Reductions in degree of mineralization and enzymatic collagen cross-links and increases in glycation-induced pentosidine in the femoral neck cortex in cases of femoral neck fracture

Introduction: Enzymatic and glycation-induced nonenzymatic cross-links play important roles in the expression of bone strength. The cross-link pattern is affected by tissue maturation and senescence. The aim of our study was to understand the distinctive posttranslational modifications of collagen in areas with different degrees of mineralization with and without hip fracture. Methods: Sixteen female cases of intracapsular hip fracture (78 +/- 6 years) and 16 age- and gender-matched postmortem controls (76 +/- 6 years) were included in this study. A sample of each femoral neck cortex was fractionated into low (1.7 to 2.0 g/ml) and high (> 2.0 g/ml) density portions. The contents of enzymatic cross-links (dihydroxylysinonorleucine, hydroxylysinonorleucine, lysinonorleucine, pyridinoline, and deoxypyridinoline) and nonenzymatic cross-links (pentosidine) and the extent of lysine (Lys) hydroxylation were determined in each fraction. Results: In the controls, there was no significant difference in the contents of enzymatic cross-links between low- and high-mineralized bone fractions whereas pentosidine content was significantly higher in high-mineralized bone compared with low-mineralized bone (p=0.0014). When comparing enzymatic cross-link contents between controls and fracture cases, a trend toward lower (p=0.0961) cross-link content in low-mineralized bone and a significant reduction (p < 0.0001) in high-mineralized bone were observed. Pentosidine content of low-mineralized bone was significantly higher in fracture cases than in controls (p < 0.0001). The extent of Lys hydroxylation was significantly higher in fracture cases than in controls (p < 0.001). The higher hydroxylation of Lys in collagen from fracture cases relative to controls was associated with significantly higher values of hydroxylysine-derived cross-link such that the enzymatic cross-link patterns correlated with the extent of Lys hydroxylation in the collagen molecules. Conclusions: These results suggest that reductions in the degree of mineralization and enzymatic cross-links and excessive formation of pentosidine may play an important role in explaining poor bone quality in osteoporosis.