Markers of Bone Turnover in Bone Metastasis from Prostate Cancer
Bone homeostasis is achieved through a continuous remodelling process on the bone surface of the balanced resorption of old bone by osteoclasts and the formation of new bone by osteoblasts. Local and systemic growth factors regulate the differentiation an
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Markers of Bone Turnover in Bone Metastasis from Prostate Cancer Francesco Bertoldo
Bone homeostasis is achieved through a continuous remodelling process on the bone surface of the balanced resorption of old bone by osteoclasts and the formation of new bone by osteoblasts. Local and systemic growth factors regulate the differentiation and activity of the osteoclasts and osteoblasts (and osteocytes). Maintenance and repair of normal bone result in the release of enzymes, peptides and mineral components that have been characterised as serum and urinary biochemical markers of bone remodelling [1]. High bone turnover in cancer patients is crucial for all the steps of bone metastatic disease, from the homing of circulating cancer cells into the bone (premetastatic niche) to the complication of bone metastasis (BMT) (skeletally related events [SREs]). Therefore, elevated bone turnover marker could predict bone metastasis, risk of bone progression and risk of SREs, potentially becoming a potent prognostic predictor (Fig. 2.1). For this reason, biochemical markers of bone remodelling are potentially an ideal tool for evaluating changes in bone turnover, such as those associated with malignant bone lesions and response to treatment. Osteoclast and osteoblast activity (and probably that of cancer cells) is
F. Bertoldo, MD Metabolic Bone Diseases and Osteo-oncology Unit, Internal Medicine, Department of Medicine, University of Verona, Verona, Italy e-mail: [email protected]
associated with the release of distinct biochemical markers that are amenable to non-invasive measurements of the blood or urine. Breakdown products of type I collagen by osteolysis as cross-linked collagen peptides (the amino (N)- and carboxy (C)-terminal cross-linked telopeptide of type I collagen, NTX and CTX, respectively), and the terminal peptides that are cleaved from procollagen before its integration into new bone matrix (e.g. procollagen type I N-terminal and C-terminal peptides, or P1NP and P1CP), can provide meaningful insights into the ongoing effects of tumour growth on bone turnover (Fig. 2.2). Bone-specific alkaline phosphatase (bone ALP) concentrations in serum reflect the ongoing rate of osteogenesis [2]. The International Osteoporosis Foundation and the International Federation of Clinical Chemistry and Laboratory Medicine recommend that a marker of bone formation (serum procollagen type I N propeptide) and a marker of bone resorption (serum C-terminal telopeptide of type I collagen) be used as reference analytes for bone turnover markers in clinical studies [2] (Fig. 2.3). Nowadays, a number of bone markers can be determined using enzyme immunological procedures (enzyme-linked immunosorbant assay) by means of a commercial kit that can be easily adapted to laboratory automated machines to achieve greater analytical reliability during determination compared with manual methods [3]. Although a great deal of the data in the literature are obtained on markers analysed
© Springer International Publishing Switzerland 2017 F. Bert
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