and then treated with saline (Veh), zoledronic acid (ZA), or concomitant zoledronic acid and dexamethasone (ZA/Dx) for 12 weeks. Eight weeks after starting drug administration, pulpal exposure was conducted on the lower left first molar. Four weeks after pulpal exposure, all mice were sacrificed and the mandibles were collected for radiological and histological examinations. RESULTS: Microcomputed tomography (µ-CT) examination showed significantly reduced periapical bone resorption in the ZA/Dx group and decreased periodontal bone resorption in both ZA and ZA/Dx groups. Higher bone mineral density (BMD) and strengthened microstructure were found in ZA and ZA/Dx groups. More empty lacunae were found in ZA and ZA/Dx groups. CONCLUSIONS: Apical periodontitis aggravates MRONJ under immunocompromised circumstances. Concurrent use of ZA and steroids inhibits alveolar bone resorption but increases the risk of developing MRONJ.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Doenças Periapicais/tratamento farmacológico , Ácido Zoledrônico/uso terapêutico , Perda do Osso Alveolar/diagnóstico por imagem , Perda do Osso Alveolar/tratamento farmacológico , Perda do Osso Alveolar/patologia , Animais , Densidade Óssea/efeitos dos fármacos , Dexametasona/farmacologia , Modelos Animais de Doenças , Feminino , Mandíbula/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Dente Molar/efeitos dos fármacos , Osteonecrose/tratamento farmacológico , Ovariectomia , Doenças Periapicais/diagnóstico por imagem , Doenças Periapicais/patologia , Microtomografia por Raio-X
4.
Biomed Res Int ; 2019: 5138175, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31930124

RESUMO

Bisphosphonates (BPs) have been extensively used for management of bone diseases with pathologically high resorption. Despite the great clinical benefits, a severe complication known as medication-related osteonecrosis of the jaw (MRONJ) has been reported. It is found that most of the reported MRONJ cases were limited in the jawbones/craniofacial bones instead of long bones. The present study aims to investigate the differential bone response to surgical procedures between jawbones and long bones exposed to BPs. Forty-eight skeletal mature Sprague Dawley female rats were administered oncologic dose of zoledronic acid (ZA) or normal saline for 4 weeks and then subjected to tooth extraction on the mandible and maxilla, and a bone defect creation on the femur. After surgical procedures, ZA or saline treatment were continued until sacrifice at week 2, week 4, and week 8, post-operatively. The samples were subjected to micro-computerized tomography (micro-CT) and histological assessment. Osteonecrosis was only found in jawbones in ZA-treated rats. ZA-treated rats showed significantly higher bone mineral density with greater bone volume in all surgical sites than that in the controls. The length of exposure of ZA did not seem to affect trabecular microstructure, and it only showed higher bone volume and BMD with longer healing time which is expected in the healing process.


Assuntos
Fêmur/efeitos dos fármacos , Fêmur/cirurgia , Mandíbula/efeitos dos fármacos , Mandíbula/cirurgia , Maxila/efeitos dos fármacos , Maxila/cirurgia , Ácido Zoledrônico/farmacologia , Animais , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/tratamento farmacológico , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/cirurgia , Conservadores da Densidade Óssea/farmacologia , Difosfonatos/farmacologia , Feminino , Ratos , Ratos Sprague-Dawley , Extração Dentária/métodos , Cicatrização/efeitos dos fármacos
5.
Biomed Res Int ; 2017: 1560175, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29109954

RESUMO

OBJECTIVE: The present study aimed to investigate the role of periapical diseases in inducing medication-related osteonecrosis of the jaws (MRONJ) using an ovariectomized (OVX) mice model. MATERIALS AND METHODS: Twenty C57BL/6N female mice were randomly assigned to two groups. All mice were subjected to bilateral ovariectomy and then treated with oncologic dose of zoledronic acid (ZA) or vehicle for twelve weeks. Eight weeks after commence of drug administration, a pulpal exposure (PE) operation was performed on the first right lower molar to induce periapical periodontitis; the contralateral non-PE tooth was used as control. All animals were sacrificed four weeks after pulpal exposure, and the mandibles were harvested for radiological and histomorphometrical analysis. RESULTS: Micro computed tomography (µ-CT) examination demonstrated that periapical diseases significantly increased alveolar bone resorption, and the resorption was greatly attenuated by ZA treatment. Concurrent ZA therapy significantly increased bone density and histological osteocyte necrosis in the presence of periapical lesions. CONCLUSION: ZA treatment reduced bone absorption resulting from periapical disease but increased the risk of developing MRONJ in the ovariectomized mouse model.


Assuntos
Difosfonatos/administração & dosagem , Imidazóis/administração & dosagem , Necrose/fisiopatologia , Osteonecrose/tratamento farmacológico , Doenças Periapicais/tratamento farmacológico , Perda do Osso Alveolar/tratamento farmacológico , Perda do Osso Alveolar/fisiopatologia , Animais , Densidade Óssea/efeitos dos fármacos , Conservadores da Densidade Óssea/administração & dosagem , Modelos Animais de Doenças , Humanos , Arcada Osseodentária/efeitos dos fármacos , Arcada Osseodentária/fisiopatologia , Mandíbula/efeitos dos fármacos , Mandíbula/fisiopatologia , Camundongos , Dente Molar/efeitos dos fármacos , Dente Molar/fisiopatologia , Dente Molar/cirurgia , Osteócitos/efeitos dos fármacos , Osteonecrose/induzido quimicamente , Osteonecrose/fisiopatologia , Doenças Periapicais/fisiopatologia , Tomografia Computadorizada por Raios X , Ácido Zoledrônico
6.
Clin Oral Implants Res ; 28(5): 586-593, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-27038192

RESUMO

OBJECTIVES: The compromised capacity of bone healing in osteoporotic population renders a serious concern of patients and clinicians. This study aimed to investigate the influence of G-CSF on bone reconstruction using an osteoporotic animal model. MATERIALS AND METHODS: Sixty skeletal mature female Spraque-Dawley rats underwent bilateral ovariectomy (OVX) and were assigned into three groups (n = 20). Three months after OVX, defects of 5 mm in cranial and 2 mm in femur were surgically created on all the animals. The defects were left unfilled, filled with gelatin sponge (GS), or filled with granulocyte-colony stimulating factor (G-CSF) infused GS. Specimens were retrieved for histomorphometric and micro-CT analyses at weeks 1, 4, 8, and 12 after surgery. RESULTS: At early stage of week 1 to week 8, the histomorphometric and micro-CT analysis demonstrated more advanced bone formation in femur in the control group; by week 12, all groups achieved cortical closure. In cranial bone, more advanced bone formation was exhibited in G-CSF-treated group at both early and late stages, although this observation was not statistically significant. CONCLUSIONS: The results indicated that in osteoporotic bone, G-CSF may advance bone healing in cranial bone where spontaneous bone formation was insufficient.


Assuntos
Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Osteoporose/tratamento farmacológico , Animais , Feminino , Fêmur/diagnóstico por imagem , Fêmur/efeitos dos fármacos , Fêmur/cirurgia , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Osteogênese/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Crânio/diagnóstico por imagem , Crânio/efeitos dos fármacos , Crânio/cirurgia , Microtomografia por Raio-X
7.
Injury ; 42(8): 796-802, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21367413

RESUMO

BACKGROUND: Bone regeneration approaches that mimic the natural processes of bone repair have generated significant attention. We hypothesized that early delivery of an angiogenic factor combined with sustained exposure to an osteogenic factor would recapitulate the critical aspects of natural bone repair. MATERIALS AND METHODS: Basic fibroblast growth factor (bFGF) and sonic hedgehog (Shh) were constructed to the recombinant adeno-associated virus, respectively (rAAV2-tet-off-bFGF and rAAV2-Shh). The previous viral vector allowed for regulation of the bFGF expression by the addition of doxycycline, a tetracycline analogue. These two viral vectors were used to cotransduce bone marrow-derived mesenchymal stem cells (BMSCs). Several osteogenic markers such as core-binding factor a-1, alkaline phosphatase and osteocalcin were detected by quantitative real-time reverse transcriptase polymerase chain reaction. Meanwhile, protein expressions of transgenes were measured by western blot. Furthermore, these cotransduced BMSCs were seeded on ß-tricalcium phosphate (ß-TCP) granules and then were implanted into the calvarium defect in a rat model. A sample of 30 Sprague-Dawley rats was divided into six groups (n=5); an 8-mm critical-sized bone defect was made in calvarium of all subjects. Each group was treated with various transgenic BMSCs and ß-TCP composites; and the sixth group is the negative control which was implanted with nothing. At 4 weeks after treatment, the samples were evaluated with histological staining. RESULTS: The expression of osteogenic marker mRNA had an increased tendency after two genes transduction (p<0.05). In addition, dramatically enhanced regeneration of critical-sized calvarial defects was observed in the groups which were implanted with two transgenic BMSCs and ß-TCP composites. And in these experimental groups, bone areas and vascular densities were increased significantly (p<0.05) than other groups. CONCLUSION: Sequential delivery of angiogenic and osteogenic factors likely has a synergistic effect, mimicking the molecular events of natural bone regeneration.


Assuntos
Regeneração Óssea/fisiologia , Fator 2 de Crescimento de Fibroblastos/metabolismo , Consolidação da Fratura/fisiologia , Proteínas Hedgehog/metabolismo , Osteogênese/fisiologia , Fosfatase Alcalina/metabolismo , Animais , Western Blotting , Fator 2 de Crescimento de Fibroblastos/administração & dosagem , Fator 2 de Crescimento de Fibroblastos/genética , Expressão Gênica , Vetores Genéticos/administração & dosagem , Proteínas Hedgehog/administração & dosagem , Proteínas Hedgehog/genética , Transplante de Células-Tronco Mesenquimais/métodos , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Crânio/irrigação sanguínea , Transdução Genética/métodos
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