Nonenzymatic Cross-Linking Pentosidine Increase in Bone Collagen and Are Associated with Disorders of Bone Mineralization in Dialysis Patients

Abstract

Disorders of bone and mineral metabolism are common complications in chronic kidney disease (CKD) patients and lead to significantly increased fracture risk, morbidity, and mortality of cardiovascular disease due to ectopic calcifications, contributing to a worsening prognosis. Bone strength is determined by not only bone mineral density but also bone quality, which is dependent on bone collagen cross-links. Collagen cross-links are classified into enzymatic immature and mature types and nonenzymatic advanced glycation end products (AGEs). Pentosidine is well established as one of the AGEs that accumulates markedly in CKD patients. The chemistry, function, and clinical relevance of cross-links have been revealed, whereas bone quality and the relationship with bone mineralization in CKD patients are not clear. We performed transiliac bone biopsies on 22 dialysis patients (mean age 56 ± 9 years) with severe secondary hyperparathyroidism and measured cross-links by evaluating bone histomorphometry. Cross-links data were compared with age-matched non-CKD subjects (mean age 58 ± 8 years, n = 17). Enzymatic collagen cross-links were formed to a similar extent compared with non-CKD subjects and showed a positive correlation with plasma intact parathyroid hormone. Pentosidine was remarkably increased in dialysis patients and inversely correlated with bone-formation rate/bone volume and mineral apposition rate. This study suggests that AGE collagen cross-links strongly associate with disorders of bone metabolism in dialysis patients.