Clinical application of biochemical markers of bone turnover / Marcadores bioquímicos da remodelação óssea

With the ageing population in most countries, disorders of bone and mineral metabolism are becoming increasingly relevant to every day clinical practice. Consequently, the interest in, and the need for effective measures to be used in the screening, diagnosis and follow-up of such pathologies have markedly grown. Together with clinical and imaging techniques, biochemical tests play an important role in the assessment and differential diagnosis of metabolic bone disease. In recent years, the isolation and characterisation of cellular and extracellular components of the skeletal matrix have resulted in the development of molecular markers that are considered to reflect either bone formation or bone resorption. These biochemical indices are non-invasive, comparatively inexpensive and, when applied and interpreted correctly, helpful tools in the diagnostic and therapeutic assessment of metabolic bone disease. This review provides an overview of the current evidence regarding the clinical use of biochemical markers of bone remodelling in bone disease, with an emphasis on osteoporosis.

Tendo em vista o crescimento da população idosa na maioria dos países, os distúrbios do metabolismo ósseo e mineral estão tornando-se cada vez mais relevantes na prática clínica diária. Conseqüentemente, o interesse e a necessidade de medidas efetivas para serem usadas no rastreamento, diagnóstico e seguimento de tais patologias vêm crescendo acentuadamente. Além da avaliação clínica e de técnicas de imagens, os marcadores bioquímicos desempenham um importante papel na avaliação e diagnóstico das doenças ósseas metabólicas. Recentemente, a melhor caracterização dos componentes intracelulares e extracelulares da matriz óssea resultou no desenvolvimento dos marcadores moleculares, os quais refletem tanto a formação como a reabsorção óssea. Estes marcadores bioquímicos não são invasivos e comparativamente são de mais baixo custo, e quando aplicados e interpretados corretamente são instrumentos úteis no diagnóstico e tratamento das doenças ósseas metabólicas. Esta revisão abordará evidências atuais, levando em consideração o uso clínico dos marcadores bioquímicos da remodelação óssea nas doenças metabólicas ósseas, com ênfase na osteoporose.

The Effects of Sulphasalazine on Urinary Excretion of the Hydroxypyridinium Crosslinks of Collagen in Patients with Rheumatoid Arthritis

Secondary osteoporosis is a feature of rheumatoid arthritis (RA). In recent years, several attempts have been made to develop specific markers for monitoring connective tissue metabolism in arthritic diseases. Our purpose, in this study was to assess pyridinium crosslinks (PYD and DPYD) excretion in relation to the activity of RA (changes related to sulphasalazine treatment). Fourty premenopausal female patients with active RA (mean age; 36.0 7.2 years), 20 postmenopausal women with active RA (mean age; 60.0 6.8 years), 23 postmenopausal women with OA (mean age; 56.1 6.6 years) and 17 premenopausal healthy subjects (mean age; 28.3 4.28 years) were enrolled in our study. All of the 40 premenopausal female patients with active RA were given sulphasalazine. The mean follow up period for these patients was 10.3 1.1 months. In all of these patients, urine samples were collected both in the active and in the inactive periods. Urine PYD and DPYD levels were measured by ELISA. Urine PYD levels were significantly higher in the active period (14.01 3.16 nmol/mmol cr) than in the inactive (8.25 4.23 nmol/mmol cr) period in patients with premenopausal RA (p 0.05). Urine PYD levels were significantly high in postmenopausal active RA patients (19.06 3.26 nmol/mmol cr) compared to premenopausal active and ind inactive, postmenopausal inactive RA patients, osteoarthritis and healthy controls. Urine DPYD excretion was similar in patients with premenopausal RA in the active (7.46 2.13 nmol/mmol cr) and inactive periods (5.08 0.87 nmol/mmol cr) (p 0.05). In active premenopausal RA patients, a correlation was found between PYD excretion and RAI, ESR, CRP and functional capacity (r=0.5729 p 0.01, r=0.5953 p 0.01, r=0.6125 p 0.01 and r=0.6232, p 0.01 respectively). But in the inactive period, no such correlation was was evident. In disease activity parameters did not correlate with DPYD excretion in either the active or the inactive period. As a result, urine PYD excretion was significantly high in patients with active RA. During sulphasalazine treatment, urine PYD levels decreased. This is attributed to improvement in bone destruction.

Trastornos de los mecanismos renales de acidificacion en pacientes osteoporóticos / Renal acidification mechanism disorders in patients with osteoporosis

Se apresentaron 8 pacientes (6 mujeres y 2 varones de entre 40 y 67 años) con osteoporosis probablemente secundaria a, o agravada por, defectos tubulares renales. Três de las mujeres eran premenopáusicas; las restantes tenían 9,20 y 22 años de postmenopausia y 2 de ellas recibían terapia de reemplazo hormonal. Dos pacientes tenían nefrolitiasis (un varón con cálculos fosfocálcicos recurrentes y coraliforme izquierdo actual, y una mujer con nefrocalcionosis por riñon en esponja e hipercalciuria). En los restantes enfermos, la sospecha clínica se fundó en: a) Fractura de cadera a los 44 años en mujer premenopáusica sin factores de riesgo aparentes; b) múltiples aplastamientos vertebrales en varón de 45 años sin hipogonadismo ni otros factores presiponentes; c) falta de respuesta favorable a regímines terapéuticos anti-osteoporóticos bien cumplidos en 3 mujeres. Se determinó el nível de bicarbonato sérico en todos los pacientes y se practicó además una prueba de acidificación urinaria aguda con CINH4 o con furosemida oral. Tres pacientes tenían un defecto proximal, cuatro un defecto distal, y uno mixto. Las densidades minerales óseas expresadas en puntaje Z(x ñ e.s) fueron, en columna lumbar, -1,75 ñ 0,08 (n=8), y en cuello femoral -1,57 ñ 0,09 (n=4). Luego de un año de terapia con álcali por vía oral 5 enfermos tuvieron incrementos del calcio esquelético total que oscilaron entre 3 y 10 por ciento. Se concluye que seria conveniente incorporar el bicarbonato sérico a la bateía de pruebas de laboratorio en la evaluación inicial de pacientes osteopénicos, y que deberia sospecharse acidosis tubular renal en pacientes nefrolitiásicos osteopénicos, tengan o no hipercalciuria, y en enfermos osteoporóticos que no respondan a tratamientos probadamente efectivos