COLLAGEN CROSS-LINKS IN MINERALIZING TISSUES - A REVIEW OF THEIR CHEMISTRY, FUNCTION, AND CLINICAL RELEVANCE

Bone collagen cross-links are now widely used to assess bone resorptio n levels in many metabolic bone diseases, The posttranslational modifi cations of bone and other mineralizing collagens are significantly dif ferent from those of other type I collagen matrices, a fact that has b een exploited during recent advances in the development of biochemical markers of bone resorption. The enzymatic collagen cross-linking mech anism is based upon aldehyde formation from specific telopeptide lysin e or hydroxylysine residues, The immature ketoimine cross-links in bon e form via the condensation of a telopeptide aldehyde with a helical l ysine or hydroxylysine, Subsequent maturation to the pyridinoline and pyrrole crosslinks occur by further reaction of the ketoimines with te lopeptide aldehydes, In mineralizing tissues, a relatively low level o f lysyl hydroxylation results in low levels of hydroxylysyl pyridinoli ne, and the occurrence of the largely bone specific lysyl pyridinoline and pyrrolic cross-links, The collagen post-translational modificatio ns appear to play an integral role in matrix mineralization. The matri x of the turkey tendon only mineralizes after a remodeling of the coll agen and the subsequent formation of a modified matrix more typical of bone than tendon, Further, disturbances in the post-translational mod ification of collagen can also affect the mineralization density and c rystal structure of the tissue, In addition to their use as a convenie nt measure of matrix degradation, collagen cross-links are of signific ant importance for the biomechanical integrity of bone, Recent studies of osteoporotic bone, for example, have demonstrated that subtle pert urbations in the pattern of lysine hydroxylation result in changes in the cross-link profile, These alterations, specifically changes in the level of the pyrrolic cross-link, also correlate with the strength of the bone, Further research into the biochemistry of bone collagen cro ss-links may expand current understanding and their clinical applicati on in metabolic bone disease, This review also demonstrates the potent ial for further study into this area to provide more subtle informatio n into the mechanisms and etiology of disease and aging of mineralizin g tissues. (C) 1998 by Elsevier Science Inc. All rights reserved.