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Clinical and Technical Review - Tecomedical

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6<br />

Collagen metabolites <strong>and</strong> epitopes<br />

DPD:<br />

Deoxypyridinoline. Breakdown product from Type I collagen<br />

degradation.<br />

PYD:<br />

Pyridinoline. Breakdown product from Type I collagen<br />

degradation.<br />

NTX:<br />

Cross-linked N-terminal telopeptide resulting from<br />

Type I collagen degradation. NTX = new synthesized <strong>and</strong><br />

agemodified bone matrix.<br />

CTX:<br />

C-terminal telopeptide resulting from Type I collagen<br />

degradation, CTX alpha (New Bone Matrix), CTX beta (Old<br />

Bone Matrix).<br />

ICTP=CTX-MMP:<br />

Carboxy-terminal telopeptide of type I collagen.<br />

Larger epitope containing the smaller CTX epitope.<br />

Helical Peptide:<br />

Peptide derived from the helical region of the α-1 chain of<br />

Type 1 collagen.<br />

Note:<br />

The concentration of the different biomarker are partly<br />

dependent on age, gender, race as well as influenced by<br />

diurnal rhythm, food intake etc. (see table on page 8). Age<br />

dependency is of high importance if biomarker are used for<br />

preclinical testing, especially in juvenile laboratory animals<br />

(rat, mice).<br />

Bone turnover regulators<br />

Calcitonin:<br />

Inhibits bone resorption, directly acts on osteoclasts.<br />

Parathyroid hormone (PTH):<br />

Key factor in the maintenance of calcium <strong>and</strong> phosphate<br />

homeostasis. Stimulates osteoclasts activity.<br />

1,25(OH) 2D3 :<br />

1,25 dihydroxy vitamin D3 (or 1,25-dihydroxycholecalciferol)<br />

is the biologically active form of vitamin D. It is<br />

synthesized in the kidney from 25-vitamin D (25-hydroxycholecalciferol).<br />

1,25(OH) 2D3 is the principal regulator<br />

of calcium homeostasis in the body. It enhances the<br />

efficiency of calcium.<br />

Fetuin A:<br />

Glycoprotein synthesized by liver, secreted into blood.<br />

Deposited as noncollagenous protein in mineralized bones.<br />

Potent inhibitor of soft tissue (vascular) calcification by binding<br />

excess mineral in serum. Regulates calcium metabolism<br />

<strong>and</strong> osteogenesis.<br />

FGF-23:<br />

Fibroblast Growth Factor 23. Important regulator of<br />

phosphate homeostasis. Able to “block” renal reabsorption<br />

of Pi. FGF-23 abnormalities are involved in renal phos-phate<br />

wasting disorders leading to “hypophosphatemia”.<br />

Literature:<br />

1. Leeming DJ, Koizumi M, Byrjalsen I, Li B, Qvist P, Tanko LB.<br />

The relative use of eight collagenous <strong>and</strong> noncollagenous markers<br />

for diagnosis of skeletal metastases in breast, prostate, or<br />

lung cancer patients.<br />

Cancer Epidemiol Biomarkers Prev. 2006; 15(1):32-8.<br />

2. Caulfield MP, Reitz RE. Biochemical markers of bone turnover <strong>and</strong><br />

their utility in osteoporosis. MLO-online April 2004.<br />

Schaller S, Henriksen K, Hoegh-Andersen P, Søndergaard BC,<br />

Sumer EU, Tanko LB, Qvist P <strong>and</strong> Karsdal MA. In vitro, ex vivo, <strong>and</strong><br />

in vivo methodological approaches for studying<br />

therapeutic targets of osteoporosis <strong>and</strong> degenerative joint<br />

diseases: How biomarkers can assist? Assay And Drug<br />

Development Technologies 2005; 3:553-580.<br />

3. Delmas PD, Eastell R, Garnero P, Seibel MJ <strong>and</strong> Stephan J. The use<br />

of biochemical markers of bone turnover in osteoporosis.<br />

Osteoporosis Int 2000: Supp 6: S2-17.

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