RESUMO
This study aimed to evaluate the effects of bisphosphonates on the mandibular bone. Bisphosphonates are drugs which are commonly used in the treatment of many diseases related to bone metabolism such as osteoporosis, breast cancer capable of bone metastasis, prostate and lung cancer and bone cancer such as multiple myeloma. Our study group consisted of a total of 100 panoramic radiographs which were obtained from the examinations of 50 individuals using bisphosphonate and 50 individuals in the control group who applied for routine dental examination to the Department of Oral and Maxillofacial Radiology of Akdeniz University Dentistry Faculty between years 2015 and 2016.The calculations of the mandibular cortical thickness (MCT), mandibular cortical index (MCI), panoramic mandibular index (PMI), condylar angle (CA), gonial angle (GA), antegonial angle (AGA), antegonial depth (AGD) and antegonial index (AGI) were made for each patient. It was found that both left and the right MCT and only the left PMI were affected by age. Only the left AGA and both the left and right MCT and AGD were affected by gender. The left and right AGI measurements of the patients using bisphosphonates were statistically lower than those of the individuals in the control group. Our results suggested that bisphosphonates had various effects on the jaw bones. However, further comprehensive studies need to be made to evaluate the longterm effect of bisphosphonates on bone metabolism.
Este estudio tuvo como objetivo evaluar los efectos de los bifosfonatos en el hueso mandibular. Los bifosfonatos son medicamentos que se usan comúnmente en el tratamiento de muchas enfermedades relacionadas con el metabolismo óseo, como la osteoporosis, el cáncer de mama, metástasis óseas, cáncer de próstata y pulmón y el cáncer de hueso como el mieloma múltiple. Nuestro grupo de estudio consistió en un total de 100 radiografías panorámicas que se obtuvieron de los exámenes de 50 individuos que utilizaron bisfosfonato y 50 individuos en el grupo de control que solicitaron un examen dental de rutina al Departamento de Radiología Oral y Maxilofacial de la Facultad de Odontología de la Universidad de Akdeniz, entre los años 2015 y 2016. En cada paciente se realizaron los cálculos del grosor cortical mandibular (GCM), índice cortical mandibular (ICM), índice mandibular panorámico (IMP), ángulo condilar (AC), ángulo gonial (AG), ángulo antegonial (AAG), profundidad antegonial ( PAG) y el índice antegonial (IAG). Se encontró que tanto el GCM izquierdo como el derecho y solo el IMP izquierdo estaban afectados por la edad. Solo el AAG izquierdo y el GCM izquierdo y derecho y el AGD fueron afectados de acuerdo al sexo. Las mediciones de IAG izquierdo y derecho de los pacientes que utilizan bifosfonatos fueron estadísticamente más bajas que las de los individuos en el grupo de control. Nuestros resultados sugirieron que los bifosfonatos tienen varios efectos en los huesos de la mandíbula. Sin embargo, es necesario realizar estudios más exhaustivos para evaluar el efecto a largo plazo de los bifosfonatos en el metabolismo óseo.
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Difosfonatos/farmacologia , Mandíbula/efeitos dos fármacos , Mandíbula/diagnóstico por imagem , Radiografia Panorâmica , Fatores Sexuais , Estudos Retrospectivos , Côndilo Mandibular/efeitos dos fármacos , Côndilo Mandibular/diagnóstico por imagemRESUMO
BACKGROUND: Masseter muscle paralysis induced by botulinum toxin type A (BoNTA) evokes subchondral bone loss in mandibular heads of adult rats and growing mice after 4 weeks. However, the primary cellular and molecular events leading to altered bone remodeling remain unexplored. Thus, the aim of the current work has been to assess the molecular response that precedes the early microanatomical changes in the masseter muscle and subchondral bone of the mandibular head in adult mice after BoNTA intervention. METHODS: A pre-clinical in vivo study was performed by a single intramuscular injection of 0.2â¯U BoNTA in the right masseter (experimental) of adult BALB/c mice. The contralateral masseter was injected with vehicle (control). Changes in mRNA levels of molecular markers of bone loss or muscle atrophy/regeneration were addressed by qPCR at day 2 or 7, respectively. mRNA levels of receptor activator of nuclear factor-κB ligand (RANKL) was assessed in mandibular heads, whilst mRNA levels of Atrogin-1/MAFbx, MuRF-1 and Myogenin were addressed in masseter muscles. In order to identify the early microanatomical changes at day 14, fiber diameters in transversal sections of masseter muscles were quantified, and histomorphometric analysis was used to determine the bone per tissue area and the trabecular thickness of subchondral bone of the mandibular heads. RESULTS: An increase of up to 4-fold in RANKL mRNA levels were detected in mandibular heads of the BoNTA-injected sides as early as 2 days after intervention. Moreover, a 4-6 fold increase in Atrogin-1/MAFbx and MuRF-1 and an up to 25 fold increase in Myogenin mRNA level were detected in masseter muscles 7 days after BoNTA injections. Masseter muscle mass, as well as individual muscle fiber diameter, were significantly reduced in BoNTA-injected side after 14 days post-intervention. At the same time, in the mandibular heads from the treated side, the subchondral bone loss was evinced by a significant reduction in bone per tissue area (-40%) and trabecular thickness (-55%). CONCLUSIONS: Our results show that masseter muscle paralysis induced by BoNTA leads to significant microanatomical changes by day 14, preceded by molecular changes as early as 2 days in bone, and 7 days in muscle. Therefore, masseter muscle atrophy and subchondral bone loss detected at 14 days are preceded by molecular responses that occur during the first week after BoNTA intervention.
Assuntos
Toxinas Botulínicas Tipo A/farmacologia , Côndilo Mandibular/efeitos dos fármacos , Côndilo Mandibular/ultraestrutura , Músculo Masseter/efeitos dos fármacos , Músculo Masseter/ultraestrutura , Fármacos Neuromusculares/farmacologia , Animais , Atrofia , Injeções Intramusculares , Masculino , Côndilo Mandibular/metabolismo , Músculo Masseter/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Proteínas Musculares/biossíntese , Osteoporose/patologia , Paralisia/induzido quimicamente , RNA Mensageiro/análise , RNA Mensageiro/biossínteseRESUMO
Anxiolytic agents, mainly benzodiazepines, have been used to treat symptomatic disorders of the temporomandibular joint (TMJ). Our aim was to evaluate the effect of diazepam on the TMJ of rats with increased occlusal vertical dimension (iOVD). Forty male rats were randomly assigned to 4 groups: control rats were given sham iOVD plus saline solution daily for 7 days. The first experimental group was given sham iOVD plus diazepam 2.5mg/kg/intramuscularly daily for 7 days (diazepam alone group); the second had iOVD induced in molars for 7 days plus saline daily for 7 days (iOVD alone group); and the third had iOVD induced in molars for 7 days plus diazepam 2.5mg/kg/intramuscularly daily for 7 days (iOVD plus diazepam group). At the end of each experiment the animals were killed and their bilateral TMJs were removed, randomly stained with haematoxylin and eosin and sirius-red, and immunoassayed. The thickness of condylar cartilage and of fibrous, proliferating, mature, and hypertrophic layers, number of collagen fibres, and the articular area were measured. Proinflammatory cytokines (interleukin (IL)-1α, IL-1ß, IL-6, and tumour necrosis factor (TNF)-α) were also measured. ANOVA and Tukey's tests or the Kruskal-Wallis test were used to compare data among groups (α=5%). Condylar cartilage was thicker in the control group than in the other groups, the diazepam alone group being thicker than the other 2 experimental groups. There were fewer collagen fibres in the 2 groups given diazepam than in the other 2 groups, and there were no significant differences in the area of cartilage among groups. The controls had lower concentrations of all cytokines (p<0.05) than the 3 experimental groups, except for IL-6. Both iOVD groups had higher concentrations of IL-1α, IL-1ß, and IL-6 than the diazepam alone group. Diazepam alone was associated with increased concentrations of all cytokines except IL-6. We conclude that both iOVD and diazepam induced significant changes in rats' articular cartilage.
Assuntos
Ansiolíticos/farmacologia , Diazepam/farmacologia , Má Oclusão/fisiopatologia , Articulação Temporomandibular/efeitos dos fármacos , Dimensão Vertical , Animais , Cartilagem Articular/efeitos dos fármacos , Cartilagem Articular/patologia , Proliferação de Células/efeitos dos fármacos , Colágeno/efeitos dos fármacos , Matriz Extracelular/efeitos dos fármacos , Matriz Extracelular/patologia , Fibrose , Hipertrofia , Interleucina-1alfa/análise , Interleucina-1beta/análise , Interleucina-6/análise , Masculino , Côndilo Mandibular/efeitos dos fármacos , Côndilo Mandibular/patologia , Dente Molar/patologia , Distribuição Aleatória , Ratos , Ratos Wistar , Articulação Temporomandibular/patologia , Fatores de Tempo , Fator de Necrose Tumoral alfa/efeitos dos fármacosRESUMO
BACKGROUND: Methotrexate (MTX) is an anti-metabolite used in rheumatology and oncology. High doses are indicated for oncological treatment, whereas low doses are indicated for chronic inflammatory diseases. This study evaluated the effect of two MTX treatment schedules on the bone healing of the temporomandibular joint fracture in rats. METHODS: Seventy-five adult male Wistar rats were used to generate an experimental unilateral medially rotated condylar fracture model that allows an evaluation of bone healing and the articular structures. The animals were subdivided into three groups that each received one of the following treatments intraperitoneally: saline (1 mL/week), low-dose MTX (3 mg/kg/week) and high-dose MTX (30 mg/kg). The histological study comprised fracture site and temporomandibular joint evaluations and bone neoformation was evaluated by histomorphometric analysis. A biochemical parameter of bone formation was also assessed. RESULTS: When compared with saline, high-dose MTX delayed bone fracture repairs. In this latter group, after 90 days, the histological analysis revealed atrophy of the fibrocartilage and the presence of fibrous tissue in the joint space. The histomorphometric analysis revealed diminished bone neoformation. The alkaline phosphatase levels also decreased after MTX treatment. CONCLUSION: It was concluded that high-dose MTX impaired mandibular condyle repair and induced degenerative articular changes.
Assuntos
Consolidação da Fratura/efeitos dos fármacos , Imunossupressores/uso terapêutico , Côndilo Mandibular/efeitos dos fármacos , Fraturas Mandibulares/tratamento farmacológico , Metotrexato/uso terapêutico , Fosfatase Alcalina/análise , Fosfatase Alcalina/efeitos dos fármacos , Animais , Atrofia , Remodelação Óssea/efeitos dos fármacos , Reabsorção Óssea/patologia , Calo Ósseo/efeitos dos fármacos , Calo Ósseo/patologia , Cartilagem Articular/efeitos dos fármacos , Cartilagem Articular/patologia , Tecido Conjuntivo/efeitos dos fármacos , Tecido Conjuntivo/patologia , Modelos Animais de Doenças , Fibrocartilagem/efeitos dos fármacos , Fibrocartilagem/patologia , Imunossupressores/administração & dosagem , Injeções Intraperitoneais , Masculino , Côndilo Mandibular/lesões , Côndilo Mandibular/patologia , Fraturas Mandibulares/patologia , Metotrexato/administração & dosagem , Osteogênese/efeitos dos fármacos , Distribuição Aleatória , Ratos , Ratos Wistar , Articulação Temporomandibular/efeitos dos fármacos , Articulação Temporomandibular/lesões , Sobrevivência de Tecidos/efeitos dos fármacosRESUMO
PURPOSE: To investigate the facial symmetry of high and low dose methotrexate (MTX) treated rats submitted to experimentally displaced mandibular condyle fracture through the recording of cephalometric measurements. METHODS: One hundred male Wistar rats underwent surgery using an experimental model of right condylar fracture. Animals were divided into four groups: A - saline solution (1 mL/week); B - dexamethasone (DEX) (0,15 mg/Kg); C - MTX low dose (3 mg/Kg/week); D - MTX high dose (30 mg/Kg). Animals were sacrificed at 1, 7, 15, 30 and 90 days postoperatively (n=5). Body weight was recorded. Specimens were submitted to axial radiographic incidence, and cephalometric mensurations were made using a computer system. Linear measurements of skull and mandible, as well as angular measurements of mandibular deviation were taken. Data were subjected to statistical analyses among the groups, periods of sacrifice and between the sides in each group (α=0.05). RESULTS: Animals regained body weight over time, except in group D. There was reduction in the mandibular length and also changes in the maxilla as well as progressive deviation in the mandible in relation to the skull basis in group D. CONCLUSION: Treatment with high dose methotrexate had deleterious effect on facial symmetry of rats submitted to experimentally displaced condylar process fracture.
Assuntos
Assimetria Facial , Imunossupressores/efeitos adversos , Luxações Articulares/tratamento farmacológico , Côndilo Mandibular/crescimento & desenvolvimento , Fraturas Mandibulares/tratamento farmacológico , Metotrexato/efeitos adversos , Transtornos da Articulação Temporomandibular/tratamento farmacológico , Análise de Variância , Animais , Peso Corporal/efeitos dos fármacos , Cefalometria , Modelos Animais de Doenças , Assimetria Facial/diagnóstico por imagem , Imunossupressores/administração & dosagem , Masculino , Côndilo Mandibular/efeitos dos fármacos , Côndilo Mandibular/lesões , Maxila/efeitos dos fármacos , Maxila/crescimento & desenvolvimento , Metotrexato/administração & dosagem , Radiografia , Distribuição Aleatória , Ratos , Ratos WistarRESUMO
PURPOSE: To investigate the facial symmetry of high and low dose methotrexate (MTX) treated rats submitted to experimentally displaced mandibular condyle fracture through the recording of cephalometric measurements. METHODS: One hundred male Wistar rats underwent surgery using an experimental model of right condylar fracture. Animals were divided into four groups: A - saline solution (1mL/week); B - dexamethasone (DEX) (0,15mg/Kg); C - MTX low dose (3 mg/Kg/week); D - MTX high dose (30 mg/Kg). Animals were sacrificed at 1, 7, 15, 30 and 90 days postoperatively (n=5). Body weight was recorded. Specimens were submitted to axial radiographic incidence, and cephalometric mensurations were made using a computer system. Linear measurements of skull and mandible, as well as angular measurements of mandibular deviation were taken. Data were subjected to statistical analyses among the groups, periods of sacrifice and between the sides in each group (α=0.05). RESULTS: Animals regained body weight over time, except in group D. There was reduction in the mandibular length and also changes in the maxilla as well as progressive deviation in the mandible in relation to the skull basis in group D. CONCLUSION: Treatment with high dose methotrexate had deleterious effect on facial symmetry of rats submitted to experimentally displaced condylar process fracture.
OBJETIVO: Avaliar a simetria facial de ratos tratados com metotrexato (MTX), em dose alta e baixa, submetidos à fratura experimental do processo condilar com desvio por meio de mensurações cefalométricas. MÉTODOS: Cem ratos Wistar machos foram submetidos a procedimento cirúrgico utilizando modelo experimental de fratura de côndilo do lado direito. Os animais foram distribuídos em quatro grupos: A - soro fisiológico (1mL/semana); B - dexametasona (DEX) (0,15mg/Kg); C - MTX baixa dose (3mg/Kg/semana); D - MTX alta dose (30mg/Kg). Os períodos de sacrifício foram de 1, 7, 15, 30 e 90 dias de pós-operatório (n=5). O peso dos animais foi documentado. Foram realizadas mensurações lineares da maxila e da mandíbula, bem como angulares do desvio mandibular. Os dados foram submetidos a análises estatísticas entre os grupos, períodos de sacrifício e entre os lados em cada grupo (α=0,05). RESULTADOS: Os animais recuperaram peso ao longo do tempo, exceto no grupo D. Houve redução no comprimento mandibular com alterações também na maxila e desvio progressivo da mandíbula em relação à base do crânio no grupo D. CONCLUSÃO: O tratamento com metotrexato em alta dose teve efeito deletério na simetria facial de ratos submetidos à fratura do processo condilar.
Assuntos
Animais , Masculino , Ratos , Luxações Articulares/tratamento farmacológico , Assimetria Facial , Imunossupressores/efeitos adversos , Côndilo Mandibular/crescimento & desenvolvimento , Fraturas Mandibulares/tratamento farmacológico , Metotrexato/efeitos adversos , Transtornos da Articulação Temporomandibular/tratamento farmacológico , Análise de Variância , Peso Corporal/efeitos dos fármacos , Cefalometria , Modelos Animais de Doenças , Assimetria Facial , Imunossupressores/administração & dosagem , Côndilo Mandibular/efeitos dos fármacos , Côndilo Mandibular/lesões , Maxila/efeitos dos fármacos , Maxila/crescimento & desenvolvimento , Metotrexato/administração & dosagem , Distribuição Aleatória , Ratos WistarRESUMO
With the purpose of studying the effect of diphenylhydantoin on mandibular skeletal-unit growth, 28 male Wistar rats weighing 60.0 +/- 0.8 g were assigned to five different groups. One group received saline serving as normal controls; three others were injected intra peritoneally once daily with either 25, 50 or 100 mg/kg body wt diphenylhydantoin for 30 days; the fifth group was put on a restricted diet (20% below normal intake) for the same time. On day 31, the rats were killed by ether overdose and their mandibles were evaluated for differential skeletal-unit growth. Body-weight gain of diphenylhydantoin-injected rats was up to 24% less than controls, regardless of drug dose. Diet-restricted rats showed a similar difference. The amount of food consumed by diphenylhydantoin-injected rats was 21% less than that consumed by controls, regardless of drug doses. The concentration of alkaline phosphatase and haemoglobin in rats treated with 50 or 100 mg/kg diphenylhydantoin was lower than in controls and diet-restricted rats. However, plasma urea and total calcium were similar in diphenylhydantoin-treated rats and controls. Mean appetite quotient, and the efficiency of protein and energy utilization, did not appear to change in response to the particular diphenylhydantoin dose or to the restricted diet. Mandibular dimensions of rats injected with 25 or 50 mg/kg diphenylhydantoin were not statistically different from those of the control and diet-restricted groups. With using 100 mg/kg diphenylhydantoin for 30 days, the growth of symphysial and basal heights, condylar and angular lengths and condylar width was significantly less than in the control and diet-restricted groups. The remaining mandibular skeletal units did not exhibit significant differences from those of control and diet-restricted rats. The disharmonious growth of the mandible does not appear to depend on suboptimal energy intake, efficiency of protein-energy utilization, renal failure and anaemia, but would suggest a differential toxicological effect of diphenylhydantoin on the osseous component and/or its associated non-skeletal tissues.