Collagen cross-links as a determinant of bone quality: a possible explanation for bone fragility in aging, osteoporosis, and diabetes mellitus

• Published in: Osteoporosis international Vol. 21; no. 2; pp. 195 - 214
• Main Authors: Saito, M., Marumo, K.
• Format: Journal Article
• Language: English
• Published: London Springer-Verlag 01.02.2010; Springer; Springer Nature B.V
• Subjects: Aging; Aging - physiology; Biological and medical sciences; Biomarkers; Bone and Bones - metabolism; Bone Density - physiology; Bones; Collagen - metabolism; Diabetes; Diabetes Mellitus, Type 2 - metabolism; Diabetes Mellitus, Type 2 - physiopathology; Diabetes. Impaired glucose tolerance; Diseases of the osteoarticular system; Endocrine pancreas. Apud cells (diseases); Endocrinology; Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Fractures; Glycation End Products, Advanced - metabolism; Humans; Medical sciences; Medicine; Medicine & Public Health; Orthopedics; Osteoporosis; Osteoporosis - metabolism; Osteoporosis - physiopathology; Osteoporosis. Osteomalacia. Paget disease; Proteins; Quality; Review; Rheumatology; Risk factors; Cross-links; Osteoporosis; Bone quality; Advanced glycation end products; Diabetes; Collagen; Endocrinopathy; Diabetes mellitus; Diseases of the osteoarticular system; Rheumatology; Glycation; Quality; Bone
• ISSN: 0937-941X; 1433-2965; 1433-2965
• DOI: 10.1007/s00198-009-1066-z

Collagen cross-linking, a major post-translational modification of collagen, plays important roles in the biological and biomechanical features of bone. Collagen cross-links can be divided into lysyl hydroxylase and lysyl oxidase-mediated enzymatic immature divalent cross-links, mature trivalent pyridinoline and pyrrole cross-links, and glycation- or oxidation-induced non-enzymatic cross-links (advanced glycation end products) such as glucosepane and pentosidine. These types of cross-links differ in the mechanism of formation and in function. Material properties of newly synthesized collagen matrix may differ in tissue maturity and senescence from older matrix in terms of cross-link formation. Additionally, newly synthesized matrix in osteoporotic patients or diabetic patients may not necessarily be as well-made as age-matched healthy subjects. Data have accumulated that collagen cross-link formation affects not only the mineralization process but also microdamage formation. Consequently, collagen cross-linking is thought to affect the mechanical properties of bone. Furthermore, recent basic and clinical investigations of collagen cross-links seem to face a new era. For instance, serum or urine pentosidine levels are now being used to estimate future fracture risk in osteoporosis and diabetes. In this review, we describe age-related changes in collagen cross-links in bone and abnormalities of cross-links in osteoporosis and diabetes that have been reported in the literature.