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Purpose/Introduction Clinical data have documented a clear increase in fracture risk associated with chronic kidney disease (CKD). Preclinical studies have shown reductions in bone mechanical properties although the tissue-level mechanisms for these differences remain unclear. The goal of this study was to assess collagen cross-links and matrix hydration, two variables known to affect mechanical properties, in animals with either high or low turnover CKD. Methods At 35 weeks of age (> 75% reduction in kidney function), the femoral diaphysis of male Cy/+ rats with high or low bone turnover rates, along with normal littermate (NL) controls, were assessed for collagen cross-links (pyridinoline (PYD), deoxypyridinoline (DPD), and pentosidine (PE)) using a high performance liquid chromatography (HPLC) assay as well as pore and bound water per volume (pw and bw) using a 1H nuclear magnetic resonance (NMR) technique. Material-level biomechanical properties were calculated based on previously published whole bone mechanical tests. Results Cortical bone from animals with high turnover disease had lower Pyd and Dpd crosslink levels (−21% each), lower bw (−10%), higher PE (+71%), and higher pw (+46%), compared to NL. Animals with low turnover had higher Dpd, PE (+71%), and bw (+7%) along with lower pw (−60%) compared to NL. Both high and low turnover animals had reduced material-level bone toughness compared to NL animals as determined by three-point bending. Conclusions These data document an increase in skeletal PE with advanced CKD that is independent of bone turnover rate and inversely related to decline in kidney function. Although hydration changes occur in both high and low turnover disease, the data suggest that non-enzymatic collagen crosslinks may be a key factor in compromised mechanical properties of CKD. PMID:25466530

Ielja strik steroids

ielja strik steroids

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