Diferencias entre los métodos de determinación de 2.a y 3.a generación de la parathormona sérica sobre la mortalidad en el paciente en hemodiálisis

Parathormone plays a key role in controlling mineral metabolism. PTH is considered a uremic toxin causing cardiovascular damage and cardiovascular mortality in dialysis patients. There are two different assays to measure PTH called 2nd generation or intact PTH (iPTH) and 3rd generation or bioPTH (PTHbio). Objective: To evaluate the differences in mortality of dialysis patients between both assays to measure PTH, as well as the possible prognostic role of the PTHbio/iPTH ratio. Methods: 145 haemodialysis patients were included with 2-year monitoring including baseline laboratory test and annually thereafter. Results: 21 patients died in the first year and 28 in the second. No correlation was found between PTH, PTHbio and PTHbio/iPTH ratio with mortality. Both PTH have a perfect correlation between them and correlate similarly with other molecules of the mineral metabolism. The extreme baseline values of PTH are those of higher mortality. In survival by iPTH intervals (according to guidelines and COSMOS study), a J curve is observed. When iPTH increases, the ratio decreases, possibly when increasing fragments no. 1–84. There is no greater prognostic approximation on mortality with PTHbio than PTHi. There was also no difference in mortality when progression ratio PTHbio/PTHi was analysed. Conclusions: We didn’t find any advantages to using bioPTH vs. PTHi as a marker of mortality. BioPTH limits of normality must be reevaluated because its relationship with iPTH is not consistent. Not knowing these limits affects its prognostic valueLa paratohormona tiene un papel fundamental en el control del metabolismo mineral. Además es considerada como una toxina urémica al originar dan˜ o cardiovascular e influir en la mortalidad cardiovascular del paciente en diálisis. Existen dos métodos de medición denominados de 2.a generación o PTH intacta (PTHi) y de 3.a generación o bioPTH (PTHbio). Objetivo: Evaluar las diferencias en la mortalidad del paciente en diálisis entre ambas formas de medición de PTH, así como el posible papel pronóstico de su cociente. Métodos: Se incluyeron 145 pacientes en hemodiálisis con un seguimiento de 2 an˜ os con determinación analítica basal y posteriormente de forma anual. Resultados: Veintiún pacientes fallecieron el primer an˜ o y 28 el segundo. No se encontró correlación entre PTHi, PTHbio y cociente PTHbio/PTHi con la mortalidad. Ambas PTH tienen una buena correlación entre ellas y correlacionan de manera similar con otras moléculas del metabolismo mineral. Los valores basales de PTH extremos son los de mayor mortalidad. En la supervivencia por tramos de PTHi (según guías y estudio COSMOS) se observa una curva en J. A mayor aumento de PTHi el cociente desciende, posiblemente al aumentar los fragmentos no 1-84. No existe una mayor aproximación pronóstica sobre mortalidad con PTHbio que con PTHi. No se observan diferencias en el valor predictivo del cociente sobre la mortalidad. Tampoco hubo diferencias en mortalidad cuando se analiza la progresión del cociente PTHbio/PTHi. Conclusiones: No encontramos ventajas en la utilización de PTHbio sobre la PTHi como marcador de mortalidad. Se deben reevaluar los límites de la PTHbio pues su relación con la PTHi no es constante. El no conocer esos límites condiciona su utilidad pronósticaOur thanks to Maribel Villarino for the help with the development of the study. L.R.-O. is a Health Professional on Research Training “Rio Hortega r” (CM13/00131), Ministry of Education, Government of Spain. R.V.B. is a professional with postdoctoral contract “Sara Borrell” (CD14/00198) and a project (SAF2014- 60699-JIN) of the Ministry of Economy (MINECO) and FEDER funds. PI14/00386. PI16/01298. FEDER funds ISCIII-RETIC REDinREN/ RD06/0016, RD12/002

Biochemical markers of bone turnover and clinical outcome in patients with renal cell and bladder carcinoma with bone metastases following treatment with zoledronic acid: The TUGAMO study

Background: Levels of bone turnover markers (BTM) might be correlated with outcome in terms of skeletal-related events (SRE), disease progression, and death in patients with bladder cancer (BC) and renal cell carcinoma (RCC) with bone metastases (BM). We try to evaluate this possible correlation in patients who receive treatment with zoledronic acid (ZOL). Methods: This observational, prospective, and multicenter study analysed BTM and clinical outcome in these patients. Serum levels of bone alkaline phosphatase (BALP), procollagen type I amino-terminal propeptide (PINP), and beta-isomer of carboxyterminal telopeptide of type I collagen (b-CTX) were analysed. Results: Patients with RCC who died or progressed had higher baseline b-CTX levels and those who experienced SRE during follow-up showed high baseline BALP levels. In BC, a poor rate of survival was related with high baseline b-CTX and BALP levels, and new SRE with increased PINP levels. Cox univariate analysis showed that b-CTX levels were associated with higher mortality and disease progression in RCC and higher mortality in BC. Bone alkaline phosphatase was associated with increased risk of premature SRE appearance in RCC and death in BC. Conclusion: Beta-isomer of carboxy-terminal telopeptide of type I collagen and BALP can be considered a complementary tool for prediction of clinical outcomes in patients with BC and RCC with BM treated with ZOLNovartis Oncology Spain for supporting this stud

Usefulness of bone turnover markers as predictors of mortality risk, disease progression and skeletal-related events appearance in patients with prostate cancer with bone metastases following treatment with zoledronic acid: TUGAMO study

Owing to the limited validity of clinical data on the treatment of prostate cancer (PCa) and bone metastases, biochemical markers are a promising tool for predicting survival, disease progression and skeletal-related events (SREs) in these patients. The aim of this study was to evaluate the predictive capacity of biochemical markers of bone turnover for mortality risk, disease progression and SREs in patients with PCa and bone metastases undergoing treatment with zoledronic acid (ZA). Methods: This was an observational, prospective and multicenter study in which ninety-eight patients were included. Patients were treated with ZA (4mg every 4 weeks for 18 months). Data were collected at baseline and 3, 6, 9, 12, 15 and 18 months after the beginning of treatment. Serum levels of bone alkaline phosphtase (BALP), aminoterminal propeptide of procollagen type I (P1NP) and beta-isomer of carboxiterminal telopeptide of collagen I (b-CTX) were analysed at all points in the study. Data on disease progression, SREs development and survival were recorded. Results: Cox regression models with clinical data and bone markers showed that the levels of the three markers studied were predictive of survival time, with b-CTX being especially powerful, in which a lack of normalisation in visit 1 (3 months after the beginning of treatment) showed a 6.3-times more risk for death than in normalised patients. Levels of these markers were also predictive for SREs, although in this case BALP and P1NP proved to be better predictors. We did not find any relationship between bone markers and disease progression. Conclusion: In patients with PCa and bone metastases treated with ZA, b-CTX and P1NP can be considered suitable predictors for mortality risk, while BALP and P1NP are appropriate for SREs. The levels of these biomarkers 3 months after the beginning of treatment are especially importantThis study was supported by Novartis Oncology Spai

Gestión del conocimiento. Perspectiva multidisciplinaria. Volumen 17

El libro “Gestión del Conocimiento. Perspectiva Multidisciplinaria”, Volumen 17 de la Colección Unión Global, es resultado de investigaciones. Los capítulos del libro, son resultados de investigaciones desarrolladas por sus autores. El libro es una publicación internacional, seriada, continua, arbitrada, de acceso abierto a todas las áreas del conocimiento, orientada a contribuir con procesos de gestión del conocimiento científico, tecnológico y humanístico. Con esta colección, se aspira contribuir con el cultivo, la comprensión, la recopilación y la apropiación social del conocimiento en cuanto a patrimonio intangible de la humanidad, con el propósito de hacer aportes con la transformación de las relaciones socioculturales que sustentan la construcción social de los saberes y su reconocimiento como bien público

Valores de normalidad del propéptido aminoterminal del colágeno tipo I (PINP) y del isómero beta del telopéptido carboxiterminal del colageno I (b-CTX) en el suero de mujeres sanas premenopáusicas de la Comunidad de Madrid.

Introduction: In the laboratory it is sometimes difficult to find the normality intervals of the population itself, there being a tendency to give the normality value specified by the manufacturer of the reagent. The aim of this work was to calculate the normality values for aminoterminal propeptide of type I collagen (PINP) and for the beta isomer of carboxy-terminal telopeptide of type I collagen (b-CTX) in the blood of a group of premenopausal women from the autonomous Community of Madrid. Materials and methods: The study was carried out in 50 healthy premenopausal women between 27 and 40 years of age (mean ± standard deviation of 34±3 years, working in a hospital and a pharmaceutical laboratory in Madrid. Blood levels of PINP and b-CTX were determined using the technique of electrochemiluminescence (Elecsys, Roche). Results: Normal values of 36.2±12.9 ng/ml (range 10.4 to 62) for PINP and 0.306±0.121 ng/ml (range of 0.064 to 0.548) for b-CTX were obtained. Conclusions: Although the population sample used was small and localised, we consider that these values may be used as the normality interval for Spanish women.Introducción: En el laboratorio resulta complejo en ocasiones tener intervalos de normalidad de la propia población, y se tiende a mostrar el valor de normalidad indicado por el fabricante del reactivo. El objetivo de este trabajo fue calcular los valores de normalidad del propéptido aminoterminal del colágeno tipo I (PINP) y del isomero beta del telopeptido carboxiterminal del colágeno I (�À-CTX) en el suero de un grupo de mujeres sanas premenopáusicas de la Comunidad de Madrid. Materiales y métodos: El estudio se realizó en 50 mujeres sanas premenopáusicas de entre 27 y 40 años de edad (media +/- desviacion estandar: 34�+/-3 años), trabajadoras de un hospital y un laboratorio farmacéutico situado en Madrid. Se determinaron el PINP y el �À-CTX en suero mediante una técnica de electroquimioluminiscencia (Elecsys, Roche). Resultados: Se obtuvieron unos valores normales de 36,2�+/-12,9 ng/ml (rango 10,4-62) para el PINP y de 0,306�+/-0,121 ng/ml (rango de 0,064 a 0,548) para el �À-CTX. Conclusiones: Aunque se trata de una muestra poblacional pequeña y localizada, consideramos que estos valores pudieran utilizarse como intervalo de normalidad para la mujer española

Relationship between vitamin D deficiency, bone remodelling and iron status in iron-deficient young women consuming an iron fortified food

This study was supported by Project AGL2009-11437 and Grupo Leche PascualPeer Reviewe

Hiperparatiroidismo secundario al déficit de vitamina D

Introduction: Vitamin D is increasingly recognized as playing a significant role in combatting many diseases. One is the development of secondary hyperthyroidism due vitamin D deficiency. To date, laboratory quantification methods of serum vitamin D were not well standardized. It could not be established with certainty from which levels of vitamin D certains abnormalities take place, like an elevation of PTH. The present study was aimed at determining below what vitamin D levels we will find abnormally high levels of PTH, carrying out the vitamin D determination in the laboratory with a standardized, reliable technique. Methods: This descriptive, retrospective study was conducted with patients over 18 years in which determinations were made simultaneously with PTH, 25 (OH) vitamin D (25OHD) and which also have normal values of calcium, glomerular filtration rate and phosphorus. For determining vitamin D, standardized electrochemiluminescence method was used with gas chromatography-mass spectrometry method. Using the Stava version 11 statistical program, the 25OHD was calculated where PTH value was above 70 pg/ml with greater sensitivity and specificity. Results: In all, 4,083 patients were included, of whom 2,858 were women (70%) and 1,225 (30%) males. The mean age of the study population was 60.60 years (standard deviation, 15.29). 74% of the population had a serum PTH under 70 pg/ml (normal values) and 26% had a serum PTH higher tan 70 ng/ml. By constructing the ROC curve levels of 25OHD, depending on PTH values below or above 70 pg/ml, the area under the curve was 0.5962 (p<0.0001). The cut having jointly account the sensitivity and specificity that determined vitamin D levels to predict PTH values above 70 pg/ml was 24 ng/ml. Of the patients with normal PTH, 71% presented normal vitamin D values, while patients with elevated PTH (Greater than 70 pg/ml), almost half had a vitamin D below 24 ng / ml, which increased as the PTH percentage was elevated. Conclusions: The 25OHD value that presents better specificity and sensitivity to predict abnormally high PTH is 24 ng/ml, which is higher than the level reported in previous work, (about 18 ng/ml) value. The results of this study, carried out with an appropriately calibrated method, showed that 44.9% of patients with vitamin D values of less than 24 ng/ml PTH had abnormally high levels, with a normal value of calcium and phosphorus and normal renal function. This percentage is less in those individuals between 18 and 40 years (24%) and reaches 49% beyond 60 years. These patients could be treated with vitamin D to prevent possible secondary hyperparathyroidism due to vitamin deficiency. It is noteworthy that the method of determining vitamin D used must be properly standardized with respect to gas chromatography-tandem mass spectrometry method.Introducción: Cada vez está más demostrado el papel de la vitamina D en múltiples patologías, una de ellas el desarrollo de un hiperparatiroidismo secundario al déficit de vitamina D. Los métodos de laboratorio de cuantificación de vitamina D en suero no estaban bien estandarizados hasta ahora, por lo que no podía establecerse con certeza a partir de qué niveles de vitamina D se producían determinadas anomalías como la elevación de la PTH. Nuestro estudio pretende determinar por debajo de qué niveles de vitamina D nos encontraremos con niveles de PTH anormalmente elevados, realizando la determinación de vitamina D en el laboratorio con una técnica debidamente estandarizada y fiable. Métodos: El estudio descriptivo y retrospectivo se realizó con pacientes mayores de 18 años en los que se hicieron simultáneamente determinaciones de PTH, 25(OH) vitamina D (25OHD) y que además tuvieran valores normales de calcio, filtrado glomerular y fósforo. Para la determinación de vitamina D se utilizó un método de electroquimioluminiscencia estandarizado con respecto a la técnica de gases-masas. Por el programa estadístico Stava versión 11 se calculó el valor de 25OHD para el que la PTH se elevaba por encima de 70 pg/ml con la mayor sensibilidad y especificidad. Resultados: Se incluyeron 4.083 pacientes, de los que 2.858 eran mujeres (70%) y 1.225 (30%) varones. La edad media de la población estudiada fue 60,60 años (desviación estándar, 15,29). El 74% de la población tenía una PTH en suero por debajo de 70 pg/ml (valores considerados normales) y el 26% mayor de 70 pg/ml. Al construir la curva de ROC de los niveles de 25OHD, en función de valores de PTH por debajo o por encima de 70 pg/ml, el área bajo la curva fue 0,5962 (p<0,0001). El punto de corte teniendo en cuenta conjuntamente la sensibilidad y la especificidad que determinaban los valores de vitamina D para predecir los valores de PTH por encima de 70 pg/ml fue 24 ng/ml. De los pacientes con PTH normal, el 71% tenían valores de vitamina D normales, mientras que, de los pacientes con PTH elevada (mayor de 70 pg/ml), casi la mitad presentaban una vitamina D menor de 24 ng/ml, porcentaje que aumentaba según se iba elevando la PTH. Conclusiones: El valor de 25OHD que muestra una mejor especificidad y sensibilidad para predecir valores anormalmente elevados de PTH es 24 ng/ml, valor superior al presentado en trabajos anteriores (alrededor de 18 ng/ml). Con los resultados de este estudio, realizado con un método debidamente calibrado, se puede decir que el 44,9% de pacientes con valores de vitamina D menores de 24 ng/ml presenta niveles de PTH anormalmente elevados, con una función renal normal y valores de calcio y fósforo normales. Este porcentaje es menor entre los 18 y 40 años (24%) y llega al 49% por encima de los 60 años. Estos pacientes podrían tratarse con vitamina D para evitar un posible hiperparatiroidismo secundario al déficit de dicha vitamina. Es importante tener en cuenta que el método de determinación de vitamina D utilizado debe estar debidamente estandarizado con respecto al método de gases-masas

Effects of Virgin Olive Oil on Bone Health in Ovariectomized Rats

Osteoporosis is a pressing concern facing public health, thus making research into the effects of nutrients on bone health particularly important. Evidence from preclinical studies using animal models and a limited number of studies in human suggests that olive oil (OO) is a protective agent for bone. The aim of this work is to study the effects of virgin olive oil (VOO) consumption by ovariectomized rats on bone health. A total of 48 6-month-old female Wistar rats weighing 320 &plusmn; 10 g (mean &plusmn; SD) were divided into the following groups: SHAM (n = 12), simulated intervention; OVX (n = 12), ovariectomized; OVX + 100 (n = 12), ovariectomized and treated with VOO (100 &micro;L/day by oral gavage); and OVX + 200 (n = 12) ovariectomized and treated with VOO (200 &micro;L/day by oral gavage), all over 3 months. Femoral (F) and lumbar (L) bone mineral density (FBMD and LBMD), microtomographic parameters, fractal dimension D2D and D3D, and biomechanical properties were studied. After 3 months of VOO treatment, although FBMD and LBMD were not affected, bone quality was improved, as the elasticity of bone and fractal dimension (complexity of bone) were more similar to healthy bone. Our results support the findings of previous research suggesting that dietary intake of olive oil may exert beneficial effect on some bone characteristics

Comparación entre dos inmunoensayos automatizados por quimioluminiscencia para la cuantificación de 25(OH) vitamina D

Introduction: Quantifying total blood 25 (OH) vitamin D is the most accurate marker of an individual’s vitamin D status. The gold standard technique for measurement is liquid chromatography tandem mass spectrometry (LC-MS/MS), although currently clinical laboratories tend to use chemiluminescence techniques. The objective of this study was to compare 25 (OH) vitamin D concentrations obtained by two commercially-produced automated methods and study the correlation of these methods with the LC-MS/MS reference technique. Material and methods: The 25(OH) vitamin D levels were quantified in 1,000 serum samples from the Jimenez Diaz Biochemistry Foundation Laboratory using 2 automated methods for chemiluminescence detection: ADVIA CENTAURO ® (SIEMENS) and LUMIPULSE G1200 (Fujirebio). Among all the samples tested, the 50 most discordant to each other were sent to be evaluated by LC-MS/MS reference technique. Results: The results indicate that there is good correlation between the two methods: CCI=0.923 (0.914-0.932), with the G1200 LUMIPULSE ® ® values 10% being higher than CENTAURO . Regarding the 50 samples selected, we can see that there is a good correlation between the two immunoassays with LC-MS/MS, although both methods significantly underestimate 25 (OH) vitamin D results with respect to the gold standard. Discussion: Although both techniques are suitable for use, it is worth considering whether the worldwide vitamin D deficiency epidemic is due to the analysis methodology used. This variability between immunoassays could be solved by standardizing the different commercial techniques in line with NISTproduced reference materials. ®Introducción: La cuantificación de 25(OH) vitamina D total en sangre es el marcador más preciso del estado de vitamina D en un individuo. La técnica patrón-oro para su medición es la cromatografía líquida/espectrometría de masas en tándem (LC-MS/MS), aunque actualmente los laboratorios clínicos utilizan de rutina técnicas de quimioluminiscencia. El objetivo del estudio fue comparar las concentraciones de 25(OH) vitamina D obtenidas mediante dos métodos automatizados comerciales y estudiar la correlación de dichos métodos con la técnica de referencia LC-MS/MS. Material y método: Se cuantificaron los niveles de 25(OH) vitamina D en 1.000 muestras de suero del laboratorio de Bioquímica de la Fundación Jiménez Díaz mediante 2 métodos automatizados comerciales por detección de quimioluminiscencia: ADVIA CENTAURO ® (SIEMENS) y LUMIPULSE G1200 (FUJIREBIO). Entre todas las muestras analizadas, las 50 más discordantes entre sí se enviaron para ser evaluadas por la técnica de referencia LC-MS/MS. Resultados: Los resultados obtenidos indican que existe una buena correlación entre los dos métodos: CCI=0,923 (0,914-0,932), siendo los valores de LUMIPULSE G1200 un 10% superiores a los de CENTAURO ® ® . Con respecto a las 50 muestras seleccionadas, podemos observar que existe una buena correlación entre los dos inmunoensayos con la técnica LC-MS/MS, aunque ambos métodos infraestiman considerablemente los resultados de 25(OH) vitamina D con respecto al patrón-oro. Discusión: Aunque ambas técnicas son adecuadas para su utilización, habría que plantearse si la “epidemia” mundial de hipovitaminosis D se debe a la metodología de análisis utilizada. Esta variabilidad entre inmunoensayos se solucionaría estandarizando las diferentes técnicas comerciales con los materiales de referencia elaborados por el NIST.

Bone remodelling is not affected by consumption of a sodium-rich carbonated mineral water in healthy postmenopausal women

This study was designed to investigate the possible effects of consuming Na-rich carbonated mineral water on bone remodelling and urinary mineral excretion in postmenopausal women. Women (n 18) included were amenorrhoeic (> 1 year), healthy and not obese (BMI < 30 kg/m2). No woman was taking oestrogen replacement therapy, mineral and vitamin supplements, phyto-oestrogens or medications known to affect bone and lipid metabolism. In two consecutive interventions that lasted 8 weeks each, women drank 1 litre of control mineral water daily and 1 litre of carbonated mineral water, rich in Na, HCO3 - and Cl-, daily. Body weight and height were measured, BMI was calculated and blood pressure was measured. Blood samples were taken from fasting subjects and serum obtained to analyse the biochemical bone markers, procollagen I amino-terminal propeptide (PINP) and β-carboxy-terminal telopeptide of collagen (β-CTX). At the end of each period, 24 h urine samples were collected to determine Ca, Mg, P, Na +, K+, Cl-, urine excretion and urinary pH. No changes in body weight, BMI or blood pressure were observed during the experimental period. Ca excretion was lower after the intake of carbonated water than after intake of the control water (P=0.037) while P excretion was higher (P=0.015). Total urine, Na and Cl- excretion did not differ between the two periods but urinary pH was increased after the intake of carbonated mineral water. PINP and β-CTX did not differ between the two periods. Daily consumption of 1 litre of Na-rich carbonated mineral water for 8 weeks does not affect bone remodelling in healthy postmenopausal women. © The Authors 2005.Peer Reviewe