Search

Summary: 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 H 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. [ABSTRACT FROM AUTHOR]

Summary: Bisphosphonates reduce skeletal loss and fracture risk, but their use has been limited in patients with chronic kidney disease. This study shows skeletal benefits of zoledronic acid in an animal model of chronic kidney disease. Introduction: Bisphosphonates are routinely used to reduce fractures but limited data exists concerning their efficacy in non-dialysis chronic kidney disease. The goal of this study was to test the hypothesis that zoledronic acid produces similar skeletal effects in normal animals and those with kidney disease. Methods: At 25 weeks of age, normal rats were treated with a single dose of saline vehicle or 100 μg/kg of zoledronic acid while animals with kidney disease (approximately 30 % of normal kidney function) were treated with vehicle, low dose (20 μg/kg), or high dose (100 μg/kg) zoledronic acid, or calcium gluconate (3 % in the drinking water). Skeletal properties were assessed 5 weeks later using micro-computed tomography, dynamic histomorphometry, and mechanical testing. Results: Animals with kidney disease had significantly higher trabecular bone remodeling compared to normal animals. Zoledronic acid significantly suppressed remodeling in both normal and diseased animals yet the remodeling response to zoledronic acid was no different in normal and animals with kidney disease. Animals with kidney disease had significantly lower cortical bone biomechanical properties; these were partially normalized by treatment. Conclusions: Based on these results, we conclude that zoledronic acid produces similar amounts of remodeling suppression in animals with high turnover kidney disease as it does in normal animals, and has positive effects on select biomechanical properties that are similar in normal animals and those with chronic kidney disease. [ABSTRACT FROM AUTHOR]

Background: Hypertension is a major, modifiable risk factor for cardiovascular and kidney disease and premature mortality that is improved by the DASH (Dietary Approaches to Stop Hypertension) diet. The DASH diet emphasizes increased consumption of fruit and vegetables, whole grains, low-fat dairy, nuts, and poultry and fish and reduced intakes of fats, red meats (including pork), sodium, and added sugars., Objective: We sought to evaluate whether the consumption of lean pork compared with the consumption of chicken and fish as the predominant protein source in a DASH-style diet affected blood pressure (BP) control in men and women with elevated BP., Design: In a randomized crossover study, 13 women and 6 men [mean ± SEM age: 61 ± 2 y; BMI (in kg/m²): 31.2 ± 1.4] with elevated BP [systolic blood pressure (SBP)/diastolic blood pressure (DBP): 130 ± 2/85 ± 2 mm Hg] consumed a DASH-style diet for two 6-wk controlled dietary interventions (with a 4-wk diet washout between interventions) with either lean pork [DASH diet with pork (DASH-P)] or chicken and fish [DASH diet with chicken and fish (DASH-CF), the control diet] as the major protein source (55% of total protein intake). SBP and DBP were measured manually and with a 24-h BP monitoring system on 3 d before and 3 d at the end of each diet intervention., Results: Preintervention manual BP (DASH-P: 130/84 ± 2/1 mm Hg; DASH-CF: 129/84 ± 2/1 mg Hg) and postintervention manual BP (DASH-P: 122/79 ± 2/1 mm Hg; DASH-CF: 123/78 ± 3/1) were not different between the DASH-P and DASH-CF. Consumption of these DASH-style diets for 6 wk reduced all measures of BP (P < 0.05) with no differences in responses between the DASH-CF and DASH-P., Conclusion: The results indicate that adults with elevated BP may effectively incorporate lean pork into a DASH-style diet for BP reduction., (© 2015 American Society for Nutrition.)