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1.
J Appl Oral Sci ; 28: e20200204, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32997086

RESUMO

OBJECTIVE: This study aims to evaluate bone repair and the development of the medication related osteonecrosis of the jaw (MRONJ) associated with the use of zoledronic acid in Wistar rats. METHODOLOGY: 48 male Wistar rats were divided into four groups: ZA, treated with intraperitoneal zoledronic acid, 0.6 mg/kg every 28 days, totaling five doses; control (C), treated with 0.9% sodium chloride; ZA-surgical (SZA) and C-surgical (SC), submitted to extraction of the right upper molars 45 days after the first application. Alveolar bone repair was evaluated by macroscopic and histological analysis. Protein expression evaluations were performed by qPCR. RESULTS: Macroscopic evaluation showed that 91.66% (11) of the animals in the SZA group and 41.66% (5) from the SC group presented solution of epithelium continuity (P<0.05). All animals in the SZA group and none in the SC group had bone sequestration. The area of osteonecrosis was higher in the SZA group than in the SC group (P<0.05). In molecular evaluation, the SZA group presented changes in the expression of markers for osteoclasts, with increased RANK and RANKL, and a decrease in OPG. CONCLUSION: The results highlighted strong and evident interference of zoledronic acid in bone repair of the socket, causing osteonecrosis and delayed bone remodeling.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/fisiopatologia , Conservadores da Densidade Óssea/efeitos adversos , Ácido Zoledrônico/efeitos adversos , Animais , Masculino , Ratos , Ratos Wistar , Extração Dentária/efeitos adversos
2.
Stem Cell Res Ther ; 10(1): 209, 2019 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-31311585

RESUMO

BACKGROUND: Definitive treatment strategies for bisphosphonate-related osteonecrosis of the jaw (BRONJ) have not been developed. Cell-based therapy is an attractive treatment method for intractable diseases in the medical and dental fields; however, approval has been challenging in dentistry. Recently, we developed quality- and quantity (QQ)-controlled peripheral blood mononuclear cells (PBMNCs) that have anti-inflammatory and pro-angiogenesis effects. The aim of this study was to investigate the effects of QQ-controlled PBMNC transplantation on BRONJ-like lesions in mice. METHODS: To create high-prevalence BRONJ-like lesions, cyclophosphamide (CY) and zoledronate (ZA) were used with tooth extraction. Drug treatment was performed for 5 weeks. QQ-controlled PBMNC transplantation was performed immediately following tooth extraction of both maxillary first molars at 3 weeks after drug administration. Mice were euthanized at 2 weeks post-extraction. Histomorphometric and immunohistochemical analyses, microcomputed tomography assessment, and quantitative polymerase chain reaction evaluation were conducted using maxillae and long bones. RESULTS: ZA effects on long bones were noted, regardless of CY. Severely inhibited osseous and soft tissue wound healing of tooth extraction sockets was induced by CY/ZA combination therapy, which was diagnosed as BRONJ-like lesions. QQ-controlled PBMNC transplantation reduced BRONJ-like lesions by improving soft tissue healing with increased M1 and M2 macrophages and enhanced neovascularization in the connective tissue of tooth extraction sockets. QQ-controlled PBMNC transplantation also reduced inflammation by decreasing polymorphonuclear cells and TNF-α expression in the tooth extraction sockets. Additionally, QQ-controlled PBMNC transplantation partially improved osseous healing of tooth extraction sockets. Interestingly, only 20,000 QQ-controlled PBMNCs per mouse induced these transplantation effects. QQ-controlled PBMNC transplantation did not affect the systemic microenvironment. CONCLUSIONS: Our findings suggest that transplantation of a small amount of QQ-controlled PBMNCs may become novel therapeutic or prevention strategies for BRONJ without any adverse side effects.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/terapia , Macrófagos/transplante , Transplante de Células-Tronco de Sangue Periférico , Cicatrização , Animais , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/diagnóstico por imagem , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/etiologia , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/fisiopatologia , Ciclofosfamida/toxicidade , Modelos Animais de Doenças , Humanos , Leucócitos Mononucleares/transplante , Camundongos , Dente Molar/diagnóstico por imagem , Dente Molar/efeitos dos fármacos , Dente Molar/crescimento & desenvolvimento , Extração Dentária , Microtomografia por Raio-X , Ácido Zoledrônico/toxicidade
3.
Braz Oral Res ; 33: e050, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31269114

RESUMO

The present study aimed to investigate the use of platelet-rich plasma (PRP) on tooth extraction sites in rats treated with bisphosphonates. Thirty Albinus Wistar male rats were administered 0.035 mg/kg zoledronic acid intravenously for 8 weeks, divided into four administrations with a 2-week interval between each application, after which their upper right central incisors were extracted to induce the development of bisphosphonate-related osteonecrosis of the jaw (BRONJ). The samples were divided into the following two groups: Group 1 (G1) underwent marginal resection of BRONJ followed by the use of PRP, while Group 2 (G2) underwent resection of BRONJ but without the use of PRP. The treatment groups were evaluated after 14, 28, and 42 days. Clinical, microtomographic, microscopic, and immunohistochemical (IHC) evaluations were performed. Microtomography results revealed no significant difference between the groups (p <0.05) in any time period. Histomorphometric analysis showed increased bone formation over time for both groups (p < 0.001). G1 demonstrated a greater amount of new bone formation than G2 at 28 and 42 days (p < 0.001), with G1 presenting greater vascularization and a slightly higher VEGF expression. For both groups, RANKL/OPG expression levels were sufficient as a parameter for indicating the rate of bone remodeling in a previously treated area of osteonecrosis groups. Taken together, our findings indicated that the use of PRP improves the resolution process of BRONJ.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/terapia , Conservadores da Densidade Óssea/uso terapêutico , Difosfonatos/uso terapêutico , Plasma Rico em Plaquetas , Animais , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/patologia , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/fisiopatologia , Modelos Animais de Doenças , Masculino , Osteoclastos/efeitos dos fármacos , Ratos , Ratos Wistar , Extração Dentária/efeitos adversos , Cicatrização
4.
Clin Interv Aging ; 14: 797-804, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31123397

RESUMO

Purpose: Osteonecrosis of the jaw (ONJ), both medication-related and non medication-related, mainly occurs in aged patients. It needs surgical intervention. Refractory healing after an operation of ONJ can significantly lower the quality of life of elderly patients. The purpose of this study was to determine risk factors associated with refractory healing in aged patients. Patients and methods: We performed a retrospective study of ONJ in aged patients who underwent surgical treatments in a single institute during a 12-year period. Multiple logistic regression analysis was used to determine independent risk factors associated with refractory healing. Results: A total of 122 patients were included. Of them, 25 patients were identified as the refractory group and 97 patients as the control group. Diabetes mellitus (DM) (AOR=5.03, 95% CI: 1.74-14.52) and glucocorticoid administration (AOR=7.97, 95% CI: 2.52-25.23) were found to be significant risk factors for refractory healing of ONJ. Conclusion: DM and medication of glucocorticoid might be risk factors for refractory healing of ONJ.


Assuntos
Doenças Maxilomandibulares/fisiopatologia , Doenças Maxilomandibulares/cirurgia , Osteonecrose/fisiopatologia , Osteonecrose/cirurgia , Cicatrização/fisiologia , Idoso , Idoso de 80 Anos ou mais , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/fisiopatologia , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/cirurgia , Comorbidade , Feminino , Glucocorticoides/efeitos adversos , Humanos , Modelos Logísticos , Masculino , Qualidade de Vida , Estudos Retrospectivos , Fatores de Risco
6.
Biomed Res Int ; 2019: 8345309, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31011580

RESUMO

This retrospective cohort study aims to describe characteristics of patients with MRONJ, to identify factors associated with MRONJ development, and to examine variables associated with favourable outcome. Totally 32 patients were followed and observed: 21 females and 11 males, in the age range 35-84 in the period from 2009 to 2018. Clinical, radiological examination (Orthopantomograph and CBCT) and biopsy were performed in order to achieve diagnosis. Demographic and clinical variables were taken into consideration: sex, age, primary disease, medication type, mode of delivery, anatomic location, drug treatment duration, timing of tooth extraction, chemotherapy, presence of bone metastasis, aetiology of MRONJ, disease stage, and treatment modality. MRONJ developed under osteoporosis and malignant disease in 11 and 21 patients, respectively. MRONJ development was triggered by tooth extraction or trauma in 30 out of 32 cases, whereas the two patients developed MRONJ spontaneously. Stages I, II, and III were confirmed in 5 (16%), 18 (58%), and 9 (28%) patients, respectively. Mandible was affected in 23 (72%) patients. MRONJ was treated in our department by conservative and surgical modality. In this study we found that 65% of all patients were classified in the cured/improvement group and 35% in the stable/progression group. The female gender, osteoporosis as primary disease, oral regime intake, shorter period on BPs, earlier stage of disease, and specific anatomic localisation (frontal and premolar maxilla) were factors associated with better response to therapy and favourable clinical outcome. Comprehensive treatment protocol and further randomized studies are necessary for further improvements.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/etiologia , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Conservadores da Densidade Óssea/efeitos adversos , Neoplasias Ósseas/fisiopatologia , Difosfonatos/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoporose/fisiopatologia , Radiografia Panorâmica/efeitos adversos , Estudos Retrospectivos , Fatores de Risco , Extração Dentária/efeitos adversos
7.
Ultrasound Med Biol ; 45(7): 1721-1732, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31006496

RESUMO

We developed a rat model of bisphosphonate-related osteonecrosis of the jaw (BRONJ) by removing a maxillary molar tooth (M1) from ovariectomized rats after treatment with alendronate. To mimic periodontitis, some of the rats were administered Porphyromonas gingivalis (p. gingivalis) at the M1 site every 2 to 3 d for 2 wk. Rats pretreated with alendronate plus p. gingivalis showed delayed healing of socket epithelia, periosteal reaction of alveolar bone formation and lower bone mineral density in the alveolus above adjacent M2 teeth. These abnormalities were prevented by tooth socket exposure to 20 min/d low-intensity pulsed ultrasound (LIPUS), which restored diminished expression of RANKL, Bcl-2, IL-6, Hsp70, NF-κB and TNF-α messenger ribonucleic acids in remote bone marrow, suggesting LIPUS prevented development of BRONJ-like pathophysiology in rat by inducing systemic responses for regeneration, in addition to accelerating local healing. Non-invasive treatment by LIPUS, as well as low-level laser therapy, may be useful for medication-related osteonecrosis of the jaw patients.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/prevenção & controle , Osteogênese/fisiologia , Periodontite/terapia , Alvéolo Dental/fisiopatologia , Terapia por Ultrassom/métodos , Ondas Ultrassônicas , Animais , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/fisiopatologia , Modelos Animais de Doenças , Feminino , Ratos , Ratos Wistar
8.
Arch Oral Biol ; 96: 195-200, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30292055

RESUMO

The alveolar bone has a unique capacity to follow the teeth's movements. It is formed around erupting teeth and their periodontal ligaments: the more the teeth have erupted, the larger the alveolar process. Throughout life the teeth erupt and migrate in an occlusal and mesial direction to compensate for attrition, an evolutionary trait. After tooth extraction, the alveolar process is resorbed to varying degrees. The mandibular alveolar bone mirrors skeletal bone condition. Due to fast bone turnover (which is the fastest in the whole skeleton), low bone mass and increased fracture risk may first be seen here. If a periapical radiograph of the mandibular premolars shows a dense trabeculation with well-mineralized trabeculae and small intertrabecular spaces, it is a reliable sign of normal skeletal bone density (BMD) and low skeletal fracture risk, whereas a sparse trabecular pattern indicates osteopenia and high fracture risk. The bone turnover rate in the mandible is twice that of the maxilla, and may, hypothetically, play a role in the development of osteonecrosis of the jaw (ONJ), which has been found mainly in the mandibular alveolar process?


Assuntos
Processo Alveolar/fisiologia , Mandíbula/fisiologia , Processo Alveolar/metabolismo , Animais , Biomarcadores/metabolismo , Fenômenos Biomecânicos/fisiologia , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/fisiopatologia , Densidade Óssea/fisiologia , Remodelação Óssea/fisiologia , Humanos , Mandíbula/metabolismo , Osteoporose/fisiopatologia , Erupção Dentária/fisiologia , Extração Dentária , Técnicas de Movimentação Dentária
9.
Biometals ; 31(3): 445-455, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29435826

RESUMO

Osteonecrosis of the jaws is an emerging pathological condition characterized by un-exposure or exposure of the necrotic bone, independently from the etiology. This term is usually referred to medication-related osteonecrosis of the jaws due to severe adverse reaction to certain medicines, as bisphosphonates, used for the treatment of cancer and osteoporosis. The management of patients with Bisphosphonate-Related Osteonecrosis of the Jaws (BRONJ) remains challenging because surgical and medical interventions may not eradicate this pathology. The goal of treatment of patients at risk of developing BRONJ or of those who have active disease is the preservation of quality of life by controlling pain, managing infection, and preventing the development of new areas of necrosis. The treatment of osteonecrosis consists in the surgical removal of necrotic bone followed by antibiotic therapy and application of sterile greasy gauze until the wound closure. The classical medical treatment has been compared with the innovative one consisting in the application of sterile greasy gauze soaked with bovine lactoferrin (bLf) after surgery. Here, for the first time, bLf efficacy on wound repair in subjects suffering from BRONJ with the progressive destruction of bone in the mandible or maxilla has been demonstrated. The positive results consist in a significant shorter time of wound closure (1 or 2 weeks) compared to that observed with classical surgical treatment (2-3 months). These promising results are an interesting tool for the innovative treatment of this pathology and for increasing the quality of life of these patients.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/tratamento farmacológico , Conservadores da Densidade Óssea/administração & dosagem , Lactoferrina/administração & dosagem , Necrose/tratamento farmacológico , Administração Oral , Idoso , Animais , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/fisiopatologia , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/cirurgia , Bovinos , Difosfonatos/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Necrose/induzido quimicamente , Necrose/cirurgia , Qualidade de Vida
10.
Cranio ; 36(6): 373-380, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28854059

RESUMO

OBJECTIVE: To compare the characteristics and outcomes of patients who underwent surgical treatment for stage 2 medication-related osteonecrosis of the jaw (MRONJ) versus osteomyelitis. METHODS: This retrospective study compared the following variables in 73 patients with stage 2 MRONJ versus 89 patients with osteomyelitis: impaired wound healing after surgery, sex, age, the presence of actinomycosis, location of the jaw lesion, and involvement of the inferior alveolar nerve (IAN). RESULTS: There were significant differences between the groups in age, sex, rates of impaired wound healing, actinomycosis, and the location (anterior/posterior) of the lesion. Impaired wound healing after surgical treatment in the stage 2 MRONJ group was associated with patient age. All patients with impaired wound healing after the initial surgery recovered fully after reoperation. CONCLUSIONS: These findings for surgical treatment of stage 2 MRONJ may help clinicians plan surgical treatment of MRONJ.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/cirurgia , Osteomielite/cirurgia , Actinomicose , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/fisiopatologia , Feminino , Humanos , Masculino , Nervo Mandibular , Pessoa de Meia-Idade , Osteomielite/fisiopatologia , Reoperação , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do Tratamento , Cicatrização
11.
J Dent Res ; 97(3): 312-320, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-28954199

RESUMO

Osteonecrosis of the jaws (ONJ) is a rare but severe complication of antiresorptive medications, such as bisphosphonates, used in the treatment of bone malignancy or osteoporosis. Tooth extraction and dental disease have been strongly associated with ONJ development. Here, we investigated molecular and cellular markers of socket healing after extraction of healthy or teeth with experimental periodontitis (EP) in Wistar-Han rats treated with zoledronic acid (ZA). We included 4 experimental groups: vehicle-treated animals with extraction of healthy teeth or teeth with ligature-induced EP and ZA-treated animals with extraction of healthy teeth or teeth with EP. Animals were pretreated with vehicle or ZA for a week, and EP was induced. Four weeks later, the second maxillary molars were extracted; sockets were allowed to heal for 4 wk; animals were euthanized; and maxillae were isolated. Radiographically, extraction sockets in groups 1, 2, and 3 demonstrated normal healing. Contrary incomplete socket healing was noted after extraction of teeth with EP in ZA-treated rats of group 4. Histologically, persistent inflammation and extensive osteonecrosis were seen in group 4. Disorganization of the collagen network, collagen type III predominance, and lack of collagen fiber insertion in the necrotic bone were associated with impaired socket healing. Cells positive for MMP-9, MMP-13, and α-SMA expression were present at the areas of epithelial invagination and adjacent to osteonecrotic bone. Importantly, human biopsies from patients with ONJ showed similar findings. Our data emphasize the importance of dental disease and tooth extraction in ONJ pathogenesis and help delineate an altered profile in wound-healing markers during ONJ development.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/fisiopatologia , Alvéolo Dental/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Ácido Zoledrônico/efeitos adversos , Idoso , Animais , Feminino , Humanos , Imuno-Histoquímica , Periodontite/fisiopatologia , Ratos , Ratos Wistar , Extração Dentária , Microtomografia por Raio-X
12.
J Biol Regul Homeost Agents ; 31(3): 811-816, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28958140

RESUMO

Bisphosphonates are antiresorptive pharmacological agents used in the treatment of osteoporosis. Recently, osteonecrosis of the jaw has been recognized as a potential side effect in patients on long-term bisphosphonate therapy. This condition, popularly called bisphosphonate-related osteonecrosis of the jaw (BRONJ), has been rechristened as MRONJ (medication-related osteonecrosis of the jaw) to accommodate the increasing number of cases of osteonecrosis of jaws associated with various other antiresorptive and antigiogenic pharmacological therapies. The aim of the present study was to assess the outcome of using platelet-rich fibrin (PRF) for the treatment of MRONJ in a single study group. Twenty-three consecutive patients (15 females and 8 males; aged 52-73 years) with MRONJ were enrolled in this study. These patients presented a history of bisphosphonate medication of varying duration, presence of exposed bone in the maxillofacial region for more than eight weeks, and no history of radiation therapy to the jaws. These patients were managed by surgical curettage and application of platelet rich fibrin (PRF). The outcomes were assessed using clinical and histopathological methods. On the basis of the present findings, we can conclude that PRF can act as an effective barrier membrane between the alveolar bone and the oral cavity and may offer a fast, easy and effective alternative method for the closure of bone exposure in MRONJ patients.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/terapia , Fibrina Rica em Plaquetas , Idoso , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/metabolismo , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/patologia , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
13.
Med. oral patol. oral cir. bucal (Internet) ; 22(2): e177-e184, mar. 2017. ilus, graf, tab
Artigo em Inglês | IBECS | ID: ibc-161234

RESUMO

Background: Bisphosphonate-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 Methods: Thirty-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. Results: At 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. Conclusions: The 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 (AU)


No disponible


Assuntos
Animais , Ratos , Extração Dentária , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/fisiopatologia , Difosfonatos/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Modelos Animais de Doenças
14.
Bauru; s.n; 2017. 89 p. ilus, tab, graf.
Tese em Português | LILACS, BBO - Odontologia | ID: biblio-883240

RESUMO

Os bisfosfonatos (BF) são amplamente utilizados no tratamento de doenças osteolíticas como metástases ósseas e osteoporose. A osteonecrose dos maxilares associada ao uso de BF (OMAB) é caracterizada pela presença de osso exposto ou que pode ser sondado através de uma fístula que persiste por mais de oito semanas em pacientes com história de terapia de BF e sem história de radioterapia na região de cabeça e pescoço e/ou sem doença metastática nos maxilares. A incidência de OMAB aumenta com a potência, duração do tratamento e dose de BF recebida. Até o presente momento, a fisiopatologia da OMAB não está clara, dificultando a prevenção e o tratamento. O objetivo deste estudo foi avaliar o efeito da administração de altas doses Ácido Zoledrônico (AZ) por período prolongado no osso esponjoso da mandíbula e da metáfise proximal do fêmur de ratos Wistar. Para relacionar as descobertas à fisiopatologia da OMAB, o regime de administração de BF de um modelo animal relevante desta lesão foi reproduzido. Seis animais receberam AZ (0,6 mg / kg) e seis receberam solução salina no mesmo volume (Controles). Os compostos foram administrados por via intraperitoneal em cinco doses a cada 28 dias. A eutanásia dos animais ocorreu após 150 dias de início da terapia. As hemimandíbulas e fêmures direitos foram escaneados usando Micro-tomografia computadorizada (Micro-CT) de alta resolução (14 m). Para a primeira análise realizada neste estudo, os dados morfométricos do osso esponjoso foram calculados na região do segundo e primeiro molar na mandíbula e na metáfise do fêmur usando CTAnalyzer (Bruker, Bélgica). Para a segunda análise, cinco amostras de hemimandíbulas de cada grupo foram cortadas em lâminas histológicas (5 m) e coradas com Hematoxilina e Eosina. Para comparar os parâmetros morfométricos na Micro-CT e histologia, as imagens de Micro-CT foram espacialmente alinhadas à histologia. Os dados morfométricos do osso alveolar foram calculados usando o software CTAnalyzer (Bruker, Bélgica) na região entre as raízes mesial e distal do primeiro molar. A densidade da área vascular (área vascular/área total; VA/TA) e os dados histomorfométricos ósseos foram estimados usando Axiovision na mesma região (entre as raízes mesial e distal do primeiro molar). Foi adotada significância estatística de 5% ( = 0,05). Os animais tratados com AZ apresentaram aumento significativo na porcentagem de volume ósseo (p <0,05) com trabéculas mais espessas, osso mais compacto com menor separação trabecular na mandíbula e no fêmur. Na mandíbula, o aumento da densidade óssea e diminuição da separação trabecular foram fortemente correlacionados com a diminuição da área vascular observada no grupo AZ (p <0,05). Em conclusão, o tratamento de longa duração com altas doses de AZ foi significativamente associado ao aumento na densidade óssea e à diminuição dos espaços medulares, canais nutritivos e vasculatura do osso alveolar. A análise com Micro-CT revelou alterações semelhantes na estrutura óssea tanto na mandíbula quanto no fêmur do grupo AZ.(AU)


Bisphosphonates (BFs) are widely used in the treatment of osteolytic diseases such as bone metastases and osteoporosis. The osteonecrosis of the jaws related to BF (ONB) is characterized by the presence of exposed bone or bone that can be probed through a fistula that persists for more than eight weeks in patients with a history of BF therapy and without history of head and neck radiotherapy and / or without metastatic disease in the jaws. The incidence of ONB increases with potency, duration of treatment and dose of BF received. Thus far, the pathophysiology of ONB is unclear, hampering prevention and treatment. The aim of this study was to objectively assess the effect of long-term high-dose Zoledronic Acid (ZA) on cancellous bone in the jaw and femur of Wistar rats. In order to link our findings to the physiopathology of ONB, the therapeutic regiment of a relevant ONB animal model was reproduced. Twelve Wistar rats were randomly divided in two groups: six received Zoledronic acid (ZA; 0.6 mg / kg) and six (Controls) received saline solution in the same volume. The compounds were administrated intraperitoneally in five doses each 28 days. The rats were killed after 150 days of the therapy onset. Mandibles and femurs were scanned using a high-resolution (14m) micro-computerized tomography (Micro-CT). For the first analysis carried in this study, cancellous bone morphometric data were calculates in the region of the second and first molar in the mandible and in the proximal femur using CTAnalyzer (Bruker, Belgium). For the second analysis five samples were cut into histological slices (5m) and stained with Hematoxylin and Eosin. In order to compare the same morphological structures in Micro-CT and histology, the Micro-CT images were aligned to histology. Alveolar bone morphometric data (Micro-CT) was calculated using CTAnalyzer (Bruker, Belgium) in the region between the mesial and distal roots of the first molar. Blood vessels density and bone histomorphometric data were calculated using Axiovision (Carl Zeiss, Germany) in the same region used for Micro-CT evaluation. Statistical significance of 5% (=0.05) was adopted. ZA treated rats presented significant increase in the percentage of bone volume (p<0.05) with thicker trabeculae and more compact bone with smaller marrow spaces in the mandible and femur. In the mandible, the increase in bone density and decrease of marrow spaces size was strongly correlated with the decrease in the vascular area noticed in the ZA group (p<0.05). In conclusion, long-term high-dose ZA treatment was significant associated with the increase of bone density and the diminution of medullary spaces and nutritive canals size as well as decrease in vascularity of the alveolar bone. Micro-CT investigation showed similar changes in bone structure in the mandible and femur in the ZA group.(AU)


Assuntos
Animais , Ratos , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/tratamento farmacológico , Conservadores da Densidade Óssea/administração & dosagem , Osso Esponjoso/efeitos dos fármacos , Difosfonatos/administração & dosagem , Fêmur/efeitos dos fármacos , Imidazóis/administração & dosagem , Doenças Mandibulares/tratamento farmacológico , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/fisiopatologia , Densidade Óssea , Distribuição Aleatória , Ratos Wistar , Reprodutibilidade dos Testes , Fatores de Tempo , Resultado do Tratamento , Microtomografia por Raio-X
15.
Curr Osteoporos Rep ; 14(5): 219-25, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27474028

RESUMO

A known complication that can occur in patients using bisphosphonates (BPs) is osteonecrosis of the jaw (ONJ). ONJ features bone exposure that may be associated with severe pain, swelling, local infection, and pathological fracture of the jaw. Current literature indicates that a complex combination of factors is necessary to induce ONJ. Several hypotheses about the pathophysiology of ONJ were previously reported. Here, we review these hypotheses and introduce new ideas and suggestions on this topic, focusing on bone site-specific cells, and the effect that BPs and other anti-resorptive drugs have on those cells. Gaining more insight into bone site-specific effects may help to better understand the pathogenesis ONJ, and contribute to the development of new bone site-specific anti-resorptive drugs.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/metabolismo , Medula Óssea , Remodelação Óssea , Osso e Ossos/metabolismo , Microambiente Celular , Osteoblastos , Osteoclastos , Animais , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/fisiopatologia , Modelos Animais de Doenças , Humanos
16.
Med. oral patol. oral cir. bucal (Internet) ; 21(2): e236-e240, mar. 2016.
Artigo em Inglês | IBECS | ID: ibc-151070

RESUMO

Background: It is estimated that over 190 million bisphosphonates have been prescribed worldwide. But this drug can produce adverse effects, of which osteonecrosis of the jaw and severe hypocalcemia are the most serious. It is evident that bisphosphonate administration affects multiple and diverse biochemical mediators related to bone metabolism. Material and Methods: This review of literature investigates four basic parameters in patients treated with bisphosphonates - parathyroid hormone (PTH), bisphosphonates, vitamin D, calcium, and jaw osteonecrosis - which are fundamental for assessing bone metabolism and so the efficacy and correct use of the drug. The imbalances generated by vitamin D and calcium deficiencies, together with their multiple systemic repercussions, have been widely researched but the outcomes of these imbalances in relation to bisphosphonate administration are not well known, and some research has indicated that they may be associated with osteonecrosis of the jaw (ONJ). Results: The present review set out to explain the functioning of bone metabolism, the importance of different chemical mediators, the imbalances produced by incorrect use of this drug, in order to forewarn against the possible relation of these parameters with ONJ, whose physiopathology remains unknown. Conclusions: Medical and dental clinics should keep detailed anamneses of the use of vitamin D and calcium supplements, as it is of vital importance to maintain their correct levels in blood, given that these are related to ONJ as well as other adverse effects; this procedure is also necessary in order to ensure the correct use of the drug (AU)


No disponible


Assuntos
Humanos , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/fisiopatologia , Vitamina D/administração & dosagem , Hormônio Paratireóideo/administração & dosagem , Compostos de Cálcio/administração & dosagem , Difosfonatos/efeitos adversos , Segurança do Paciente
18.
Sanid. mil ; 71(4): 232-238, oct.-dic. 2015. tab, ilus
Artigo em Espanhol | IBECS | ID: ibc-146592

RESUMO

ANTECEDENTES Y OBJETIVOS: El aumento del consumo de bifosfonatos en la sociedad actual, puede incrementar el riesgo de osteonecrosis mandibular. Se realizó este estudio para valorar si tras la extracción dentaria, después de la administración subcutánea de ácido zoledrónico 7,5 mig/Kg o 35 mig/Kg (Zometa®) en ratas Wistar, aparecen signos clínicos, radiográficos e histopatológicos de osteonecrosis y/o inflamación. Lugar de realización: Centro Experimentación Animal del Hospital de Defensa. Material y MÉTODOS: Estudio experimental, in vitro, randomizado, intervencionista. Se utilizaron un total de 30 ratas Wistar (adultas, sanas), repartiéndolas en tres grupos de 10 animales, según sexo, grupo y fármaco: G0: Sin tratamiento con ácido zoledrónico. G1: Con tratamiento de ácido zoledrónico 7,5 mig/Kg subcutáneo una dosis en los días 1, 15 y 30. G2: Con tratamiento de ácido zoledrónico 35 mig/Kg subcutáneo una dosis en los días 1, 15 y 30. En todos los grupos se realizó exodoncia del primer molar inferior derecho el día 30, sacrificando los animales a las cuatro semanas postextracción, observando clínica, histológica y radiográficamente la aparición de osteonecrosis e inflamación. RESULTADOS: Clínicamente se observaron en un 26,6% falta de epitelización compatible con signos precoces de osteonecrosis mandibular, según criterios de la American Association of Oral Maxillofacial Súrgeons (AAOMS). Esta es dosis dependiente en 3 animales de G1 (10%) y 5 animales de G2 (16,6%). Los resultados presentaron significación estadística p < 0,001 e inflamación p < 0,001 en todos los grupos. CONCLUSIONES: La administración subcutánea de 7,5 mig/Kg o 35 mig/Kg de ácido zoledrónico durante cuatro semanas, tras la realización de una extracción dentaria, no da lugar a signos histopatológicos de osteonecrosis e inflamación (p < 0,001) pero si a alteraciones clínicas dosis dependientes (p < 0,011) compatibles con estadios iniciales de osteonecrosis mandibular según criterios de la AAOMS


RECORDS AND OBJECTIVES: The increase of biphosphonates consumption on current society may increase the risk of mandibular osteonecrosis. This study was developed in order to value if, after dental extraction with a subcutaneous administration of zoledronic acid 7,5 μg/Kg or 35 μg/Kg (Zometa®) on Wistar rats, any clinic, radiographic or histopathological evidence of os-teonecrosis or inflammation appear. Place of execution: Animal Experimentation Centre of the Hospital of Defence. MATERIALS AND METHODS: Experimental study, in vitro, randomized interventionist. A total amount of 30 Wistar rats were used (adults and healthy), divided into 3 groups of 10 animals according to sex, group and medicine. G0: no Zoledronic Acid treatment. G1: Zoledronic Acid treatment 7,5 μg/Kg subcutaneous, one dose on days 1, 15 and 30. G2: Zoledronic Acid treatment 35 μg/Kg subcutaneous, one dose on days 1, 15 and 30. On all the groups an extraction of the lower right first molar was done on day 30, killing the animals four weeks post-extraction, observing clinically, histologically and radiographically the appearance of osteonecrosis and inflammation. RESULTS: Clinically, a 26,6% showed a lack of epithelization compatible with early signs of mandibular osteonecrosis, according to the American Association of Oral Maxillofacial Surgeos (AAOMS) criteria. This is a dependent dose on 3 animals from G1 (10%) and 5 animals from G2 (16,6%). These results presented statistic signification p < 0,011. Histological and radiological absence of osteonecrosis p < 0,001 and inflammation p < 0,001 in all the groups. CONCLUSION: Subcutaneous administration 7,5 μg/Kg or 35μg/Kg of Zoledronic Acid during four weeks, after the dental extraction, does not lead to histopathological signs of osteonecrosis and inflammation (p < 0,001) but leads to clinical alterations dose-dependent (p < 0,011) compatible with early stages of mandibular osteo-necrosis according to AAOMS criteria


Assuntos
Animais , Ratos , Difosfonatos/efeitos adversos , Difosfonatos/uso terapêutico , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/complicações , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/fisiopatologia , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/veterinária , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/cirurgia , Modelos Animais , Extração Dentária/métodos , Placebos/uso terapêutico
19.
Prim Dent J ; 4(3): 30-3, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26556516

RESUMO

Bisphosphonates are a group of drugs that are commonly used to alter bone metabolism in order to prevent bone loss in diseases such as osteoporosis and bone cancers. Unfortunately, the use of bisphosphonates has been associated with bisphosphonate-related osteonecrosis of the jaws. The debate as to whether it is wise to consider implant therapy in patients being treated with bisphosphonate therapy remains a grey area. This review will present the latest evidence and guidelines available on bisphosphonates and their possible effects on implant dentistry. The risk factors, co-morbidities, clinical presentation and findings from various imaging modalities for bisphosphonate-related osteonecrosis of the jaws are highlighted. The management of patients being treated with bisphosphonates, in whom dental implants might be considered or have already been placed, will also be discussed. Finally, the areas requiring future research are considered.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Implantes Dentários , Difosfonatos/uso terapêutico , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/fisiopatologia , Conservadores da Densidade Óssea/efeitos adversos , Difosfonatos/efeitos adversos , Humanos , Fatores de Risco
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