Revisión sistemática de los efectos de microvibración de baja magnitud alta frecuencia en osteocitos cultivados / Systematic review of the effects of low intensity high frequency microvibration on osteocytes cultivated

Introducción: El hueso, reservorio de minerales y moléculas orgánicas, es un tejido dinámico que detecta y se adapta a las cargas mecánicas de los órganos y tejidos del cuerpo, el cual mantiene la estructura ósea del esqueleto durante el crecimiento y a través de la vida del ser humano. Las células óseas son sensibles a las cargas mecánicas y microvibra- ciones que recibe el esqueleto. Objetivo: El propósito de este estudio fue realizar una revisión sistemática acerca de los efectos que ejerce la microvibración de alta frecuencia-baja intensidad, en osteocitos cultivados in vitro sobre la síntesis de factores solubles, con el propósito de entender si la microvibración tiene influencia en la aceleración del movimiento dentario. Material y métodos: Se realizó una búsqueda de artículos de revisión de osteocitos y otras células óseas in vitro, a través de la estrategia PICO (Paciente, Intervención, Comparación, Resultado [Outcome]), con el empleo de palabras clave como: «os- teocitos¼, «microvibración¼, «remodelación¼, «osteoclastogénesis¼, «citocinas¼ y «osteoblastos¼. Se estructuró por medio de PRISMA (informe de revisiones sistemáticas y meta-análisis). La captación de datos finales se hizo por medio del método de puntuación de calidad Jadad y Cochrane (modelo de correlación) como herramientas para evaluar el riesgo de sesgo de cada uno de los artículos. Se incluyeron 11 artículos con alta calidad metodológica. Resultados: La mayoría de los experimentos in vitro demostraron que la microvibración tuvo un aumento estadísticamente significativo en la proliferación y dife- renciación de las células madre mesenquimales (MSC), en osteoblastos (MC3T3-E1), en la expresión de proteínas para inducir osteogénesis y en los osteocitos (MLO-Y4). Asimismo, sobrerregularon la expresión de osteoprotegerina (OPG), prostaglandina (PGE2) y óxido nitroso (NO) al alterar y regular los factores solubles como las citocinas, factores de crecimiento y quimiocinas, de las demás células, además de mostrar una disminución en la actividad de los osteoclastos (RAW246.7) en la resorción ósea. Conclusión: La microvibración induce remodelación ósea. Los osteocitos son sensibles a los estímulos mecánicos y producen factores solubles para inducir la remodelación ósea, razón por la cual se emplea la microvibración como una terapia innovadora y prometedora, no invasiva y no farmacológica en la estimulación de la formación ósea de la superficie del hueso (AU)

Impacto del tratamiento de adultos mayores con ISRS y su relación con los tratamientos odontológicos / The impact of treating older adults with SSRI and its relationship with dental treatments

La población mayor de 60 años es el grupo etario de mayor crecimiento en el mundo. Debido a que la depresión es una patología frecuente en la persona adulta mayor y anciana, los inhibidores de la recap- tación de la serotonina (ISRS) son el tratamiento de primera línea de elección. Este trabajo referencia la asociación del consumo de estos fármacos con la disminución de la densidad ósea mineral (DMO), el riesgo de fracturas y su repercusión en la atención odontológica. Además, incluye una breve descripción de la homeostasis ósea y la relación depresión-carga alostática. El trabajo interdisciplinario y una correcta anamnesis pueden detectar posibles complicaciones y riesgos vinculados con este tipo de medicamen- tos. Ello facilitaría un mejor manejo, más aún en el adulto mayor, donde una pequeña variable puede repercutir en su integridad (AU)

The population over 60 is the fastest growing age group in the world. Depression is a frequent pathology in the elderly and the elderly, with serotonin reuptake inhibitors (SSRI) being the 1st line treatment of choice. The association of the consumption of this drug with a decrease in bone mineral density (BMD), risk of fractures and its impact on dental care are referenced in this work. In addition, it includes a brief description of bone homeostasis and the depression-allostatic load relationship. Interdisciplinary work and a correct anamnesis can detect possible complications and risks linked to this type of medication, facilitating better management and even more so in the elderly, where a small variable can affect their integrity (AU)

The Use of Bio-Inks and the Era of Bioengineering and Tooth Regeneration

Abstract Objective: To review existing literature and provide an update on the current use of Bio-Inks and potential future use. Material and Methods: A MeSH keyword search was conducted to find out relevant articles for this short review. Results: Bio inks used in 3D printing grafting require various properties essential for the selection. Combining multiple methods and improved properties is essential for developing successful bio-inks for 3D grafting of functional tissues and tooth pulp regeneration from stem cells. To date, researchers have made many efforts to grow teeth based on stem cells and inculcate regeneration of teeth along with surrounding tissues like alveolar bones and periodontal ligaments. Conclusion: 3D printing with Bio-Inks requires strict adherence to safety protocols for successful outcomes, making it difficult to employ this routinely.

Immediate autogenous extracted tooth as a grafting material for fresh socket preservation: a systematic review / Diente autógeno de extracción inmediata como material de injerto para la conservación de alvéolos frescos: una revisión sistemática

Objectives: To evaluate the use of extracted autogenous teeth for socket preservation after tooth extraction. Material and Methods: Cochrane, Scopus, and PubMed databases search was conducted to identify human clinical studies reporting the clinical, radiographic and/or histological outcomes of socket preservation techniques with autogenous extracted tooth Only studies published in English language in the last 10 years were included in the study. Results: In total, 82 articles were identified. Five articles were included in the review. They included 58 teeth that were prepared as a graft for socket preservation. The grafts derived from autogenous teeth were presented in three forms: particles, blocks and powder. The mean bone loss ranged from 0.28 mm to 0.41mm in height and 0.15 mm in width. Conclusion: Immediate autogenous extracted tooth as a grafting material for fresh socket preservation is promising for future daily clinical practice. More clinical comparative studies are needed.

Objetivo: Evaluar el uso de dientes extraídos autógenos para la preservación del alveolo tras la extracción dental.Material y Métodos: Se realizó una búsqueda en las bases de datos Cochrane, Scopus y PubMed para identificar estudios clínicos en humanos que informaban los resultados clínicos, radiográficos y / o histológicos de las técnicas de preservación de alveolos con dientes extraídos autógenos. Solo se incluyeron estudios publicados en inglés en los últimos 10 años. Resultados: En total se identificaron 82 artículos. Se incluyeron cinco artículos en la revisión. Incluyeron 58 dientes que se prepararon como injerto para la preservación del alveolo. Los injertos derivados de dientes autógenos se presentaron en tres formas: partículas, bloques y polvo. La pérdida ósea media osciló entre 0,28 mm y 0,41 mm de altura y 0,15 mm de ancho. Conclusión: El diente autógeno extraído de forma inmediata utilizado como material de injerto para la conservación del alveolo fresco es prometedor para la práctica clínica diaria futura. Se necesitan más estudios clínicos comparativos.

Citotoxicidade e efeito indutor de mineralização de flavonoides sobre células osteoblásticas / Cytotoxicity and inducing effect of mineralization of flavonoids on osteoblastic cells

A perda óssea dentária e a formação de lesões periapicais surgem como uma consequênc ia do desequilíbrio da homeostase óssea. Os osteoblastos, juntamente com os osteoclastos e osteócitos, atuam na formação e na reabsorção óssea. Vários marcadores de formação óssea são produzidos por osteoblastos ativos e refletem diferentes aspectos da dif erenciação osteoblástica e da remodelação óssea. Com isso, muitos autores têm explorado o uso de fitoterápicos, visando obter novos compostos que apresentem propriedades terapêuticas, como os flavonoides, e que estimulem a neoformação óssea e o reparo da r egião periapical. O objetivo deste estudo foi avaliar in vitro a citotoxicidade e efeito indutor de mineralização de flavonoides sobre células osteoblásticas humanas. Para isso, células osteoblásticas da linhagem Saos expostas aos seguintes flavono2 foram ides: quercetina, miricetina e seus derivados taxifolina, isoquercitrina, rutina, ampelopsina e EGCG, além de pinocembrina, crisina e canferol, de forma isolada e combinada. Foi avaliado o efeito citotóxico, a atividade de fosfatase alcalina e indução de n mé todo de Shapiroódulos de mineralização. Os resultados foram analisados p elo Wilk, e as variáveis foram submetidas à análise de ANOVA seguida pelo teste de Tukey para comparar entre os grupos e/ou concentrações ou teste de Dunnett para comparar entre cada grupo e o controle, com nível de significância de 5%. A viabilidade da cultura de osteoblastos não teve uma redução estatisticamente significativa na presença da maioria dos compostos, exceto crisina a 100µM. Taxifolina, isoquercitrina, rutina, ampelopsina e EGCG foram os compostos que estimularam significativamente a atividade da fosfatase alcalina, juntamente com as combinações taxifolina+isoquercitrina, taxifolina+ampelopsina e taxifolina+rutina a 25/25 µM. Quanto a formação de nódulos de mine ralização, ampelopsina, isoquercitrina, rutina, pinocembrina e miricetina isolados e taxifolina+isoquercitrina, taxifolina+ampelopsina e taxifolina+rutina combinados obtiveram os melhores resultados, variando de acordo com as concentrações. Concluise que a taxifolina, isoquercitrina, rutina e ampelopsina e combinações de taxifolina com esses flavonoides são citocompatíveis e apresentam efeito indutor de mineralização em osteoblastos Saos-2(AU)

Dental bone loss and the formation of periapical lesions arise as a consequence of imbalance of bone homeostasis. Osteoblasts, together with osteoclasts and osteocytes, act in bone formation and resorption. Several markers of bone formation are produced by active osteoblasts and reflect different aspects of osteoblastic differentiation and bone remodeling. Thus, many authors have explored the use of phytotherapics in order to obtain new compounds with therapeutic properties, such as flavonoids, and also stimulate bone neoformation and periapical region repair. The objective of this study was to evaluate in vitro the cytotoxicity and inducing effect of flavonoid mineralization on human osteoblastic cells. For this, osteoblastic cells of the Saos-2 lineage were exposed to the following flavonoids: quercetin, myricetin and its derivatives taxifoline, isoquercitrin, rutin, ampelopsin and EGCG, in addition to pinocembrin, chrysin and kaempferol, in an isolated and combined manner. The cytotoxic effect, the activity of alkaline phosphatase and the induction of mineralization nodules were evaluated. The results were analyzed using the Shapiro-Wilk method, and the variables were submitted to ANOVA analysis followed by the Tukey test to compare between groups and/or concentrations or Dunnett's test to compare between each group and the control, with a level of 5% significance. The viability of the osteoblast culture did not have a statistically significant reduction in the presence of most compounds, except 100 µM chrysin. Taxifoline, isoquercitrin, rutin, ampelopsin and EGCG were the compounds that significantly stimulated the activity of alkaline phosphatase, together with the combinations taxifoline+isoquercitrin, taxifoline+ampelopsin and taxifoline+rutin at 25/25 µM. As for the formation of mineralization nodules, ampelopsin, isoquercitrin, rutin, pinocembrin and myricetin alone and taxifoline+isoquercitrin, taxifoline+ampelopsin and taxifoline+rutin combined obtained the best results, varying according to the concentrations. It is concluded that taxifoline, isoquercitrin, rutin and ampelopsin and combinations of taxifolin with these flavonoids are cytocompatible and have a mineralization-inducing effect on Saos-2 osteoblasts(AU)

Análise do fêmur de ratas tratadas com ocitocina e submetidas ao treinamento de força durante a periestropausa / Analysis of the femur of rats treated with oxytocin and submitted to strength training during periestropause

A diminuição nas concentrações de estrógeno, como o que ocorre no período da perimenopausa e menopausa, contribui para o aumento do turnover ósseo, com taxa de reabsorção superior à de formação óssea que favorece a instalação da osteoporose, doença silenciosa que determina fragilidade óssea e maior probabilidade de fraturas. Entre as intervenções utilizadas para prevenção da osteoporose, destaca-se o treinamento de força (TF) e a ocitocina (OT), hormônio promissor com ação anabólica no osso. O objetivo deste estudo foi verificar a ação da associação da OT ao TF, em comparação às intervenções isoladas, no processo de remodelamento ósseo do colo do fêmur de ratas Wistar na periestropausa (18 a 21 meses). Quarenta ratas Wistar com ciclo estral irregular (18 meses) foram randomizadas nos grupos: 1- Veículo (Veh); 2-Ocitocina (Ot); 3-Treinamento de força (Tf); 4-Ot+Tf. Os animais do grupo 1 receberam salina (0,15 mol/L) e dos grupos 2 e 4 receberam OT (134 µg/kg), sendo duas injeções intraperitoneais com intervalo de 12 horas a cada 30 dias, totalizando 8 injeções ao final do período experimental. Os animais dos grupos 3 e 4 realizaram TF em escada 3 vezes por semana com realização mensal do teste de capacidade de carga máxima voluntária (CCMV). Após 120 dias, os animais foram eutanasiados, os fêmures foram coletados para análises de ensaio mecânico, densitometria, microtomografia óssea, espectroscopia de Raman e técnica de reação em cadeia da polimerase de transcrição reversa em tempo real (qRT-PCR), e o sangue para análises de marcadores bioquímicos do metabolismo ósseo, dano hepático e estresse oxidativo. A principal novidade deste estudo é a adição da OT ao TF, a qual apresentou, no ensaio de compressão, maior força máxima em relação ao Veh e menor elasticidade em relação ao Tf e, no ensaio de flexão de três pontos, maior rigidez em relação ao Veh e Ot, menor rigidez e menor elasticidade em relação ao Veh; maior espessura cortical (Ct.Th) em relação aos demais grupos, menor número de poros (Po.N) em relação ao Veh e Ot, e maior momento polar médio (J) em relação ao Tf. Houve também maior volume do osso trabecular (BV/TV) em relação ao Ot e maior espessura trabecular (Tb.Th) em relação aos demais grupos. A densidade mineral óssea areal (aDMO) do colo do fêmur foi maior que o Ot, e a DMO do fêmur total foi maior que os demais grupos. Quanto a expressão gênica, houve maior expressão do fator de transcrição relacionado ao Runt 2 (Runx2) em relação ao Veh, o fator de transcrição Osterix (Osx/Sp7) foi menor que o Ot e Tf. A proteína morfogenética óssea 2 (Bmp2) apresentou menor expressão em relação ao Veh, e a expressão da fosfatase alcalina óssea (Fal) foi maior que os demais grupos. A expressão do membro da família do fator de necrose tumoral 11b (Opg) e do ligante do fator de necrose tumoral (Rankl) foi maior que os outros grupos, a expressão do membro do fator de necrose tumoral 11a (Rank) e catepsina K (Ctsk) foi maior que Veh e Ot. Também foi observado menor atividade de fosfatase ácida resistente ao tartarato (TRAP) e capacidade antioxidante total (CAT) no ensaio bioquímico em relação aos demais grupos. Na intervenção com OT, houve maior elasticidade no ensaio de flexão de três pontos, e maior Ct.Th em relação ao Veh. A expressão gênica de Runx2, Osx/Sp7 foi maior e Bmp2 foi menor que o grupo Veh. No TF houve maior elasticidade que o Veh e Ot no ensaio de compressão, maior rigidez e elasticidade em relação ao Veh no ensaio de flexão de três pontos. Houve menor Ct.Th em relação ao Ot, maior DMO do fêmur total em relação ao Veh, e a taxa de mineralização foi maior que o Veh e Ot. Na expressão gênica, Runx2 e Osx/Sp7 foram maiores que o Veh. A Bmp2 e osteocalcina/proteína óssea gama-carboxiglutamato (Ocn) foram menores que o Veh, e a Fal foi menor que Ot. Em relação a Rank e Ctsk, estas foram maiores que Veh e Ot. Por fim, a atividade de aspartato aminotransferase (AST) foi menor que o Veh. Esses resultados mostraram que a associação de intervenções é estratégia anabólica promissora para a prevenção da osteoporose no período da periestropausa, destacando-se dos efeitos das intervenções isoladas, ao preservar aspectos mecânicos, estruturais e gênicos do osso, além de parecer controlar fatores relacionados ao cross-talk entre tecido ósseo e tecido adiposo a favor da homeostase oxidativa e de fatores relacionados a atividade de marcadores ósseos(AU)

The decrease in estrogen concentrations, such as that which occurs during perimenopause and menopause, contributes to an increase in bone turnover, with a rate of resorption higher than that of bone formation, which favors the installation of osteoporosis, a silent disease that determines bone fragility and greater probability of fractures. Among the interventions used to prevent osteoporosis, strength training (ST) and oxytocin (OT), a promising hormone with anabolic action on bone, stand out. The objective of this study was to verify the action of the association of OT and ST, compared to isolated interventions, in the process of bone remodeling of the femoral neck of Wistar rats in periestropause (18 to 21 months). Forty Wistar rats with irregular estrous cycle (18 months) were randomized into groups: 1-Vehicle (Veh); 2-Oxytocin (Ot); 3-Strength training (St); 4-Ot+St. The animals in group 1 received saline (0.15 mol/L) and in groups 2 and 4 received OT (134 µg/kg), with two intraperitoneal injections with an interval of 12 hours every 30 days, totaling 8 injections at the end of the period. trial period. The animals in groups 3 and 4 performed ST on a ladder 3 times a week with monthly performance of the maximum voluntary carrying capacity test (MVCC). After 120 days, the animals were euthanized, the femurs were collected for mechanical assay analysis, densitometry, bone microtomography, Raman spectroscopy and real-time reverse transcription polymerase chain reaction (qRT-PCR) technique, and blood for analysis of biochemical markers of bone metabolism, liver damage and oxidative stress. The main novelty of this study is the addition of OT to ST, which presented, in the compression test, greater maximum force in relation to Veh and less elasticity in relation to St and, in the three-point bending test, greater stiffness in relation to to Veh and Ot, less rigidity and less elasticity in relation to Veh; greater cortical thickness (Ct.Th) in relation to the other groups, smaller number of pores (Po.N) in relation to Veh and Ot, and greater mean polar moment (J) in relation to St. There was also greater trabecular bone volume (BV/TV) in relation to Ot and greater trabecular thickness (Tb.Th) in relation to the other groups. The areal bone mineral density (aBMD) of the femoral neck was higher than the Ot, and the BMD of the total femur was higher than the other groups. As for gene expression, there was greater expression of the transcription factor related to Runt 2 (Runx2) in relation to Veh, the transcription factor Osterix (Osx/Sp7) was lower than Ot and St. Bone morphogenetic protein 2 (Bmp2) showed lower expression compared to Veh, and boné alkaline phosphatase (Alp) expression was higher than the other groups. The expression of tumor necrosis factor 11b family member (Opg) and tumor necrosis factor ligand (Rankl) was higher than the other groups, tumor necrosis factor 11a member (Rank) and cathepsin K (Ctsk) was greater than Veh and Ot. It was also observed lower activity of tartrate resistant acid phosphatase (TRAP) and total antioxidant capacity (CAT) in the biochemical assay in relation to the other groups. In the intervention with OT, there was greater elasticity in the three-point bending test, and greater Ct.Th in relation to Veh. The gene expression of Runx2, Osx/Sp7 was higher and Bmp2 was lower than the Veh group. In ST intervention there was greater elasticity than Veh and Ot in the compression test, greater stiffness and elasticity in relation to Veh in the three-point bending test. There was lower Ct.Th in relation to Ot, higher BMD of the total femur in relation to Veh, and the mineralization rate was higher than Veh and Ot. In gene expression, Runx2 and Osx/Sp7 were higher than Veh. Bmp2 and osteocalcin/bone protein gammacarboxyglutamate (Ocn) were lower than Veh, and Fal was higher than Ot. In relation to Rank and Ctsk, these were higher than Veh and Ot. Finally, aspartate aminotransferase (AST) activity was lower than Veh. These results showed that the association of interventions is a promising anabolic strategy for the prevention of osteoporosis in the periestropause period, standing out from the effects of isolated interventions, by preserving mechanical, structural and genetic aspects of the bone, in addition to seeming to control factors related to the cross -talk between bone tissue and adipose tissue in favor of oxidative homeostasis and factors related to the activity of bone markers(AU)

Recombinant human insulin-like growth factor-1 promotes osteoclast formation and accelerates orthodontic tooth movement in rats

Abstract Background: IGF-1 may be an important factor in bone remodeling, but its mechanism of action on osteoclasts during orthodontic tooth movement is complex and unclear. Methodology: The closed-coil spring was placed between the left maxillary first molar and upper incisors with a force of 50 g to establish an orthodontic movement model. Eighty SD rats were randomized to receive phosphate buffer saline or 400 ng rhIGF-1 in the lateral buccal mucosa of the left maxillary first molar every two days. Tissue sections were stained for tartrate-resistant acidic phosphatase (TRAP), the number of TRAP-positive cells was estimated and tooth movement measured. Results: The rhIGF-1 group exhibited evidential bone resorption and lacuna appeared on the alveolar bone compared to the control group. Moreover, the number of osteoclasts in compression side of the periodontal ligament in the rhIGF-1 group peaked at day 4 (11.37±0.95 compared to 5.28±0.47 in the control group) after the orthodontic force was applied and was significantly higher than that of the control group (p<0.01). Furthermore, the distance of tooth movement in the rhIGF-1 group was significantly larger than that of the control group from day 4 to day 14 (p<0.01), suggesting that rhIGF-1 accelerated orthodontic tooth movement. Conclusion: Our study has showed that rhIGF-1 could stimulate the formation of osteoclasts in the periodontal ligament, and accelerate bone remodeling and orthodontic tooth movement.

Mechanism, prevention, and treatment for medication-related osteonecrosis of the jaws / 华西口腔医学杂志

The morbidity rate of medication-related osteonecrosis of the jaws (MRONJ) increased rapidly in recent years. Thusfar, the mechanism of MRONJ has no consensus. The possible mechanisms may include bone remodeling inhibition theory, angiogenesis inhibition theory, oral microorganism infection theory, immunosuppression theory, cytotoxicity-targeted oral epithelial cells, microcrack formation of maxillary or mandibular bone, and single nucleotide polymorphism. However, the efficacy of prevention and treatment based on a single mechanism is not ideal. Routine oral examination before MRONJ-related drug treatment, treatment of related dental diseases, and regular oral follow-up during drug treatment are of great significance for the prevention of MRONJ. During the treatment of MRONJ, the stage of MRONJ must be determined accurately, treatment must be standardized in accordance with the guidelines, and personalized adjustments must be made considering the specific conditions of patients. This review aimed to combine the latest research and guidelines for MRONJ and the experiences on the treatment of MRONJ in the Maxillofacial Surgery Department of West China Hospital of Stomatology, Sichuan University, and discuss the strategies to improve the clinical process.

Salivary molecules of bone remodeling and tissue repair after head and neck radiotherapy

Abstract Head and neck radiotherapy causes quantitative and qualitative changes in saliva. The objective of this case-control study was to evaluate the salivary biomarkers associated with bone remodeling and tissue repair in patients submitted to radiotherapy for head and neck cancer treatment, compared with non-irradiated individuals. Total unstimulated saliva was collected for ELISA assay analysis of receptor activator for nuclear factor κ B (RANK) and its ligand (RANK-L), osteoprotegerin, matrix metalloproteinase-9/ tissue inhibitor of metalloproteinase-2, vascular endothelial growth factor, and epidermal growth factor. Statistics were performed, and revealed that salivary RANK (p = 0.0304), RANK-L (p = 0.0005), matrix metalloproteinase-9/ tissue inhibitor of metalloproteinase-2 (p = 0.0067), vascular endothelial growth factor (p = 0.0060), and epidermal growth factor (p < 0.0001) were reduced in patients, compared with the control group. Osteoprotegerin did not differ between the groups (p = 0.3765). Salivary biomarkers did not differ according to radiotherapy completion time (p > 0.05). In conclusion, the lower output of the salivary molecules - essential for bone remodeling and tissue repair - may disrupt tissue homeostasis and play a role in the pathogenesis of the radiotherapy-induced deleterious effects in the oral cavity.

Graft application and dexamethasone treatment influences new bone formation in rat tibial bone defects / Aplicación de injerto y tratamiento con dexametasona influyen en la formación de hueso nuevo en los defectos en la tibia de rata

SUMMARY: The objective of this study were bone defect complications that occur due to traumas or infections. Bone grafts are required to provide support, fill gaps and improve biological repair in skeletal damage. Dexamethasone plays role in calcium signaling modulation and used in diseases. Aim of this study was to evaluate osteonectin and osteopontin expressions in new bone development after dexamethasone application on tibial bone defects. Rats were divided into defect, defect+graft and defect+graft+dexamethasone treated groups. Tibial bone defect created, and rats were kept immobile for 28 days. Alloplastic material was placed in defect area in second and group third groups. 2.5 mg/kg Dex and normal saline were injected to dexamethasone and defect groups twice a week for 56 days. Inflammation and congestion were increased in defect and defect+graft groups. Defect+graft+dexamethasone group; increased number of osteoblast and osteocyte cells, dense bone matrix, formation of new bone trabeculae was observed. Defect+graft group; osteonectin expression in graft regions, osteoblast cells, some connective tissue cells and fibers were seen whereas in defect+graft+dexamethasone group; osteopontin expression in osteoblast and osteocyte cells of new bone trabeculae were observed. Dexamethasone may lead to formation of new bone trabeculae into the graft material resulting in increased osteoconduction and osteoinductive effect for differentiation of osteon.

RESUMEN: Los defectos óseos son complicaciones que ocurren debido a traumas o infecciones. Se requieren injertos óseos para proporcionar apoyo, llenar los espacios y mejorar la reparación biológica en el hueso dañado. La dexametasona desempeña un papel importante en la modulación de la señalización del calcio y se usa en enfermedades. El objetivo de este estudio fue evaluar las expresiones de osteonectina y osteopontina en el desarrollo óseo después de la aplicación de dexametasona en defectos óseos tibiales. Las ratas se dividieron en grupos: defecto, defecto + injerto y defecto + injerto + grupos tratados con dexametasona. Se creó un defecto óseo tibial, y las ratas se mantuvieron inmóviles durante 28 días. El material aloplástico se colocó en el área del defecto en el segundo y tercer grupo. Se inyectaron 2,5 mg / kg de dexametasona y solución salina normal a grupos de defectos dos veces por semana durante 56 días. La inflamación y la congestión aumentaron en los grupos de defectos y defectos + injerto; En el grupo defecto + injerto + grupo tratado con dexametasona se observó un aumento en el número de osteoblastos y osteocitos, de matriz ósea densa y en la formación de nuevas trabéculas óseas. En el grupo defecto + grupo de injerto se observó la expresión de osteonectina en las áreas de injerto, osteoblastos, algunas células y fibras de tejido conectivo, mientras que en el grupo defecto + injerto + dexametasona se observó la expresión de osteopontina en osteoblastos y osteocitos y formación de nuevas trabéculas óseas . En conclusión la dexametasona puede conducir a la formación de nuevas trabéculas óseas en el material de injerto, lo que resulta en un aumento de la osteoconducción y un efecto osteoinductivo para la diferenciación del osteón.

Rol de los fitoestrógenos en la calcificación vascular e interacciones óseo-vasculares / Role of phytoestrogens in vascular calcification and bonevascular interactions

La osteoporosis y las enfermedades cardiovasculares son patologías prevalentes en mujeres posmenopáusicas. La calcificación vascular es un proceso en el que se produce una distorsión de la arquitectura natural del tejido arterial con una transformación símil osteogénica. La fisiología vascular y la osteogénesis (formación y remodelación ósea) comparten una complejidad metabólica y funcional crítica, que ha sido poco explorada en forma conjunta, lo que ha impulsado la concepción del Eje Óseo-Vascular como nueva área de investigación, con una visión de estudio integradora con la finalidad de identificar vínculos entre ambos sistemas. En virtud de la controversia planteada sobre los riesgos/beneficios de la terapia de reemplazo hormonal para prevenir enfermedades asociadas a la menopausia, se ha incentivado la búsqueda de nuevas opciones de tratamiento. Los fitoestrógenos, como compuestos nutracéuticos, surgen como una potencial alternativa terapéutica. En particular, las isoflavonas presentan gran analogía estructural con el estrógeno humano 17ß-estradiol, lo que les permite unirse al receptor de estrógenos e inducir acciones estrogénicas tanto en células animales como humanas. Basado en la experiencia propia como en lo reportado en la bibliografía, este artículo analiza la información disponible sobre las acciones vasculares y óseas de los fitoestrógenos (específicamente la isoflavona genisteína), con una visión de ciencia traslacional. Es de esperar que los avances en el conocimiento derivado de la ciencia básica, en un futuro cercano, pueda contribuir a decisiones clínicas a favor de promover terapias naturales de potencial acción dual, para la prevención de enfermedades de alta prevalencia y significativo costo social y económico para la población. (AU)

Osteoporosis and cardiovascular diseases are prevalent diseases in postmenopausal women. Vascular calcification is a cellmediated process that leads to the loss of the natural architecture of the arterial vessels due to osteogenic transdifferentiation of smooth muscle cells, and matrix mineralization. Vascular physiology and osteogenesis (bone formation and remodeling) share a critical metabolic and functional complexity. Given the emerging integrative nature of the bonevascular axis, links between both systems are a matter of ongoing interest. In view of the controversy stated about the risks/benefits of hormone replacement therapy to prevent diseases associated with menopause, phytoestrogens arise as a potential natural therapeutic alternative. In particular, isoflavones have a strong structural analogy with the human estrogen 17ß-estradiol, that allows them to bind to the estrogen receptor and induce estrogenic actions in animal and human cells. Based in on our own experience and the information available in the literature, in this paper we provide an overview of the role of phytoestrogens on vascular and bone tissues, with focus on Genistein actions. We wish that the basic knowledge acquired may contribute to guide clinical decisions for the promotion of natural therapies for the treatment of diseases that conspire against human health. (AU)

Capacidad funcional, densidad mineral ósea y marcadores de neoformación-reabsorción ósea en pacientes menores de 18 años con movilidad reducida / Functional capacity, bone mineral density and neoformation-resorption bone markers in patients under 18 years of age with reduced mobility

Resumen: Introducción: La inmovilización prolongada asociada a diversas enfermedades neurológicas, causa osteoporosis secundaria con fracturas patológicas y dolor óseo persistente. Objetivos: Establecer la asociación entre densidad mineral ósea (DMO), marcadores de neoformación y reabsorción ósea y grado de capacidad funcional en pacientes menores de 18 años con movilidad reducida. Pacientes y Método: Estudio transversal, realizado entre 1/1/2016 y 31/12/2017 en pacientes de 6 a 18 años diagnosticados de distintas enfermedades neurológicas en Ciudad Real (España). Se analizaron las variables biodemográficas, capacidad funcional según la Functional Mobility Scale (FMS), que valora la movilidad en 5, 50 y 500 metros, DMO, 25-hidroxi-vitamina D, fosfatasa alcalina, osteocalcina en sangre y telopéptido amino terminal de cadena cruzada de colágeno tipo I en orina (NTX-I). Se expresan DMO, fosfatasa alcalina, osteocalcina y NTX-I en Z score según valores de referencia para edad y sexo. Se utilizaron estadísticas descriptivas y correlaciones de Pearson y Spearman. Resulta dos: 36 pacientes (52,7% niñas), edad media de 8,6 ± 4,7 años. Valor medio de FMS: 5,3 sobre 18. DMO media: -1,99 ± 1,7 desviaciones estándar (DE), fosfatasa alcalina media: -2,64 ± 1,08, osteocalcina media: -2,15 ± 1,39, y NTX-I medio: +3 ± 1,72. Hubo asociación significativa entre DMO y FMS para 5 metros (r = 0,395; p = 0,017) y para la puntuación total (r = 0,365; p = 0,029). No se encon traron diferencias significativas según estadios de desarrollo puberal. Conclusiones: En la población estudiada se observa disminución en la DMO y en marcadores de neoformación ósea y elevación de marcadores de reabsorción ósea sin asociación con el desarrollo puberal. Los pacientes con menor grado de movilidad presentan una DMO inferior.

Abstract: Introduction: Prolonged immobilization associated with several neurological disorders causes se condary osteoporosis with pathological fractures and persistent bone pain. Objectives: To establish the association between bone mineral density (BMD), neoformation and bone resorption markers and the degree of functional capacity in children under 18 years of age with reduced mobility. Pa tients and Method: Cross-sectional study conducted in Ciudad Real, Spain between January 1, 2016, and December 31, 2017 with patients aged between 6 and 18 years diagnosed with different neurological disorders. The following variables were analyzed: age, sex, pubertal stage, functional capacity according to the Functional Mobility Scale (FMS), which assesses the ability to walk from 5, 50 to 500 meters, BMD, 25-hydroxy-vitamin D, alkaline phosphatase and osteocalcin in blood, and N-terminal telopeptide crosslinks in collagen type I (NTX-I) in urine. BMD, alkaline phosphatase, osteocalcin, and NTX-I values are expressed in Z score according to reference values for age and sex. The Pear son and Spearman correlations were used for data analysis. Results: 36 patients (52.7% girls) with an average age of 8.6±4.7 years. Mean FMS value: 5.3 out of 18. Mean BMD: -1.99 ± 1.7 standard deviations (SD), mean alkaline phosphatase: -2.64 ± 1.08, mean osteocalcin: -2.15 ± 1.39, and mean NTX-I: +3 ± 1.72. There was a significant association between BMD and FMS for 5 meters (r = 0.395; p = 0.017) and for total score (r = 0.365; p = 0.029). There were no significant differences according to the stages of pubertal development. Conclusions: In this population, there was a decrease in BMD and bone neoformation markers, and an increase of bone resorption markers with no association with pubertal development. Patients with a lower degree of mobility present a lower BMD.

Digital radiography as an alternative method in the evaluation of bone density in uremic rats / Radiografia digital como método alternativo na avaliação da densidade óssea em ratos urêmicos

ABSTRACT Introduction: Digital radiography (DRx) may provide a suitable alternative to investigate mineral and bone disorder (MBD) and loss of bone density (BD) in rodent models of chronic kidney disease (CKD). The objective of this study was to use DRx to evaluate BD in CKD rats, and to evaluate the correlation between DRx findings and serum MBD markers and bone histomorphometry. Methods: Uremia was induced by feeding Wistar rats an adenine-enriched diet (0.75% for 4 weeks/0.10% for 3 weeks); outcomes were compared to a control group at experimental weeks 3, 4, and 7. The following biochemical markers were measured: creatinine clearance (CrC), phosphate (P), calcium (Ca), fractional excretion of P (FeP), alkaline phosphatase (ALP), fibroblast growth factor-23 (FGF-23), and parathyroid hormone (PTH). DRx imaging was performed and histomorphometry analysis was conducted using the left femur. Results: As expected, at week 7, uremic rats presented with reduced CrC and higher levels of P, FeP, and ALP compared to controls. DRx confirmed the lower BD in uremic animals (0.57±0.07 vs. 0.68 ± 0.06 a.u.; p = 0.016) compared to controls at the end of week 7, when MBD was more prominent. A severe form of high-turnover bone disease accompanied these biochemical changes. BD measured on DRx correlated to P (r=-0.81; p = 0.002), ALP (r = -0.69, p = 0.01), PTH (r = -0.83, p = 0.01), OS/BS (r = -0.70; p = 0.02), and ObS/BS (r = -0.70; p = 0.02). Conclusion: BD quantified by DRx was associated with the typical complications of MBD in CKD and showed to be viable in the evaluation of bone alterations in CKD.

RESUMO Introdução: A radiografia digital (RxD) pode representar uma alternativa adequada para investigar o distúrbio mineral e ósseo (DMO) e a perda de densidade óssea (DO) em modelos de roedores da doença renal crônica (DRC). O objetivo deste estudo foi utilizar a RxD para avaliar a DO em ratos com DRC, e avaliar a correlação entre os achados da RxD e marcadores séricos de DMO e histomorfometria óssea. Métodos: A uremia foi induzida pela alimentação de ratos Wistar com dieta enriquecida com adenina (0,75% por 4 semanas/0,10% por 3 semanas); os resultados foram comparados com um grupo controle nas semanas experimentais 3, 4 e 7. Os seguintes marcadores bioquímicos foram medidos: clearance de creatinina (CCr), fosfato (P), cálcio (Ca), fração excretada de P (FeP), fosfatase alcalina (ALP), fator de crescimento de fibroblastos-23 (FGF-23) e paratormônio (PTH). A imagem da RxD foi obtida e a análise histomorfométrica foi realizada com o fêmur esquerdo. Resultados: como esperado, na semana 7, os ratos urêmicos apresentaram redução do CCr e níveis mais altos de P, FeP e ALP em comparação aos controles. A RxD confirmou a menor DO em animais urêmicos (0,57 ± 0,07 vs. 0,68 ± 0,06 u.a.; p = 0,016) em comparação aos controles no final da semana 7, quando a DMO foi mais proeminente. Uma forma grave de doença óssea de alta renovação celular acompanhou essas mudanças bioquímicas. A DO, medida na RxD foi correlacionada a P (r = -0,81; p = 0,002), ALP (r = -0,69, p = 0,01), PTH (r = -0,83, p = 0,01), OS/BS (r = -0,70 p = 0,02) e Ob.S/BS (r = -0,70; p = 0,02). Conclusão: A DO quantificada por RxD esteve associada às complicações típicas da DMO na DRC e mostrou-se viável na avaliação de alterações ósseas na DRC.

Biomechanical Analysis of Orthopedic Screw Under Bone Remodeling / 中国医疗器械杂志

In order to evaluate the biomechanical stability of titanium alloy screw with different structural parameters under bone remodeling, some three-dimensional finite element models were established and the bone remodeling process after implanting the screw was simulated. Three-dimensional finite element models consist of bone and screw with different lengths and diameters. Bone remodeling process was simulated by user-defined subroutine. It is found that the stress on the bone is concentrated on the groove and root of the internal thread. The screw stress is mainly on the beginning of the thread, and the whole stress decreases along the long axis of the screw. The stress distribution trend of bone and screw did not change significantly during the bone remodeling. The maximum equivalent stress value was different, the maximum equivalent stress on the screw and cancellous bone increased while the maximum equivalent stress value on the cortical bone decreased.

Osseointegração de implantes com superfícies modificadas por LASER com e sem recobrimento de hidroxiapatita: caracterização topográfica, análises biomecânica e histológica / Osseointegration of LASER modified surface implants with and without hydroxyapatite coating: topographic characterization, biomechanical and histologic analyses

Objetivo: Avaliar o processo de reparo ao redor de implantes com as superfícies usinada (SU), superfície disponível comercialmente modificada por jateamento de óxido de alumínio seguido do condicionamento ácido (SJA), modificada por feixe de LASER (SL) e modificada por feixe de LASER com posterior recobrimento de hidroxiapatita através do método biomimético sem tratamento térmico (SLH). Material e Métodos: As superfícies foram analisadas através de microscopia eletrônica de varredura acoplado a espectroscopia por energia dispersiva de raios X (MEV-EDX) previamente a cirurgia. Vinte coelhos receberam randomicamente 40 implantes em suas tíbias direita e esquerda, sendo um implante de cada superfície em cada tíbia. No procedimento cirúrgicos e nos períodos de 2 e 4 semanas foi mensurado o coeficiente de estabilidade do implante através da análise de frequência por ressonância (FR), seguida da remoção por contra-torque dos implantes nos períodos de análise. Os dados obtidos foram submetidos à análise de variância e ao teste t de Tukey (FR) e Kruskal-Wallis (análise biomecânica). Resultados: MEV e EDX mostraram diferenças na topografia das superfícies. Não houve diferença estatisticamente significante entre os grupos na análise de frequência por ressonância. Foi observada diferença estatisticamente significante no torque de remoção entre o grupo SL e SLH quando comparados ao grupo SU no período de 2 semanas. Já no período de 4 semanas, foi observada diferença estatística entre as 2 superfícies experimentais SL e SLH quando comparadas as superfícies SU e SJA. Na análise histológica os grupos SL e SLH apresentaram remodelação óssea no período de 2 semanas e osso maduro no período de 4 semanas, diferente de SU e SJA que apresentaram um atraso no reparo perante as superfícies experimentais. Conclusão: Os implantes com superfície SL e SLH apresentaram propriedades topográficas, e biomecânicas superiores às das superfícies SU e SJA(AU)

Purpose: To evaluate the repair process around implants with the machined surfaces (SU), commercially available surface modified by aluminum oxide blasting followed by acid etching (SJA), modified by LASER beam (SL) and modified by LASER beam with subsequent coating of hydroxyapatite using the biomimetic method without thermal treatment (SLH). Material and Methods: The surfaces were analyzed using scanning electron microscopy coupled with dispersive energy X-ray spectroscopy (SEM-EDX) prior to surgery. Twenty rabbits randomly received 40 implants in their right and left tibiae, with one implant on each surface in each tibia. In the surgical procedure and in the periods of 2 and 4 weeks, the implant stability coefficient was measured through the resonance frequency (ISQ), followed by the removal by counter-torque of the implants in the analysis periods. The data obtained were subjected to analysis of variance and Tukey's t test (ISQ) and Kruskal-Wallis (biomechanical analysis). Results: SEM and EDX showed differences in surface topography. There was no statistically significant difference between the groups in the resonance frequency. There was a statistically significant difference in the removal torque between the SL and SLH group when compared to the SU group in the period of 2 weeks. In the 4-week period, a statistical difference was observed between the 2 experimental surfaces SL and SLH when comparing the SU and SJA surfaces. In the histological analysis, the SL and SLH groups presented bone remodeling in the period of 2 weeks and mature bone in the period of 4 weeks, unlike SU and SJA which presented a delay in repair before the experimental surfaces. Conclusion: Implants with SL and SLH surfaces showed topographic and biomechanical properties superior to those of SU and SJA surfaces(AU)

Análise do processo de reparo alveolar em camundongos fêmeas senescentes 129/Sv-WT e 129/Sv 5-LOKO sob terapia com bifosfonato de alta potência / Alveolar bone repair of 129/Sv WT and 129/Sv 5LOKO female senescent mice under therapy with high potency bisphosphonate

O processo de senescência acarreta uma série de modificações fisiológicas com declínio das funções das atividades celulares e sistêmicas que se manifestam de maneira mais importante na população feminina pelo evento da menopausa, como a osteoporose. A fim de se minimizar tais efeitos, há a possibilidade de se utilizar medicamentos que diminuem o processo de remodelação óssea como os bifosfonatos nitrogenados (BF). Entretanto, o uso dessas drogas está intimamente relacionado ao desenvolvimento de osteonecrose dos maxilares (OM), principalmente quando associado a outros fatores de risco como as cirurgias bucais. Sabe-se que fisiologicamente a dinâmica do tecido ósseo depende também de eicosanóides derivados do metabolismo do ácido araquidônico (AA), como as enzimas cicloxigenase (COX) e 5 lipoxigenase (5LO). Deste modo, o objetivo do presente trabalho foi analisar o efeito BF ácido zoledrônico (ZL) e sua relação com o desenvolvimento da OM em camundongos fêmeas senescentes 129/Sv com e sem modificação genética para a enzima 5LO. Para tanto, foram utilizados 40 camundongos fêmeas senescentes 129/Sv, sendo 20 WT e 20 com alteração no gene 5LO (129 Alox5tm1Fun/J) (5LOKO), divididas em grupos: WT, tratadas com 0,01 ml de solução salina 0,9% estéril (SS) via intraperitoneal (IP) e ZL, tratadas com 250µg/Kg de ácido zoledrônico (ZL) IP diluído em solução salina estéril, ambas administradas 1 vez/semana por 7 semanas. Os grupos foram compostos por 5 animais cada (WT Controle ­ 7 e 21dias, WT ZL ­ 7 e 21 dias, 5LOKO Controle ­ 7 e 21 dias, 5LOKO ZL ­ 7 e 21dias), sendo as maxilas coletadas para análises em microCT, histopatológica, birrefringência, técnica imunohistoquímica e histomorfométricas. De modo geral, a microCT revelou deficiência significativa na microarquitetura óssea nos animais WT ZL em comparação com os demais. Do mesmo modo, a partir da análise histopatológica e de birrefringência da matriz colagenosa, observou-se padrão compatível com o desenvolvimento de OM no grupo WT ZL, com presença de infiltrado inflamatório intenso, atraso na neoformação óssea, presença de fraturas patológicas, e deficiência da matriz colagenosa e de células Runx-2+, TRAP+ e F4/80+. Os animais 5LOKO ZL apresentaram alterações compatíveis com atraso no processo de reparo especialmente no período de 7 dias, com menor quantidade de células Runx-2+ em comparação com o grupo 5LOKO Controle e pela qualidade da matriz óssea colagenosa com menor quantidade de fibras do espectro vermelho neste período, se igualando, porém, aos 21 dias. Deste modo, concluiu-se que o processo de reparo em camundongos fêmeas senescentes da linhagem 129/Sv WT e 5LOKO associados ao uso do BF ZL ocorreu de modo distinto, levando a quadro de OM nos animais WT e atraso nos animais 5LOKO, sem sinais histopatológicos que caracterizassem a doença. Deste modo, a inibição da enzima 5LO parece influenciar de maneira positiva o processo de reparo ósseo intramembranoso alveolar, mesmo na presença de fenótipo esqueletal osteopetrótico, sugerindo outros fatores relacionados à droga que favoreçam o desenvolvimento da OM no presente modelo animal(AU)

Senescence brings a number of physiological modifications with the decrease of cell and systemic activities and function that manifest in an important way in female population due to the event of menopause, as osteoporosis. In order to diminish these effects, there is the possibility of taking medication that decrease bone remodeling process, as the bisphosphonates containing nitrogen (BF). However, the use of these drugs is intimate related with the development of the osteonecrosis of the jaws (ON), especially when associated to other risk factors as oral surgery. It is known that physiologically, the dynamics of bone tissue also depends on the eicosanoids derivate from the arachidonic acid metabolism (AA), such as cyclooxygenase (COX) and 5 lipoxygenase (5LO) enzymes. In this way, the aim of the present study was to analyze the effects of the BF zoledrônico acid (ZL) and its relation with de development of ON in 129/SV old female mice with or without genetic modification for 5LO. Forty animals, 20 WT and 20 with 5LO gene alteration (129 Alox5tm1Fun/J) (5LOKO) were divided in groups: WT, treated with 0.01 ml of sterile 0.9% saline solution (SS) intraperitoneal (IP), and ZL, treated with 250µg/Kg of ZL IP diluted in SS, both administered once a week for 7 weeks. Groups contained 5 animals each (WT Control ­ 7 and 21 days, WT ZL ,7 and 21 days, 5LOKO Control, 7 and 21 days, and 5LOKO ZL, 7 and 21 days), and the maxillae removed for microCT, histopathology, birefringence, immunohistochemistry, and histomorphometric analysis. In general, microCT revealed significant deficiency in bone microarchitecture in WT ZL group in comparison to the other groups. In the same way, histopathological and birefringence analysis revealed histological pattern compatible with ON development in WT ZL group, presenting intense inflammatory infiltrate, late new bone formation, presence of pathological fractures, and deficiency in collagenous matrix, and also in Runx-2+, TRAP+, and F4/80. 5LOKO ZL animals presented alterations compatible with a late bone repair, especially at day 7, with decreased number of Runx-2+ cells in comparison to 5LOKO Control, and by the quality of collagenous bone matrix with decreased number of red spectra fibers in this period, however, being similar at day 21. From this, it could be concluded that alveolar bone repair of 129/SV WT and 5LOKO old female mice associated with the administration of ZL occurred in different ways, leading to a picture of ON in the WT animals, and late bone repair in the 5LOKO animals, without histopathological signs that could characterize the disease. In this way, inhibition of 5LO seems to influence intramembranous alveolar bone repair in a positive way, even in the presence of osteopetrotic skeletal phenotype, suggesting other factors related to the drug that favors the development of the ON in the present animal model(AU)

A influência da ocitocina e do antagonista do receptor de ocitocina no metabolismo ósseo, estresse oxidativo, padrões da marcha e análise do tipo ansioso de ratas senescentes / The influence of oxytocin and the oxytocin receptor antagonist on bone metabolism, oxidative stress, gait and analysis of the anxious type of senescent rats

O objetivo deste estudo foi avaliar a ação da ocitocina (OT) endógena, bem como o efeito potencializador da OT exógena sobre o metabolismo ósseo, estresse oxidativo, marcha e análise do tipo ansioso de ratas na periestropausa. Ao completar 19 meses, os animais receberam injeções de solução salina (0,15M/ip), Atosiban (AT) (At; 300 µg/Kg/ip), OT (Ot; 134 µg/Kg/ip) ou At+Ot (injeções de OT 5 minutos após AT), sendo duas injeções de cada substância por dia, com intervalos de 12 horas entre elas, a cada 30 dias até a idade de 21 meses. Após trinta dias sem tratamentos, foi realizada a coleta de amostras biológicas. Aspartato aminotransferase (AST), marcador de dano hepático, foi menor em Ot e At+Ot. Substância ácida reativa ao ácido tiobarbitúrico (TBARs É¥mol/L), marcador do dano oxidativo lipídico, foi maior no grupo Ot comparado ao At (p = 0,0093), e menor no At+Ot em relação ao Ot (p = 0,0040). Houve maior defesa antioxidante enzimática avaliada por meio da superóxido dismutase (SOD) no grupo Ot em comparação ao Veh (p < 0,0312). Por sua vez, no grupo At houve maior atividade enzimática da fosfatase alcalina (FAL) em relação ao Veh e Ot (p < 0,0001; At+Ot: p = 0,0015). A espessura do tecido ósseo compacto foi menor no grupo At em relação ao Veh (p = 0,0228), no entanto, foi maior no grupo Ot em relação ao Veh e At (p = 0,0132, p < 0,0001); no grupo At+Ot foi menor quando comparado ao grupo Ot (p = 0,0003). O número de trabéculas ósseas foi menor no grupo At comparado ao Veh (p = 0,0240), e maior em Ot em relação ao At (p = 0,0084). Quanto a análise imunoistoquímica realizada no osso cortical do colo do fêmur, o grupo Ot apresentou maior expressão de osteocalcina (OCN) em comparação aos grupos Veh e At (p = 0,05 e 0,0033), e menor expressão no grupo At+Ot em relação ao grupo Ot (p = 0,05). A expressão de fosfatase ácida resistente ao tartarato (TRAP) foi menor no grupo Ot comparado aos grupos Veh e At (p = 0,05 e 0,0033), contudo foi maior no grupo At+Ot comparado ao Ot (p = 0,05). A densidade mineral óssea areal (DMO) foi significativamente maior nos grupos Ot e At+Ot em relação à Veh (p < 0,0001) e grupo At (p = 0,0231, p = 0,0418). Por sua vez, a relação mineral-matriz (vPO4/Proline) foi maior e a substituição de carbonato tipo B (CO3/vPO4) foi menor no grupo Veh. O teste de deambulação por comprimento (cm) usado para avaliar função musculoesquelética, aumentou em última análise no grupo Ot em relação ao grupo Veh - F (p = 0,0078), At - F (p = 0,0023), bem como aumentou sobre Ot - I (p = 0,0094). O teste do labirinto, usado para estudar o comportamento chamado "tipo ansioso", demonstrou que a OT inverte a redução nas entradas dos braços fechados, reduz o tempo gasto no centro causado pelo At. Os resultados obtidos neste estudo demonstram que a OT ajuda a modular o ciclo de remodelação óssea de ratas senescentes, melhorando os parâmetros de densitometria óssea e os parâmetros funcionais musculoesquelético(AU)

The objective of this study was to evaluate the endogenous oxytocin (OT) action, as well as the potentiating effect of exogenous OT on the bone metabolism, oxidative stress, gait and analysis of the anxious type of rats in periestropause. Upon completing 19 months, the animals received injections of saline solution (0.15M/ip), Atosiban (AT) (At; 300 µg/Kg/ip), OT (Ot; 134 µg/Kg/ip) or At+Ot (OT injections 5 minutes after AT), being two injections of each substance per day, with intervals of 12 hours between them, every 30 days until the age of 21 months. After thirty days without treatment, biological samples were collected. Aspartate aminotransferase (AST), a marker of liver damage, was lower after Ot and At+Ot. Acid reactive substance to thiobarbituric acid (TBARs µmol/L), marker of lipid oxidative damage, was higher in the Ot group compared to At (p = 0.0093), and lower in At+Ot compared to Ot (p = 0.0040). There was a higher antioxidant enzymatic defense evaluated by means of superoxide dismutase (SOD) in the Ot group compared to Veh (p < 0.0312). In turn, in the At group there was greater alkaline phosphatase (FAL) enzymatic activity in relation to Veh and Ot (p < 0.0001; At+Ot: p = 0.0015). The thickness of the compact bone tissue was smaller in the At group in relation to Veh (p = 0.0228), however, it was greater in the Ot group in relation to Veh and At (p = 0.0132, p < 0.0001); in the At+Ot group it was smaller when compared to Ot (p = 0.0003). The number of bone trabecules was smaller in the At group compared to the Veh (p = 0.0240), and greater in Ot in relation to the At (p = 0.0084). As for the immunohistochemical analysis performed on the cortical bone of the femoral neck, the Ot group presented a higher expression of osteocalcin (OCN) compared to the Veh and At groups (p = 0.05 and 0.0033), and lower expression in the At+Ot group compared to the Ot group (p = 0.05). The tartrate-resistant acid phosphatase (TRAP) expression was lower in the Ot group compared to the Veh and At groups (p = 0.05 and 0.0033), however it was higher in the At+Ot group compared to Ot (p = 0.05). The sandal mineral density (BMD) was significantly higher in the Ot and At+Ot groups compared to Veh (p < 0.0001) and At group (p = 0.0231, p = 0.0418). In turn, the parent mineral ratio (vPO4/Proline) was higher and the replacement of carbonate type B (CO3/vPO4) was lower in the Veh group. The walking test per length (cm) used to evaluate musculoskeletal function was ultimately increased in group Ot in relation to group Veh - F (p = 0.0078), At - F (p = 0.0023), as well as increased over Ot - I (p = 0.0094). The labyrinth test, used to study the so-called "anxious type" behavior, demonstrated that the OT reverses the reduction in the entries of the closed arms, reducing the time spent in the center caused by At. The results obtained in this study show that the OT helps to modulate the cycle of bone remodeling of senescent rats, improving the parameters of bone densitometry and the musculoskeletal functional parameters(AU)

Micro-ARNs y células óseas / Micro RNAs and bone cells

Los micro-ARNs (miARNs) son pequeñas moléculas de ARN no codificante (de aproximadamente 15-25 nucleótidos), que regulan la expresión de genes involucrados en numerosas funciones biológicas, a través de la inhibición o degradación de un ARN mensajero diana. La homeostasis ósea se mantiene por el balance entre la formación osteoblástica y la resorción osteoclástica. La sobreexpresión o inhibición de miARNs específicos afecta la proliferación, diferenciación y actividad de osteoblastos, osteocitos y osteoclastos. Estas acciones son llevadas a cabo modulando la expresión de distintos factores transcripcionales y moléculas de señalización de las vías esenciales para la osteoblastogénesis u osteoclastogénesis. Estos efectos modifican el balance entre la formación y la resorción, determinando cambios en la homeostasis ósea. Esta revisión enumera una serie de miARNs que participan en la homeostasis ósea. Profundizando en el conocimiento de los mecanismos por medio de los cuales los miARNs actúan sobre el hueso, podrían revelarse nuevos usos potenciales futuros, entre los que se encuentran su utilidad como nuevos biomarcadores óseos o como agentes terapéuticos para el tratamiento de trastornos metabólicos óseos, pérdida de masa ósea o enfermedades óseas. (AU)

MicroRNAs (miRNAs) are endogenous small noncoding RNA molecules (of approximately 15­25 nucleotides), which regulate the expression of genes controlling numerous biological functions, through the inhibition or degradation of the target messenger RNA. Bone homeostasis is maintained by a balance between osteoblastic bone formation and osteoclastic bone resorption. The overexpression or inhibition of specific miRNAs affects cell proliferation, differentiation and activity of osteoblast, osteocytes and osteoclast. This action is done by modulating the expression of different transcription factors and signaling molecules of the most relevant pathways of osteoblastogenesis or osteoclastogenesis. This effect is able to modify the balance between bone formation and resorption, determining changes in bone homeostasis. The present review is an overview of a series of miRNAs involved in bone homeostasis. An in depth knowledge of the mechanisms by which miRNAs act on bone may reveal potential uses in the future as new bone biomarkers or therapeutic agents for treating metabolic bone disorders, bone loss and bone diseases. (AU)

Reference Intervals for Bone Turnover Markers in Korean Healthy Women

BACKGROUND: Adequate suppression of bone turnover rate is important to decrease fracture risk without mineralization defect due to oversuppression. This study was performed to determine reference intervals (RIs) for 2 bone turnover markers, serum C-terminal telopeptide of type I collagen (CTX) and osteocalcin, in Korean women.METHODS: A total of 461 Korean women (287 premenopausal and 174 postmenopausal) without any disease or drug history affecting bone metabolism was included. Serum CTX and osteocalcin were measured after overnight fasting. Bone mineral density (BMD) was measured at the 1st to 4th lumbar vertebra using dual energy X-ray absorptiometry. Subjects with normal spinal BMD (T-score ≥−1.0) were included in this study.RESULTS: After stable concentrations were maintained, both CTX and osteocalcin were abruptly increased in 50 to 59 years, and then decreased with increasing age. Median levels and interquartile range of serum CTX and osteocalcin in all subjects were 0.322 (0.212–0.461) ng/mL and 15.68 (11.38–19.91) ng/mL. RIs for serum CTX and osteocalcin in all subjects were 0.115 to 0.861 ng/mL and 6.46 to 36.76 ng/mL. Those were higher in postmenopausal women (CTX, 0.124–1.020 ng/mL, osteocalcin, 5.42–41.57 ng/mL) than in premenopausal women (CTX, 0.101–0.632 ng/mL, osteocalcin, 6.73–24.27 ng/mL). If we use target reference levels as lower half of premenopausal 30 to 45 years in patients with antiresorptive drugs, those were 0.101 to 0.251 ng/mL and 6.40 to 13.36 ng/mL.CONCLUSIONS: We established RIs for serum CTX and osteocalcin in healthy Korean women with normal lumbar spine BMD. Premenopausal RIs for serum CTX and osteocalcin would be useful to monitor patients with low bone mass using osteoporosis drugs.