Abstract

ABSTRACTIntroduction:Digital radiography (DRx) may provide a suitable alternative to investigate mineral and bone disorder (MBD) and loss of bone density (BD) in rodent models of chronic kidney disease (CKD). The objective of this study was to use DRx to evaluate BD in CKD rats, and to evaluate the correlation between DRx findings and serum MBD markers and bone histomorphometry.Methods:Uremia was induced by feeding Wistar rats an adenine-enriched diet (0.75% for 4 weeks/0.10% for 3 weeks); outcomes were compared to a control group at experimental weeks 3, 4, and 7. The following biochemical markers were measured: creatinine clearance (CrC), phosphate (P), calcium (Ca), fractional excretion of P (FeP), alkaline phosphatase (ALP), fibroblast growth factor-23 (FGF-23), and parathyroid hormone (PTH). DRx imaging was performed and histomorphometry analysis was conducted using the left femur.Results:As expected, at week 7, uremic rats presented with reduced CrC and higher levels of P, FeP, and ALP compared to controls. DRx confirmed the lower BD in uremic animals (0.57±0.07 vs. 0.68 ± 0.06 a.u.; p = 0.016) compared to controls at the end of week 7, when MBD was more prominent. A severe form of high-turnover bone disease accompanied these biochemical changes. BD measured on DRx correlated to P (r=-0.81; p = 0.002), ALP (r = -0.69, p = 0.01), PTH (r = -0.83, p = 0.01), OS/BS (r = -0.70; p = 0.02), and ObS/BS (r = -0.70; p = 0.02).Conclusion:BD quantified by DRx was associated with the typical complications of MBD in CKD and showed to be viable in the evaluation of bone alterations in CKD.

Highlights

  • Digital radiography (DRx) may provide a suitable alternative to investigate mineral and bone disorder (MBD) and loss of bone density (BD) in rodent models of chronic kidney disease (CKD)

  • As expected, at week 7, uremic rats presented with reduced CrC and higher levels of P, fractional excretion of P (FeP), and alkaline phosphatase (ALP) compared to controls

  • CrC was markedly decreased in the Uremic group at week 4, following the initial diet with 0.75% adenine enrichment for 4 weeks, with levels of 0.11 ± 0.04 mL/min/100g compared to 0.75 ± 0.44 mL/min/100g for animals in the Control group (p = 0.016)

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Summary

Introduction

Digital radiography (DRx) may provide a suitable alternative to investigate mineral and bone disorder (MBD) and loss of bone density (BD) in rodent models of chronic kidney disease (CKD). Results: As expected, at week 7, uremic rats presented with reduced CrC and higher levels of P, FeP, and ALP compared to controls. Trabecular bone has a turnover rate approximately 8 times faster than that of compact bone, and it is highly responsive to metabolic stimuli[1]. This high turnover rate makes trabecular bone the primary site for the detection of early bone loss that precedes fractures, and for monitoring the efficacy of different treatments aiming to prevent or slow down bone loss in clinical settings[2]. As BD decreases, less photons are absorbed, resulting in the attenuation of the radiographic signal[4,5]

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