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Bone turnover markers (BTMs) are released during the bone remodelling cycle and are measurable in blood or urine, reflecting bone remodelling rate. They have been useful in elucidating the pharmacodynamics and effectiveness of osteoporosis medication in clinical trials and are increasingly used in routine clinical management of osteoporosis, especially for monitoring therapy, in addition to their use in other metabolic bone disease such as Paget's disease of bone and osteomalacia. Serum ß isomerised C-terminal telopeptide of type I collagen and pro-collagen I N-terminal propeptide have been designated as reference BTMs for use in osteoporosis. In addition, bone-specific isoenzyme of alkaline phosphatase (B-ALP) secreted by osteoblasts and tartrate-resistant acid phosphatase 5b (TRACP-5b) secreted by osteoclasts are also found to be specific markers of bone formation and resorption, respectively. The concentrations of the latter enzymes in blood measured by immunoassay provide reliable measures of bone turnover even in the presence of renal failure. B-ALP is recommended for use in the assessment of renal bone disease of chronic kidney disease, and TRACP-5b shows promise as a marker of bone resorption in that condition. BTMs in blood do not suffer from biological variation to the same extent as the older BTMs that were measured in urine. Appropriate patient preparation and sample handling are important in obtaining accurate measures of BTMs for clinical use. Reference change values and treatment targets have been determined for the reference BTMs for their use in monitoring osteoporosis treatment. Further ongoing studies will enhance their clinical applications.
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Enfermedades Óseas Metabólicas , Osteoporosis , Humanos , Fosfatasa Ácida Tartratorresistente , Osteoporosis/tratamiento farmacológico , Colágeno Tipo I , Fosfatasa Alcalina , Remodelación Ósea , BiomarcadoresRESUMEN
Objectives High-sensitivity (hs) cardiac troponin (cTn) assays can quantitate small fluctuations in cTn concentration. Determining biological variation allows calculation of reference change values (RCV), to define significant changes. We assessed the short- and long-term biological variation of cardiac troponin I (cTnI) in healthy individuals and patients with renal failure requiring haemodialysis or cardiomyopathy. Methods Plasma samples were collected hourly for 4 h and weekly for seven further weeks from 20 healthy individuals, 9 renal failure patients and 20 cardiomyopathy patients. Pre- and post-haemodialysis samples were collected weekly for 7 weeks. Samples were analysed using a hs-cTnI assay (Abbott Alinity ci-series). Within-subject biological variation (CVI), analytical variation (CVA) and between-subject biological variation (CVG) was used to calculate RCVs and index of individuality (II). Results For healthy individuals, CVI, CVA, CVG, RCV and II values were 8.8, 14.0, 43.1, 45.8% and 0.38 respectively for short-term, and 41.4, 14.0, 25.8, 121.0% and 1.69 for long-term. For renal failure patients, these were 2.6, 5.8, 50.5, 17.6% and 0.30 respectively for short-term, and 19.1, 5.8, 11.2, 55.2% and 1.78 for long-term. For cardiomyopathy patients, these were 4.2, 10.0, 65.9, 30.0% and 0.16 respectively for short-term, and 17.5, 10.0, 63.1, 55.8% and 0.32 for long-term. Mean cTnI concentration was lower post-haemodialysis (15.2 vs. 17.8 ng/L, p < 0.0001), with a 16.9% mean relative change. Conclusions The biological variation of cTnI is similar between end-stage renal failure and cardiomyopathy patients, but proportionately greater in well-selected healthy individuals with very low baseline cTnI concentrations.
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Variación Biológica Individual , Cardiomiopatías/sangre , Fallo Renal Crónico/sangre , Troponina I/sangre , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Diálisis Renal , Factores de Tiempo , Adulto JovenRESUMEN
The objective was to determine the clinical and biochemical success rates and assess the nature of follow-up after adrenalectomy in patients with unilateral primary aldosteronism (PA), subtyped by adrenal vein sampling (AVS) in West Australia (WA) using the Primary Aldosteronism Surgical Outcome (PASO) criteria. Clinical and biochemical outcomes were retrospectively evaluated in patients with unilateral PA who underwent adrenalectomy according to AVS between September 2017 and September 2020. Pre- and post-surgical data were collected using a standardised questionnaire, review of clinic letters and examination of private and public pathology results and radiological reports. Follow-up data were available for 47 patients post-adrenalectomy; biochemical outcome data were available for 37 patients, clinical outcome data for 40 patients, with 30 patients having both outcomes available. Final assessment was performed between 0 to 3 months in 23/37 (62.2%) patients with biochemical outcomes, 15/40 (37.5%) with clinical outcomes, and 17/30 (56.7%) with both clinical and biochemical outcomes. Complete biochemical success was achieved in 83.8% (31/37) of patients, with 26.7% (8/30) obtaining both complete clinical and biochemical success. Complete clinical success was achieved in 35.0% (14/40) of patients, with 47.5% (19/40) obtaining partial clinical success. Overall, 93.6% (44/47) of patients derived benefit from adrenalectomy. The outcomes of adrenalectomy for unilateral PA in Western Australian using standardised PASO criteria demonstrate highly comparable clinical and biochemical success rates to international data. However, further standardisation of post-operative follow-up care needs to be implemented to ensure the recommended repeat follow-up assessment criteria are collected.
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Adrenalectomía , Hiperaldosteronismo , Humanos , Adrenalectomía/métodos , Estudios Retrospectivos , Australia , Hiperaldosteronismo/diagnóstico , Hiperaldosteronismo/cirugía , Hiperaldosteronismo/patología , Evaluación de Resultado en la Atención de Salud/métodos , Glándulas Suprarrenales/cirugía , Glándulas Suprarrenales/patologíaRESUMEN
The adult bone is continuously being remodelled to repair microdamage, preserve bone strength and mechanical competence as well as maintain calcium homeostasis. Bone turnover markers are products of osteoblasts (bone formation markers) and osteoclasts (bone resorption markers) providing a dynamic assessment of remodelling (turnover). Resorption-specific bone turnover markers are typically degradation products of bone collagen molecules (N- [NTX] and C-telopeptide cross-linked type 1 collagen [CTX]), which are released into the circulation and excreted in urine; or enzymatic activities reflecting osteoclastic resorption, tartrate-resistant acid phosphatase [TRACP]. Formation-specific bone turnover markers embrace different osteoblastic activities: type 1 collagen synthesis (Procollagen type I N- propeptide [PINP]), osteoblast enzymes (bone-specific alkaline phosphatase [BALP]), or bone matrix proteins [osteocalcin]. Among individuals not receiving osteoporosis treatment, resorption and formation markers are tightly linked and highly correlated (r = 0.6-0.8). Significant biological variability was reported in the past, but these issues have been greatly improved with automated assays and attention to pre-analytical and analytical factors that are known to influence bone turnover marker levels. Bone turnover markers are not useful in the diagnosis of osteoporosis, the individual prediction of bone loss, fracture, or rare complications, or in the selection of pharmacological treatment. Despite remaining issues with reference intervals and assays harmonization, bone turnover markers have proven to be useful in elucidating the pharmacodynamics and effectiveness of osteoporosis medications in clinical trials. As an alternative to BMD testing, BTMs may be useful to monitor osteoporosis therapies.
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Colágeno Tipo I , Osteoporosis , Adulto , Humanos , Procolágeno , Fragmentos de Péptidos , Biomarcadores/metabolismo , Osteoporosis/diagnóstico , Osteoporosis/tratamiento farmacológico , Remodelación Ósea , Fosfatasa Alcalina , Densidad ÓseaRESUMEN
Serum procollagen type I N-propeptide (PINP) is designated the reference marker of bone formation in osteoporosis; the reference marker for resorption is C-terminal telopeptide of type I collagen (CTX). PINP has very low circadian and biological variation, is not affected by food intake, and is very stable in serum after venepuncture. The two automated commercial assays for PINP provide similar results in subjects with normal renal function, allowing reference intervals to be used interchangeably. Bone turnover markers (BTM) are currently not recommended for fracture risk assessment and therefore not included in fracture risk calculators. In the management of osteoporosis, the main utility of BTM including PINP is for monitoring therapy, both antiresorptive as well as anabolic agents; monitoring is thought to help improve adherence. PINP as well as CTX may also be used in assessing offset of drug action following a pause in bisphosphonate therapy, to help decide when to re-instate therapy, or following cessation of denosumab therapy to assess efficacy of follow-on bisphosphonate therapy. PINP may also be used in the diagnosis of Paget's disease of bone as well as in monitoring response to therapy and for recurrence. Although BTM other than bone alkaline phosphatase are currently not recommended for use in metabolic bone disease of chronic kidney disease, PINP measured by assays specific to the intact molecule has potential in this condition. Further studies are needed to examine this area, as well as in malignant bone disease.
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Procollagen type I N-propeptide (PINP) and the C-terminal telopeptide of type I collagen (ß-CTX) in blood have been designated as reference bone turnover markers in osteoporosis by the International Osteoporosis Foundation (IOF) and International Federation of Clinical Chemistry and Laboratory Medicine (IFCC). The IFCC Committee on Bone Metabolism (C-BM) has examined current commercial assays and performed a multicentre study to examine the agreement between assays for PINP and ß-CTX in serum and plasma. The results of these studies will inform our work towards the harmonization of PINP assays and the standardization of ß-CTX assays in blood, with the development of common calibrators and reference measurement procedures in collaboration with the reagent manufacturing industry. Successful achievement of these goals will help develop universally acceptable practice guidelines for the management of osteoporosis with the inclusion of common reference intervals and treatment targets for PINP and ß-CTX.
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Fragmentos de Péptidos , Procolágeno , Biomarcadores , Remodelación Ósea , Colágeno Tipo I , Humanos , PéptidosRESUMEN
Vitamin D, an important hormone with a central role in calcium and phosphate homeostasis, is required for bone and muscle development as well as preservation of musculoskeletal function. The most abundant vitamin D metabolite is 25-hydroxyvitamin D [25(OH)D], which is currently considered the best marker to evaluate overall vitamin D status. 25(OH)D is therefore the most commonly measured metabolite in clinical practice. However, several other metabolites, although not broadly measured, are useful in certain clinical situations. Vitamin D and all its metabolites are circulating in blood bound to vitamin D binding protein, (VDBP). This highly polymorphic protein is not only the major transport protein which, along with albumin, binds over 99% of the circulating vitamin D metabolites, but also participates in the transport of the 25(OH)D into the cell via a megalin/cubilin complex. The accurate measurement of 25(OH)D has proved a difficult task. Although a reference method and standardization program are available for 25(OH)D, the other vitamin D metabolites still lack this. Interpretation of results, creation of clinical supplementation, and generation of therapeutic guidelines require not only accurate measurements of vitamin D metabolites, but also the accurate measurements of several other "molecules" related with bone metabolism. IFCC understood this priority and a committee has been established with the task to support and continue the standardization processes of vitamin D metabolites along with other bone-related biomarkers. In this review, we present the position of this IFCC Committee on Bone Metabolism on the latest developments concerning the measurement and standardization of vitamin D metabolites and its binding protein, as well as clinical indications for their measurement and interpretation of the results.
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Huesos/metabolismo , Proteína de Unión a Vitamina D , Vitamina D , Biomarcadores , Calcifediol , HumanosRESUMEN
OBJECTIVE: To evaluate ischaemia modified albumin (IMA) as an early negative predictor of acute coronary syndrome (ACS) in different time to presentation groups and different cardiac risk groups. METHODS: A prospective observational study was performed in the emergency department at Royal Perth Hospital. Consecutive patients with symptoms suggestive of ACS needing delayed troponin measurements were recruited. All enrolled patients had both IMA and troponin measurements performed on their initial blood samples. The time of the initial blood tests and thrombolysis in myocardial ischaemia (TIMI) risk scores were recorded. Initial IMA results were compared with 12 h troponin levels and a discharge diagnosis of ACS. More detailed analyses were made according to different times to presentation (0-4 h, 5-12 h) and cardiac risk (TIMI score 0-1, 2-7). Sensitivity, specificity, positive predictive value, negative predictive value and likelihood ratio were calculated. Receiver operating characteristic (ROC) curves were plotted to determine the best diagnostic cut-off for IMA. RESULTS: 248 patients were enrolled (151 (61%) men, mean age 65 years). All 248 patients had 'positive' IMA results using the 85 U/ml cut-off value recommended by the manufacturer. ROC curves failed to show improved cut-off points for diagnosing raised 12 h troponin levels or ACS; the area under the curve (AUC) was 0.52 and 0.53, respectively. ROC curves produced similar poor results in all subgroups. In the subgroup with time to presentation 0-4 h and TIMI score 0-1 for diagnosing ACS, the AUC was slightly better at 0.58. CONCLUSION: This study does not support the use of IMA as a negative predictor for ACS.
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Síndrome Coronario Agudo/diagnóstico , Isquemia Miocárdica/diagnóstico , Albúmina Sérica/análisis , Troponina/sangre , Síndrome Coronario Agudo/sangre , Anciano , Área Bajo la Curva , Biomarcadores/sangre , Diagnóstico Diferencial , Servicio de Urgencia en Hospital , Femenino , Humanos , Masculino , Arterias Mamarias/fisiopatología , Persona de Mediana Edad , Isquemia Miocárdica/sangre , Estudios Prospectivos , Curva ROCRESUMEN
BACKGROUND: The correlation between hemoglobin A(1c) (Hb A(1c)) and risk for complications in diabetic patients heightens the need to measure Hb A(1c) with accuracy. We evaluated the current performance for measuring Hb A(1c) in the Asian and Pacific region by examining data submitted by laboratories participating in the Taiwan proficiency-testing program. METHODS: Five fresh-pooled blood samples were sent to participating laboratories twice each year. The results were evaluated against target values assigned by the National Glycohemoglobin Standardization Program network laboratories; a passing criterion of +/-7% of the target value was used. Measurement uncertainty at Hb A(1c) concentrations of 7.0% and 8.0% were determined. RESULTS: A total of 276 laboratories from 11 countries took part in the Hb A(1c) survey. At the Hb A(1c) concentrations tested method-specific interlaboratory imprecision (CVs) were 1.1%-13.9% in 2005, 1.3%-10.1% in 2006, 1.2%-8.2% in 2007, and 1.1%-6.1% in 2008. Differences between target values and median values from the commonly used methods ranged from -0.24% to 0.22% Hb A(1c) in 2008. In 2005 83% of laboratories passed the survey, and in 2008 93% passed. At 7.0% Hb A(1c), measurement uncertainty was on average 0.49% Hb A(1c). CONCLUSIONS: The use of accuracy-based proficiency testing with stringent quality criteria has improved the performance of Hb A(1c) testing in the Asian and Pacific laboratories during the 4 years of assessment.
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Pruebas de Química Clínica/normas , Hemoglobina Glucada/análisis , Asia Occidental , Australasia , Asia Oriental , Humanos , Malasia , Control de CalidadRESUMEN
BACKGROUND: Interpretative commenting is an important activity of the clinical diagnostic laboratory. We describe a study of interpretative commenting abilities among senior laboratory professionals in the Asia-Pacific region and Africa. METHODS: Five sets of laboratory results reflecting common and important problems encountered in clinical chemistry were distributed at 4-weekly intervals to 31 registered participants from countries in the Asia-Pacific region and Africa. Participants were asked to attach an interpretative comment to the results assuming that the requesting doctor had asked for an interpretation of the result. RESULTS: Twelve pathologists and 19 scientists from seven countries registered to participate and the overall reply rate was approximately 50% for the five cases. The quality of the comments returned by participants was diverse and some reflected incorrect or misleading interpretation and advice. CONCLUSIONS: While interpretative commenting is an important laboratory activity, the results of this study suggest that there is room for improvement in the quality of interpretative comments offered by senior laboratory professionals, even for commonly reported results relating to most prevalent and important public health conditions. Interpretative commenting should be formally taught during training of pathologists and scientists, and continuing professional development in this area is required for the provision of a quality interpretative service.
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Química Clínica/normas , Competencia Clínica/normas , Técnicas de Laboratorio Clínico/normas , África , Humanos , Océano Pacífico , Garantía de la Calidad de Atención de Salud/normas , Encuestas y CuestionariosRESUMEN
BACKGROUND: In the laboratory evaluation of suspected paracetamol poisoning, a non-invasive sample type that avoids venepuncture would be an attractive alternative to plasma, particularly in the paediatric setting. Salivary paracetamol measurement has not previously been evaluated in the published medical literature in the setting of deliberate self-poisoning (DSP). METHODS: In-house validation experiments (recovery, stability and lower limit-of-detection) were performed on pooled saliva samples using a Roche Acetaminophen assay on a Roche/Hitachi 917 analyser. A clinical study of comparison of paired saliva and plasma samples was also conducted involving adult patients presenting with DSP of paracetamol, the results of which were published previously. RESULTS: The validation experiments using pooled saliva samples showed: (i) mean recovery (paracetamol concentration 37.5-525 mg/L) 100.01% (+/-0.02 SD); (ii) precision of repeated assay over 24-h period CV <4%; (iii) lower limit-of-detection 0.9 mg/L. The clinical study of 21 patients with mean plasma paracetamol concentration of 48 mg/L (range 0-130) and mean saliva concentration 62 mg/L (range 0-183) showed good correlation between saliva and plasma concentrations (r(2) = 0.91). CONCLUSIONS: The Roche Hitachi 917 Acetaminophen assay is suitable for the measurement of paracetamol in saliva. Further studies comparing plasma and saliva samples from patients with DSP and plasma paracetamol concentrations in the hepatotoxic range are warranted. If salivary samples are suitable for risk-stratifying patients with paracetamol DSP, venepuncture may be avoided, which would be attractive, especially in the paediatric setting.
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Acetaminofén/análisis , Saliva/química , Acetaminofén/envenenamiento , Adulto , Colorimetría/métodos , HumanosRESUMEN
Background The Framingham Risk Score estimates the 10-year risk of cardiovascular events. However, it performs poorly in older adults. We evaluated the incremental benefit of adding high-sensitivity cardiac troponin I (hs-cTnI) to the Framingham Risk Score. Methods and Results The HIMS (Health in Men Study) is a cohort study of community-dwelling men aged 70 to 89 years in Western Australia. Participants were identified from the electoral roll, with a subset undergoing plasma analysis. Hs- cTnI (Abbott Architect i2000 SR ) was measured in 1151 men without prior cardiovascular disease. The Western Australia Data Linkage System was used to identify incident cardiovascular events. After 10 years of follow-up, 252 men (22%) had a cardiovascular event ( CVE +) and 899 did not (CVE-). The Framingham Risk Score placed 148 (59%) CVE + and 415 (46%) CVE- in the high-risk category. In CVE - men, adding hs- cTnI affected the risk categories of 244 (27.2%) men, with 64.8% appropriately reclassified to a lower and 35.2% to a higher category, which decreased the number of high-risk men in the CVE- to 39%. In CVE + men, adding hs- cTnI affected the risk categories of 61 (24.2%), with 50.8% appropriately reclassified to a higher and 49.2% to a lower category and 82.5% remaining above the 15% risk treatment threshold. The net reclassification index was 0.305 ( P<0.001). Adding hs- cTnI increased the C-statistic modestly from 0.588 (95% CI , 0.552-0.624) to 0.624 (95% CI , 0.589-0.659) and improved model fit (likelihood ratio test, P<0.001). Conclusions Adding hs- cTnI to the Framingham Risk Score provided incremental prognostic benefit in older men, especially aiding reclassification of individuals into a lower risk category.
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Enfermedades Cardiovasculares/diagnóstico , Troponina I/sangre , Factores de Edad , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/epidemiología , Comorbilidad , Estado de Salud , Humanos , Incidencia , Masculino , Valor Predictivo de las Pruebas , Pronóstico , Medición de Riesgo , Factores de Riesgo , Factores Sexuales , Factores de Tiempo , Australia Occidental/epidemiologíaRESUMEN
Biochemical markers of bone turnover (bone-turnover markers) are released during bone formation or resorption and can be measured in blood and/or urine. The concentration of bone-turnover markers in serum or urine reflect bone remodeling activity and can potentially be used as surrogate markers of the rate of bone formation or bone resorption. While the diagnosis of osteoporosis is based on bone mineral density (BMD), the absolute fracture risk for a particular BMD measurement varies several fold depending on age and is also influenced by other clinical risk factors. The measurement of bone-turnover markers may be of additional value to BMD and clinical risk factors in fracture risk assessment by improving the sensitivity and specificity of prediction of future fractures. In clinical practice, bone-turnover markers may help make cost-effective treatment decisions in patients with borderline absolute risk. BMD changes following treatment cannot be detected with confidence for 12-24 months due to measurement imprecision. Bone-turnover markers, which show an early response following treatment, may be useful for monitoring therapy, identifying non-compliance and non-responders, and predicting early response to therapy. This review concludes by identifying the need for internationally agreed-upon standards for bone resorption and formation.
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Biomarcadores/metabolismo , Densidad Ósea , Resorción Ósea/fisiopatología , Huesos/fisiopatología , Osteoporosis/fisiopatología , Osteoporosis/terapia , Animales , Humanos , Osteoporosis/diagnósticoRESUMEN
Calprotectin is a calcium- and zinc-binding protein of the S-100 protein family which is mainly found within neutrophils and throughout the human body. The presence of calprotectin in faeces is a consequence of neutrophil migration into the gastrointestinal tissue due to an inflammatory process. Faecal calprotectin concentrations demonstrate good correlation with intestinal inflammation and faecal calprotectin is used as a biomarker in gastrointestinal disorders. Faecal calprotectin is a very sensitive marker for inflammation in the gastrointestinal tract, and useful for the differentiation of inflammatory bowel disease (IBD) from irritable bowel syndrome (IBS). Faecal calprotectin is used for the diagnosis, monitoring disease activity, treatment guidance and prediction of disease relapse and post-operative recurrence in IBD. There may also potentially be a role for faecal calprotectin in the management of infectious gastroenteritis, acute appendicitis, peptic ulcer disease, cystic fibrosis, coeliac disease, transplant rejection and graft versus host disease. Further studies are needed to confirm its utility in these conditions. Analysis of faecal calprotectin consists of an extraction step followed by quantification by immunoassay. Over the past few decades, several assays and extraction devices including point-of-care methods have been introduced by manufacturers. The manufacturer-quoted cut-off values for different faecal calprotectin assays are generally similar. However, the sensitivities and specificities at a given cut-off, and therefore the optimum cut-off values, are different between assays. A reference standard for calprotectin is lacking. Therefore, assay standardisation is required for more accurate and traceable test results for faecal calprotectin.
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Objective Primary aldosteronism is a curable cause of hypertension which can be treated surgically or medically depending on the findings of adrenal vein sampling studies. Adrenal vein sampling studies are technically demanding with a high failure rate in many centres. The use of intraprocedural cortisol measurement could improve the success rates of adrenal vein sampling but may be impracticable due to cost and effects on procedural duration. Design Retrospective review of the results of adrenal vein sampling procedures since commencement of point-of-care cortisol measurement using a novel single-use semi-quantitative measuring device for cortisol, the adrenal vein sampling Accuracy Kit. MEASUREMENTS: Success rate and complications of adrenal vein sampling procedures before and after use of the adrenal vein sampling Accuracy Kit. Routine use of the adrenal vein sampling Accuracy Kit device for intraprocedural measurement of cortisol commenced in 2016. Results Technical success rate of adrenal vein sampling increased from 63% of 99 procedures to 90% of 48 procedures ( P = 0.0007) after implementation of the adrenal vein sampling Accuracy Kit. Failure of right adrenal vein cannulation was the main reason for an unsuccessful study. Radiation dose decreased from 34.2 Gy.cm2 (interquartile range, 15.8-85.9) to 15.7 Gy.cm2 (6.9-47.3) ( P = 0.009). No complications were noted, and implementation costs were minimal. Conclusions Point-of-care cortisol measurement during adrenal vein sampling improved cannulation success rates and reduced radiation exposure. The use of the adrenal vein sampling Accuracy Kit is now standard practice at our centre.
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Glándulas Suprarrenales , Recolección de Muestras de Sangre , Hidrocortisona/análisis , Sistemas de Atención de Punto , Venas , Glándulas Suprarrenales/química , Recolección de Muestras de Sangre/métodos , Recolección de Muestras de Sangre/tendencias , Humanos , Sistemas de Atención de Punto/tendencias , Dosis de Radiación , Estudios Retrospectivos , Factores de TiempoRESUMEN
Biochemical markers of bone turnover (BTM) are released during bone remodeling and can be measured in blood or urine as noninvasive surrogate markers for the bone remodeling rate. The C-terminal cross-linked telopeptide of type I collagen (ßCTX) is released during bone resorption and is specific to bone tissue. Assays have been developed to measure ßCTX in blood and in urine; most current use of ßCTX measurement for research and in clinical practice is performed on a blood sample. Method-specific differences for serum and plasma ßCTX have led to initiatives to standardize or harmonize ßCTX commercial assays. ßCTX demonstrates significant biological variation due to circadian rhythm and effect of food which can be minimized by standardized sample collection in the fasting state in the morning. While ßCTX predicts fracture risk independent of bone mineral density, lack of data has precluded its inclusion in fracture risk calculators. The changes seen in ßCTX with antiresorptive therapies have been well characterized and this has led to its widespread use for monitoring therapy in osteoporosis. However, more fracture-based data on appropriate treatment goals for monitoring need to be developed. Evidence is lacking for the use of ßCTX in managing "drug holidays" of bisphosphonate treatment in osteoporosis or risk stratifying those at increased risk of developing osteonecrosis of the jaw. ßCTX is useful as an adjunct to imaging techniques for the diagnosis of Paget's disease of bone and for monitoring therapy and detecting recurrence. ßCTX also shows promise in the management of metastatic bone disease.
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Colágeno Tipo I/sangre , Osteoporosis/sangre , Péptidos/sangre , Biomarcadores/sangre , Remodelación Ósea , HumanosRESUMEN
Procalcitonin (PCT), regarded as a biomarker specific for bacterial infections, is used in a variety of clinical settings including primary care, emergency department and intensive care. PCT measurement aids in the diagnosis of sepsis and to guide and monitor antibiotic therapy. This article gives a brief overview of PCT and its use in guiding antibiotic therapy in various clinical settings, as well as its limitations. PCT performance in comparison with other biomarkers of infection in particular CRP is also reviewed. Owing to its greater availability, CRP has been widely used as a biomarker of infection and sepsis. PCT is often reported to be more superior to CRP, being more specific for sepsis and bacterial infection. PCT starts to rise earlier and returns to normal concentration more rapidly than CRP, allowing for an earlier diagnosis and better monitoring of disease progression.
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BACKGROUND AND PURPOSE: A higher plasma concentration of total homocysteine (tHcy) is associated with a greater risk of cardiovascular events. Previous studies, largely in younger individuals, have shown that B vitamins lowered tHcy by substantial amounts and that this effect is greater in people with higher tHcy and lower folate levels. METHODS: We undertook a 2-year, double-blind, placebo-controlled, randomized trial in 299 men aged > or =75 years, comparing treatment with a daily tablet containing 2 mg of folate, 25 mg of B6, and 400 microg of B12 or placebo. The study groups were balanced regarding age (mean+/-SD, 78.9+/-2.8 years), B vitamins, and tHcy at baseline. RESULTS: Among the 13% with B12 deficiency, the difference in mean changes in treatment and control groups for tHcy was 6.74 micromol/L (95% CI, 3.94 to 9.55 micromol/L) compared with 2.88 micromol/L (95% CI, 0.07 to 5.69 micromol/L) for all others. Among the 20% with hyperhomocysteinaemia, the difference between mean changes in treatment and control groups for men with high plasma tHcy compared with the rest of the group was 2.8 micromol/L (95% CI, 0.6 to 4.9 micromol/L). Baseline vitamin B12, serum folate, and tHcy were significantly associated with changes in plasma tHcy at follow-up (r=0.252, r=0.522, and r=-0.903, respectively; P=0.003, <0.001, and <0.001, respectively) in the vitamin group. CONCLUSIONS: The tHcy-lowering effect of B vitamins was maximal in those who had low B12 or high tHcy levels. Community-dwelling older men, who are likely to be deficient in B12 or have hyperhomocysteinemia, may be most likely to benefit from treatment with B vitamins.