and the 2Clinical Pharmacology Unit, Royal Bath Hospital, Harrogate SUMMARY An enzyme linked immunoassay (ELISA) for the collagen cross link, pyridinoline, has been developed using affinity purified antibodies, with a sensitivity down to about 0.1 ng of cross link. Measurements of urinary pyridinoline were made in patients with rheumatoid arthritis (RA), osteoarthritis (OA), and a control group showing no signs of joint disease. Expressed relative to creatinine values, pyridinoline was significantly increased in both RA and OA groups compared with controls: these differences were much larger than could be attributed to any age related effects or to changes in urinary creatinine concentrations. These findings were confirmed by analysis of a series of 24 h urine collections which showed that the total pyridinoline excretions were significantly higher in both RA and OA groups than in the controls. As pyridinoline is much more prevalent in cartilage than in bone collagen, measurement of this compound in urine may provide an index for monitoring the increased joint destruction that occurs in arthritic disease. for collagen degradation based on the release of cross linking components has potential advantages over previous methods both in specificity and sensitivity. In particular, measurement of cross links would indicate degradation of mature collagen fibrils rather than release from all intermediates formed during the extensive postribosomal processing of collagen.Pyridinoline is a 3-hydroxypyridinium compound9 that is formed by interactions involving an intermediate bifunctional cross linkl 01 to give a stable amino acid derivative linking three collagen chains.'2 The compound is most prevalent in cartil-
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