Browsing by Subject "bone material properties"

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    Changes in skeletal collagen crosslinks and matrix hydration in high and low turnover chronic kidney disease
    (2014-12-03) Allen, Matthew R.; Newman, Christopher L.; Chen, Neal; Granke, Mathilde; Nyman, Jeffry S.; Moe, Sharon M.
    Chronic kidney disease (CKD) increases fracture risk. The results of this work point to changes in bone collagen and bone hydration as playing a role in bone fragility associated with CKD. 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 cross-link 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 nonenzymatic collagen cross-links may be a key factor in compromised mechanical properties of CKD.
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    Variability of in vivo reference point indentation in skeletally mature inbred rats.
    (Elsevier, 2014) Allen, Matthew R.; Newman, Christopher L.; Smith, Eric; Brown, Drew M.; Organ, Jason M.
    Reference point indentation (RPI) has emerged as a novel tool to measure material-level biomechanical properties in vivo. Human studies have been able to differentiate fracture versus non-fracture patients while a dog study has shown the technique can differentiate drug treatment effects. The goal of this study was to extend this technology to the in vivo measurement of rats, one of the most common animal models used to study bone, with assessment of intra- and inter-animal variability. Seventy-two skeletally mature male Sprague-Dawley rats were subjected to in vivo RPI on the region between the tibial diaphysis and proximal metaphysis. RPI data were assessed using a custom MATLAB program to determine several outcome parameters, including first cycle indentation distance (ID-1st), indentation distance increase (IDI), total indentation distance (TID), first cycle unloading slope (US-1st), and first cycle energy dissipation (ED-1st). Intra-animal variability ranged from 13-21% with US-1st and Tot Ed 1st-L being the least variable properties and IDI the most highly variable. Inter-animal variability ranged from 16% (US-1st) to 25% (ED-1st 31 and IDI). Based on these data, group size estimates would need to range from 9-18/group to achieve sufficient power for detecting a 25% difference in a two-group experiment. Repeat tests on the contralateral limb of a small cohort of animals (n=17) showed non-significant differences over 28 days ranging from -6% to -18%. These results provide important data on RPI variability (intra- and inter-animal) in rats that can be used to properly power future experiments using this technique.