Uso de microvibración e inhibidores de la catepsina K en tratamientos de regeneración ósea dental / Use of micro-vibration and cathepsin K inhibitors in dental bone regeneration treatments

Introducción: el hueso está en remodelación constante para mantener la estructura del esqueleto, tener un ciclo de resorción por los osteoclastos y formación de hueso nuevo a cargo de los osteoblastos; el hueso también es susceptible a enfermedades sistémicas, traumas, edad y trastornos genéticos que afectarán el remodelado óseo, produciendo una pérdida masiva de masa ósea regulado por hormonas, citocinas, enzimas, etcétera. El objetivo es realizar una revisión sistemática de artículos que muestren cambio o alteración al utilizar tratamientos con microvibraciones y farmacológicos sobre la catepsina K en el hueso alveolar. Material y métodos: para realizar una comparación entre la efectividad del tratamiento a base de microvibraciones y con inhibidores de la catepsina K, se realizó una revisión sistemática en nueve bases de datos (Wiley Online Library, PubMed, Google Academic, Scopus, ScienceDirect, SciELO, Medline, EBSCO y Springer Link). La población de estudio fueron ratas y ratones. Resultados: en este estudio se incluyeron 20 artículos cuya investigación se realizó en estudios clínicos. En los resultados podemos observar cómo todos los tratamientos de alguna forma mejoran el proceso de remodelado óseo. Es difícil comparar cuál de los tratamientos dentro de cada grupo es mejor que otro, debido a que los resultados expresados son cualitativos. Conclusión: acorde a los resultados expresados se opta por realizar un tratamiento con microvibraciones debido a que el uso de inhibidores de la catepsina K aún no se encuentra completamente desarrollado y no se comprenden sus consecuencias debido a su manera sistémica de actuar (AU)

Introduction: the bone is in constant remodeling to maintain the skeletal structure, having a cycle of resorption by osteoclasts and formation of new bone by osteoblasts, the bone is also susceptible to systemic diseases, trauma, age and genetic disorders that affect bone remodeling, producing a massive loss of bone mass regulated by hormones, cytokines, enzymes, etcetera. The objective is to perform a systematic review of articles that show a change or alteration when using micro-vibration and pharmacological treatments on cathepsin K in the alveolar bone. Material and methods: in order to make a comparison between the effectiveness of micro-vibration and cathepsin K inhibitor treatments, a systemic review was carried out in nine databases (Wiley Online Library, PubMed, Google Academic, Scopus, ScienceDirect, SciELO, Medline, EBSCO and Springer Link). The study population was rats and mice. Results: this study included 20 articles whose research was carried out in clinical studies. In the results we can see how all the treatments in some way improve the bone remodeling process, it is difficult to compare which treatment within each group is better than the other, because the results expressed are qualitative. Conclusion: according to the results expressed, it is decided that it is better to perform a treatment with micro vibrations because the use of cathepsin K inhibitors are not yet fully developed and their consequences are not understood due to their systemic way of acting (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)

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.

Analysis of Estrogen Effects on Eruption of Rat Molars / Análisis de los Efectos del Estrógeno en la Erupción de Molares de Rata

ABSTRACT: Tooth eruption requires resorption of the alveolar bone interposed between the tooth germ and the oral mucosa (coronal bone). The cells responsible for bone resorption are the osteoclasts and their activity can be reduced or inactivated by estrogen hormone. We aimed to investigate the effects of estrogen on the process of tooth eruption in rats. Thirty-three Wistar rats, aged two-to-17-days, were divided into control, sham and estrogen-treated groups. After daily injections with estrogen, the animals were euthanized and the jaws removed and processed for histological analysis. We performed clinical examination, morphological analysis, quantification of the number of osteoclasts on the surface of the coronal bone and immunohistochemical analysis of estrogen receptor type alpha (ERα). Estrogen therapy was effective, which could be confirmed by the higher estrogen plasma levels on treated animals. However, it had no effect on tooth development or tooth eruption. Progressive bone resorption was observed and the number of osteoclasts on coronal bone was not affected on hormoneinjected animals, allowing tooth to erupt at the same time observed in untreated animals. Immunohistochemistry for ERα confirmed the presence of this type of receptor in osteoclasts, osteoblasts and osteocytes. Taken together, our results showed that estrogen stimulation was not sufficient to decrease the number of osteoclasts on the coronal bone, supporting the idea that, although estrogen may have a protective activity on bone resorption, this may not apply to the alveolar bone that is meant to be resorbed during eruptive process.

RESUMEN: La erupción dental requiere la resorción del hueso alveolar interpuesto entre el germen dental y la mucosa oral (hueso coronal). Las células responsables de la resorción ósea son los osteoclastos y su actividad puede reducirse o inactivarse por la hormona del estrógeno. Objetivos: apuntamos a investigar los efectos del estrógeno en el proceso de la erupción dental en ratas. Treinta y tres ratas Wistar, de dos a 17 días de edad, se dividieron en grupos de control, Sham y se trataron con estrógenos. Los animales fueron eutanizados después del tratamento con estrógeno y se procesaron las mandíbulas para el análisis histológico. Se realizó el examen clínico, el análisis morfológico, la cuantificación del número de osteoclastos en la superficie del hueso coronal y el análisis inmunohistoquímico del tipo de receptor de estrógeno alfa (ERα). La terapia de estrógeno fue eficaz, lo que podría ser confirmado por los niveles plasmáticos más altos de estrógeno en los animales tratados. Sin embargo, no se observó ningún efecto sobre el desarrollo de los dientes o la erupción dental. Se observó una resorción ósea progresiva y el número de osteoclastos en el hueso coronal no se vio afectado en los animales inyectados con hormonas, permitiendo que el diente erupcionó durante el mismo período de tiempo observado en animales no tratados. La inmunohistoquímica para el ERα confirmó la presencia de este tipo de receptor en los osteoclastos, osteoblastos y osteocitos. Nuestros resultados mostraron que la estimulación del estrógeno no fue suficiente para reducir el número de osteoclastos en el hueso coronal confirmando que, si bien el estrógeno puede tener una actividad protectora en la resorción ósea, esto puede no se aplica al hueso alveolar que está destinado a ser rerecurrido durante el proceso eruptivo.

On the genetic determinants of hypovitaminosis D

Hypovitaminosis D, defined by low serum levels of 25(OH)D, is a recognized worldwide public health problem. The most accepted definition considers that deficiency occurs with serum levels fall below 12 ng/ml of 25(OH)D. Long term vitamin D deficiency results in decreased bone mineralization, secondary hyperparathyroidism, increased cortical bone loss (pathogenesis of osteoporosis and hip fractures), differentiation and division of various cell types, muscle strength, diabetes type 2, blood pressure, etc. Twin- and family-based studies indicate that genetic factors influence serum 25(OH)D levels. Genetic studies have shown single-nucleotide polymorphisms (SNPs) are linked to low serum 25(OH)D concentrations through changes in the activity of the enzymes of the 1α,25(OH)2D metabolic pathway. Carriers of high genetic risk scores would need a h igher amount of vitamin D supplementation to achieve adequate serum 25(OH)D concentrations. Clinicians would not need to indicate studies to identify patients with vitamin D insufficiency of genetic origin. They should instruct their patients on their own care, to control the intake of vitamin D and the serum 25(OH)D levels until the latter are adequate. Overall, the literature reveals that the consequences of hypovitaminosis D on bone health are observed in old and infrequently in young subjects. A probable explanation for the latter is: if the rate of bone remodeling allows it, bone tissue has endogenous (genetics, hormones) and exogenous determinants (diet, physical activity) that may compensate the variables of bone health. The consequences of vitamin D deficit on bone health, has not been completely uncovered.

La hipovitaminosis D, definida por bajos niveles séricos de 25(OH)D (<12 ng/ml), es un reconocido problema de salud pública mundial. La deficiencia de vitamina D a largo plazo resulta en una disminución de la mi neralización ósea, hiperparatiroidismo secundario, pérdida de hueso cortical (patogénesis de la osteoporosis y fracturas de cadera), diferenciación y división de varios tipos de células, fuerza muscular, diabetes tipo 2, pres ión arterial, etc. Estudios genéticos han demostrado que algunos "polimorfismos de un solo nucleótido" (SNP) están relacionados con bajas concentraciones séricas de 25(OH)D a través de reducción en la actividad de las enzimas implicadas en la síntesis de 1α,25(OH)2D. Los médicos no necesitan indicar un estudio genético para identificar a la insuficiencia de vitamina D de causa genética. Bastará con instruir a los pacientes sobre su propio cuidado y controlar la ingesta de vitamina D y los niveles séricos de 25(OH)D hasta que estos últimos sean adecuados. En general, la literatura revela que las consecuencias de la hipovitaminosis D sobre la salud ósea se observan en las personas añosas y con poca frecuencia en sujetos jóvenes. Una explicación probable para esta situación es: si la tasa de remodelación ósea lo permite, el tejido óseo tiene factores endógenos (genéticos, hormonales) y exógenos (dieta, actividad física) que pueden compensar las variables de la salud ósea. Las consecuencias del déficit de vitamina D sobre la salud ósea aún no se conocen completamente.

Efeitos do campo eletromagnético pulsátil (CEMP) na doença peridontal induzida em ratas ovariectomizadas: análises histomorfométrica, imunoistoquímica e microtomografia computadorizada MicroCT / Effects of the pulsed electromagnetic field (PEMF) on induced peridontal disease in ovariectomized rats: histomorphometric, immunohistochemical and computerized microtomography (microCT) analyzes

A doença periodontal (DP) resulta de uma infecção polimicrobiana complexa, levando à destruição dos tecidos periodontais, como consequência da perturbação da homeostase entre a microbiota subgengival e os mecanismos de defesas do hospedeiro em indivíduos suscetíveis. A deficiência estrogênica (DE) é a causa mais comum de osteoporose. A osteoporose é definida como uma doença crônica, multifatorial, provenientes de uma desordem esquelética que promove fragilidade óssea pela redução de sua massa. Vários estudos experimentais têm demonstrado que a estimulação com Campo Eletromagnético Pulsátil (CEMP) pode promover a osteogênese e potencialmente aumentar a mineralização óssea e também, reduzir a inflamação aguda e crônica em tecidos moles e duros. Frente a isso, este estudo teve como objetivo, avaliar por meio da histomorfometria, imunoistoquímica e microtomografia computadorizada (MicroCT), a influência do CEMP na DP induzida em ratas ovariectomizadas e Sham. Para a pesquisa, foram utilizadas 60 ratas adultas (Rattus norvegicus, variação albinus, Wistar) com 3 meses de idade, pesando em torno de 300 gramas e em todos os animais a DP foi induzida. As ratas foram randomizadas em dois grupos experimentais, contendo 30 animais cada, classificados em ovariectomia simulada (Sham) e Ovariectomizada (Ovz), respectivamente. Os grupos foram divididos em dois subgrupos com 15 animais cada: Sham-S (n=15): não receberam terapia com CEMP e este foi nosso grupo controle. Sham-CEMP (n=15): receberam terapia com CEMP. Ovz­O (n=15): não receberam terapia com CEMP. Ovz­CEMP (n=15): receberam terapia com CEMP. As análises histomorfométrica, e MicroCT foram realizadas e os dados obtidos foram submetidos à análise de variância (ANOVA) e teste de Tukey, ambos com nível de significância convencional de 95% e não apresentaram nenhuma diferença estatisticamente significante. Na análise semiquantitativa para os biomarcadores RANKL e OPG, o subgrupo Ovz-O apresentou maior expressão do biomarcador RANKL e menor expressão do biomarcador OPG em relação aos outros subgrupos. Na análise quantitativa da expressão do biomarcador TRAP não foi encontrado nenhuma diferença estatisticamente significante. Apesar de não encontramos evidências significativas da terapia com CEMP na DP em ratas ovariectomizadas, o presente estudo nos sugere que o CEMP pode apresentar um efeito benéfico na remodelação óssea(AU)

Periodontal disease (PD) results from a complex polymicrobial infection, leading to the destruction of periodontal tissues as a consequence of the disturbance of homeostasis between the subgingival microbiota and the host defense mechanisms in susceptible individuals. Estrogen deficiency is the most common cause of osteoporosis. Osteoporosis is defined as a chronic, multifactorial disease from a skeletal disorder that promotes bone fragility by reducing its mass. Several experimental studies have shown that Pulsed Electromagnetic Field (PEMF) stimulation can promote osteogenesis and potentially increase bone mineralization and also reduce acute and chronic inflammation in soft and hard tissues. The aim of this study was to evaluate, through histomorphometry, immunohistochemistry and computerized microtomography (MicroCT), the influence of PEMF on PD induced in ovariectomized and Sham rats. For the research, 60 adult rats (Rattus norvegicus, albinus variant, Wistar) at 3 months of age, weighing around 300 grams were used and in all animals PD was induced. The rats were randomized into two experimental groups, containing 30 animals each, classified as simulated ovariectomy (Sham) and Ovariectomized (Ovz), respectively. The groups were divided into two subgroups with 15 animals each: Sham-S (n = 15): did not receive PEMF therapy and this was our control group. Sham-PEMF (n = 15): received PEMF therapy. Ovz-O (n = 15): did not receive PEMF therapy. Ovz-PEMF (n = 15): received PEMF therapy. The histomorphometric and MicroCT analyzes were performed and the data were submitted to analysis of variance (ANOVA) and Tukey's test, both with a 95% significance level and did not present any statistically significant difference. In the semiquantitative analysis for RANKL and OPG biomarkers, the Ovz-O subgroup showed higher expression of the RANKL biomarker and lower expression of the OPG biomarker in relation to the other subgroups. In the quantitative analysis of TRAP biomarker expression no statistically significant difference was found. Although we did not find significant evidence of PEMF therapy in PD in ovariectomized rats, the present study suggests that PEMF may have a beneficial effect on bone remodeling(AU)

Updating the role of matrix metalloproteinases in mineralized tissue and related diseases

Abstract Bone development and healing processes involve a complex cascade of biological events requiring well-orchestrated synergism with bone cells, growth factors, and other trophic signaling molecules and cellular structures. Beyond health processes, MMPs play several key roles in the installation of heart and blood vessel related diseases and cancer, ranging from accelerating metastatic cells to ectopic vascular mineralization by smooth muscle cells in complementary manner. The tissue inhibitors of MMPs (TIMPs) have an important role in controlling proteolysis. Paired with the post-transcriptional efficiency of specific miRNAs, they modulate MMP performance. If druggable, these molecules are suggested to be a platform for development of "smart" medications and further clinical trials. Thus, considering the pleiotropic effect of MMPs on mammals, the purpose of this review is to update the role of those multifaceted proteases in mineralized tissues in health, such as bone, and pathophysiological disorders, such as ectopic vascular calcification and cancer.

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)

Preservation of dental sockets filled with composite bovine bone. A single-blind randomized clinical trial

Abstract The purpose of this study was to evaluate the preservation of alveolar dimensions in human fresh extraction sockets filled with a composite bovine bone graft by means of design of single-blind randomized clinical trial. Forty participants had monoradicular teeth extracted (one teeth in each participant), and after were randomly divided into 2 groups: individuals whose fresh sockets were filled with the composite heterologous bone graft (Biomaterial Group), or with blood clot (Control Group). After extraction, the fresh sockets were measured at their greatest mesiodistal (MD) and bucco-lingual/palatal (BL/P) distance. Primary closure of the soft tissue was performed with a fibro-mucosal plug. After 120 post-operative days, the re-entry procedure was performed and the largest MD and BL/P measurements were again obtained to calculate the remodeling of the alveolar bone measured in percentage. In the biomaterial group, a percentage reduction of 1.62% and 3.29% in the MD and BL/P dimensions was observed 120 days after the extractions, whereas a reduction of 4.97% and 7.18% in the MD and BL/P dimensions occurred in the control group. There was a statistically significant difference (p<0.05) between the two groups for the bucco-palatal and mesiodistal measurements in the maxilla. In view of the results obtained, it can be concluded that composite bovine bone graft limited but did not impede alveolar bone remodeling.

Resumo O objetivo deste estudo foi avaliar em humanos a manutenção do volume em alvéolos frescos preenchidos por osso integral de origem bovina por meio de um estudo clínico randomizado com monocegamento. Quarenta dentes uni radiculares foram extraídos em 40 pacientes (um dente em cada participante), e apos estes pacientes foram divididos aleatoriamente em 2 grupos: indivíduos que tiveram o alvéolo fresco preenchido por osso integral de origem bovina (Grupo Biomaterial) ou por coagulo sanguíneo (Grupo Controle). Apos a exodontia os alvéolos foram medidos em suas maiores distancias mesio-distal (MD) e vestíbulo lingual/palatina (VL/P) por meio de compasso de ponta seca. O fechamento primário dos alvéolos foi realizado com um tampão fibromucoso. Apos 120 dias pós-operatórios durante o procedimento de reabertura foram obtidas novamente as maiores medidas MD e VL/P para calcular em porcentagem o nível de remodelação do osso alveolar. No grupo biomaterial observou-se uma redução em porcentagem de 1,62% e 3,29% nas medidas MD e VL/P 120 dias apos as extrações, enquanto no grupo controle houve uma redução de 4,97% e 7,18% nas medidas MD e VL/P no mesmo período. Houve diferença estatisticamente significante (p<0,05) entre os dois grupos para as medidas vestíbulo/palatina e mesiodistal na maxila. Diante dos resultados obtidos conclui-se que o osso integral de origem bovina limitou, mas não impediu a remodelação óssea alveolar.

Potencial of different hydroxyapatites as biomaterials in the bone remodeling

Abstract Purpose: To analyze the therapeutic potentials of different hydroxyapatites used for the correction of bone defects in rats. Methods: Forty rats, male, albino wistar, were distributed in 4 groups. They were submitted to a 3.5 mm defect in tibia. They received low purity hydroxyapatite, Strontium hydroxyapatite and hydroxyapatite doped with gallium, having a seven day evaluation time. Histopathology slides were stained with hematoxylin-eosin, for morphological evaluation. Were analyzed inflammatory processes, necrosis, presence of osteoclasts and osteoblasts, presence of the material, presence of white cells, neovascularization and bone neoformation. Results: It was observed that the groups HAPSr and HAPGa, presented better results of trabecular bone, hyaline cartilage and bone marrow more organized. Conclusion: There was improvement in the repair of the bone defect produced, showing that these hydroxyapatites are effective osteoinductive, osteoconductive, osteintegrant agents and have biocompatibility, and may be indicated for use in defect repairs.

Histomorphometric reference data of transiliac bone biopsy in children from 8 to 17 years old / Datos histomorfométricos de referencia de la biopsia ósea en niños de 8 a 17 años

Abstract: Background: Histomorphometric analysis of bone samples is a key tool for studying bone metabolism; however, only a few pediatric reference data exist. The aim of the present study is to report more reference data and to investigate if histomorphometric differences exist between age and gender. Methods: We obtained 19 transiliac bone samples previously marked with tetracycline, from children between 8 and 17 years (13 were male), with normal blood test results and urine biochemical bone markers. We evaluated bone histomorphometric parameters using a digitalizing table with osteomeasure to obtain normative data of means and standard deviations, as well as median and range. Due to the small sample, a Monte Carlo simulation was applied. Structural, static, dynamic, and resorptic histomorphometric parameters were evaluated by age and gender following the American Society for Bone and Mineral Research recommendations. Results: Bone volume (in the older children) and mineral apposition rate (in the younger children), the eroded surface (in boys), and the new bone wall thickness (in girls) were significantly increased. On the trabecular area of mineralization front, the modeling and the remodeling bone formation were similar (16 and 18%). The rest of the histomorphometric bone parameters by age and gender showed no significant difference. Conclusion: In healthy children, these bone histomorphometric findings, with these techniques and for this ages could be used as reference values.

Resumen: Introducción: El análisis histomorfométrico del tejido óseo para el estudio de las enfermedades metabólicas óseas, cuando se correlacionan los hallazgos clínicos, sigue siendo la herramienta con mayor sensibilidad y especificidad para la mayoría de los diagnósticos. En los niños existen pocos reportes histomorfométricos del tejido óseo metabólico normal, por lo que nuestro propósito es reportar más datos de referencia e investigar si hay diferencias histomorfométricas entre edades y sexos. Métodos: Estudio realizado en 19 niños de 8 a 17 años (13 masculinos) sin anomalías clínicas ni bioquímicas evidentes. Se tomaron muestras de tejido óseo transilíaco marcadas con tetraciclina. Se obtuvieron medias, desviaciones y rangos histomorfométricos totales, y correlación por edad y sexo, siguiendo las recomendaciones para la histomorfometría de la American Society for Bone and Mineral Research. Se realizó una simulación Montecarlo. Resultados: El volumen óseo (en niños mayores), la velocidad de agregación del mineral (en niños menores), la erosión trabecular periférica (en niños) y el grosor de la pared ósea nueva (en niñas) exhibieron aumentos significativos. En el área trabecular del frente de mineralización, el modelado y el remodelado de la formación ósea fueron similares (16 y 18%). El resto de los parámetros histomorfométricos óseos no mostraron diferencias significativas. Conclusiones: Estos hallazgos histomorfométricos del tejido óseo de niños normales con estas técnicas y para estas edades pueden ser utilizados como valores de referencia.

Oral implant osseointegration model in C57Bl/6 mice: microtomographic, histological, histomorphometric and molecular characterization

Abstract Despite the successful clinical application of titanium (Ti) as a biomaterial, the exact cellular and molecular mechanisms responsible for Ti osseointegration remains unclear, especially because of the limited methodological tools available in this field. Objective: In this study, we present a microscopic and molecular characterization of an oral implant osseointegration model using C57Bl/6 mice. Material and Methods: Forty-eight male wild-type mice received a Ti implant on the edentulous alveolar crest and the peri-implant sites were evaluated through microscopic (μCT, histological and birefringence) and molecular (RealTimePCRarray) analysis in different points in time after surgery (3, 7, 14 and 21 days). Results: The early stages of osseointegration were marked by an increased expression of growth factors and MSC markers. Subsequently, a provisional granulation tissue was formed, with high expression of VEGFb and earlier osteogenic markers (BMPs, ALP and Runx2). The immune/inflammatory phase was evidenced by an increased density of inflammatory cells, and high expression of cytokines (TNF, IL6, IL1) chemokines (CXCL3, CCL2, CCL5 and CXC3CL1) and chemokine receptors (CCR2 and CCR5). Also, iNOS expression remained low, while ARG1 was upregulated, indicating predominance of a M2-type response. At later points in time, the bone matrix density and volume were increased, in agreement with a high expression of Col1a1 and Col21a2. The remodelling process was marked by peaks of MMPs, RANKL and OPG expression at 14 days, and an increased density of osteoclasts. At 21 days, intimate Ti/bone contact was observed, with expression of final osteoblast differentiation markers (PHEX, SOST), as well as red spectrum collagen fibers. Conclusions: This study demonstrated a unique molecular view of oral osseointegration kinetics in C57Bl/6 mice, evidencing potential elements responsible for orchestrating cell migration, proliferation, ECM deposition and maturation, angiogenesis, bone formation and remodeling at the bone-implant interface in parallel with a novel microscopic analysis.

Alveolar bone healing in rats: micro-CT, immunohistochemical and molecular analysis

Abstract Alveolar bone healing after upper incisor extraction in rats is a classical model of preclinical studies. The underlying morphometric, cellular and molecular mechanism, however, remains imprecise in a unique study. Objectives The aim of this study was therefore to characterize the alveolar bone healing after upper incisor extraction in rats by micro computed tomographic (Micro-CT), immunohistochemical and real-time polymerase chain reaction (RT-PCR) analysis. Material and Methods Thirty animals (Rattus norvegicus, Albinus Wistar) were divided into three groups after upper incisors extraction at 7, 14, and 28 days. Micro-CT was evaluated based on the morphometric parameters. Subsequently, the histological analyses and immunostaining of osteoprotegerin (OPG), receptor activator of nuclear kappa B ligand (RANKL) and tartrate resistant acid phosphate (TRAP) was performed. In addition, RT-PCR analyses of OPG, RANKL, the runt-related transcription factor 2 (RUNX2), osteocalcin (OC), osteopontin (OPN), osterix (OST) and receptor activator of nuclear kappa B (RANK) were performed to determine the expression of these proteins in the alveolar bone healing. Results Micro-CT: The morphometric parameters of bone volume and trabecular thickness progressively increased over time. Consequently, a gradual decrease in trabecular separation, trabecular space and total bone porosity was observed. Immunohistochemical: There were no differences statistically significant between the positive labeling for OPG, RANKL and TRAP in the different periods. RT-PCR: At 28 days, there was a significant increase in OPG expression, while RANKL expression and the RANKL/OPG ratio both decreased over time. Conclusion Micro-CT showed the newly formed bone had favorable morphometric characteristics of quality and quantity. Beyond the RUNX2, OC, OPN, OST, and RANK proteins expressed in the alveolar bone healing, OPG and RANKL activity showed to be essential for activation of basic multicellular units during the alveolar bone healing.

Bone turnover after bariatric surgery

ABSTRACT Objective The aim of the present study was to evaluate parameters of bone and mineral metabolism after bariatric surgery. Subjects and methods This sectional study included data from medical records from 61 bariatric surgery (BS) patients (minimum period of 6 months after the procedure) and from 30 class II and III obese patients as a control group (Cont), consisting of daily dietary intake of macronutrients, calcium and sodium, serum 25(OH)D and parathyroid hormone (PTH) and other biochemical serum and urinary parameters. Bone alkaline phosphatase (BAP), leptin, fibroblast growth factor-23 (FGF-23) and deoxypyridinoline (DPYD) were determined from available banked serum and urinary samples. Results Mean body mass index (BMI), median energy, carbohydrate, protein and sodium chloride consumption were significantly lower in the BS versus Cont, but calcium and lipids were not. No significant differences were found in ionized calcium, 25(OH)D, PTH and fibroblast growth factor 23 (FGF-23) between groups. Mean serum BAP was significantly higher for BS versus Cont and had a positive correlation with time after the surgical procedure. Mean serum leptin was significantly lower and median urinary DPYD higher in BS versus Cont. Conclusion The present study showed an increase in bone markers of both bone formation and resorption among bariatric patients up to more than 7 years after the surgical procedure, suggesting that an increased bone turnover persists even at a very long-term follow-up in such patients.

Marcadores de formación y resorción ósea y su utilidad para determinar el final del periodo de aposición ósea / Bone formation and resorption markers to evaluate the end of bone apposition

El pico de masa ósea (PMO) se alcanza entre los 20 y 35 años, pero la aposición ósea continúa hasta alcanzar el pico de fortaleza ósea (PFO). Se crea así una ventana entre ambos picos que podría ser evaluada mediante marcadores bioquímicos de recambio óseo, ya que durante dicho período la densidad mineral permanece constante. El objetivo fue determinar el final de la aposición ósea mediante marcadores bioquímicos óseos. Se evaluaron por décadas entre 20 y 49 años de edad 139 sujetos sanos de ambos sexos (69 hombres y 70 mujeres), determinando fosfatasa alcalina ósea (FAO), osteocalcina (OC), propéptido amino terminal del colágeno tipo 1 (P1NP) y telopéptido C-terminal del colágeno tipo 1 (CTX). Los marcadores correlacionan negativamente con la edad (OC: r= -0,3; p<0,01; P1NP: r= -0,4; p< 0,01 y CTX: r= -0,4; p<0,01), exceptuando FAO. En hombres de 20-29 años, P1NP y el CTX fueron significativamente mayores vs. 30-39 años (p<0,05 y p<0,001, respectivamente), y entre 30-39 años vs. de 40-49 años en P1NP y CTX (p<0,05; p<0,001, respectivamente). En mujeres de 20-29 años, P1NP y CTX fueron significativamente mayores vs. 30-39 años (p<0,0001 y p<0,01, respectivamente). Conclusión: los marcadores de remodelado óseo más sensibles y específicos permitirían determinar bioquímicamente el fin de la aposición ósea que se produce entre el PMO y el PFO. Si bien es necesario ampliar el número de sujetos evaluados, los datos que surgen de la presente investigación sentarían las bases para futuros estudios epidemiológicos referidos al fin de la aposición ósea. (AU)

Peak bone mass is achieved between 20-35 years; however bone apposition continues to reach an optimal skeleton strength. The window between peak bone mass and peak bone apposition may be evaluated by biochemical bone turnover markers. The objective of this study was to determine the end of bone apposition through biochemical bone markers in both sexes. A total of 139 subjects (69 men and 70 women) were divided by decades between 20 and 49 years of age. Bone alkaline phosphatase (BAL), osteocalcin (OC), type I collagen propeptide (P1NP) and type I collagen C-terminal telopeptide (CTX) were evaluated. Except BAL, the other bone markers negatively correlated with the age [OC (r= -0.3; p<0.01); P1NP (r= -0.4; p<0.01) and CTX (r= -0.4; p<0.01)]. Regarding men aged 20 to 29 years, P1NP and CTX were significantly higher vs. 30-39 years (p<0.05 y p<0.001, respectively) and. vs. 40-49 years (p<0.05; p<0.001, respectively). In women, the results were similar. Regarding 20-29 years, P1NP and CTX were higher vs. 30-39 years (p<0.001 y p<0.01, respectively). Bone remodeling rate decreases after the third decade, suggesting the end of the apposition period of peak bone mass. Conclusion: The most specific and sensitive bone markers would biochemically determine the end of bone apposition that extends between the peak of bone mass and the peak of bone strength. Although it is necessary to increase the number of subjects evaluated, the data that emerge from the present study would establish the bases for future epidemiological studies referring to the end of bone apposition. (AU)

Bone turnover markers in sheep and goat: A review of the scientific literature

ABSTRACT Bone turnover markers (BTMs) are product of bone cell activity and are generally divided in bone formation and bone resorption markers. The purpose of this review was to structure the available information on the use of BTMs in studies on small ruminants, especially for monitoring their variations related to diet, exercise, gestation and metabolic lactation state, circadian and seasonal variations, and also during skeletal growth. Pre-clinical and translational studies using BTMs with sheep and goats as animal models in orthopaedic research studies to help in the evaluation of the fracture healing process and osteoporosis research are also described in this review. The available information from the reviewed studies was systematically organized in order to highlight the most promising BTMs in small ruminant research, as well as provide a wide view of the use of sheep and goat as animal models in orthopaedic research, type of markers and commercial assay kits with cross-reactivity in sheep and goat, method of sample and storage of serum and urine for bone turnover markers determination and the usefulness and limitations of bone turnover markers in the different studies, therefore an effective tool for researchers that seek answers to different questions while using BTMs in small ruminants.

Marcadores de remodelamiento óseo en pacientes con enfermedad periodontal / Bone remodeling biomarkers in patients with periodontal disease

La Fosfatasa Alcalina Ósea (FAO) es una isoforma de la Fosfatasa Alcalina (FAL). La medición de su actividad en saliva es una medida indirecta del proceso de formación ósea, más sensible y específica que la FAL. La catepsina K es la principal colagenasa del proceso de resorción ósea, es capaz de degradar al colágeno tipo I en varios sitios dando lugar a pequeños péptidos N- y C- terminales. El telopéptido C-terminal (CTx) es el marcador más sensible y específico en el aumento de la resorción ósea, ya que el colágeno tipo I constituye más del 90 por ciento de la matriz orgánica del hueso...

Bone healing after biodegradable mini-plate fixation

ABSTRACT PURPOSE: To compare bone healing in mandibular vertical body osteotomies (MVBO) after fixation with a resorbable 2.0mm-profile fixation system in the first and third postoperative months in rabbits. METHODS: Twenty hemimandibles of ten rabbits were divided into two groups according to duration of resorbable fixation-one or three months. The MVBOs were performed and one four-hole, resorbable, 2.0mm mini-plate fixation system was used on each side. The computed tomography (CT) scans, scanning electron microscopy (SEM), and histomorphometric outcomes of groups I and II were compared. RESULTS: Significant differences were found between the one- and three- month assessments in terms of newly formed bone ratio values (p<0.05). There was more new bone formation at the third month on both the CT and histomorphometric examinations. A better adaptation of the bone tissues to the resorbable mini-plate and screws was observed on SEM at three months. CONCLUSION: The resorbable mini-plates provided a fixation stable enough to allow immediate oral alimentation and callus formation in both groups.

The role of daily physical activity and nutritional status on bone turnover in cystic fibrosis: a cross-sectional study

ABSTRACT Background Nutritional status and daily physical activity (PA) may be an excellent tool for the maintenance of bone health in patients with cystic fibrosis (CF). Objective To evaluate the relationship between nutritional status, daily physical activity and bone turnover in cystic fibrosis patients. Method A cross-sectional study of adolescent and adult patients diagnosed with clinically stable cystic fibrosis was conducted. Total body, femoral neck, and lumbar spine bone mineral density (BMD) were determined by dual energy X-ray absorptiometry and bone metabolism markers ALP, P1NP, PICP, and ß-CrossLaps. PA monitoring was assessed for 5 consecutive days using a portable device. Exercise capacity was also determined. Serum 25-hydroxyvitamin D and vitamin K were also determined in all participants. Results Fifty patients (median age: 24.4 years; range: 16-46) were included. BMI had positive correlation with all BMD parameters, with Spearman’s coefficients ranging from 0.31 to 0.47. Total hip bone mineral density and femoral neck BMD had positive correlation with the daily time spent on moderate PA (>4.8 metabolic equivalent-minutes/day; r=0.74, p<0.001 and r=0.72 p<0.001 respectively), daily time spent on vigorous PA (>7.2 metabolic equivalent-minutes/day; r=0.45 p<0.001), body mass index (r=0.44, p=0.001), and muscle mass in limbs (r=0.41, p=0.004). Levels of carboxy-terminal propeptide of type 1 collagen were positively associated with the daily time spent on moderate (r=0.33 p=0.023) and vigorous PA (r=0.53, p<0.001). Conclusions BMI and the daily time spent on moderate PA were found to be correlated with femoral neck BMD in CF patients. The association between daily PA and biochemical markers of bone formation suggests that the level of daily PA may be linked to bone health in this patient group. Further research is needed to confirm these findings.