Clinical and Technical Review - Tecomedical

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6 Collagen metabolites and epitopes DPD: Deoxypyridinoline. Breakdown product from Type I collagen degradation. PYD: Pyridinoline. Breakdown product from Type I collagen degradation. NTX: Cross-linked N-terminal telopeptide resulting from Type I collagen degradation. NTX = new synthesized and agemodified bone matrix. CTX: C-terminal telopeptide resulting from Type I collagen degradation, CTX alpha (New Bone Matrix), CTX beta (Old Bone Matrix). ICTP=CTX-MMP: Carboxy-terminal telopeptide of type I collagen. Larger epitope containing the smaller CTX epitope. Helical Peptide: Peptide derived from the helical region of the α-1 chain of Type 1 collagen. Note: The concentration of the different biomarker are partly dependent on age, gender, race as well as influenced by diurnal rhythm, food intake etc. (see table on page 8). Age dependency is of high importance if biomarker are used for preclinical testing, especially in juvenile laboratory animals (rat, mice). Bone turnover regulators Calcitonin: Inhibits bone resorption, directly acts on osteoclasts. Parathyroid hormone (PTH): Key factor in the maintenance of calcium and phosphate homeostasis. Stimulates osteoclasts activity. 1,25(OH) 2D3 : 1,25 dihydroxy vitamin D3 (or 1,25-dihydroxycholecalciferol) is the biologically active form of vitamin D. It is synthesized in the kidney from 25-vitamin D (25-hydroxycholecalciferol). 1,25(OH) 2D3 is the principal regulator of calcium homeostasis in the body. It enhances the efficiency of calcium. Fetuin A: Glycoprotein synthesized by liver, secreted into blood. Deposited as noncollagenous protein in mineralized bones. Potent inhibitor of soft tissue (vascular) calcification by binding excess mineral in serum. Regulates calcium metabolism and osteogenesis. FGF-23: Fibroblast Growth Factor 23. Important regulator of phosphate homeostasis. Able to “block” renal reabsorption of Pi. FGF-23 abnormalities are involved in renal phos-phate wasting disorders leading to “hypophosphatemia”. Literature: 1. Leeming DJ, Koizumi M, Byrjalsen I, Li B, Qvist P, Tanko LB. The relative use of eight collagenous and noncollagenous markers for diagnosis of skeletal metastases in breast, prostate, or lung cancer patients. Cancer Epidemiol Biomarkers Prev. 2006; 15(1):32-8. 2. Caulfield MP, Reitz RE. Biochemical markers of bone turnover and their utility in osteoporosis. MLO-online April 2004. Schaller S, Henriksen K, Hoegh-Andersen P, Søndergaard BC, Sumer EU, Tanko LB, Qvist P and Karsdal MA. In vitro, ex vivo, and in vivo methodological approaches for studying therapeutic targets of osteoporosis and degenerative joint diseases: How biomarkers can assist? Assay And Drug Development Technologies 2005; 3:553-580. 3. Delmas PD, Eastell R, Garnero P, Seibel MJ and Stephan J. The use of biochemical markers of bone turnover in osteoporosis. Osteoporosis Int 2000: Supp 6: S2-17.
Bone Turnover – Biochemical Marker Sclerostin: inhibits differentiation and function of osteoblasts through BMP DKK-1 regultes osteoblast differentiation P * C I P MMPs BAP (bone-specific alkaline phosphatase) “calcification of the matrix” ICTP ** ICP * P , P N I P Helical Peptide ** Not so relevant in Osteoporosis Fetuin A * CICP = PICP 7
Page 1 and 2: Author: Peter Haima, Ph Clinical an
Page 3 and 4: Figure 1: Soloway 0 = Patients with
Page 5: Bone Resorption Osteoclast: Large m
Page 9 and 10: Bone marker and their behavior in v
Page 11 and 12: Biomarker according to NIH Osteoart
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Page 19 and 20: Specific recommendations BAP Osteoc
Page 21 and 22: Bone marker - Reference values in a
Page 23 and 24: Cross reactivity - different specie

Clinical and Technical Review - Tecomedical

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