Technical Report Abstracts

Collagen breakdown, and thus bone resorption, can now be assessed by measuring the urinary excretion of the collagen crosslinks, pyridinoline (Pyd) and deoxypyridinoline (Dpd). In a pilot study we measured Pyd and Dpd in 20 patients with breast cancer, ten with known bone metastases and ten with no recognised metastases in bone or elsewhere after 1 year's subsequent follow up. Eight out of the ten patients with metastases had crosslink excretion values higher than the reference interval, but so did some patients without known metastatic disease. For both crosslinks there was a clear correlation with serum alkaline phosphatase activity measured at about the same time. We consider that measurement of urinary collagen crosslink assays may have a place in the early detection of metastatic spread to bone. Until recently the biochemical assessment of bone resorption has been limited by the lack of specificity of the methods available. Urinary hydroxyproline has been widely used. While greatly raised values are found in patients with a very high bone turnover such as Paget's disease, hydroxyproline assays have been less useful in demonstrating smaller changes in bone turnover, for example, in osteoporosis or primary hyperparathyroidism (Kivirikko, 1970; Stepan et al., 1989; Deacon et al., 1987). The clinical usefulness of hydroxypro-line is further limited by its derivation from tissues other than bone and from processes other than mature collagen turnover (Krane et al., 1977; Robins, 1982a); it is also limited by the need for dietary restrictions to obtain the most reproducible results. In the assessment of patients with breast malignancy, the place of hydroxyproline excretion has been explored; high values are seen in some patients with known bone metastases but many have values indistinguishable from normal (Roberts et al., 1975; Cuschieri, 1977; Frenay et al., 1988). The assay has proved to be of only limited value in the screening of patients in the follow up clinics. Following the identification of collagen crosslink components in urine (Gunja-Smith & Boucek, 1981) an alternative method for assessing collagen breakdown was developed by using an immunoassay for pyridinoline (Robins, 1982b). Pyri-dinoline (Pyd) is a derivative of 3-hydroxyproline (Fujimoto et al., 1978; Robins, 1983) and is present only in extracellular collagen fibrils. It is the principal crosslink of cartilage colla-gen and to a smaller extent of bone collagen; it is not found in skin collagen. High values of urinary Pyd have been demonstrated in patients with rheumatoid arthritis and osteo-arthritis …