Cone-Beam Computed Tomography to evaluate changes in trabecular lower jawbone microstructure caused by bone loss and antiresorptive treatment / CBCT para evaluar cambios en la microarquitectura ósea de la mandíbula por pérdida ósea y tratamiento antirresortivo

ABSTRACT For decades, conventional histomorphometry has been the gold standard for analyzing trabecular bone microarchitecture. In recent years, micro-computed tomography (μCT) devices have been validated and are now considered the gold standard for quantifying bone microstructure Aim The aim of this preliminary report is to evaluate the usefulness of CBCT to assess trabecular mandible microstructural properties in normal ewes and to compare the quantitative changes associated with ovariectomy and antiresorptive treatment Material and Method Twelve adult Corriedale ewes (n=4/group) aged 3-4 years were divided into 3 groups and studied for 28 months. Eight ewes were ovariectomized (OVX) and divided into OVX and OVX+ZOL groups (n=4/group) which were treated as follows, by jugular injection: OVX received saline solution and OVX+ZOL received zoledronate (Zol) (Gador SA, CABA, Argentina) (4 mg/month). Another four ewes were subjected to sham surgery (SHAM group) and received saline solution Results Densitometry showed that jaw mineral content (BMC) and density (BMD) were significantly lower in OVX than in SHAM and OVX+ZOL ewes; no difference was observed between OVX+ ZOL and SHAM groups. CBCT analysis showed that bone volume (BV/TV%); trabecular thickness (TbTh); connectivity density (CD) and anisotropy degree (AD) were significantly lower, and trabecular spacing (TbSp), significantly higher in OVX than in SHAM ewes. AD was significantly higher and TbSp significantly lower in OVX+ZOL than in OVX groups. BV/TV%, TbTh and CD showed a clear tendency to being higher in OVX+ZOL than in OVX groups. No statistical difference was observed between OVX+ZOL and SHAM ewes. CBCT in a nondestructive, fast, very precise procedure for measuring bone morphometric indices without biopsies, which are not indicated for morphometric evaluation in osteoporosis Conclusions The current study demonstrated the potential of the high-resolution CBCT imaging to assess in vivo quantitative bone morphometry and bone quality of lower jaw cancellous bone under normal conditions and to differentiate changes associated with excessive bone loss induced by estrogen withdrawal and antiresorptive intervention.

RESUMEN Objetivo El presente informe preliminar evaluó la utilidad de Tomografía Computada de Haz Cónico (CBCT) para analizar las propiedades microestructurales trabeculares del maxilar inferior de ovejas y comparar los cambios cuantitativos asociados con la ovariectomía y tratamiento antirresortivo. Se estudiaron dieciséis ovejas Corriedale adultas de 3-4 años Materiales y Método Doce ovejas fueron ovariectomizadas (OVX) y divididas en 2 grupos: OVX y OVX+ZOL (n=4/grupo) cuyo tratamiento por inyección endovenosa en la yugular durante 28 meses fue el siguiente: OVX con solución salina y OVX+ZOL con zoledronato (Gador S.A. CABA. Argentina) (Zol) (4 mg/mes); 4 ovejas fueron sometidas a cirugía simulada (grupo SHAM) Resultados La densitometría (Lunar DPX) mostró que el contenido mineral del hueso maxilar (CMO) y la densidad (DMO) fueron significativamente más bajos en OVX que en SHAM y OVX+ZOL; no se observaron diferencias entre los grupos OVX+ZOL y SHAM. El análisis de las imágenes por CBCT (Planmeca Promax 3D Classic) mostró que el volumen óseo (BV/TV%); el espesor trabecular (TbTh); la densidad de conectividad (CD) y el grado de anisotropía (AD) fueron significativamente menores (p<0.05), y el espaciado trabecular (TbSp), significativamente mayor en OVX que en SHAM (p<0.05). AD fue significativamente mayor (p<0.05) y TbSp, significativamente menor en OVX+ZOL que en OVX (p<0.05). BV/TV%, TbTh y CD mostró una clara tendencia a ser mayor en OVX+ZOL que en OVX. No se observaron diferencias estadísticas entre OVX+ZOL y SHAM Conclusiones En base a nuestros resultados consideramos que CBCT presenta suficiente confiabilidad y validez para evaluar in vivo la morfometría cuantitativa y la calidad del hueso esponjoso del maxilar inferior en condiciones normales, así como para diferenciar los cambios en dichos parámetros asociados a la pérdida ósea excesiva por la caída estrogénica e intervención antirresortiva. Aunque se necesitan estudios futuros, nuestros resultados agregarían una herramienta no invasiva adicional para diferenciar la microestructura del hueso trabecular mandibular en estudios preclínicos , sentando las bases para su futura aplicación en la práctica clínica.

MicroARN circulantes y su potencialidad como futuros biomarcadores óseos / Circulating microRNAs and their potential use as future bone biomarkers / MicroRNAs circulantes e a sua potencialidade como futuros biomarcadores ósseos

Resumen El remodelamiento óseo es ejercido por la actividad de osteoblastos y osteoclastos y puede evaluarse por marcadores bioquímicos de formación y resorción ósea. Sin embargo, el nivel de los marcadores óseos está sometido a una enorme cantidad de variables y, además, carece o presenta escaso valor pronóstico. Los microARN (miARN) fueron recientemente estudiados como una alternativa potencial para ser utilizados como nuevos marcadores óseos. Los miARN son pequeñas moléculas de ARN no codificantes (15-25 nucleótidos) que, a través de la inhibición o degradación de ARN mensajeros, modifican una serie de funciones biológicas. Los miARN específicos de hueso ejercen funciones reguladoras sobre factores transcripcionales involucrados en la osteoblastogénesis y osteoclastogénesis, modificando el remodelamiento óseo. La mayoría de los miARN permanecen dentro de la célula, pero algunos son liberados a la circulación donde pueden ser dosados. Los miARN circulantes presentan gran estabilidad en fluidos biológicos, lo que los hace potenciales candidatos a ser utilizados como nuevos biomarcadores óseos. Cambios en el patrón normal de miARN circulantes específicos de hueso reflejarán modificaciones en el metabolismo óseo y señalan el posible inicio o progresión de enfermedades óseas, como la osteoporosis. Si bien es promisorio, el uso en la práctica clínica de los miARN específicos circulantes como nuevos biomarcadores óseos, ello implica primeramente cumplir con una serie de requisitos que permitan estandarizar las condiciones preanalíticas, analíticas y posanalíticas de estas moléculas. La presente revisión brinda información reciente sobre los estudios clínicos tendientes a determinar el posible uso de los miARN circulantes como nuevos biomarcadores óseos, ya que cuentan con elevada sensibilidad y especificidad diagnósticas, valor predictivo positivo y valor predictivo negativo.

Abstract Osteoblasts and osteoclasts activity determines the level of the bone remodelling process which can be assessed by biochemical markers of bone formation and resorption. However, bone marker levels are subject to a series of variables resand, furthermore, they lack or have little prognostic values. MicroRNAs (miRNAs) were recently studied as a potential alternative to be used as new bone biomarkers. The miRNAs are endogenous small noncoding RNA molecules (15-25 nucleotides) that regulate many biological functions by inhibiting or degrading specific messenger RNAs. Bone-specific miRNAs exert regulatory functions on key transcriptional factors involved in osteoblastogenesis and osteoclastogenesis, modifying the bone remodelling process. Most miRNAs remain within the cell, but some of them are released into circulation. Circulating miRNAs show great stability in biological fluids, which makes them excellent candidates to be used as new bone biomarkers. Modifications in the normal pattern of bone-specific circulating miRNA might reflect changes in bone metabolism, signalling the possible onset or progression of bone diseases, such as osteoporosis. Although promising, the use of specific circulating miRNAs as new bone biomarkers in clinical practice implies fulfilling a series of requirements that lead to standardising the pre-analytical, analytical and post-analytical conditions of these molecules. The present review gives an overview on the clinical studies related to the possible use of specific circulating miRNAs as new bone biomarkers.

Resumo A remodelação óssea é exercida pela atividade dos osteoblastos e osteoclastos e pode ser avaliada para a medição dos marcadores bioquímicos de formação e reabsorção óssea. No entanto, o nível dos marcadores ósseos está sujeito a grande quantidade de variáveis e, além disso, carece ou tem pouco valor prognóstico. Os microARN (miARN) foram estudados recentemente como uma alternativa potencial para serem utilizados como novos marcadores ósseos. Os MicroRNAs (miRNAs) são pequenas moléculas de RNA não codificantes (15-25 nucleotídeos) que, através da inibição ou degradação de RNA mensageiros modificam uma série de funções biológicas. Os miRNAs específicos de osso exercem funções reguladoras sobre fatores transcricionais envolvidos na osteoblastogênese e na osteoclastogênese, modificando o processo de remodelação óssea. A maioria dos miRNAs permanece dentro da célula, mas de RNA mensageiros alguns são liberados na circulação, onde podem ser determinados bioquimicamente. Os miRNAs circulantes apresentam grande estabilidade em fluidos biológicos, o que os torna excelentes candidatos para serem usados como novos biomarcadores ósseos. Mudanças no padrão normal de miRNA circulantes específicos do osso mostrarão mudanças no metabolismo ósseo, sinalizando o possível início ou progressão de doenças ósseas, como osteoporose. Embora promissor, o uso de miRNAs específicas circulantes na prática clínica como novos biomarcadores ósseos, implica primeiramente, atender uma série de requisitos que permitem padronizar as condições pré-analíticas, analíticas e pós-analíticas dessas moléculas. A presente revisão fornece informações recentes sobre estudos clínicos destinados a determinar o possível uso dos miRNAs circulantes como novos biomarcadores ósseos, visto que contam com elevada sensibilidade e especificidade diagnósticas, valor preditivo positivo e valor preditivo negativo.

Cone-Beam Computed Tomography to evaluate changes in trabecular lower jawbone microstructure caused by bone loss and antiresorptive treatment.

For decades, conventional histomorphometry has been the gold standard for analyzing trabecular bone microarchitecture. In recent years, micro-computed tomography (µCT) devices have been validated and are now considered the gold standard for quantifying bone microstructure. Aim: The aim of this preliminary report is to evaluate the usefulness of CBCT to assess trabecular mandible microstructural properties in normal ewes and to compare the quantitative changes associated with ovariectomy and antiresorptive treatment. Material and Method: Twelve adult Corriedale ewes (n=4/group) aged 3-4 years were divided into 3 groups and studied for 28 months. Eight ewes were ovariectomized (OVX) and divided into OVX and OVX+ZOL groups (n=4/group) which were treated as follows, by jugular injection: OVX received saline solution and OVX+ZOL received zoledronate (Zol) (Gador SA, CABA, Argentina) (4 mg/month). Another four ewes were subjected to sham surgery (SHAM group) and received saline solution. Results: Densitometry showed that jaw mineral content (BMC) and density (BMD) were significantly lower in OVX than in SHAM and OVX+ZOL ewes; no difference was observed between OVX+ ZOL and SHAM groups. CBCT analysis showed that bone volume (BV/TV%); trabecular thickness (TbTh); connectivity density (CD) and anisotropy degree (AD) were significantly lower, and trabecular spacing (TbSp), significantly higher in OVX than in SHAM ewes. AD was significantly higher and TbSp significantly lower in OVX+ZOL than in OVX groups. BV/TV%, TbTh and CD showed a clear tendency to being higher in OVX+ZOL than in OVX groups. No statistical difference was observed between OVX+ZOL and SHAM ewes. CBCT in a nondestructive, fast, very precise procedure for measuring bone morphometric indices without biopsies, which are not indicated for morphometric evaluation in osteoporosis. Conclusions: The current study demonstrated the potential of the high-resolution CBCT imaging to assess in vivo quantitative bone morphometry and bone quality of lower jaw cancellous bone under normal conditions and to differentiate changes associated with excessive bone loss induced by estrogen withdrawal and antiresorptive intervention.

Objetivo: El presente informe preliminar evaluó la utilidad de Tomografía Computada de Haz Cónico (CBCT) para analizar las propiedades microestructurales trabeculares del maxilar inferior de ovejas y comparar los cambios cuantitativos asociados con la ovariectomía y tratamiento antirresortivo. Se estudiaron dieciséis ovejas Corriedale adultas de 3-4 años. Materiales y Método: Doce ovejas fueron ovariectomizadas (OVX) y divididas en 2 grupos: OVX y OVX+ZOL (n=4/grupo) cuyo tratamiento por inyección endovenosa en la yugular durante 28 meses fue el siguiente: OVX con solución salina y OVX+ZOL con zoledronato (Gador S.A. CABA. Argentina) (Zol) (4 mg/mes); 4 ovejas fueron sometidas a cirugía simulada (grupo SHAM). Resultados: La densitometría (Lunar DPX) mostró que el contenido mineral del hueso maxilar (CMO) y la densidad (DMO) fueron significativamente más bajos en OVX que en SHAM y OVX+ZOL; no se observaron diferencias entre los grupos OVX+ZOL y SHAM. El análisis de las imágenes por CBCT (Planmeca Promax 3D Classic) mostró que el volumen óseo (BV/TV%); el espesor trabecular (TbTh); la densidad de conectividad (CD) y el grado de anisotropía (AD) fueron significativamente menores (p<0.05), y el espaciado trabecular (TbSp), significativamente mayor en OVX que en SHAM (p<0.05). AD fue significativamente mayor (p<0.05) y TbSp, significativamente menor en OVX+ZOL que en OVX (p<0.05). BV/TV%, TbTh y CD mostró una clara tendencia a ser mayor en OVX+ZOL que en OVX. No se observaron diferencias estadísticas entre OVX+ZOL y SHAM. Conclusiones: En base a nuestros resultados consideramos que CBCT presenta suficiente confiabilidad y validez para evaluar in vivo la morfometría cuantitativa y la calidad del hueso esponjoso del maxilar inferior en condiciones normales, así como para diferenciar los cambios en dichos parámetros asociados a la pérdida ósea excesiva por la caída estrogénica e intervención antirresortiva. Aunque se necesitan estudios futuros, nuestros resultados agregarían una herramienta no invasiva adicional para diferenciar la microestructura del hueso trabecular mandibular en estudios preclínicos , sentando las bases para su futura aplicación en la práctica clínica.

Absorción mineral y retención ósea en ratas normales en crecimiento por el consumo de un yogur experimental reducido en lactosa que contiene galactooligosacáridos (GOS) / Mineral absorption and bone retention in normal growing rats by consumption of an experimental lactose-reduced yogurt containing galactooligosaccharides (GOS)

Introducción: Los GOS son prebióticos naturales presentes en la leche materna que pue-den obtenerse enzimáticamente a partir de la lactosa de leche de vaca durante la fabricación de yogur. El producto lácteo resultante será reducido en lactosa y contendrá prebióticos y bacterias potencialmente probióticas. Sin embargo, mantendrá la baja relación Ca/Pi que aporta la leche de vaca, lo que podría alterar el remodelamiento óseo y la mineralización. Objetivo: comparar si un yogur reducido en lactosa que contiene GOS (YE) ofrece ventajas adicionales respecto de un yogur regular sin GOS (YR) sobre las absorciones (Abs) de Ca y Pi, retención y calidad ósea durante el crecimiento normal. Al destete, ratas machos fueron divididas en 3 grupos alimentados con AIN ́93-G (C), YE o YR durante 28 días. Resultados: YE mostró el mayor aumento de lactobacilos fecales; producción de ácidos grasos de cadena corta especialmente p, profundidad de las criptas colónicas y menor pH cecal. El %AbsCa y %AbsPi aumentó en el siguiente órden: YE> YR> C (p < 0,05). El contenido de Ca y Pi en fémur, la densidad y contenido mineral óseos y los parámetros biomecánicos fueron similares en YE y C, mientras que YR mostró valores significativa-mente menores (p < 0,05). Conclusiones: YE aumentó las Abs y biodisponibilidad de minerales, alcanzando la retención y calidad ósea de C. El aumento en las Abs observado en YR no logró obtener la retención y calidad ósea de C. Conclusión: YE habría contrarrestado el efecto negativo del mayor aporte de Pi de la leche de vaca y sería una buena estrategia para lograr el pico de masa ósea y calidad del hueso adecuados, especialmente en individuos intolerantes a la lactosa. (AU)

Breast milk contains an optimal calcium/phosphate (Ca/Pi) ratio and GOS. These natural prebiotics can be enzymatically produced via cow's milk lactose inyogurt manufacture. This milk product is low in lactose and contains prebiotics and potentially probiotic bacteria but maintains a low Ca/Pi ratio that could alter bone remodeling and mineralization. We evaluated if a lactose-reduced yogurt containing GOS (YE) offers additional advantages over regular yogurt without GOS (YR) on Ca and Pi absorption (Abs), bone retention and quality during normal growth. Weaning male rats were divided into 3 groups fed AIN'93-G (C), YE or YR for 28 days. Results: YE showed the highest increase in fecal lactobacilli; short-chain fatty acids production, especially propionate and butyrate; intestine crypt depth, and the lowest cecal pH. AbsCa% and AbsPi% increased in this order: YE> YR> C (p <0.05). Ca and Pi content in femur, bone density and mineral content, and biomechanical parameters were similar in YE and C, while YR showed the significantly lowest value (p < 0.05). Conclusions: YE increased mineral Abs reaching the retention and bone quality of C. Although YR increased Abs, bone retention and quality did not achieve C values. Seemingly, YE compensated for the negative effect of the higher Pi supply and would be a good strategy to achieve adequate peak bone mass and bone quality, especially in lactose intolerant individuals. (AU)

Does Vitamin D Insufficiency Influence Prebiotic Effect on Calcium Absorption and Bone Retention?

Higher calcium (Ca) absorption would partially compensate for Ca intake below requirements for bone health. Previously, we found that GOS/FOS prebiotic mixture (PM) increases Ca absorption in the colon and retention in bone. Ca absorption and retention are regulated by vitamin D (VD). Hence, it is relevant to explore whether VD insufficiency influences the effect of the PM in the colon. The effect of the PM on Ca, phosphate (IP), and magnesium (Mg) absorption and retention under conditions of VD sufficiency and insufficiency (VDInsuff) was compared using a preclinical model of VDInsuff and low bone mass. Ovariectomized rats were fed isocaloric semisynthetic diets according to AIN-93 M. The diets varied in Ca (0.5% or 0.3%), VD [100 IU% (+ D) or 0 IU% (- D)], and PM (2.5% or 0%) content. The following eight groups were studied: + D0.5; + D0.3; + DPM0.5; + DPM0.3; - D0.5; - D0.3; - DPM0.5; and - DPM0.3. Irrespective of Ca content, VDInsuff did not affect the prebiotic effect of the PM on caecum pH, lactobacillus colony growth, or Mg absorption but significantly decreased its effect on colonic crypt length and cell/crypt and Ca and IP absorption. The PM failed to counterbalance the pro-inflammatory effect of VDInsuff. Moreover, bone retention i.e., bone mineral content and density, bone volume, and bone quality parameters were significantly lower (p < 0.05) and bone turnover significantly was higher (p < 0.05). Although the PM is a useful tool to improve mineral absorption and bone retention, it would seem important to monitor VD nutritional status to ensure the full prebiotic effect in the large intestine.

Efectos de la administración local de PTH 1-34 a bajas dosis en un modelo experimental de periodontitis: estudio piloto / Local effects of low dose of PTH 1-34 on experimental periodontitis: pilot study

La periodontitis es una patología inflamatoria que aumenta la resorción de hueso alveolar (HA), pérdida de la inserción dentaria y posible exfoliación. Evaluamos el efecto de la administración intermitente de bajas dosis de parathormona (PTH) 1-34 sobre la recuperación de la masa ósea pérdida en un modelo experimental de periodontitis inducida por una ligadura periodontal (LP) con hilo de algodón alrededor de la pieza dentaria. Las ratas fueron divididas luego de 5 días en instaurada la periodontitis en: CT LP sin trata-miento y PTH LP tratados con 0,2 µg/kg PTH 1-34 subcutánea local, tres veces por semana por 17 días. El control absoluto fue un tercer grupo sin LP (CT). Se estudiaron parámetros antropométricos, bioquímicos e histomosfométricos en tibias y hemimandibulas. La calcemia, fosfatemia, CTX sérico, PTHi y vo-lumen óseo (BV/TV%) de tibias fueron similares en los tres grupos. El BV/TV% del HA fue significativamente menor en PTH LP respecto de CT pero mayor que CT LP (p<0.05). La pérdida ósea de HA porcentual fue significativamente mayor en CT LP (p<0.05). La altura del ligamento periodontal fue significativamente menor en PTH LP que en CT (p<0.05) y mayor respecto de CT LP, sin alcanzar diferencias significativas. Los resultados del presente estudio piloto sugieren que la administración intermitente de PTH en bajas dosis y durante un periodo de tiempo corto disminuye la progresión de la enfermedad periodontal sin generar efectos sistémicos. Como no se logró regenerar totalmente el tejido periodontal se requieren estudios adicionales. (AU)

Periodontitis is an inflammatory chronic disease with high prevalence in adults that induces a progressive alveolar bone (AB) loss leading to tooth loss. Experimental periodontitis can be induced in rats by cotton ligature placement (LP) in the gingival sulcus around the molar teeth. The biofilm accumulation and disruption of the gingival epithelium lead to bone resorption. We investigated whether intermittent administration of a low dose of PTH 1-34 may recover the alveolar bone loss in the experimental periodontitis induced in female Wistar rats. Animals were randomly divided in two groups which were subcutaneously injected with: saline solution (CT LP) or 0,2 µg/kg PTH 1-34 (PTH LP) three times per week during 17 days. Unligated rats were taken as healthy controls (CT). Anthropometric, biochemical and histologic analysis of tibia and hemimandible were done. No differences in serum calcium, phosphorus, CTX, PTHi or subchondral tibia bone volume (BV/TV%) were observed between the three groups. AB BV/TV% was significantly lower in PTH LP than in CT but higher than in CT LP (p<0.05). The highest percentage of AB loss was observed in CT LP. The height of periodontal ligament was lower in PTH LP than in CT (p<0.05) but not significantly higher than CT LP.The increase in AB loss by experimental periodontitis appears to be corrected by the intermittent administration of low doses of PTH without systemic effect. As the recovery of periodontal tissue was only partial, additional studies should be done.

Aminobisphosphonate-treated ewes as a model of osteonecrosis of the jaw and of dental implant failure.

BACKGROUND: Bisphosphonate (BP)-related osteonecrosis of the jaw (BRONJ) and dental implant failure are two negative side effects of chronic aminoBP treatment. METHODS: Eleven ovariectomized (OVX) ewes and four ewes subjected to sham surgery (SHAM) were treated as follows: OVX (n = 5): OVX plus saline solution; zoledronic acid-treated group (ZOL) (n = 6): OVX plus ZOL; SHAM (n = 4): SHAM plus saline solution. Extraction of the first upper molar was performed at 1 year, dental implant placement at 2 years, and sacrifice at 28 months. RESULTS: Implants remained in place in SHAM and OVX ewes but were lost in all ZOL ewes. ZOL sheep (2/6) showed inflammation and necrotic bone at mandibular region. No differences in serum calcium (Ca), inorganic phosphate (Pi) or 25-hydroxyvitamin D were observed, whereas bone alkaline phosphatase levels decreased in the three studied groups (P < 0.05). The significantly lowest levels of carboxy-terminal telopeptide of type I collagen were observed in ZOL (P < 0.05), and showed no differences between SHAM and OVX. OVX showed the lowest and ZOL the highest Ca and Pi contents in femur and maxilla (P < 0.05). Bone volume (BV/TV%) and iliac crest were similar at baseline and at month 4. At the end of the study, BV/TV%, proximal femur and hemi-mandible bone mineral content and bone mineral density, and trabeculae number were similar in SHAM and ZOL, and lower in OVX (P < 0.05). CONCLUSION: All ZOL-treated ewes on a schedule similar to that used in cancer patients showed extensive suppression of bone remodeling and implant failure. Some of the ZOL ewes developed BRONJ.

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)

Sinus floor elevation using a new bovine bone grafting material: case report and bone grafting materials update / Actualización en materiales de relleno óseo: reporte de un caso clínico de elevamiento del piso del seno maxilar usando un nuevo material de relleno óseo bovino

Bone grafting is important to preserve the alveolar bone ridge height and volume for dental implant placement. Even though implant-supported overdentures present highly successful outcomes, it seems that a great number of edentulous individuals have not pursued implant-based rehabilitation. The cost of the treatment is one of the reasons of discrepancy between highly successful therapy and its acceptance. Therefore, the development of biomaterials for bone grafting with comparable characteristics and biological effects than those renowned internationally, is necessary. In addition, domestic manufacture would reduce the high costs in public health arising from the application of these biomaterials in the dental feld. The purpose of this clinical case report is to provide preliminary clinical evidence of the efficacy of a new bovine bone graft in the bone healing process when used for sinus floor elevation. (AU)

El uso de injertos óseos es importante para preservar la altura y el volumen de la cresta alveolar para la colocación de implantes dentales. Si bien las sobredentaduras implanto-soportadas presentan resultados altamente exitosos, la mayoría de las personas desdentadas no han sido rehabilitadas mediante implantes dentales. Uno de los principales motivos por los cuales los pacientes no aceptan este tipo de tratamiento, altamente exitoso, es el elevado costo del mismo. Por ello, es necesario el desarrollo de biomateriales de injerto óseo con características y efectos biológicos comparables a los reconocidos internacionalmente. Asimismo, la fabricación nacional reduciría los altos costos en Salud Pública derivados de la aplicación de estos biomateriales en el campo dental. El objetivo de esta comunicación es presentar un caso clínico a fin de proporcionar evidencia preliminar acerca de la eficacia de un nuevo injerto de hueso bovino en el proceso de cicatrización ósea en el levantamiento del piso del seno maxilar. (AU)

Rol de la osteocalcina más allá del hueso / Role of osteocalcin beyond bone

Los hallazgos osteológicos se intensi!caron en los últimos años. Se demostró que el esqueleto se comporta, además de sus funciones clásicas, como un órgano de secreción endocrina que sintetiza al menos dos hormonas: el factor de crecimiento de !broblastos 23 (FGF-23) y la osteocalcina (Ocn). La Ocn es un péptido pequeño que contiene 3 residuos de ácido glutámico. Estos residuos se carboxilan postraduccionalmente, quedando retenida en la matriz ósea. La forma decarboxilada en el primer residuo de ácido glutámico (GluOcn) fue reportada por poseer efectos biológicos; la resorción ósea es el mecanismo clave para su bioactivación. La presente revisión se centra en los conocimientos actuales sobre la función hormonal de la Ocn. A la fecha se reporta que la Ocn regularía el metabolismo energético aumentando la proliferación de células ` pancreáticas, y la secreción de insulina y de adiponectina. Sobre el músculo esquelético actuaría favoreciendo la absorción y el catabolismo de nutrientes. La función reproductiva masculina estaría regulada mediante el estímulo a las células de Leydig para sintetizar testosterona; en el desarrollo cerebral y la cognición, la Ocn aumentaría la síntesis de neurotransmisores monoaminados y disminuiría el neurotransmisor inhibidor GABA. Si bien son indispensables mayores evidencias para dilucidar los mecanismos reguladores por medio de los cuales actuaría la Ocn, los resultados enumerados en los distintos estudios experimentales establecen la importancia de este novedoso integrante molecular. Dilucidar su rol dentro de estos procesos interrelacionados en seres humanos abriría la posibilidad de utilizar a la Ocn en el tratamiento de enfermedades endocrino-metabólicas. (AU)

Osteological !ndings have intensi!ed in recent years. The skeleton behaves as an endocrine secretion organ that synthesizes at least two hormones: osteocalcin (Ocn) and !broblast growth factor 23 (FGF-23). Ocn is a small peptide that contains 3 glutamic acid residues. After translation, these residues are carboxylated to make possible its retention into the bone matrix. Decarboxylation on the !rst glutamic acid residue (GluOcn) has been reported to have biological effects. Bone resorption is the key mechanism for its bioactivation. This review focuses on current knowledge on Ocn hormonal function. It has been reported that Ocn regulates energy metabolism by increasing the proliferation of pancreatic ` cells, and the secretion of insulin and adiponectin. On the skeletal muscle, it may act by favoring the absorption and catabolism of nutrients. Male reproductive function might be regulated by stimulating Leydig cells to synthesize testosterone. Regarding brain development and cognition, Ocn would increase monoamine neurotransmitters synthesis and decrease inhibitory neurotransmitter GABA. Although more evidence is needed to elucidate the regulatory mechanisms of Ocn, different experimental studies establish the importance of this novel molecular mediator. Clarifying its role within interrelated processes in humans, might open the possibility of using Ocn in different treatments of endocrine-metabolic diseases. (AU)

Effect of Adding a Galacto-Oligosaccharides/Fructo-Oligosaccharides (GOS/FOS®) Mixture to a Normal and Low Calcium Diet, on Calcium Absorption and Bone Health in Ovariectomy-Induced Osteopenic Rats.

Menopause is associated with bone loss. Prebiotics increase Ca, inorganic phosphorus (Pi), and Mg absorption, improving bone health. These increases would supply an extra amount of minerals, decreasing bone resorption and possibly reversing ovariectomy-induced bone loss. The present experimental study sought to evaluate the effect of adding a prebiotic GOS/FOS® mixture to a normal or a low Ca diet on Ca, Pi, and Mg absorption, in osteopenic rats. Four groups of n = 8 rats each were OVX, and 8 rats were SHAM operated. All rats were fed a commercial diet for 45 days. They were then fed one of the following diet for 45 days: C-0.5%: SHAM fed AIN 93 M containing 0.5%Ca; O-0.5% and O-0.3%: OVX rats fed AIN 93 M, containing 0.5% or 0.3%Ca, respectively; GF-0.5% and GF-0.3%: OVX rats fed AIN 93 M, containing 0.5% or 0.3%Ca+ 2.5% GOS/FOS®, respectively. At the end of the experimental time point, Ca, P, and MgAbs% was significantly higher in GF-0.5% and GF-0.3% as compared to the remaining groups (p < 0.01). Irrespective of diet Ca content, CTX decreased whereas femur Ca and P content, tibia BV/TV and GPC.Th, lumbar spine and proximal tibia BMD, bone strength, bone stiffness, and elastic modulus increased in the GF-0.5% and GF-0.3% groups as compared to O-0.5% and O-0.3%, respectively (p < 0.05). This prebiotic mixture would be a useful tool to prevent the increase in bone loss associated with menopause and aging.

Desarrollo de un modelo experimental de osteonecrosis de maxilar asociada al tratamiento crónico con aminobisfosfonatos / Experimental model of osteonecrosis of the jaw associated to chronic treatment with aminobisphosphonates

La osteonecrosis de maxilar asociada a aminobisfosfonatos (BRONJ) constituye un efecto secundario del tratamiento crónico con los más potentes. Un modelo experimental permitiría determinar la patogenia de dicha alteración. La oveja presenta características orales y del metabolismo óseo similar al humano y permite realizar manipulaciones bucales. Se evaluaron cambios clínicos, remodelación ósea y masa ósea maxilar en ovejas hembras adultas tratadas con zolendronato (ZOL), durante 22 meses y utilizando dosis equivalente al tratamiento de neoplasias. Seis ovariectomizadas (OVX) recibieron ZOL; 5 OVX y 4 SHAM (control) recibieron solución fisiológica. Al inicio, 4 y 22 meses se evaluó calcemia, fosfatemia, crosslaps (CTX) y fosfatasa alcalina ósea. Al final, se evaluó contenido mineral óseo de la hemimandíbula superior (CMO: mg/cm2). Al final del estudio, CTX disminuyó significativamente en ZOL (p<0,05) sin diferencias entre SHAM y OVX. En maxilar, los contenidos de Ca y P (g/g tejido) y CMO (g/cm2 ) disminuyeron en OVX vs. SHAM (p<0,05) y solo Ca y CMO respecto de ZOL (p<0,05). ZOL incrementó el contenido de Ca y CMO, mientras que el de P permaneció significativamente disminuido respecto de SHAM. La sobrevida en SHAM y OVX fue del 100% y en ZOL 77% (2 muertes); 2 ovejas del grupo ZOL presentaron necrosis de maxilar. Conclusiones: fue posible obtener desarrollo de BRONJ por tratamiento crónico con ZOL, el cual redujo notablemente la resorción y, según la relación Ca/P, posiblemente haya afectado la mineralización ósea. (AU)

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a complication of chronic treatment with the most powerful aminobisphosphonates (BPs). An experimental animal model would allow to determine the pathogenesis of this complication. Ewes exhibit similar oral cavity characteristics and bone metabolism as humans, and they are suitable for oral cavity interventions. We examined herein the clinical manifestations, bone remodeling status, and maxillary bone mass in adult female ewes treated with zoledronate (ZOL) for 22 months. Six ovariectomized (OVX) ewes received ZOL; and 5 OVX and 4 SHAM animals received saline solution. At the start of the experiment, and at the 4 and 22 month-time points serum Ca, P, crosslaps (CTX), and bone alkaline phosphatase were measured. Bone mineral content (BMC) of the superior hemimandible was measured at the end of the experiment. At this time point, CTX was significantly decreased only in the ZOL group (p<0.05). Ca and P content (g/g tissue) and BMC in the mandible were significantly decreased in the OVX group compared to SHAM animals (p<0.05) and only Ca content and BMC were decreased when compared to ZOL (p<0.05). ZOL treatment increased the Ca content and BMC, whereas the P content remained low compared to the SHAM group (p<0.05). All ewes from the SHAM and OVX groups and 77% of the animals from the ZOL group survived until the end of the experiment, whereas two ewes of ZOL group exhibited BRONJ. Conclusion: under our experimental conditions, it was possible to induce BRONJ by the chronic ZOL administration, which in turn induced a high reduction in bone resorption as well as possibly impaired bone mineralization, based on the Ca/P ratio in the mandible. (AU)

Preliminary study on the biocompatibility and osteoconductive properties of a new bovine bone graft / Estudio preliminar sobre las propiedades de biocompatibilidad y osteoconductividad de un nuevo injerto de hueso bovino

To prevent post-extraction resorption and preserve the integrity of the alveolar ridges, the placement of bone grafts at the time of extraction is recommended. Bovine bone grafts are biocompatibile and osteoconductive, allowing new bone apposition by osteoprogenitor cells. Although there are trademarks recognized internationally regarding bovine bone grafts, they are expensive and even difficult to acquire. Therefore, domestic industry development of high quality biomaterials will reduce the public health high costs in the dental field. Here, we evaluated and compared the effects of an Argentinean manufactured bovine bone graft (Synergy Bone Matrix) with a bovine bone graft recognized for its osteoconductive effects (Bio-Oss), on bone healing in an experimental model in rats. We created critical sized bone defects in rat tibiae and filled them with either one of the bovine bone grafts or control. Clinical responses, X-ray findings, bone mineral density, and histological parameters were evaluated. No abscess, encapsulation, suppuration or inflammation of lymphatic nodes were observed. Radiographically, all implants were amalgamated to the surrounding bony margins, suggesting proper healing. On the other hand, control tibiae exhibited no signs of recovery and remained either unfilled or showed fibrous tissue formation. No statistical differences were observed in BMC and BMD between tibiae filled with Synergy Bone Matrix or Bio-Oss. Histological analysis revealed particles of both bone grafts surrounded by laminar bone tissue indicating osteoconductivity, without any inflammatory sign. This preliminary study suggests that Synergy Bone Matrix, as well as Bio-Oss, present similar properties of biocompatibility and osteoconductivity. (AU)

Para prevenir la resorción post-exodoncia y preservar la integridad de los rebordes alveolares, se recomienda la colocación de injertos óseos en el momento de la extracción. Los injertos de hueso bovino son biocompatibles y osteoconductivos, permitiendo nueva aposición ósea por células osteoprogenitoras. Existen marcas internacionales de injertos de hueso bovino, pero resultan caros e incluso difíciles de adquirir. Por ello, la elaboración de biomateriales de alta calidad, nacionales, reduciría los altos costos de salud pública en odontología. En este estudio, se evaluaron y compararon los efectos de un injerto de hueso bovino fabricado en Argentina (Synergy Bone Matrix) versus un injerto de hueso bovino reconocido por sus efectos osteoconductivos (Bio-Oss), en el proceso de cicatrización ósea en un modelo experimental en ratas. Para ello, creamos un defecto óseo crítico en tibia de rata el cual se rellenó con uno de los injertos de hueso bovino o control. Se evaluó: respuesta clínica y radiográfica, densidad mineral ósea e histología. No se observaron abscesos, encapsulación, supuración o inflamación de los ganglios linfáticos. Radiográficamente, todos los implantes se integraron a los márgenes óseos circundantes, sugiriendo una cicatrización adecuada. Por el contrario, las tibias control no mostraron signos de recuperación con formación de tejido fibroso. No se observaron diferencias estadísticas en las BMC y BMD entre las tibias Synergy Bone Matrix o Bio-Oss. La histología reveló partículas de ambos injertos óseos rodeadas por tejido óseo laminar indicando osteoconductividad sin signos inflamatorios. Este estudio preliminar sugiere que Synergy Bone Matrix presenta propiedades similares de biocompatibilidad y osteoconductividad que Bio-Oss. (AU)

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)

Conexiones entre tejido óseo y tejido graso: efecto de la obesidad sobre la salud ósea / Bone and fat connection: obesity effect on bone health / Conexões entre tecido ósseo e tecido gorduroso: efeito da obesidade na saúde óssea

La prevalencia de dos desórdenes crónicos como la osteoporosis y la obesidad se encuentra en aumento. La fisiopatología de ambas alteraciones metabólicas es multifactorial e incluye factores genéticos, factores ambientales y hormonales. Diversos estudios clínicos y experimentales demuestran la existencia de una interacción entre el tejido adiposo y el esqueleto, similar a la que ocurre entre las patologías mencionadas. Si bien se pensaba que la obesidad protegía al hueso, actualmente se postula que un exceso de tejido graso, fundamentalmente grasa abdominal, sería un factor de riesgo para el desarrollo de osteoporosis y fracturas por fragilidad. Diversos factores secretados por el tejido graso incrementados por efecto de la obesidad jugarían un rol clave en la salud ósea. Las adipoquinas, citokinas y ácidos grasos libres regulan el remodelamiento óseo, disminuyendo la formación e incrementando la resorción, al mismo tiempo que inducen estrés oxidativo e hiperglucemia, que exacerba el efecto negativo sobre la masa ósea. Esta revisión trata de profundizar el conocimiento de las interacciones entre hueso y tejido adiposo y de las implicancias clínicas que surgen de la interrelación entre obesidad y osteoporosis.

Osteoporosis and obesity are chronic disorders that are increasing in prevalence. The pathophysiology of these diseases is multifactorial and it includes genetic, environmental and hormonal determinants. Basic and clinical studies support an important interaction between adipose tissue and the skeleton similar to that found in osteoporosis and obesity. The belief that obesity is protective for bone has recently been revised. In fact, excess of fat mass might be a risk factor for osteoporosis and fragility fractures. Increasing evidence seems to indicate that different factors released by the fat tissue could play a key role in skeletal health. Adipokines, cytokines and free-fatty acids secreted by the obese fat mass can regulate bone remodelling decreasing bone formation and increasing bone resorption. Moreover they increase oxidative stress, increasing even more the negative effect on bone mass. This review considers literature data to understand bone-fat interactions and the clinical implications of linking obesity to osteoporosis.

A prevalência de duas doenças crônicas, como a osteoporose e a obesidade estão aumentando. A fisiopatologia de ambas as doenças metabólicas é multifatorial e inclui fatores genéticos, fatores ambientais e hormonais. Estudos clínicos e experimentais demonstram a existência de interação entre o tecido adiposo e o esqueleto, semelhante ao encontrado nas patologias mencionadas. Embora exista a crença de que a obesidade protegia o osso, atualmente se postula que um excesso de tecido gorduroso, fundamentalmente gordura abdominal seria um fator de risco para desenvolver osteoporose e fraturas por fragilidade. Diversos fatores secretados pelo tecido gorduroso aumentado por efeito da obesidade teria um papel chave na saúde óssea. As adipocinas, citocinas e ácidos graxos livres regulam a remodelação óssea, diminuindo a formação e aumentando a reabsorção, ao mesmo tempo que eles induzem estresse oxidativo e hiperglicemia, aumentando ainda mais o efeito negativo sobre a massa óssea. Esta revisão visa aprofundar o conhecimento das interações entre o osso e o tecido adiposo e nas implicações clínicas que surgem da interação entre obesidade a osteoporose.

Hipovitaminosis D y desarrollo de Síndrome Metabólico / Hypovitaminosis D and Metabolic Syndrome development / A deficiência de vitamina D e desenvolvimento de Sindrome Metabolica

El Síndrome Metabólico (SM) es una patología heterogénea que en rangos generales se podría definir como la combinación de factores de riesgo asociados a la enfermedad cardiovascular (ECV) y diabetes, caracterizados por insulino-resistencia, hipertensión, elevada presión arterial, elevados niveles de triglicéridos (TGL) y obesidad abdominal.La hipovitaminosis D induciría perturbaciones metabólicas (hipertensión, aterogenicidad, incremento de ECV, de insulino-resistencia, de diabetes tipo II y de obesidad central) que favorecen el desarrollo de SM. El estado nutricional respecto de la vitamina D se evalúa por los niveles de 25hidroxivitamina D (25OHD), principal metabolito circulante de dicha vitamina. Diversos estudios han sugerido la existencia de una relación inversa entre los niveles de 25OHD y el desarrollo de SM. La adiposidad central, la resistencia a la insulina y aterogenicidad son importantes factores de riesgo para el desarrollo de SM. Todos ellos se asocian a la hipovitaminosis D. La suplementación con vitamina D, al aumentar los niveles de 25OHD, reduciría el riesgo de desarrollar SM, lo que tendría importantes implicancias para el individuo en particular y la Salud Pública en general. Para clarificar todos estos puntos se hace necesario realizar estudios prospectivos randomizados, controlados, a doble ciego para evaluar los efectos a largo plazo y la causalidad entre el estado nutricional de vitamina D y el riesgo de desarrollar SM.

The metabolic syndrome (MS) is an heterophasic pathology, which in general terms, could be defined as the combination of risk factors associated with cardiovascular disease (CVD) and diabetes, characterized by insulin resistance, hypertension, high blood pressure, high levels of triglycerides (TGL) and abdominal obesity. Vitamin D deficiency may induce metabolic disturbances (hypertension, atherogeny, increased CVD, insulin-resistance, type II diabetes and central obesity), which favour the development of MS. The nutritional status for vitamin D could be evaluated by serum 25-hydroxyvitamin D levels (25OHD). Several studies have suggested the existence of an inverse relationship between 25OHD levels and the increased risk of SM. Central adiposity, insulin resistance and atherogeny are important risk factors for the development of SM. All of these factors are associated with vitamin D deficiency. Supplementation with vitamin D increases 25OHD levels and could reduce the risk of developing MS. To assess the long-term effects and the causal link between the nutritional status of vitamin D and the risk of developing MS it is necessary to perform prospective randomized, controlled, double-blind studies.

A síndrome metabólica (SM) é uma patologia heterogênea que, em termos gerais, pode ser definida como a combinação de fatores de risco associados com doença cardiovascular (DCV) e diabetes, caracterizados por resistência à insulina, hipertensão, níveis altos de pressão arterial, níveis elevados de triglicérides (TGL) e obesidade abdominal. A hipovitaminose D induziria distúrbios metabólicos (hipertensão, aterogenicidade, aumento da DCV, resistência à insulina, diabetes tipo II e obesidade central), que favorecem o desenvolvimento de SM. O estado nutricional a respeito da vitamina D é avaliado pelos níveis de 25-hidroxivitamina D (25OHD), principal metabólito circulante de tal vitamina. Vários estudos têm sugerido a existência de uma relação inversa entre os níveis de 25OHD e o desenvolvimento da SM. A adiposidade central, a resistência à insulina central e aterogenicidade são fatores de risco importantes para o desenvolvimento da SM. Todos eles se associam à hipovitaminose D. A suplementação com vitamina D, aumentando os níveis de 25OHD, reduziria o risco de desenvolvimento de SM, o que teria importantes consequências para a do indivíduo em particular e a Saúde Pública em geral. Para esclarecer todos esses pontos é necessário realizar estudos prospectivos, randomizados, controlados, duplo-cego para avaliar os efeitos no longo prazo e a causalidade entre o estado nutricional de vitamina D e o risco de desenvolver SM.

Effect of a mixture of GOS/FOS® on calcium absorption and retention during recovery from protein malnutrition: experimental model in growing rats.

INTRODUCTION: During growth, protein deprivation impairs epiphyseal growth plate (EGP) height, bone volume (BV) and endochondral ossification. During catch-up growth, Ca availability becomes essential to ensure the extra amount needed to achieve optimal peak bone mass and strength. GOS and FOS improve mineral absorption in the colon. PURPOSE: The effect of a mixture of GOS/FOS® 9:1 added to a 0.5 %Ca (NCa) and a 0.3 %Ca (LCa) diets on Ca, P and Mg absorptions and bone mineralization, density and structure using an experimental model of growing rats recovering from early protein malnutrition was investigated. METHODS: To induce protein malnutrition, rats were fed a low protein diet: 4 % (LPD) during 1 week and then were randomly assigned to recovery groups (R) until day 50 (T = 50) as follows: R0.5 %: NCa; RP0.5 %: NCa + 5.3 % GOS/FOS®; R0.3 %: LCa and RP0.3 %: LCa + 5.3 % GOS/FOS®. Control groups received the 0.5 %Ca or 0.3 %Ca diet from weaning until day 40 or 50. RESULTS: Body weight and length increased in C groups throughout the study; both were arrested in all R during LPD consumption and increased immediately after re-feeding. Independently of dietary Ca content, LS counts, ß-glucosidase and Ca, P and Mg absorption increased, whereas cecum pH, ß-glucuronidase, urease and tryptophanase decreased in RP0.5 %: and RP0.3 %: as compared to the other studied groups (p < 0.01). Prebiotic consumption decreased CTX levels and increased femur Ca, Mg and P contents, total skeleton bone mineral content, proximal tibia and spine BMD, BV, EGP height and hypertrophic zone thickness, stiffness and elastic modulus as compared to recovery groups fed the prebiotic-free diets. CONCLUSION: Under the present experimental conditions, GOS/FOS® mixture induced colonic positive effects, which increased Ca, P and Mg absorption. Thus, consuming the prebiotic-containing diet resulted in an extra amount of minerals that improved bone development in growing rats recovering from protein malnutrition.

Effect of a combination GOS/FOS® prebiotic mixture and interaction with calcium intake on mineral absorption and bone parameters in growing rats.

AIM: Increasing calcium intake is the most effective strategy for avoiding Ca deficit. However, if intake remains inadequate, improving Ca absorption becomes an important tool to optimize Ca homeostasis and bone health. PURPOSE: The effect of a mixture of GOS/FOS(®) 9:1 added to a normal- or low-Ca diets on Ca absorption and bone mineralization, density and structure was investigated, in a model of growing rats. Several colonic parameters to help support the findings were also evaluated. RESULTS: Weanling Wistar rats received one of the four experimental AIN-93G diets: C5: 0.5% Ca; C3: 0.3% Ca; P5: 0.5% Ca + 5.3% GOS/FOS(®); P3: 0.3% Ca + 5.3% GOS/FOS(®) until 50 days (T = 50). At T = 50, lactobacillus and cecum weights were higher, whereas cecum pH was lower in P5 and P3 versus C5 and C3 (p < 0.001). At T = 50, fecal Ca, Mg and P were lower and their absorptions (mg/dL) were higher in P5 and P3 versus C5 and C3, respectively (p < 0.05). Ca, Mg and P absorption % was higher in P5 and P3 versus C5 and C3 (p < 0.001). Femur Ca and P content, bone mineral content, trabecular bone mineral density, tibia length, bone volume, osteoblast surface, stiffness and elastic modulus were higher in P5 and P3 versus C5 and C3 (p < 0.05). Despite the lower Ca content, P3 group reached similar values than C5 in all these latter parameters. CONCLUSIONS: Supplementing diets with the GOS/FOS(®) mixture increased bone mineralization, density and structure due to an increase in Ca, P and Mg absorptions. Thus, this prebiotic mixture may help to improve bone development in a period of high calcium requirements.