Pyridinium Cross‐Links in Bone of Patients with Osteogenesis Imperfecta: Evidence of a Normal Intrafibrillar Collagen Packing

• Published in: Journal of bone and mineral research Vol. 15; no. 7; pp. 1330 - 1336
• Main Authors: Bank, Ruud A., Tekoppele, Johan M., Janus, Guus J. M., Wassen, Maurice H. M., Pruijs, Hans E. H., van der Sluijs, Hans A. H., Sakkers, Ralph J. B.
• Format: Journal Article
• Language: English
• Published: Washington, DC John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR) 01-07-2000; American Society for Bone and Mineral Research
• Subjects: Adolescent; Adult; Amino Acids - analysis; Arginine - analogs & derivatives; Arginine - analysis; Biological and medical sciences; Biomarkers - analysis; Biopsy; bone; Bone and Bones - chemistry; Bone and Bones - pathology; Child; Child, Preschool; collagen; Collagen - analysis; Collagen - chemistry; Collagen - metabolism; cross‐link; Diseases of the osteoarticular system; Humans; hydroxylysine; Hydroxylysine - analysis; hydroxylysylpyridinoline; Infant; Lysine - analogs & derivatives; Lysine - analysis; lysylpyridinoline; Malformations and congenital and or hereditary diseases involving bones. Joint deformations; Medical sciences; osteogenesis imperfecta; Osteogenesis Imperfecta - classification; Osteogenesis Imperfecta - metabolism; Osteogenesis Imperfecta - pathology; Pepsin A; Pyridinium; Pyridinium Compounds - analysis; Reference Values; Osteoarticular system; Human; Crosslinked state; Collagen; Diseases of the osteoarticular system; Osteogenesis imperfecta; Hydroxylysine; Bone; Brittleness; Osteochondrodysplasia; Degradation product; Genetic disease
• ISSN: 0884-0431; 1523-4681
• DOI: 10.1359/jbmr.2000.15.7.1330

The brittleness of bone in patients with osteogenesis imperfecta (OI) has been attributed to an aberrant collagen network. However, the role of collagen in the loss of tissue integrity has not been well established. To gain an insight into the biochemistry and structure of the collagen network, the cross‐links hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP) and the level of triple helical hydroxylysine (Hyl) were determined in bone of OI patients (types I, III, and IV) as well as controls. The amount of triple helical Hyl was increased in all patients. LP levels in OI were not significantly different; in contrast, the amount of HP (and as a consequence the HP/LP ratio and the total pyridinoline level) was significantly increased. There was no relationship between the sum of pyridinolines and the amount of triple helical Hyl, indicating that lysyl hydroxylation of the triple helix and the telopeptides are under separate control. Cross‐linking is the result of a specific three‐dimensional arrangement of collagens within the fibril; only molecules that are correctly aligned are able to form cross‐links. Inasmuch as the total amount of pyridinoline cross‐links in OI bone is similar to control bone, the packing geometry of intrafibrillar collagen molecules is not disturbed in OI. Consequently, the brittleness of bone is not caused by a disorganized intrafibrillar collagen packing and/or loss of cross‐links. This is an unexpected finding, because mutant collagen molecules with a random distribution within the fibril are expected to result in disruptions of the alignment of neighboring collagen molecules. Pepsin digestion of OI bone revealed that collagen located at the surface of the fibril had lower cross‐link levels compared with collagen located at the inside of the fibril, indicating that mutant molecules are not distributed randomly within the fibril but are located preferentially at the surface of the fibril.