Histological Evaluation of the Effect of Alendronate on the Maxillary Bone of Wistar Rats Combined with Orthodontic Movement of Intense Force / Evaluación Histológica del Efecto del Alendronate en el Hueso Maxilar de Ratas Wistar Combinado con Movimiento de Ortodoncia de Fuerzas Intensas

SUMMARY: To evaluate the histological adverse effects of alendronate administered systemically and topically in combination with orthodontic movement by intense force. Thirty-six 24-week-old female Wistar rats, ovariectomized, were used and divided into three groups (n = 12/group): control, locally treated with saline (0.07 ml/kg/week) (group 1) and experimental, treated with alendronic acid systemically (0.07 mg/kg/week) (group 2) and locally (7 mg/kg/week) (group 3). At 14 days, an orthodontic anchor was installed in the right first molar, and a force of 144 cN was applied for 28 days. The samples were processed for histological evaluation. Descriptive statistics, Shapiro-Wilk tests, one-way ANOVA with Bonferroni correction, one-way repeated measures ANOVA and chi-square tests were performed. All tests were statistically significant at p <0.05. The adverse events found in all groups were inflammation and osteoclastic activity. In the bisphosphonate-treated groups, there were statistically significant differences (p = 0.005) in the osteoclastic activity between the two hemiarcates. All rats in group 2 presented paralytic ileus. Compared to local administration, systemic treatment with alendronic acid produces more adverse effects, such as inflammation, fibrinoid necrosis, and osteoclastic activity. During the application of intense forces, it was not possible to show that there is necrosis associated with bisphosphonates.

Evaluar los efectos adversos histológicos del alendronato administrado sistémica y tópicamente en combinación con movimientos ortodóncicos de fuerza intensa. Treinta y seis ratas Wistar hembras de 24 semanas de edad, ovariectomizadas, fueron utilizadas y divididas en tres grupos (n = 12/grupo): control, tratado localmente con solución salina (0,07 ml/kg/semana) (grupo 1) y experimental, tratados con ácido alendrónico por vía sistémica (0,07 mg/kg/semana) (grupo 2) y local (7 mg/kg/semana) (grupo 3). A los 14 días se instaló un anclaje de ortodoncia en el primer molar derecho y se aplicó una fuerza de 144 cN durante 28 días. Las muestras fueron procesadas para evaluación histológica. Se realizó estadística descriptiva, pruebas de Shapiro-Wilk, ANOVA de una vía con corrección de Bonferroni, ANOVA de medidas repetidas de una vía y pruebas de chi-cuadrado. Todas las pruebas fueron estadísticamente significativas con un p <0,05. Los eventos adversos encontrados en todos los grupos fueron inflamación y actividad osteoclástica. En los grupos tratados con bisfosfonatos hubo diferencias estadísticamente significativas (p = 0,005) en la actividad osteoclástica entre los dos hemiarcados. Todas las ratas del grupo 2 presentaron íleo paralítico. En comparación con la administración local, el tratamiento sistémico con ácido alendrónico produce más efectos adversos, como inflamación, necrosis fibrinoide y actividad osteoclástica. Durante la aplicación de fuerzas intensas, no fue posible demostrar que existe necrosis asociada con los bisfosfonatos.

La singularidad de los maxilares dentro del sistema esquelético / Singularity of the jaws within the skeletal system

En la odontología es frecuente que se describa la peculiaridad de los huesos maxilares en cuanto a la resistencia a las infecciones en comparación con otros huesos de la economía. O que se plantée un desafío cuando es necesario tomar una decisión acerca de aplicar diferentes conductas terapéuticas en pacientes con patologías óseas sistémicas. Por ello, esta actualización tuvo como objetivo realizar una revisión de la bibliografía para integrar y evidenciar las diferencias y similitudes entre los diferentes huesos de la economía haciendo hincapié en los huesos maxilares. Si bien éstos poseen una gran cantidad de similitudes con el resto de los huesos, también presentan diferencias que los hacen entidades únicas dentro del sistema esquelético como el origen embriológico en las células de las crestas neurales, su alta tasa de remodelación, sin olvidar que estos huesos alojan a órganos que poseen una parte de su estructura en el medio interno y otra porción en medio externo de la cavidad bucal: las piezas dentarias (AU)

Micro-computed tomography analysis of changes in the periodontal ligament and alveolar bone proper induced by occlusal hypofunction of rat molars / 대한치과교정학회지

OBJECTIVE: To three-dimensionally elucidate the effects of occlusal hypofunction on the periodontal ligament and alveolar bone proper of rat molars by micro-computed tomography (micro-CT). METHODS: Occlusal function in the molar area was restricted by attaching an anterior bite plate on the maxillary incisors and a metal cap on the mandibular incisors of 5-week-old male Wistar rats for 1 week. The periodontal ligament space and alveolar bone proper around roots of the mandibular first molar were assessed by histology and micro-CT. RESULTS: The periodontal ligament space was narrower and the alveolar bone proper was sparser and less continuous in the hypofunction group than in the control group. Further, both the volume of the periodontal ligament and the volumetric ratio of the alveolar bone proper to the total tissue in the region of interest were significantly lower in the hypofunction group (p < 0.05). CONCLUSIONS: Occlusal hypofunction induces atrophic changes in the periodontal ligament and alveolar bone proper of rat molars.

Compressive force regulates ephrinB2 and EphB4 in osteoblasts and osteoclasts contributing to alveolar bone resorption during experimental tooth movement / 대한치과교정학회지

OBJECTIVE: To investigate the involvement of ephrinB2 in periodontal tissue remodeling in compression areas during orthodontic tooth movement and the effects of compressive force on EphB4 and ephrinB2 expression in osteoblasts and osteoclasts. METHODS: A rat model of experimental tooth movement was established to examine the histological changes and the localization of ephrinB2 in compressed periodontal tissues during experimental tooth movement. RAW264.7 cells and ST2 cells, used as precursor cells of osteoclasts and osteoblasts, respectively, were subjected to compressive force in vitro. The gene expression of EphB4 and ephrinB2, as well as bone-associated factors including Runx2, Sp7, NFATc1, and calcitonin receptor, were examined by quantitative real-time polymerase chain reaction (PCR). RESULTS: Histological examination of the compression areas of alveolar bone from experimental rats showed that osteoclastogenic activities were promoted while osteogenic activities were inhibited. Immunohistochemistry revealed that ephrinB2 was strongly expressed in osteoclasts in these areas. Quantitative real-time PCR showed that mRNA levels of NFATc1, calcitonin receptor, and ephrinB2 were increased significantly in compressed RAW264.7 cells, and the expression of ephrinB2, EphB4, Sp7, and Runx2 was decreased significantly in compressed ST2 cells. CONCLUSIONS: Our results indicate that compressive force can regulate EphB4 and ephrinB2 expression in osteoblasts and osteoclasts, which might contribute to alveolar bone resorption in compression areas during orthodontic tooth movement.

Osteócitos: sobre o papel central dessas células na biopatologia óssea / Osteocytes: on the central role of these cells in osseous pathobiology

Os alvos principais na compreensão da biopatologia óssea centravam-se nos osteoblastos e clastos, mas nos últimos anos têm se deslocado para os osteócitos — como mecanotransdutores do tecido ósseo, a partir da rede tridimensional, pelo entrelaçamento e contato de seus prolongamentos interligando uma célula a outras 20 a 40, tal qual uma rede neural. Pela mecanotransdução e a partir de mediadores como a esclerostina e o RANKL, os osteócitos podem influenciar na biopatologia óssea por interferirem na atividade dos osteoblastos e clastos. Quando necessário mais osso, os osteócitos liberam menos esclerostina; quando é necessário inibir a formação óssea, os osteócitos liberam mais esclerostina. O RANKL está ligado à osteoclastogênese local para que se tenha mais células capazes de reabsorver a matriz mineralizada. Algumas terapêuticas inovadoras das doenças ósseas metabólicas têm tido como alvo esses mediadores e os osteócitos. Estudar a presença e os efeitos específicos da esclerostina e do RANKL na osseointegração pode levar a um maior detalhamento de seus fenômenos biológicos.

The main targets for the comprehension of bone pathobiology were focused in osteoblasts and clasts, but in recent years it has shifted to the osteocytes — as mechanotransductors of the bone tissue, from the three-dimensional network, by interconnecting its extensions linking a cell to other 20 to 40, like a neural network. By mechanotransduction and from mediators as sclerostin and RANKL, the osteocytes may influence bone pathobiology by interfering with the activity of osteoblasts and clasts. When more bone is necessary, osteocytes release less sclerostin, when it is necessary to inhibit bone formation, osteocytes release more sclerostin. RANKLis connected to local osteoclastogenesis in order to have more cells capable of reabsorbing the mineralized matrix. New therapeutic ways of controlling the metabolic bone diseases have been targeted at these mediators. Studying the presence and the specific effects of sclerostin and RANKL in osseointegration can lead to greater detailing of their biological phenomena.

Differentiation and characteristics of undifferentiated mesenchymal stem cells originating from adult premolar periodontal ligaments / 대한치과교정학회지

OBJECTIVE: The purpose of this study was to investigate the isolation and characterization of multipotent human periodontal ligament (PDL) stem cells and to assess their ability to differentiate into bone, cartilage, and adipose tissue. METHODS: PDL stem cells were isolated from 7 extracted human premolar teeth. Human PDL cells were expanded in culture, stained using anti-CD29, -CD34, -CD44, and -STRO-1 antibodies, and sorted by fluorescent activated cell sorting (FACS). Gingival fibroblasts (GFs) served as a positive control. PDL stem cells and GFs were cultured using standard conditions conducive for osteogenic, chondrogenic, or adipogenic differentiation. RESULTS: An average of 152.8 +/- 27.6 colony-forming units was present at day 7 in cultures of PDL stem cells. At day 4, PDL stem cells exhibited a significant increase in proliferation (p < 0.05), reaching nearly double the proliferation rate of GFs. About 5.6 +/- 4.5% of cells in human PDL tissues were strongly STRO-1-positive. In osteogenic cultures, calcium nodules were observed by day 21 in PDL stem cells, which showed more intense calcium staining than GF cultures. In adipogenic cultures, both cell populations showed positive Oil Red O staining by day 21. Additionally, in chondrogenic cultures, PDL stem cells expressed collagen type II by day 21. CONCLUSIONS: The PDL contains multipotent stem cells that have the potential to differentiate into osteoblasts, chondrocytes, and adipocytes. This adult PDL stem cell population can be utilized as potential sources of PDL in tissue engineering applications.

Expression of nitric oxide synthases in the mandibular condyle of anterior repositioned rat mandibles / 대한치과교정학회지

OBJECTIVE: The aim of this study was to identify the expression of nitric oxide synthases (NOS) in the mandibular condyle during mandible advancement by functional appliance and to correlate it with the histologic changes and bone remodeling. METHODS: Twenty-four female, 35-day-old Sprague-Dawley rats were randomly divided into 3 experimental groups. In all experimental groups, the mandibles of the rats were kept in a continuous forward position with a fixed bite jumping appliance. The rats were sacrificed on the 3rd, 14th, and 30th days of experiment. More than 2 rats in each group were used for staining. RESULTS: There were no remarkable histologic changes and NOS expression differences in the control group. The most prominent histologic changes occurred in the 14th day experimental group. NOS decreased in the 30th day experimental group. There was increased expression of NOS2 and NOS3 in all experimental groups, comparative to the control group. In all the experimental groups and control group, the expression of NOS2 was greater than that of NOS3. CONCLUSIONS: It is postulated that NOS2 and NOS3 in the mandibular condyle might play an important role in bone remodelling of the mandibular condyle.

Effect of Bio-Oss grafts on tooth eruption: an experimental study in a canine model

INTRODUCTION: There are few reports on tooth eruption through Bio-Oss grafts. To our knowledge, there are no reports on whether teeth can erupt normally through the grafts. The aim of this study was to examine the effect of Bio-Oss grafts on tooth eruption in a canine model. MATERIALS AND METHODS: In five 10-week-old dogs, the deciduous third mandibular molars in one jaw quadrant of each animal were extracted and the fresh extraction sockets were then filled with Bio-Oss particles (experimental side). No such treatments were performed on the contralateral side (control side). A clinical and radiological evaluation was carried out every other week to evaluate the eruption level of the permanent third mandibular premolars and compare the eruption levels between the two sides. RESULTS: At week 4 after the experiment, the permanent third premolars began to erupt on both sides. At week 12, the crown of the permanent third premolar emerged from the gingiva on both sides. At week 20, the permanent third premolars on both sides erupted enough to occlude the opposing teeth. No significant differences were found between the control and experimental sides in terms of the eruption speed of the permanent third molars. CONCLUSION: These findings demonstrate that the grafting of Bio-Oss particles into the alveolar bone defects does not affect tooth eruption.

Microarquitetura óssea de uma família portadora de osteogênese imperfeita, tipo I: análise comparativa entre as ferramentas oferecidas pela osteossonografia e osteossonometria -terceira geração falangeal e a densitometria óssea convencional / Bone microarchitecture of a family with osteogenesis imperfecta type I:comparative analysis of the parameters offered by osteosonography - third generation phalangeal and standard bone densitometry

Em cinco membros de uma família portadora de osteogênese imperfeita (OI), tipo I, com idades entre 8 e 58 anos foi realizada a análise da topologia óssea (microarquitetura e composição óssea) por meio da osteossonografia e osteossonometria – terceira geração falangeal, sendo comparada com os resultados da “densitometria óssea” convencional (Dexa-Lombar). Por meio da captação do registro elétrico do perfi l biofísico ósseo (PB) dos ossos endostal, trabecular e cortical na metáfise das falanges foram analisadas seis ferramentas, a saber: elasticidade, homogeneidade, estrutura óssea global, curvas de regressão específicas para a qualidade óssea e quantidade óssea e os cortes sonotomográficos. Os parâmetros que avaliam as propriedades mecânicas ósseas adicionaram importantes informações que facilitaram o entendimento da clínica dos portadores de OI. O estudo comparativo permitiu detectar graus variados de deterioração da matriz mesenquimal proteica óssea, colágeno ósseo, refinando, desde tenra idade e o diagnóstico da antiga doença denominada “doença dos ossos frágeis”. As ferramentas aplicadas adicionaram novas informações que facilitam a compreensão sobre os eventos de fratura. A fratura variou de 1 a 25 vezes, por paciente, ocorreu em todos os membros desde a infância e não guardou relação com a idade. O parâmetro UBPI que analisa a qualidade óssea registrou ampla dispersão em seus valores, oscilando de 0,34 a 0,83. O padrão do PB dos ossos endostal, trabecular e cortical é compatível com o padrão dos portadores de graves deteriorações na matriz mesenquimal proteica como deve ser observado na OI, condição impossível de ser definida quando avaliamos apenas a “densidade óssea” convencional. (...)

Five members of a family with osteogenesis imperfecta (OI) type I aged 8 to 58 years were submitted to complete analysis of bone topology(microarchitecture and bone composition) by third-generation phalangeal osteosonography and the results were compared to those obtained by standard bone densitometry. The following features were analyzed by the electrical recording of bone profile (BP) of endosteal, trabecular and cortical bone of the phalangeal metaphysis: elasticity, homogeneity, global bone structure, specific regression curves for ultrasound bone bone profi le index quality, bone quantity and sonotomographic sections. The parameters that evaluate the mechanical properties of bone added important information and facilitated the clinical understanding of subjects affected by OI. The comparative study permitted the detection of varying degrees of deterioration of the bone protein mesenchymal matrix and of bone collagen, with a refinement of the diagnosis of the disease long termed “brittle bone disease” from a tender age. The methods applied added new information that facilitated the understanding of fracture events. The fracture event ranged from 1 to 25 times per patient, occurred in all family members since childhood, and was not related to age. The UBPI parameter, which analyzes bone quality, showed a wide dispersal of values, ranging from 0.34 to 0.83. The BP pattern of endosteal, trabecular and cortical bone was compatible with the pattern of subjects with severe deterioration of the mesenchymal protein matrix, as observed in OI, a condition that is impossible to define when only bone “density” is evaluated. The six parameters offered by third-generation phalangeal osteosonography provided more encompassing information and satisfi ed the concepts of the New Bone Biology, as well as the more recent guidelines of the National Osteoporosis Foundation; 1999.