Role of collagen enzymatic and glycation induced cross-links as a determinant of bone quality in spontaneously diabetic WBN/Kob rats

Abstract

Diabetes is associated with an increased risk of fracture, although type 2 diabetes is often characterized by normal bone mineral density (BMD). Enzymatic and glycation-induced non-enzymatic cross-links play important roles in the expression of bone strength. The serum vitamin B6 concentration is lower in patients with diabetes than in healthy controls. The aim our study was to see if spontaneously diabetic WBN/Kob rats in the pre- and post-onset of diabetes would serve as a suitable model for studying the pathogenesis of the susceptibility to fracture in diabetes without the reduction of bone mineral density. Seventy male WBN/Kob rats were obtained at the ages of 1 to 18 months. Seventy normal male Wistar rats were used as the non-diabetic, age-matched control. The contents of enzymatic cross-links (dihydroxylysinonorleucine, hydroxylysinonorleucine, lysinonorleucine, pyridinoline and deoxypyridinoline) and non-enzymatic cross-links (pentosidine) were determined in femoral bone. We also analyzed the serum concentration of vitamin B6 (pyridoxal and pyridoxamine), femoral BMD and a three-point bending test of the femur. A low level of serum vitamin B6 was associated with a decrease in enzymatic crosslinking in bone during the subclinical diabetes stage. After the onset of diabetes, there was a steady decrease in enzymatic cross-links and a steep increase in pentosidine. Furthermore, impaired bone mechanical properties in the WBN/Kob rats despite the lack of reduction in BMD coincided with impaired enzymatic cross-link formation and increases in glycation-induced pentosidine. These results indicate that the alteration of enzymatic and non-enzymatic crosslinking in bone could be important for explaining the variation of fracture susceptibility in diabetes.