RESUMEN

OBJECTIVE: Considering the osteoarthritis (OA) model that integrates the biological, mechanical, and structural components of the disease, the present study aimed to investigate the association between urinary C-Telopeptide fragments of type II collagen (uCTX-II), knee joint moments, pain, and physical function in individuals with medial knee OA. METHODS: Twenty-five subjects radiographically diagnosed with knee OA were recruited. Participants were evaluated through three-dimensional gait analysis, uCTX-II level, the WOMAC pain and physical function scores, and the 40m walk test. The association between these variables was investigated using Pearson's product-moment correlation, followed by a hierarchical linear regression, controlled by OA severity and body mass index (BMI). RESULTS: No relationship was found between uCTX-II level and knee moments. A significant correlation between uCTX-II level and pain, physical function, and the 40m walk test was found. The hierarchical linear regression controlling for OA severity and BMI showed that uCTX-II level explained 9% of the WOMAC pain score, 27% of the WOMAC physical function score, and 7% of the 40m walk test. CONCLUSION: Greater uCTX-II level is associated with higher pain and reduced physical function and 40m walk test performance in individuals with medial knee OA.

Asunto(s)

Colágeno Tipo II/química , Colágeno Tipo I/química , Articulación de la Rodilla/fisiopatología , Osteoartritis de la Rodilla/fisiopatología , Dolor/fisiopatología , Péptidos/química , Biomarcadores , Colágeno Tipo I/orina , Humanos , Péptidos/orina

RESUMEN

A complex mixture of peptides plays a key role in the regulation of the immune system; different sources as raw materials mainly from animals and vegetables have been reported to provide these extracts. The batch-to-batch product consistency depends on in-process controls established. However, when an immunomodulator is a customized product obtained from the same volunteer who will receive the product to personalize the treatment, the criteria to establish the consistency between volunteers are different. In this sense, it is expected to have the same molecular weight range although the profile of peptide abundance is different. Here, we characterized the peptide profile of three extracts of an immunomodulator obtained from the urine of different volunteers suffering from three different diseases (i.e., allergic rhinitis, rheumatoid arthritis, and chronic rhinopharyngitis), using size exclusion chromatography (SEC) and mass spectrometry (MS). The peptides contained in the immunomodulators were stable after six months, stored in a refrigerator. Our results showed a chromatographic profile with the same range of low molecular weight (less than 17 kDa) in all analyzed samples by SEC; these results were also confirmed by MS showing an exact mass spectrum from 3 to 13 kDa. The fact that the peptide profiles were conserved during a six-month period at refrigeration conditions (2 to 8°C) maintaining the quality and stability of the immunomodulator supports the notion that it might be an alternative in the treatment of chronic hypersensibility disorders.

Asunto(s)

Factores Inmunológicos/química , Factores Inmunológicos/orina , Péptidos/química , Péptidos/orina , Cromatografía en Gel , Humanos , Enfermedades del Sistema Inmune/orina , Factores Inmunológicos/aislamiento & purificación , Espectrometría de Masas , Peso Molecular , Péptidos/aislamiento & purificación , Estabilidad Proteica , Reproducibilidad de los Resultados

RESUMEN

The aim of this study was to establish a peptidomic profile based on LC-MS/MS and random forest (RF) algorithm to distinguish the urinary peptidomic scenario of type 2 diabetes mellitus (T2DM) patients with different stages of diabetic kidney disease (DKD). Urine from 60 T2DM patients was collected: 22 normal (stage A1), 18 moderately increased (stage A2) and 20 severely increased (stage A3) albuminuria. A total of 1080 naturally occurring peptides were detected, which resulted in the identification of a total of 100 proteins, irrespective of the patients' renal status. The classification accuracy showed that the most severe DKD (A3) presented a distinct urinary peptidomic pattern. Estimates for peptide importance assessed during RF model training included multiple fragments of collagen and alpha-1 antitrypsin, previously associated to DKD. Proteasix tool predicted 48 proteases potentially involved in the generation of the 60 most important peptides identified in the urine of DM patients, including metallopeptidases, cathepsins, and calpains. Collectively, our study lightened some biomarkers possibly involved in the pathogenic mechanisms of DKD, suggesting that peptidomics is a valuable tool for identifying the molecular mechanisms underpinning the disease and thus novel therapeutic targets.

Asunto(s)

Nefropatías Diabéticas/diagnóstico , Péptidos/análisis , Péptidos/orina , Anciano , Algoritmos , Biomarcadores/orina , Cromatografía Liquida/métodos , Biología Computacional/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proteoma/análisis , Espectrometría de Masas en Tándem/métodos , Orina/química

RESUMEN

Endurance exercise can cause a decrease in serum ionized calcium (iCa) and increases in parathyroid hormone (PTH) and c-terminal telopeptide of type I collagen (CTX), which may be due to Ca loss in sweat. PURPOSE: This study aimed to determine whether exercise in a warm environment exaggerates the decrease in iCa and increases in PTH and CTX compared with a cool environment in older adults. METHODS: Twelve women and men 61-78 yr old performed two identical 60-min treadmill bouts at ~75% of maximal heart rate under warm and cool conditions. Serum iCa, PTH, and CTX were measured every 15 min starting 15 min before and continuing for 60 min after exercise. Sweat Ca loss was estimated from sweat volume and sweat Ca concentration. RESULTS: Sweat volume was low and variable; there were no differences in sweat volume or Ca concentration between conditions. iCa decreased after 15 min of exercise, and the change was similar in both conditions. Increases in PTH (warm: 16.4, 95% confidence interval [CI] = 6.2, 26.5 pg·mL; cool: 17.3, 95% CI = 8.1, 26.4 pg·mL) and CTX (warm: 0.08, 95% CI = 0.05, 0.11 ng·mL; cool: 0.08, 95% CI = 0.01, 0.16 ng·mL) from before to immediately after exercise were statistically significant and similar between conditions. Adjusting for plasma volume shifts did not change the results. CONCLUSION: The increases in PTH and CTX, despite the low sweat volume, suggest that dermal Ca loss is not a major factor in the decrease in iCa and increases in PTH and CTX observed during exercise in older adults.

Asunto(s)

Huesos/metabolismo , Calcio/sangre , Colágeno Tipo I/sangre , Calor , Hormona Paratiroidea/sangre , Péptidos/sangre , Caminata/fisiología , Anciano , Biomarcadores/sangre , Densidad Ósea , Frío , Colágeno Tipo I/orina , Femenino , Homeostasis , Humanos , Masculino , Persona de Mediana Edad , Péptidos/orina , Piel/metabolismo , Sudor/metabolismo , Sudoración/fisiología

RESUMEN

The number of substances nominally listed in the prohibited list of the World Anti-Doping Agency increases each year. Moreover, many of these substances do not have a single analytical target and must be monitored through different metabolites, artifacts, degradation products, or biomarkers. A new analytical method was developed and validated for the simultaneous analysis of peptides and organic molecules using a single sample preparation and LC-Q-HRMS detection. The simultaneous analysis of 450 target molecules was performed after cleanup on a mixed-mode solid-phase extraction cartridge, combined with untreated urine. The cleanup solvent and reconstitution solvent were the most important parameters for achieving a comprehensive sample preparation approach. A fast chromatographic run based on a multistep gradient was optimized under different flows; the detection of all substances without isomeric coelution was achieved in 11 minutes, and the chromatographic resolution was considered a critical parameter, even in high-resolution mass spectrometry detection. The mass spectrometer was set to operate by switching between positive and negative ionization mode for FULL-MS, all-ion fragmentation, and FULL-MS/MS2 . The suitable parameters for the curved linear trap (c-trap) conditions were determined and found to be the most important factors for the development of the method. Only FULL-MS/MS2 enables the detection of steroids and peptides at concentrations lower than the minimum required performance levels set by World Anti-Doping Agency (1 ng mL-1 ). The combination of the maximum injection time of the ions into the c-trap, multiplexing experiments, and loop count under optimized conditions enabled the method to be applied to over 10 000 samples in only 2 months during the 2016 Rio Summer Olympic and Paralympic Games. The procedure details all aspects, from sample preparation to mass spectrometry detection. FULL-MS data acquisition is performed in positive and negative ion mode simultaneously and can be applied to untargeted approaches.

Asunto(s)

Péptidos/análisis , Esteroides/análisis , Espectrometría de Masas en Tándem/métodos , Cromatografía Líquida de Alta Presión/métodos , Doping en los Deportes/prevención & control , Humanos , Límite de Detección , Péptidos/orina , Extracción en Fase Sólida/métodos , Esteroides/orina

RESUMEN

BACKGROUND: Calcium needs are physiologically upregulated during pregnancy and lactation to meet demands of the developing fetus and breastfeeding infant. Maternal calcium homeostasis is maintained by hormonal adaptive mechanisms, thus, the role of dietary calcium supplementation in altering maternal responses to fetal-infant demand for calcium is thought to be limited. However, increased calcium absorption is directly related to maternal calcium intake and dietary supplementation has been suggested to prevent transient bone loss associated with childbearing. METHODS: In a double-blind, randomized placebo-controlled trial, we randomly assigned 670 women in their first trimester of pregnancy to 1,200 mg/day calcium (N = 334) or placebo (N = 336). Subjects were followed through 1-month postpartum and the effect on urinary cross-linked N-telopeptides (NTx) of type I collagen, a specific marker of bone resorption, was evaluated using an intent-to-treat analysis. Women with a baseline and at least one follow-up measurement (N = 563; 84%) were included. Subsequent analyses were conducted stratifying subjects by compliance assessed using pill counts. In random subsets of participants, bone-specific alkaline phosphatase (BAP) (N = 100) and quantitative ultrasound (QUS) (N = 290) were also measured. RESULTS: Calcium was associated with an overall reduction of 15.8% in urinary NTx relative to placebo (p < 0.001). Among those who consumed ≥50%, ≥67%, and ≥75% of pills, respectively, the effect was associated with 17.3%, 21.3%, and 22.1% reductions in bone resorption (all p < 0.001). There was no significant effect of calcium on bone formation measured by BAP. However, by 1-month postpartum, those in the calcium group had significantly lower NTx/BAP ratios than those in the placebo group (p = 0.04) indicating a net reduction in bone loss in the supplement group by the end of follow-up. Among subjects who consumed ≥50% and ≥75% of pills, respectively, calcium was also associated with an increase of 26.3 m/s (p = 0.03) and 59.0 m/s (p = 0.009) in radial SOS relative to placebo by 1-month postpartum. CONCLUSIONS: Calcium administered during pregnancy and the early postpartum period, to women with intakes around adequacy, was associated with reduced bone resorption and, thus, may constitute a practical intervention to prevent transient skeletal loss associated with childbearing. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT00558623.

Asunto(s)

Resorción Ósea/prevención & control , Calcio de la Dieta/administración & dosificación , Periodo Posparto , Complicaciones del Embarazo/prevención & control , Fosfatasa Alcalina/sangre , Biomarcadores/orina , Resorción Ósea/complicaciones , Huesos/diagnóstico por imagen , Huesos/enzimología , Colágeno Tipo I/orina , Suplementos Dietéticos , Método Doble Ciego , Femenino , Humanos , México , Péptidos/orina , Placebos , Embarazo , Ultrasonografía

RESUMEN

Mexican Americans are an understudied ethnic group for determinants of bone health, although the risk of age-related osteoporosis is high in this rapidly growing sector of the U.S. population. Thus, the objective of the present study was to establish the dietary calcium requirements for bone health in Mexican-American adolescents by measuring calcium retention calculated from balance in response to a range of dietary calcium intakes and to determine predictors of skeletal calcium retention. Adolescents aged 12-15 y were studied twice on paired calcium intakes ranging from 600 to 2300 mg/d using randomized-order, crossover 3-wk balance studies. Skeletal calcium retention was calculated as dietary calcium intake minus calcium excreted in feces and urine over the last 2 wk of balance. A linear model was developed to explain the variation in calcium retention. Boys (n = 20) were taller and had higher lean mass, usual dietary calcium intake, bone mineral content, and serum alkaline phosphatase compared with girls, whereas girls (n = 20) had higher Tanner scores and greater fat mass. Calcium retention increased with calcium intake (P < 0.0001) and did not differ by sex (P = 0.66). In boys and girls considered together, calcium intake explained 33% of the variation in calcium retention. Serum alkaline phosphatase explained an additional 11% of the variation in calcium retention. Other variables measured, including the urine N-telopeptide of type I collagen/creatinine ratio, Tanner score, serum parathyroid hormone and 25-hydroxyvitamin D, weight, height, and body mass index, did not contribute to the variance in calcium retention. In adolescence, calcium retention in both Mexican-American boys and girls was higher than determined previously in adolescent nonHispanic white girls. This trial was registered at clinicaltrials.gov as NCT01277185.

Asunto(s)

Calcio de la Dieta/administración & dosificación , Americanos Mexicanos , Necesidades Nutricionales , Adolescente , Índice de Masa Corporal , Peso Corporal , Densidad Ósea/efectos de los fármacos , Densidad Ósea/fisiología , Huesos/efectos de los fármacos , Huesos/metabolismo , Niño , Colágeno Tipo I/orina , Creatinina/orina , Estudios Cruzados , Dieta , Ingestión de Energía , Femenino , Humanos , Masculino , Osteoporosis/prevención & control , Hormona Paratiroidea/sangre , Péptidos/orina , Vitamina D/análogos & derivados , Vitamina D/sangre

RESUMEN

No studies had investigated circadian and circannual rhythms of bone biomarkers in whole saliva. We evaluated the salivary daily and seasonal rhythm of carboxy-terminal telopeptide of type I collagen (CTX) and bone alkaline phosphatase (b-ALP). Forty clinical and oral healthy ambulatory pre- and postmenopausal women from two southern Argentine cities: Comodoro Rivadavia (latitude 45º S) and Ushuaia (latitude 54º S) were included in the study. CTX levels were evaluated in serum, urine, and saliva, and b-ALP levels were measured in serum and saliva. In both groups of women, salivary CTX showed a maximum percentage of change early in the morning (80%) and a minimum in the late afternoon (45%), similarly to the pattern observed in urinary samples. No daily rhythm was observed in serum or salivary b-ALP. 25-Hydroxyvitamin D levels decreased in winter vs. summer (p < 0.01) without differences between the two studied groups. Conversely, parathormone reached higher levels in winter (p < 0.05) which induced a slight non-significant increment in salivary CTX and b-ALP levels. The results showed that, as in serum and urinary samples, salivary CTX exhibits daily and a slight seasonal rhythmicity. Whole non-stimulated saliva is a useful tool to detect several oral and systemic diseases because it has important advantages compared to serum and urinary samples. Then, it may also be a promising sample to test changes in bone metabolism contributing to diagnose and to monitor the therapy of several metabolic bone diseases.

Asunto(s)

Fosfatasa Alcalina/análisis , Ritmo Circadiano , Colágeno Tipo I/análisis , Péptidos/análisis , Posmenopausia/metabolismo , Premenopausia/metabolismo , Proteínas y Péptidos Salivales/análisis , Adulto , Fosfatasa Alcalina/sangre , Biomarcadores/análisis , Biomarcadores/sangre , Biomarcadores/orina , Remodelación Ósea/fisiología , Calcio/sangre , Colágeno Tipo I/sangre , Colágeno Tipo I/orina , Femenino , Humanos , Persona de Mediana Edad , Hormona Paratiroidea/sangre , Péptidos/sangre , Péptidos/orina , Fósforo/sangre , Posmenopausia/sangre , Posmenopausia/orina , Premenopausia/sangre , Premenopausia/orina , Estaciones del Año , Vitamina D/análogos & derivados , Vitamina D/sangre

RESUMEN

UNLABELLED: Calcium metabolism of the mother is modified during pregnancy because of the mineralization of the fetus skeleton. OBJECTIVE: To evaluate the association of calcium intake and bone demineralization during pregnancy. MATERIAL AND METHODS: At each trimester of pregnancy a validated food frequency intake questionnaire was administered to assess individual daily calcium intake in a cohort of 206 pregnant women, residents of Mexico City. Samples of urine were collected to measure levels of the cross-linked N-telopeptide of type I collagen (NTx), which is a biomarker of bone resorption. The association between calcium ingestion and bone resorption was analyzed using random effects models; non-linear associations were explored using generalized additive models. RESULTS: Progressive increases in NTx levels were observed during pregnancy; with mean and standard deviation (SD) values during the first, second and third trimester of 76.50 (SD=38), 101.02 (SD=48.86) and 144.83 (SD=61.33) nmol BCE/mmol creatinine, respectively. Higher dietary calcium intake was associated with lower bone resorption (beta=-0.015; p<0.05). The association between age and NTx showed a non-linear trend with an inflexion point around 33 years: increase in maternal age below that point was associated with a decrease in bone resorption, while in older women the increase in age was associated with an increased resorption. CONCLUSIONS: Our results suggest that calcium ingestion, specifically from dairy products, reduces bone resorption during pregnancy. For each 300 mg (a glass of milk) of calcium intake there is an estimated reduction in NTx level of 4.8 nmol BCE/mmol of creatinine (p<0.05).

Asunto(s)

Remodelación Ósea/fisiología , Resorción Ósea/orina , Calcio de la Dieta/administración & dosificación , Colágeno Tipo I/orina , Péptidos/orina , Adolescente , Adulto , Factores de Edad , Biomarcadores/orina , Femenino , Humanos , Estudios Longitudinales , México , Embarazo , Trimestres del Embarazo/orina , Adulto Joven

RESUMEN

Calcium metabolism of the mother is modified during pregnancy because of the mineralization of the fetus skeleton. OBJECTIVE: To evaluate the association of calcium intake and bone demineralization during pregnancy. MATERIAL AND METHODS: At each trimester of pregnancy a validated food frequency intake questionnaire was administered to assess individual daily calcium intake in a cohort of 206 pregnant women, residents of Mexico City. Samples of urine were collected to measure levels of the cross-linked N-telopeptide of type I collagen (NTx), which is a biomarker of bone resorption. The association between calcium ingestion and bone resorption was analyzed using random effects models; non-linear associations were explored using generalized additive models. RESULTS: Progressive increases in NTx levels were observed during pregnancy; with mean and standard deviation (SD) values during the first, second and third trimester of 76.50 (SD=38), 101.02 (SD=48.86) and 144.83 (SD=61.33) nmol BCE/mmol creatinine, respectively. Higher dietary calcium intake was associated with lower bone resorption (β=-0.015; p<0.05). The association between age and NTx showed a non-linear trend with an inflexion point around 33 years: increase in maternal age below that point was associated with a decrease in bone resorption, while in older women the increase in age was associated with an increased resorption. CONCLUSIONS: Our results suggest that calcium ingestion, specifically from dairy products, reduces bone resorption during pregnancy. For each 300mg (a glass of milk) of calcium intake there is an estimated reduction in NTx level of 4.8 nmol BCE/mmol of creatinine (p<0.05).

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El metabolismo de calcio es modificado durante el embarazo debido a la mineralización del esqueleto del feto. OBJETIVO: Evaluar la asociación entre la ingesta de calcio y la desmineralización ósea durante el embarazo. MATERIAL Y MÉTODOS: Se administró un Cuestionario de Frecuencia de Consumo de alimentos en cada trimestre del embarazo para evaluar el consumo de calcio en una cohorte de 206 mujeres residentes de la Ciudad de México. Se recolectaron muestras de orina para medir los niveles de N-telopéptido de colágeno tipo I (NTx), biomarcador de resorción. Se hicieron modelos de efectos aleatorios; se estudiaron asociaciones no lineales utilizando modelos aditivos generalizados. RESULTADOS: Se observó aumento progresivo en los niveles de NTx durante el embarazo. El mayor consumo de calcio se asoció con una menor resorción ósea (β=- 0.015, p<0,05). CONCLUSIONES: Los resultados sugieren que la ingestión de calcio reduce la resorción ósea en el embarazo.

Asunto(s)

Adolescente , Adulto , Femenino , Humanos , Embarazo , Adulto Joven , Remodelación Ósea/fisiología , Resorción Ósea/orina , Calcio de la Dieta/administración & dosificación , Colágeno Tipo I/orina , Péptidos/orina , Factores de Edad , Biomarcadores/orina , Estudios Longitudinales , México , Trimestres del Embarazo/orina , Adulto Joven

RESUMEN

An increase in parathyroid hormone (PTH) levels in chronic renal failure (CRF) induces bone abnormalities known as renal osteodystrophy (ROD). The aim of the present study was to evaluate alternative biochemical methods to bone biopsy, to evaluate changes in bone remodeling in renal patients. Intact PTH (iPTH) and bone markers were measured in 43 predialysis (PD), 49 hemodialysis patients (HD) and 185 controls. betaCTXs, bone alkaline phosphatase (bAL), iPTH were higher and creatinine clearance (Ccr) was lower in PD and HD compared with controls (p < 0.0001). In both renal groups, a positive correlation was found between iPTH and both betaCTXs and bAL (p < 0.0001) and between betaCTXs and bAL (p < 0.002). PD patients with Ccr < 40 ml/min had higher iPTH, bAL and betaCTXs (p<0.004, p<0.05 and p<0.001, respectively) than patients with Ccr > 40 ml/min. betaCTXs (p < 0.05) in PD and betaCTXs and bAL in HD patients were higher than controls, even when iPTH was within normal range (< 65 pg/ml). Patients with severe secondary hyperparathyroidism showed higher bone markers than patients with normal or moderately increased iPTH (p < 0.001). These results suggest that even when there is no increase in iPTH, bone remodeling increases (possibly due to other factors) exhibiting higher bone resorption, and betaCTXs would seem to be an adequate non-invasive tool to assess early bone changes in CRF and prevent future fractures. Bone marker measurements in ROD would be useful to identify patients who may require bone biopsy. However, further studies comparing both methods must be performed before replacing bone biopsy with serum beta-CTX.

Asunto(s)

Remodelación Ósea/fisiología , Colágeno/metabolismo , Fallo Renal Crónico/fisiopatología , Péptidos/metabolismo , Adulto , Fosfatasa Alcalina/análisis , Biomarcadores/sangre , Biomarcadores/orina , Biopsia , Resorción Ósea/metabolismo , Resorción Ósea/patología , Resorción Ósea/fisiopatología , Estudios de Casos y Controles , Trastorno Mineral y Óseo Asociado a la Enfermedad Renal Crónica/metabolismo , Trastorno Mineral y Óseo Asociado a la Enfermedad Renal Crónica/patología , Trastorno Mineral y Óseo Asociado a la Enfermedad Renal Crónica/fisiopatología , Colágeno/sangre , Colágeno/orina , Colágeno Tipo I , Creatinina/orina , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Fallo Renal Crónico/metabolismo , Fallo Renal Crónico/patología , Modelos Lineales , Masculino , Persona de Mediana Edad , Hormona Paratiroidea/análisis , Péptidos/sangre , Péptidos/orina , Diálisis Renal , Estadísticas no Paramétricas

RESUMEN

Mass spectrometry is now firmly established as a powerful technique for the identification and characterization of proteins when used in conjunction with sequence databases. Various approaches involving stable-isotope labeling have been developed for quantitative comparisons between paired samples in proteomic expression analysis by mass spectrometry. However, interpretation of such mass spectra is far from being fully automated, mainly due to the difficulty of analyzing complex patterns resulting from the overlap of multiple peaks arising from the assortment of natural isotopes. In order to facilitate the interpretation of a complex mass spectrum of such a mixture, such as an MS spectrum of a stable-isotope-enriched ion species, we report on the development of a software application, 'Matching' (web accessible), that enables the automatic matching of theoretical isotope envelopes to multiple ion peaks in a raw spectrum. It is particularly useful for resolving the relative abundances of narrow-split paired peaks caused by enrichment with a stable isotope, such as 18O, 13C, 2H, or 15N.

Asunto(s)

Algoritmos , Mezclas Complejas/análisis , Péptidos/análisis , Análisis de Secuencia de Proteína/métodos , Programas Informáticos , Espectrometría de Masa por Ionización de Electrospray/métodos , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos , Secuencia de Aminoácidos , Mezclas Complejas/química , Marcaje Isotópico/métodos , Datos de Secuencia Molecular , Reconocimiento de Normas Patrones Automatizadas , Péptidos/química , Péptidos/orina , Interfaz Usuario-Computador

RESUMEN

It has been suggested that the appropriate timing of puberty is necessary for normal bone mineral acquisition which may not be achieved amongst patients with Turner's syndrome (TS). The aim of this study was to assess bone mineral density (BMD) and bone turnover in 34 patients with TS (age range 2.2-39.0 years). The areal BMD (aBMD) was determined by dual-energy X-ray absorptiometry, and the volumetric BMD was calculated. Blood and second voided urine samples were taken the morning after an overnight fast for evaluation of the biochemical markers of bone turnover: bone-specific alkaline phosphatase (BAP) and N-telopeptides of type I collagen (NTX), respectively. Both were determined by enzyme-linked immunosorbent assay. The patients were divided into three groups: group 1 (n = 13; prepubertal; age range 2.2-19.0 years), group 2 (n = 10; teenagers; age range 12.4-19.0 years), and group 3 (n = 11; adults; chronological age >20 years). They were also grouped by breast development according to Tanner stage into B1 (n = 12), B2-3 (n = 9), and B4-5 (n = 13). The aBMD was significantly lower in group 1 and was higher at Tanner stages 4 and 5 as compared with patients at Tanner stage 1. The bone turnover markers were significantly higher in group 1 (NTX: p = 0.002; BAP: p = 0.0005) and declined, as puberty progressed. A negative correlation was observed between aBMD and biochemical bone markers at the lumbar spine (NTX: r = -0.54, p = 0.05; BAP: r = -0.44, p = 0.01) and in the whole body (NTX: r = -0.60, p = 0.0008; BAP: r = -0.19, p = 0.002). We conclude that the negative relationships between aBMD and biochemical markers suggest a high bone turnover, mainly in prepubertal patients and that the results observed in relation to aBMD and puberty are imputed to the delayed puberty which occurs amongst TS patients.

Asunto(s)

Densidad Ósea , Remodelación Ósea , Pubertad , Síndrome de Turner/fisiopatología , Absorciometría de Fotón , Adolescente , Adulto , Fosfatasa Alcalina/sangre , Biomarcadores/sangre , Biomarcadores/orina , Huesos/enzimología , Niño , Preescolar , Colágeno/orina , Colágeno Tipo I , Femenino , Humanos , Vértebras Lumbares/diagnóstico por imagen , Vértebras Lumbares/metabolismo , Péptidos/orina , Síndrome de Turner/sangre , Síndrome de Turner/diagnóstico por imagen , Síndrome de Turner/orina

RESUMEN

Bisphosphonates have proven to be effective in patients with fibrous dysplasia of the bone (FD) as shown by their effect on bone pain, markers of bone turnover, or radiological changes. The aim of this study was to evaluate the usefulness of measuring bone mineral density (BMD) of affected bones to assess the efficacy of bisphosphonate treatment. Seven patients (mean age 26 years) received courses of 180 mg intravenous infusion of pamidronate every 6 months (60 mg/day during 3 days). Clinical symptoms, serum alkaline phosphatase, and urinary C-terminal cross-linking telopeptide of type I collagen were assessed every 3 months. BMD of total skeleton and X-rays of FD areas (FDa) were performed at baseline and at 12 months. BMD of FDa was compared with the contralateral side (CL) using the region of interest program on the total skeleton scan. BMD of total skeleton was normal at baseline. Average BMD of FDa was -11.4% compared with CL, a significantly greater difference than that observed between the left and right sides in healthy controls, -0.7% (P < 0.02). At 12 months bone pain diminished in all patients. Bone turnover markers decreased. Mean total skeleton BMD increased 3.3% (P < 0.02). Subregions of the total skeleton scan presenting FD lesions augmented: arms +9.6% (P < 0.02), legs +4.2%, and pelvis +3.5% (P < 0.05). The increase in mean BMD of FDa was +6.8% compared with +2.6% in CL. No changes were observed on the X-ray. These results indicate that simultaneous determination of markers of bone turnover and BMD of FDa is useful in short-term follow-up to determine the efficacy of intravenous pamidronate.

Asunto(s)

Densidad Ósea/efectos de los fármacos , Difosfonatos/administración & dosificación , Displasia Fibrosa Ósea/tratamiento farmacológico , Displasia Fibrosa Ósea/metabolismo , Adolescente , Adulto , Fosfatasa Alcalina/sangre , Estudios de Casos y Controles , Colágeno/orina , Colágeno Tipo I , Difosfonatos/efectos adversos , Femenino , Humanos , Infusiones Intravenosas , Masculino , Pamidronato , Péptidos/orina

RESUMEN

OBJECTIVE: To compare vitamin D status represented by serum 25-hydroxyvitamin D (25-OHD) levels in a group of patients with primary hyperparathyroidism, stratified by clinical manifestations. METHODS: We studied 22 patients (18 women and 4 men) with primary hyperparathyroidism--5 patients with severe osteitis fibrosa cystica, 10 symptomatic patients with active renal stone disease without overt bone disease, and 7 asymptomatic patients. Bone mineral density (BMD) measurements (T-scores) were done at the lumbar spine, femoral neck, and distal radius, and laboratory data for the three subgroups were analyzed. RESULTS: Although considerably younger than the asymptomatic group, patients with osteitis fibrosa had significantly lower mean serum 25-OHD levels (16.7 +/- 1.1 ng/mL versus 29.9 +/- 2.9 ng/mL; P = 0.003). Moreover, patients with osteitis fibrosa had significantly lower BMD in comparison with patients who had renal stone disease as well as asymptomatic patients for all sites measured. Serum parathyroid hormone levels were significantly higher in patients with osteitis fibrosa than in asymptomatic patients (1,352.8 +/- 297.2 pg/mL versus 145.0 +/- 43.7 pg/mL; P<0.02) as well as in comparison with patients who had renal stone disease (P<0.02). Patients with osteitis fibrosa had urinary N-telopeptide levels that were significantly higher than those in asymptomatic patients (501.5 +/- 201.7 versus 51.3 +/- 6.4 nmol/mmol creatinine; P = 0.02) and those in patients with renal stone disease (P = 0.01). CONCLUSION: The findings in this study demonstrate that vitamin D deficiency or insufficiency may contribute to disease severity in primary hyperparathyroidism.

Asunto(s)

Calcifediol/sangre , Hiperparatiroidismo/complicaciones , Hiperparatiroidismo/fisiopatología , Adulto , Anciano , Densidad Ósea , Colágeno/orina , Colágeno Tipo I , Femenino , Humanos , Hiperparatiroidismo/patología , Cálculos Renales/complicaciones , Masculino , Persona de Mediana Edad , Osteítis Fibrosa Quística/complicaciones , Hormona Paratiroidea/sangre , Péptidos/orina

RESUMEN

One of the aims of the treatment of Paget's disease with bisphosphonates should be the normalization of the activity of the disease with the shortest possible exposure to the drug. Olpadronate (OPD) is a new bisphosphonate characterized by the dimethylation of the amino group, its potency is near to alendronate, and more soluble in the digestive media than other aminobisphosphonates. We treated 46 patients (28 men and 18 women, mean age 70 years) with active Paget's disease with oral OPD, 200 mg/day for 12 +/- 2 days, except 2 patients who received 400 mg/day. Eight patients had never been treated before, and 38 had previously received antiosteolytic drugs. The period without treatment prior to OPD was (X +/- 1 SD) 14 +/- 12 months. Baseline bone alkaline phosphatase (BALP) (levels fell from (X +/- 1 SD) 54.0 +/- 62.7 IU/ml (range 22-396) to a lowest mean value of 16.2 +/- 6.4 IU/ml (range 8-45) (normal range 5-21 IU/ml). Forty patients normalized BALP values, in most of the cases within the first 3 months after OPD treatment. Two patients showed partial response (> 50% decrease from baseline), three patients presented poor response (< 50% decrease from baseline), and one patient did not respond at all. Two patients complained of gastric discomfort, and one patient had diarrhea, which disappeared after discontinuation of the drug. Follow-up was carried out on 36 patients; 22 patients are still in remission, with an average length of 9.0 +/- 2.6 months. Fourteen patients experienced relapse after 9 +/- 2 months remission. In conclusion, a 12-day treatment with 200 mg/day of OPD proved to be a very effective and well tolerated therapy of Paget's disease and induced biochemical remissions in the vast majority of patients, even in those with very active disease.

Asunto(s)

Difosfonatos/uso terapéutico , Osteítis Deformante/tratamiento farmacológico , Adulto , Anciano , Fosfatasa Alcalina/sangre , Colágeno/orina , Colágeno Tipo I , Femenino , Humanos , Masculino , Persona de Mediana Edad , Osteítis Deformante/sangre , Osteítis Deformante/orina , Péptidos/orina , Factores de Tiempo , Población Blanca

RESUMEN

In order to clarify the blunting effect of peptides released by pepsin from blood plasma on ANP diuretic action, 2 prokinins designated PU-16 were tested. Both of them were able to inhibit in nanomolar doses the diuretic-saluretic action of 0.5 ug i.v. bolus of ANP given to anesthetized rats either by intravenous route or introduced in the duodenal lumen. PU-16 in doses of 0.5 ug and 1 ug were able to reduce in 72 and 96.5 per cent respectively the natriuresis induced bu 0.5 ug intravenous bolus of ANP. The data support the hypothesis that prokinins liberated in the digestive tract, could be physiological factors involved in hydrosaline homeostasis, moderating the ANP mediated increase of water, Na and K excretion during digestion

Asunto(s)

Animales , Ratas , Digestión/fisiología , Sistema Digestivo , Diuresis/efectos de los fármacos , Natriuresis/fisiología , Factor Natriurético Atrial/antagonistas & inhibidores , Péptidos/orina , Factor Natriurético Atrial/farmacocinética