Browsing by Subject "pentosidine"

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    Bisphosphonates alter trabecular bone collagen cross-linking and isomerization in beagle dog vertebra
    (2008-03) Allen, Matthew R.; Gineyts, Evelyne; Leeming, Diana J.; Burr, David B.; Delmas, Pierre D.
    Changes in organic matrix may contribute to the anti-fracture efficacy of anti-remodeling agents. Following one year of treatment in beagle dogs, bisphosphonates alter the organic matrix of vertebral trabecular bone, while raloxifene had no effect. These results show that pharmacological suppression of turnover alters the organic matrix component of bone. INTRODUCTION: The collagen matrix contributes significantly to a bone's fracture resistance yet the effects of anti-remodeling agents on collagen properties are unclear. The goal of this study was to assess changes in collagen cross-linking and isomerization following anti-remodeling treatment. METHODS: Skeletally mature female beagles were treated for one year with oral doses of vehicle (VEH), risedronate (RIS; 3 doses), alendronate (ALN; 3 doses), or raloxifene (RAL; 2 doses). The middle dose of RIS and ALN and the lower dose of RAL approximate doses used for treatment of post menopausal osteoporosis. Vertebral trabecular bone matrix was assessed for collagen isomerization (ratio of alpha/beta C-telopeptide [CTX]), enzymatic (pyridinoline [PYD] and deoxypyridinoline [DPD]), and non-enzymatic (pentosidine [PEN]) cross-links. RESULTS: All doses of both RIS and ALN increased PEN (+34-58%) and the ratio of PYD/DPD (+14-26%), and decreased the ratio of alpha/beta CTX (-29-56%) compared to VEH. RAL did not alter any collagen parameters. Bone turnover rate was significantly correlated to PEN (R = -0.664), alpha/beta CTX (R = 0.586), and PYD/DPD (R = -0.470). CONCLUSIONS: Bisphosphonate treatment significantly alters properties of bone collagen suggesting a contribution of the organic matrix to the anti-fracture efficacy of this drug class.
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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.