Ciclo de mejora docente en la asignatura afecciones médicas I del grado de Fisioterapia y el doble grado en Fisioterapia y Ciencias del Deporte

En este ciclo de mejora se ha trabajado partiendo de un caso clínico sobre el que han versado todas las cuestiones que conectaban diferentes temas de la asignatura (4 temas concretamente, todos ellos relacionados con el infarto agudo de miocardio). Los alumnos han trabajado en pequeños grupos con diferentes actividades de contraste, dependiendo de la materia a trabajar (videos, cuestionarios, encuestas de opinión), todas ellas relacionadas con el caso clínico inicial y pensadas para favorecer esta metodología de aprendizaje, el debate entre ellos y la corrección de errores en el aula. La participación e implicación del alumnado ha sido alta, con una tasa de abandono prácticamente nula. Sobre la valoración de la progresión del aprendizaje de los alumnos, esta comunicación muestra la importancia de llevar a cabo una metodología centrada en el proceso de desarrollo de las escaleras de aprendizaje. Pequeños errores en el diseño, pueden subestimar esta herramienta de evaluación tan útil

Influence of obesity on microarchitecture and biomechanical properties in patients with hip fracture.

La obesidad y la osteoporosis (OP) son dos patologías muy prevalentes en nuestra sociedad actual. El efecto de la obesidad sobre la calidad ósea se encuentra en debate en la actualidad. Objetivo: Valorar el efecto del peso corporal sobre la microestructura y las propiedades biomecánicas de hueso trabecular procedente de biopsias de extremidad proximal de fémur de pacientes con fractura de cadera por fragilidad. Material y método: Estudio transversal de 16 pacientes con fractura de cadera. 2 grupos según su IMC: (A) sujetos normopeso y (B) con obesidad. Recogimos biopsias de hueso trabecular de cabeza femoral. Valoramos determinaciones bioquímicas (PTH, 25(OH) vitamina D e IGF-1), marcadores de remodelado óseo (PINP,CTX), masa ósea (DMO cuello y cadera total), microestructura ósea y estudio biomecánico (µCt). El análisis estadístico: t-Student (SPSS 22.0) significación p<0,05. Resultados: Todos los pacientes presentaron DMO de cadera en rango osteoporótico. El grupo de obesos presentó niveles superiores de PTH e inferiores de IGF-1, vitamina D y PINP. No encontramos diferencias en los parámetros relacionados con el metabolismo óseo. El grupo de obesos presentó mejores índices microestructurales alcanzando la significación: mayor volumen óseo (BV/TV: 36,6±12,7 vs. 19,4±11,4%, BS/TV: 5,5±1,1 vs. 3,9±1,3%), mayor número de trabéculas (Tb.N: 1,6±0,4 vs. 1,01±0,4), mayor anchura de trabéculas (Tb.Th: 0,22±0,003 vs. 0,17±0,05) y menor separación trabecular (Tb.Sp: 0,51±0,12 vs. 0,66±0,16). Los parámetros biomecánicos confirman una mayor resistencia del hueso trabecular en pacientes obesos. Conclusión: La obesidad puede ser un factor protector de la calidad ósea en la región femoral y tiene menos efecto sobre la densidad mineral ósea.Obesity and osteoporosis (OP) are two very prevalent diseases in our society today. The effect of obesity on bone quality is currently a subject under discussion. Objective: To assess the effect of body weight on the microstructure and biomechanical properties of trabecular bone biopsies from the proximal end of the femur in patients with hip fracture fragility. Material and methods: Cross-sectional study of 16 patients with hip fracture. The 2 groups are divided according to their BMI: (A) normal weight individuals and (B) those with obesity. We collected biopsies of cancellous bone from the femoral head and assessed biochemical determinations (PTH, 25 (OH) vitamin D and IGF-1), bone remodeling markers (PINP, CTX), bone mass (BMD neck and total hip), bone microstructure and biomechanical study (µCt). Statistical analysis: Student's t test (SPSS 22.0) significance p<0.05. Results: All patients had hip BMD in osteoporotic range. The obese group had higher levels of PTH and lower IGF-1, vitamin D and PINP. We found no differences in the parameters related to bone metabolism. The obese group showed better indices reaching microstructural significance: increased bone volume (BV/TV: 36.6±12.7 vs 19.4±11.4%, BS/TV: 5.5±1.1 vs 3.9±1.3%), higher trabecular number (Tb.N: 1.6±0.4 vs 1,01±0,4), greater trabecular width (Tb.Th: 0.22±0.003 vs 0.17±0.05) and lower trabecular separation (Tb.Sp: 0.51±0.12 vs 0.66±0.16). Biomechanical parameters confirm greater strength of trabecular bone in obese patients. Conclusion: Obesity may be a protective factor of bone quality in the femoral region and has less effect on bone mineral density

Influence of vitamin D on biomechanical microstructure and properties of patients with hip fracture.

Valorar niveles séricos de 25-hidroxivitamina D -25(OH)D-, hormonas con influencia sobre el metabolismo óseo (parathormona -PTH- y factor de crecimiento insulínico -IGF-I-), marcadores de remodelado óseo (MRO) (telopéptido carboxilo-terminal del colágeno tipo I -β-CTX- y propéptido aminoterminal del procolágeno tipo I -PINP-), densidad mineral ósea (DMO), microestructura y biomecánica de cuello de fémur, en pacientes con fractura de cadera osteoporótica (OP) vs. pacientes artrósicos (OA). Material y métodos: Estudio observacional transversal de 29 pacientes OP y 14 OA, edad ≥50 años. Cuantificamos niveles séricos hormonales y MRO (inmunoensayo), DMO de cadera (DXA), microestructura (micro-CT) y biomecánica (ensayos de compresión uniaxial, sistema IGFA). Análisis estadístico (SPSS 20.0.) Resultados: Los pacientes OP presentaron niveles inferiores de 25(OH)D (p=0,02) y DMO de cadera (p<0,05), y superiores de PTH (p=0,029) y de β-CTX (p=0,04). Los niveles de 25(OH)D se correlacionaron positivamente con IGF-I (p=0,04) y negativamente con β-CTX (p=0,003). Los valores de PTH se correlacionaron negativamente con DMO de cadera (p=0,0005) y positivamente con la separación trabecular (Tb.Th) (p=0,006). Los pacientes con niveles de 25(OH)D <20 ng/mL presentaron niveles mayores de β-CTX (p=0,006), menores de IGF-I (p=0,007) y Tb.Th (p=0,04). Conclusiones: Los niveles de vitamina D son bajos en población anciana, sobre todo en pacientes con fractura de cadera osteoporótica. Además, en estos pacientes existen niveles elevados de PTH y MRO y descendidos de DMO. Los pacientes cuyos niveles de 25(OH)D son inferiores a 20 ng/mL presentan un remodelado óseo más elevado, con menores niveles de IGF-I y alteraciones de la estructura ósea (Tb.Th) que puedan estar en relación con un mayor riesgo de fracturas.To assess serum levels of 25-hydroxyvitamin D-25 (OH) D-hormones with influence on bone metabolism (parathormone -PTH- and insulin-like growth factor (IGF)-I), bone remodeling markers (BRM) (carboxy-terminal telopeptide of collagen type I-β-CTX- and amino-peptide pro-peptide of procollagen type I -PINP), bone mineral density (BMD), microstructure and biomechanics of the femoral neck, in patients with osteoporotic hip fracture (OH) versus arthritic patients (OA). Material and methods: A cross-sectional observational study of 29 OH and 14 OA, age ≥50 years. We quantified hormonal serum levels and BRM (immunoassay), hip BMD (DXA), microstructure (micro-CT) and biomechanics (uniaxial compression tests, IGFA system). Analysis (SPSS 20.0.) Results: OH patients had lower levels of 25(OH)D (p=0.02) and hip BMD (p<0.05), and higher PTH (p=0.029) and β-CTX (p=0.04). Levels of 25(OH)D correlated positively with IGF-I (p=0.04) and negatively with β-CTX (p=0.003). The PTH values were correlated negatively with hip BMD (p=0.0005) and positively with trabecular thickness (TbTh) (p=0.006). Patients with 25(OH)D <20 ng/mL presented higher levels of β-CTX (p=0.006), lower IGF-I (p=0.007) and TbTh (p=0.04). Conclusions: Vitamin D levels are low in the elderly population, especially in patients with osteoporotic hip fracture. These patients also presented raised levels of PTH and BRM and descended from BMD. Patients whose 25(OH)D levels are below 20 ng/mL present higher bone remodeling, with lower levels of IGF-I and alterations of the bone structure (TbTh) that may be linked to a greater risk of fractures

What are microRNAs? Potential biomarkers and therapeutic targets in osteoporosis

Los micro-ARN (miRs) son pequeñas moléculas de ARN no codificantes que regulan la expresión génica a nivel post-transcripcional. Generalmente actúan sobre la expresión genética mediante el silenciamiento o degradación de los ARNm, y están implicados en la regulación de varios procesos biológicos, como la diferenciación celular, la proliferación, la apoptosis y en el desarrollo embrionario y tisular. Actualmente son un importante foco de interés para el estudio de diversas enfermedades como el cáncer o la diabetes mellitus tipo 2. A nivel del metabolismo óseo, están surgiendo diversos miRs implicados en su regulación, abriendo un campo de investigación importante para identificar nuevos biomarcadores para el diagnóstico de la enfermedad osteoporótica, de su evolución, así como para diseñar nuevas terapias farmacológicas.Micro-RNAs (miRs) are small non-coding RNA molecules that regulate gene expression at post-transcriptional level. Generally, they act on gene expression by silencing or degrading mRNAs, and are involved in regulating various biological processes, such as cell differentiation, proliferation, apoptosis and in embryonic and tissue development. They are currently a major focus of interest in the study of various diseases such as cancer or type 2 diabetes mellitus. At level of bone metabolism, various miRs are emerging that are involved in their regulation, opening an important research field to identify new biomarkers for diagnosis of osteoporosis and its development, and to design new drug therapies

Modifying RANKL/OPG mRNA expression in differentiating and growing human primary osteoblasts

The OPG / RANKL system in primary cultures of human osteoblasts has been studied by di ff erent authors. However, very few studies have been performed on gene expression of RANKL and OPG at di ff erent stages of maturation on human osteoblast cultures.The e ff ect of 17-estradiol and 1,25dihydroxyvitamin D3 on the OPG / RANKL system is not known during the di ff erent states of cellular maturation. In this work we quantifi ed OPG and RANKL protein levels (ELISA) and the mRNA of OPG, RANKL, collagen type I, alkaline phosphatase, and osteocalcin (semi-quantita-tive RT-PCR) in human osteoblasts. We analyzed these in basal conditions and after incubation with 17- -estradiol and 1,25dihydroxyvitamin D3 in the first and second phases. We found that OPG secretion and expression levels increased throughout cellular growth.RANKL proteins were detected only in the first stage, and the expression increased throughout the first phase. Thus, the RANKL / OPG ratio was higher in immature osteoblasts than in mature osteoblasts. The evolution of RANKL gene expression was related to collagen I and alkaline phosphatase, while OPG was related to osteocalcin. We observed no modi fi cations after estradiol and 1,25dihydroxyvitamin D3 treatment. Our results suggest that the OB is a positive stimulator at precocious stages of diff erentiation on osteoclastogenic modulates

Biocompatibility and osseointegration study of new prosthetic materials

Objetivos Los implantes óseos son utilizados cada vez con mayor frecuencia en la práctica clínica y, entre los materiales, el Ti o sus aleaciones son los de mejor rendimiento por sus propiedades fisicoquímicas. Aleaciones como TiNbTa han demostrado mejorar las características biomecánicas del Ti puro comercial (c.p.), sin embargo, su capacidad osteointegradora necesita ser evaluada. El objetivo del presente estudio fue valorar la citotoxicidad y la capacidad de adhesión, proliferación y diferenciación de células osteoblásticas en cultivo, influida por discos de material TiNbTa frente a Ti c.p. Material y métodos Analizamos a los 4 y 7 días del cultivo la línea celular MC3T3, la viabilidad celular (AlamarBlue Cell Viability Reagent. Invitrogen, España), así como la proliferación y diferenciación celular (actividad de fosfatasa alcalina (ALP) y microscopía electrónica de barrido (Fijación para SEM). Se realizó la prueba t de Student para determinar diferencias estadísticamente significativas entre los dos grupos de discos de estudio. Resultados Los resultados obtenidos demuestran muy buena viabilidad celular durante el periodo de estudio, sin diferencias significativas para ambos materiales. Así mismo, detectamos una caída en los niveles de ALP que fue significativa para ambos componentes entre los días 4 y 7 del estudio (p<0,05). Las imágenes de microscopía electrónica revelaron buena capacidad de adhesión al material, así como diferenciación celular frente a ambos tipos de discos. Conclusiones La aleación de TiNbTa como material para implantes óseos cuenta con una buena capacidad osteointegradora, además de resolver problemas de biomecánica que presenta el titanio puro como componente.Objetive Bone implants are increasingly used in clinical practice and, among the materials, Ti or its alloys are offer the best performance given their physicochemical properties. Alloys such as TiNbTa have been shown to improve the biomechanical characteristics of commercial pure Ti (c.p.), however, its osseointegration capacity needs to be evaluated. The objective of the present study was to assess the cytotoxicity and the adhesion, proliferation and differentiation capacity of osteoblastic cells in culture, influenced by discs of TiNbTa material versus Ti c.p. Material and methods At 4 and 7 days after culture, we analyzed the MC3T3 cell line, cell viability (AlamarBlue Cell Viability Reagent. Invitrogen, Spain), as well as cell proliferation and differentiation (alkaline phosphatase activity (ALP) and scanning electron microscopy (Fixation for SEM) Student's t test was performed to determine statistically significant differences between the two groups of study discs. Results The results obtained show very good cell viability during the study period, with no significant differences for both materials. Likewise, we detected a drop in ALP levels that was significant for both components between days 4 and 7 of the study (p <0.05). Electron microscopy images revealed good adhesion capacity to the material, as well as cell differentiation against both types of discs. Conclusions The TiNbTa alloy as a material for bone implants offers good osseointegrative capacity, in addition to solving biomechanical problems that pure titanium presents as a component

In Vitro Bone Cell Behavior on Porous Titanium Samples: Influence of Porosity by Loose Sintering and Space Holder Techniques

A great variety of powder metallurgy techniques can produce biomimetic porous titanium structures with similar mechanical properties to host bone tissue. In this work, loose sintering and space holder techniques, two frequently used metallurgical techniques, are compared to evaluate the influences of porosity (content, size, morphology and wall roughness), mechanical properties (stiffness and yield strength) and in-vitro cellular responses (adhesion and proliferation of myoblasts and osteoblasts). These comparisons are made to achieve the best balance between biomechanical and bifunctional behavior of a partial porous implant for cortical bone replacement. Cell adhesion (filopodia presence) and spreading were promoted on both porous surfaces and fully dense substrates (non-porous control surfaces). Porous scaffold samples designed using 50 vol.% NaCl space holder technique had an improved bioactive response over those obtained with the loose sintering technique due to higher roughness and scaffold pore diameter. However, the presence of large and heterogeneous pores compromises the mechanical reliability of the implant. Considering both scenarios, the substrates obtained with 40 vol.% NH4HCO3 and pore size ranges between 100 and 200 μm provide a balanced optimization of size and strength to promote in-vitro osseointegration.FEDER US-1259771University Complutense of Madrid (UCM) C2C12-GFPJunta de Andalucía US-125977

Use of Impedance Spectroscopy for the Characterization of In-Vitro Osteoblast Cell Response in Porous Titanium Bone Implants

The use of titanium implants with adequate porosity (content, size and morphology) could solve the stress shielding limitations that occur in conventional titanium implants. Experiments to assess the cellular response (adhesion, proliferation and differentiation of osteoblasts) on implants are expensive, time-consuming and delicate. In this work, we propose the use of impedance spectroscopy to evaluate the growth of osteoblasts on porous titanium implants. Osteoblasts cells were cultured on fully-dense and 40 vol.% porous discs with two ranges of pore size (100–200 μm and 355–500 μm) to study cell viability, proliferation, differentiation (Alkaline phosphatase activity) and cell morphology. The porous substrates 40 vol.% (100–200 µm) showed improved osseointegration response as achieved more than 80% of cell viability and higher levels of Cell Differentiation by Alkaline Phosphatase (ALP) at 21 days. This cell behavior was further evaluated observing an increase in the impedance modulus for all study conditions when cells were attached. However, impedance levels were higher on fully-dense due to its surface properties (flat surface) than porous substrates (flat and pore walls). Surface parameters play an important role on the global measured impedance. Impedance is useful for characterizing cell cultures in different sample types.Ministry of Science and Innovation of Spain grant PID2019-109371GB-I00Junta de Andalucía–FEDER (Spain) Project US-1259771Junta de Andalucía-Proyecto de Excelencia (Spain) P18-FR-203

Influence of Femtosecond Laser Modification on Biomechanical and Biofunctional Behavior of Porous Titanium Substrates

Bone resorption and inadequate osseointegration are considered the main problems of titanium implants. In this investigation, the texture and surface roughness of porous titanium samples obtained by the space holder technique were modified with a femtosecond Yb-doped fiber laser. Different percentages of porosity (30, 40, 50, and 60 vol.%) and particle range size (100–200 and 355–500 μm) were compared with fully-dense samples obtained by conventional powder metallurgy. After femtosecond laser treatment the formation of a rough surface with micro-columns and micro-holes occurred for all the studied substrates. The surface was covered by ripples over the micro-metric structures. This work evaluates both the influence of the macro-pores inherent to the spacer particles, as well as the micro-columns and the texture generated with the laser, on the wettability of the surface, the cell behavior (adhesion and proliferation of osteoblasts), micro-hardness (instrumented micro-indentation test, P–h curves) and scratch resistance. The titanium sample with 30 vol.% and a pore range size of 100–200 μm was the best candidate for the replacement of small damaged cortical bone tissues, based on its better biomechanical (stiffness and yield strength) and biofunctional balance (bone in-growth and in vitro osseointegration).Ministerio de Ciencia e Innovación del Gobierno de España PID2019-109371GB-100Junta de Andalucía (Spain) PAIDI P20-0067