Jornada: Envejecimiento y Osteoporosis: situación actual y perspectiva de futuro Meeting: Ageing and Osteoporosis: Current situation and future perspectives Madrid, 21 de marzo de 2012 Madrid, April 29, 2012 RESÚMENES/ABSTRACT 1. Presentación de la Jornada: ¿Se pueden regenerar los huesos?, María Vallet Regí 2. Bone Aging , Adolfo Díez Pérez 3. Biological mechanisms of angiogenesis and osteogenesis driven by calcium releasing biomaterials, Josep A. Planell and Elisabeth Engel 4. Progress in the development of bioactive materials with vascularization potential for bone regeneration, Aldo R. Boccaccini 5. Bone augmentation with injectable cement pastes, Marc Bohner 6. Consecuencias clínicas de la fragilidad y las modificaciones músculo-esqueléticas asociadas a la edad: un reto para los pacientes de edad avanzada así como para los antiguos sistemas de asistencia sanitaria, Leocadio Rodríguez Mañas FUNDACIÓN RAMÓN ARECES Jornada: Envejecimiento y Osteoporosis: situación actual y perspectiva de futuro Meeting: Ageing and Osteoporosis: Current situation and future perspectives Madrid, 21 de marzo de 2012 Madrid, April 29, 2012 RESÚMENES/ABSTRACT Presentación de la Jornada: ¿Se pueden regenerar los huesos? María Vallet Regí El envejecimiento de nuestros cuerpos como consecuencia del paso del tiempo, obliga a buscar soluciones, cada vez más urgentes porque cada vez es mayor el número de ciudadanos que llegan a edades muy avanzadas donde, problemas como la osteoporosis, van emparejados a su envejecimiento. La búsqueda de un objetivo común, remediar el dolor, la enfermedad, y el deterioro de nuestros cuerpos, obliga a investigar y diseñar en biomateriales y nanoestructuras. En esta jornada vamos a debatir si es posible regenerar los huesos, y que soluciones intermedias o alternativas existen para ello. VOLVER ↑ Bone Aging Adolfo Díez Pérez Bone is a highly complex system. Among their several functions, is obvious its rol as a scaffold and protective structure of the different organs. Moreover, is where hematopoietic medulla is hosted. Metabolically, constitutes the main reservoir of minerals, available for the regulation of biochemical and signaling functions. More recently, has been described its role as an endocrine organ, able to secrete systemic hormones. All these complex functions are made possible by a highly sophisticated and very active cellular system. The three cell lines in charge of these functions are: 1) The osteoclast, derived from the hematopoietic precursor cell, with macrophage function; 2) The osteoblast, derived from a common mesenchimal precursor that, besides osteoblasts, can differentiate alternatively to adipocyte, chondrocyte, myoblast or fibroblast, and 3) The osteocyte, the most abundant bone cell, in charge of the regulatory effects, both locally and systemic. FUNDACIÓN RAMÓN ARECES Jornada: Envejecimiento y Osteoporosis: situación actual y perspectiva de futuro Meeting: Ageing and Osteoporosis: Current situation and future perspectives Madrid, 21 de marzo de 2012 Madrid, April 29, 2012 RESÚMENES/ABSTRACT Aging has an impact on bone tissue in several ways. There is a decline in trophic elements, importantly the gonadal hormones (menopause, andropause). A breakdown of the cellular equilibrium between formation and resorption, in the remodeling cycle, causing negative balance and the subsequent bone loss is also produced. Moreover, there is an intrinsic functional decline in the activity of the bone cells. Finally, deterioration in the different components of the constituent materials (collagen, fatigue damage) weakens the mechanical competence of the tissue. Like other elements of our physiology, bone has adapted during the evolution to a life span of 4-5 decades. The dramatic increase n the life expectancy in the last century has produced a functional challenge that constitutes the ground for the progressive importance of the osteoporosis and explains their morbidity and mortality. However, from an integrative perspective, bone deterioration is a part of the decline in the bone-muscle-joint unit. These three structures are integrated in a common function and the involution in any of them (osteoporosis, sarcopenia, osteoarthritis) merges in one of the main drivers of the frailty syndrome. This frailty is, at the end, a decrease in the autonomy and functional reserve of the individual, with a striking increase in their vulnerability. There is a considerable genetic load behind the development of this aging-associated decline. However, a large variety of external factors can modulate the genetic predisposition either accelerating or delaying the physiological deterioration. When facing this clinical challenge, it is very important to integrate all the different pieces that play a role in the bone-muscle-joint functional unit and manage the problem in an integrated fashion. This is the key strategy for expanding a healthy life, with independence and good quality. In this manner, we could palliate the personal, social and economic burden that this aging process implies. We do have tools and knowledge to face the challenge. VOLVER ↑ FUNDACIÓN RAMÓN ARECES Jornada: Envejecimiento y Osteoporosis: situación actual y perspectiva de futuro Meeting: Ageing and Osteoporosis: Current situation and future perspectives Madrid, 21 de marzo de 2012 Madrid, April 29, 2012 RESÚMENES/ABSTRACT Biological mechanisms of angiogenesis and osteogenesis driven by calcium releasing biomaterials Josep A. Planell and Elisabeth Engel It is well known that the mineral phase of bone is formed mainly by a carbonated apatite [Ca10-(PO4)6(OH)2]. Using this fact, numerous calcium phosphate–containing ceramics, glass ceramics, and biological glasses have been developed for the repair and reconstruction of the bony tissue. Bioactive glasses have shown to be promising materials for the skeletal system healing, especially in vivo, where they have induced a rapid and beneficial response. A majority of these bioactive glasses is SiO 2-based exhibiting a range of low dissolution rates. In contrast, phosphate bioabsorbable glasses have the ability to solubilize completely, and their degradation time may vary from few days to several months. Such glasses are good candidates as reinforcement phase for biodegradable composite materials for the construction of scaffolds for tissue engineering. The CaP glass of the 44,5P2O5 – 44,5CaO – 6Na2O – 5TiO2 (molar composition) system, coded G5, has shown a good chemical stability and good mechanical properties. In vitro degradation studies on the G5-glass performed with SBF at physiological temperature showed that G5-glass dissolution occurs uniformly, which means that none of the ions forming the glass network is released preferentially. The incorporation of an inorganic phase into the polymeric matrix may enhance the mechanical integrity of the material, as well as its biological behavior, and can also modify the degradation mechanism of the polymer. Some calcium phosphate ceramics and biological glasses have been used with this aim. Specifically, calcium phosphate (CaP) glasses are well suited for bone remodeling given that they possess a chemical composition close to that of the mineral phase of bone and that their solubility rate can be adjusted by controlling their chemical composition. FUNDACIÓN RAMÓN ARECES Jornada: Envejecimiento y Osteoporosis: situación actual y perspectiva de futuro Meeting: Ageing and Osteoporosis: Current situation and future perspectives Madrid, 21 de marzo de 2012 Madrid, April 29, 2012 RESÚMENES/ABSTRACT The success of a 3D scaffold depends on several parameters that range from the macroto the nanoscale. Macro- and microporosity, as well as interconnectivity, are of great importance in promoting tissue ingrowth, vascularization, and the delivery of nutrients throughout the newly formed tissue. The attachment and adhesion of the cells on the material surface are protein mediated processes, where factors such as surface chemistry, surface energy, and topography can affect the cell material response. In vitro studies have shown that the biological properties of this bioactive, biodegradable calcium phosphate glass/polylactic acid composite biomaterial promote bone marrowderived endothelial progenitor cell (EPC) mobilization, differentiation and angiogenesis through the creation of a controlled bone healing-like microenvironment. The angiogenic response is triggered by biochemical and mechanical cues provided by the composite, which activate two synergistic cell signaling pathways: a biochemical one mediated by the calcium-sensing receptor and a mechanosensitive one regulated by non-muscle myosin II contraction. Together, these signals promote a synergistic response by activating EPCsmediated VEGF and VEGFR-2 synthesis, which in turn promote progenitor cell homing, differentiation and tubulogenesis. These findings highlight the importance of controlling microenvironmental cues for stem/progenitor cell tissue engineering and offer exciting new therapeutical opportunities for biomaterial-based vascularisation approaches and clinical applications. This is the first time that a composite containing a bioactive, biodegradable glass has been proven to be directly involved in angiogenesis and differentiation of endothelial progenitors. The main advantages of this approach (when compared to others such as protein immobilization or growth factor release) are the simplicity of material fabrication, low cost and off-the-shelf availability, making it a very attractive strategy for clinical applications involving musculoskeletal repair. Related to osteogenesis, in vitro studies revealed the induction of Mesenchymal Stem Cells proliferation, migration and differentiation towards osteogenic lineage and promoting FUNDACIÓN RAMÓN ARECES Jornada: Envejecimiento y Osteoporosis: situación actual y perspectiva de futuro Meeting: Ageing and Osteoporosis: Current situation and future perspectives Madrid, 21 de marzo de 2012 Madrid, April 29, 2012 RESÚMENES/ABSTRACT Alkaline Phosphatase activity and Collagen type I production at early times (3 an 7 days) in absence of osteogenic media. Also, the induction of mineralization is remarkable when there is a high extracellular calcium concentration (10 mM). In vivo studies have shown that the addition of calcium phosphate glass (G5) to PLA results in a composite material with higher angiogenic capacity than that of PLA only. Taken all together, there is an important evidence of how biomaterials based in calcium phosphates drive the bone tissue regeneration, inducing together osteogenesis and angiogenesis. VOLVER ↑ Progress in the development of bioactive materials with vascularization potential for bone regeneration Aldo R. Boccaccini Multifunctional scaffolds for application in bone regeneration approaches will be discussed, presenting recent progress and remaining challenges. After summarizing current research in the field of scaffolds for bone tissue engineering, recent results on the development and characterisation of nanostructured bioactive glass scaffolds, coated and infiltrated with biopolymers, will be presented. Technologies for fabrication foam-like bone scaffolds will be discussed highlighting the versatility of the foam replica technique for developing scaffolds that mimic trabecular bone structure. Advanced methods based on rapid prototyping and electropspinning techniques will be also considered. The contribution of biomaterials science to the tissue engineering field will be considered based on the optimization of the structure, surface properties, degradation behavior and mechanical properties of the scaffolds. For example, the coating and infiltration of bioactive glass FUNDACIÓN RAMÓN ARECES Jornada: Envejecimiento y Osteoporosis: situación actual y perspectiva de futuro Meeting: Ageing and Osteoporosis: Current situation and future perspectives Madrid, 21 de marzo de 2012 Madrid, April 29, 2012 RESÚMENES/ABSTRACT scaffolds by biodegradable polymers containing functionalised nanoscale inorganic particles of nanofibres increases the fracture resistance of scaffolds and induces the formation of nanostructured hydroxyapatite when immersed in simulated body fluid. In-vitro characterisation methods for bone scaffolds will be presented, discussing the effects of bioactive glass dissolution products on cell behaviour in relation to osteogenesis and angiogenesis. Recent in-vivo results which have assessed the vascularisation potential of new scaffolds based on bioactive glasses will be discussed and the present challenges of this branch of tissue engineering will be highlighted, e.g. the development of vascularised bone. The fabrication of novel scaffolds doped with trace elements (e.g. Sr, Cu) and investigations on the effect of these elements on the scaffold biological performance will be presented which provide experimental evidence to support the hypothesis that scaffolds with specific ion release capability (bioinorganics or therapeutic metallic ions) are attractive for bone tissue engineering. In this context, nanostructuring strategies for 3D bioactive glass (or glass-ceramic) scaffolds will be discussed, which are being investigated to support the attachment and proliferation of relevant cells. Areas of future research in the field of bioactive materials based on smart systems for engineering tissues requiring enhanced vascularisation will be addressed, including the emerging fields of tissue engineering therapeutics and regeneration of complex tissue interfaces. VOLVER ↑ Bone augmentation with injectable cement pastes Marc Bohner Osteoporotic bone fractures are often difficult to treat because the bone quality is so poor that fixation screws do not hold. As a result, broken bone pieces cannot be fixed properly. One strategy to remedy to this problem is to reinforce bone with an injectable cement FUNDACIÓN RAMÓN ARECES Jornada: Envejecimiento y Osteoporosis: situación actual y perspectiva de futuro Meeting: Ageing and Osteoporosis: Current situation and future perspectives Madrid, 21 de marzo de 2012 Madrid, April 29, 2012 RESÚMENES/ABSTRACT paste, and then place the fixation screws. Generally, poly(methyl methacrylate) (PMMA) is used for that purpose. This material has interesting mechanical properties and is cheap, but it has various drawbacks, such as a toxic monomer, a limited biocompatibility, and an absence of biodegradation. Efforts have been made in the past 20 years to replace PMMA with biodegradable cements. Particularly interesting candidates are calcium phosphate cements (CPCs). Unfortunately, CPCs tend to have poor rheological properties and are fairly weak mechanically. Furthermore, CPCs are expensive and do not have much radiographical contrast. The aim of my talk will be to give an overview on the use of injectable cement pastes for bone augmentation procedures. VOLVER ↑ Consecuencias clínicas de la fragilidad y las modificaciones músculo-esqueléticas asociadas a la edad: un reto para los pacientes de edad avanzada así como para los antiguos sistemas de asistencia sanitaria Leocadio Rodríguez Mañas Ya en el año 2001 y nuevamente en el 2012 (Fact sheet nº 344), la Organización Mundial de la Salud (OMS) alarma sobre la gran prevalencia de las caídas así como de la severidad de sus consecuencias llegando a ser la segunda causa de muerte accidental en población general. Sin embargo, son los mayores de 65 años los que sufren el mayor número de caídas fatales alcanzando en este grupo etáreo la primera causa de muerte accidental. Con estos alarmantes datos la OMS enfatiza la necesidad de promover políticas de prevención de caídas que deberían basarse en la educación poblacional, el entrenamiento específico de personal sanitario, la creación de ambientes y entornos seguros y la priorización de líneas de investigación en este campo. Entre los mayores de 65 años, el 30% sufren al menos una caída al año (de estos el 50% sufren caídas de repetición). De los pacientes que se caen el 10% sufren una consecuencia severa de la caída (fracturas, hematoma subdurales, síndrome post-caída, FUNDACIÓN RAMÓN ARECES Jornada: Envejecimiento y Osteoporosis: situación actual y perspectiva de futuro Meeting: Ageing and Osteoporosis: Current situation and future perspectives Madrid, 21 de marzo de 2012 Madrid, April 29, 2012 RESÚMENES/ABSTRACT etc), el 5-6% sufren una fractura y sólo el 1% sufre fractura de cadera. Y, por último, de los pacientes que sufren fractura de cadera, el 5% fallecen durante el ingreso, el 30% fallecen durante el primer año y, al menos, el 50% no recuperan su situación funcional previa. (Age Ageing 1988;17:365-72. N Engl J Med 1988;319:1701-7. Am J Epidemiol 1996;143:1129-36. Canadian senior`s report, 2005). Estos datos epidemiológicos han contribuido a que diferentes Servicios de Salud prioricen líneas de acción en este campo, promoviendo la creación de Unidades de Caídas y Fracturas, donde se integran estrategias de prevención de caídas, manejo de la osteoporosis y cuidado después de la caída y/o fractura (National Service Framework for Older People. National Health Service). Numerosos trabajos se han realizado en los últimos años para evaluar dichas estrategias en diferentes ámbitos. En el ámbito hospitalario las Unidades de Ortogeriatría (diseñadas en el Reino Unido para el seguimiento de los pacientes ancianos con fractura de cadera) y las consultas de valoración de riesgo de caídas con intervenciones basadas en ejercicio físico tienen un nivel de evidencia A. En el medio residencial la suplementación con vitamina D es la medida más costo-efectiva (6 dólares australianos por caída evitada, 80 dólares por hospitalización evitada); en este medio también resultaron efectivas la revisión de la medicación y las intervenciones múltiples. En el medio comunitario la medida más costoefectiva fue el Tai-chi (239 dólares australianos por caída evitada, 5179 dólares por hospitalización evitada); el cribado de caídas seguido de la derivación a las consultas de caídas y la revisión de medicación psicotropa también resultaron efectivas en este medio. VOLVER ↑ *Todos los derechos de propiedad intelectual son del autor. 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