DEVELOPMENT OF A MONOCLONAL-ANTIBODY TO URINARY DEGRADATION PRODUCTS FROM THE C-TERMINAL TELOPEPTIDE ALPHA-1 CHAIN OF TYPE-I COLLAGEN - APPLICATION IN AN ENZYME-IMMUNOASSAY AND COMPARISON TO CROSSLAPS(TM) ELISA

A monoclonal antibody MAbA7 was raised against a synthetic peptide hav ing a sequence (EKAHDGGR) specific for a part of the C-telopeptide alp ha 1 chain of type I collagen. MAbA7 was labelled with horseradish per oxide and used in a competitive one-step enzyme-linked immunosorbent a ssay (ELISA) for measurement of urinary type I collagen degradation pr oducts. The assay was technically evaluated and preliminary clinical d ata are presented. The measuring range was 200-7000 mu g l(-1) with a detection limit of 25 mu g l(-1). Within-run and total CVs were 5.5 an d 8.0%, respectively. Analytical recovery averaged 96.6%+/-5.3 (mean+/ -1SD). Values obtained in the ELISA were highly correlated (r=0.93) to values obtained by a commercially available assay (CrossLaps(TM) ELIS A) known to measure urinary degradation products derived from the C-te lopeptide of type I collagen reflecting the rate of bone resorption. I nvestigation of the urinary fragments responsible for the immunologica l response in the two assays revealed, however, that they are not iden tical. Values obtained in urine samples from postmenopausal women (n=1 08) and patients with Paget's disease (n=6) increased 43% (p<0.01) and 28-fold (p<0.001), respectively, when compared to a premenopausal lev el (n=50). A decrease in the urinary concentrations of 67% (p<0.01) wa s seen after 6 months in urine samples from postmenopausal women (n=13 ) receiving hormone replacement therapy (HRT) compared to a group rece iving placebo (n=9). Likewise, the urinary concentrations decreased 88 % (p<0.001) in early postmenopausal women receiving bisphosphonate the rapy (n=11) for a period of 9 months compared to a group receiving pla cebo (n=12). These results suggest that the monoclonal antibody and th e new assay may be useful for further investigations of the physiologi cal and clinical importance of type I collagen degradation.