Clinical application of biochemical markers of bone turnover

Abstract

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. RESUMO Marcadores Bioquímicos da Remodelação Óssea.Tendo em vista o crescimento da população idosa na maioria dos paí-ses, 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.

Bone remodeling markers and bone metastases: From cancer research to clinical implications

“…8 However, for comparison between samples, the assays should be performed in the same laboratory, as results from different laboratories, even with the same test and automated assays, could differ up to 5.6-fold. 11,29 Therefore, besides the calibration and the establishment of references for each laboratory, the ideal situation to control technical variability is to centralize the determinations in a unique laboratory. 20 ICTP ICTP, which reflects nonosteoclastic bone resorption mediated by MMPs, is liberated to the bloodstream during pathological conditions.…”

Serum total and bone alkaline phosphatase levels and their correlation with serum minerals over the lifespan of sheep

“…ing the different stages of osteoblastic proliferation and differentiation -bone alkaline phosphatase (BALP) and osteocalcin (OC), and osteoid synthesis -the amino-terminal (PINP) and carboxy-terminal propeptides of collagen type I (PICP) (Seibel, 2006). The markers of bone resorption include the products of type I collagen degradation -the N-terminal (NTX) and C-terminal telopeptide (CTX) and ICTP (a slight variant of CTX), pyridinolines -the end-products of the NTX and CTX metabolism, hydroxyproline and hydroxylysine, and the proteolytic enzymes secreted by the osteoclasts -tartrate-resistant acid phosphatase (TRAP) (Seibel, 2006).…”

“…The markers of bone resorption include the products of type I collagen degradation -the N-terminal (NTX) and C-terminal telopeptide (CTX) and ICTP (a slight variant of CTX), pyridinolines -the end-products of the NTX and CTX metabolism, hydroxyproline and hydroxylysine, and the proteolytic enzymes secreted by the osteoclasts -tartrate-resistant acid phosphatase (TRAP) (Seibel, 2006). These biomarkers could provide a simple and sensitive method for supporting the diagnosis of high-turnover bone disorders that focally involve the skeleton or diffuse disorders, where their levels usually increase in serum and urine, and have been recently used in human medicine for the assessment of post-menopausal osteoporosis and Paget's disease and to monitor their treatment (Seibel, 2006).…”

Response of bone turnover markers to raloxifene treatment in postmenopausal women with osteopenia

“…Changes in bone markers in response to treatment occur earlier and are of a greater magnitude than changes in bone density. A significant change in BMD can rarely be detected in an individual in response to oral anti-resorptive therapy in less than [18][19][20][21][22][23][24] months. Compliance with treatment is a concern in clinical practice and monitoring patients on treatment using biochemical markers can provide useful additional information for the management of patient care [14] .…”

“…Considerations for their use in clinical practice include cost effectiveness and also the variability of bone markers [16,17] . Studies have reported poor reproducibility of bone markers between laboratories [18,19] . The standardization of bone marker measurements is currently being addressed with the introduction of international reference standards [10] .…”