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تسجيل

Markers of Bone Resorption: Collagen Cross-Links

المؤلف:  Marcello Ciaccio

المصدر:  Clinical and Laboratory Medicine Textbook 2021

الجزء والصفحة:  p512

2025-12-18

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There are two types of cross-links in collagen: intramolecular cross-links between two chains of the same molecule and intermolecular cross-links between adjacent chains (Fig. 1). To this second group belong reducible links, which decrease in number as the collagen matures, and non- reducible links, which increase in number during the same process. These last bonds increase the fibers’ mechanical resistance with age progression. Among the non-reducible bonds, two forms play an essential role in the study of bone remodeling: pyridinoline (hydroxylysylpyridinoline, PYD), formed by three hydroxylysine residues, and deoxypyridinoline (lysylpyridinoline, DPD), formed by two hydroxylysine residues and one lysine residue. The two forms have different tissue specificity: PYD is predominant in cartilage but is also found in bone, tendon, and blood vessel connective tis sue; DPD is found only in bone tissue and dentin. Both forms are absent in the skin and are not affected by dietary intake of collagen-containing foods. Pyridinium cross-links are released due to the degradation of mature collagen fibrils that occurs during the phase of bone resorption by osteoclasts. They pass into the bloodstream and are subsequently eliminated by the kidney. In urine, about 60% of the cross-links are found in a form bound to peptides of various sizes and 40% in a free form. Measurement of circulating concentration, especially that of DPD, provides information on the osteoclastic activity. In 1978, Fujimoto et al. characterized the structure of pyridinium cross-links, and since then, many methods have been developed to determine these resorption markers, mainly in the urine. By high-performance liquid chromatographic procedure (HPLC), it is possible to deter mine the two cross-links pyridinoline and deoxypyridinoline, simultaneously. However, the demonstration that the direct measurement of the free portion of cross-links pro vides information on the state of bone resorption similar to that obtained by the measurement of the total cross-links has led to the development of direct immunological methods for measuring free PYD and DPD or only free DPD. RIA (RadioImmunoAssay), ELISA (Enzyme-Linked ImmunoSorbent Assay) on microplate or chemiluminescence immunoassays applied on automated instrumentation are now commercially available.

Fig1. Schematic representation of collagen and fragments. (Copyright EDISES 2021. Reproduced with permission)