Dataset Information

Low Turnover Renal Osteodystrophy With Abnormal Bone Quality and Vascular Calcification in Patients With Mild-to-Moderate CKD.

ABSTRACT:

Introduction

Limited information is available on renal osteodystrophy (ROD) and vascular calcification (VC) during early chronic kidney disease (CKD). This study was designed to evaluate ROD and VC in 32 patients with CKD stages II to IV.

Methods

Patients underwent dual-energy X-ray absorptiometry (DXA) for assessment of bone mineral density (BMD) and trabecular bone score (TBS), thoracic computed tomography for VC scoring using the Agatston method, and anterior iliac crest bone biopsy for mineralized bone histology, histomorphometry, and Fourier transform infrared spectroscopy (FTIR). Classical and novel bone markers were determined in the blood.

Results

Mean estimated glomerular filtration rate (eGFR) was 44 ± 16 ml/min per 1.73 m². Of the patients, 84% had low bone turnover. In Whites, eGFR correlated negatively with the turnover parameter activation frequency (Ac.f) (r -0.48, P = 0.019) and with parameters of bone formation. Most patients had VC (>80%) which correlated positively with levels of phosphorus, c-terminal fibroblast growth factor-23, and activin. Aortic calcifications (ACs) correlated negatively with bone formation rate (BFR) and Ac.f (rho -0.62, -0.61, P < 0.001). TBS correlated negatively with coronary calcification (rho -0.42, P = 0.019) and AC (rho -0.57, P = 0.001). These relationships remained after adjustment of age. The mineral-to-matrix ratio, an FTIR metric reflecting bone quality, was negatively related to Ac.f and positively related to AC.

Conclusion

Low bone turnover and VC are predominant in early stages of CKD. This is the first study demonstrating mineral abnormalities indicating reduced bone quality in these stages of CKD.

SUBMITTER: El-Husseini A

PROVIDER: S-EPMC9091581 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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Publications

Low Turnover Renal Osteodystrophy With Abnormal Bone Quality and Vascular Calcification in Patients With Mild-to-Moderate CKD.

El-Husseini Amr A Abdalbary Mohamed M Lima Florence F Issa Mohamed M Ahmed Mohamed-Tarek MT Winkler Michael M Srour Habib H Davenport Daniel D Wang Guodong G Faugere Marie-Claude MC Malluche Hartmut H HH

Kidney international reports 20220306 5

<h4>Introduction</h4>Limited information is available on renal osteodystrophy (ROD) and vascular calcification (VC) during early chronic kidney disease (CKD). This study was designed to evaluate ROD and VC in 32 patients with CKD stages II to IV.<h4>Methods</h4>Patients underwent dual-energy X-ray absorptiometry (DXA) for assessment of bone mineral density (BMD) and trabecular bone score (TBS), thoracic computed tomography for VC scoring using the Agatston method, and anterior iliac crest bone b ...[more]

PMID: 35570986

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Project description:A main obstacle to diagnose and manage renal osteodystrophy (ROD) is the identification of intracortical bone turnover type (low, normal, high). The gold standard, tetracycline-labeled transiliac crest bone biopsy, is impractical to obtain in most patients. The Kidney Disease Improving Global Outcomes Guidelines recommend PTH and bone-specific alkaline phosphatase (BSAP) for the diagnosis of turnover type. However, PTH and BSAP have insufficient diagnostic accuracy to differentiate low from non-low turnover and were validated for trabecular turnover. We hypothesized that four circulating microRNAs (miRNAs) that regulate osteoblast (miRNA-30b, 30c, 125b) and osteoclast development (miRNA-155) would provide superior discrimination of low from non-low turnover than biomarkers in clinical use. In 23 patients with CKD 3-5D, we obtained tetracycline-labeled transiliac crest bone biopsy and measured circulating levels of intact PTH, BSAP, and miRNA-30b, 30c, 125b, and 155. Spearman correlations assessed relationships between miRNAs and histomorphometry and PTH and BSAP. Diagnostic test characteristics for discriminating low from non-low intracortical turnover were determined by receiver operator curve analysis; areas under the curve (AUC) were compared by χ2 test. In CKD rat models of low and high turnover ROD, we performed histomorphometry and determined the expression of bone tissue miRNAs. Circulating miRNAs moderately correlated with bone formation rate and adjusted apposition rate at the endo- and intracortical envelopes (ρ = 0.43 to 0.51; p < 0.05). Discrimination of low versus non-low turnover was 0.866, 0.813, 0.813, and 0.723 for miRNA-30b, 30c, 125b, and 155, respectively, and 0.509 and 0.589 for PTH and BSAP, respectively. For all four miRNAs combined, the AUC was 0.929, which was superior to that of PTH and BSAP alone and together (p < 0.05). In CKD rats, bone tissue levels of the four miRNAs reflected the findings in human serum. These data suggest that a panel of circulating miRNAs provide accurate noninvasive identification of bone turnover in ROD. © 2020 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

Project description:BACKGROUND:Vascular calcification progression has been associated with the loss of trabecular bone in chronic kidney disease (CKD) patients. There are few data evaluating the relationship between cortical bone loss and vascular calcification in this population. The aim of this study was to prospectively evaluate the association between changes in cortical bone density and coronary artery calcification (CAC) progression in non-dialyzed CKD patients. METHODS:Changes of cortical and trabecular bone, and changes of calcium score, were analyzed using vertebral tomographic images from a prospective study. Automatic delineation of the cortical bone layer was performed by Image J software, and trabecular bone was determined by selecting a region of interest using Vitrea 2® software. Cortical and trabecular bone density (BD) were expressed in Hounsfield Units (HU), and coronary artery calcium score in Agatston Units (AU). RESULTS:Seventy asymptomatic patients [57.8?±?10.2?years, 63% males, 20% diabetic, estimated glomerular filtration rate (eGFR)?=?37.3 (24.8-51.3) mL/min/1.73m2] were followed for 24?months. The mean cortical and trabecular BD did not change over time. While 49 patients lost either bone, 29 (41%) patients lost cortical [-?4.4%/year (ranging from -?7.15 to -?0.5)] and 39 (56%) lost trabecular bone [-?3.15%/year (-?13.7 to -?0.25)]. There was no association between cortical and trabecular BD changes (p =?0.12). CAC was observed in 33 (46%) patients at baseline, and 30 (91%) of them showed CAC progression. While an inverse correlation between trabecular bone and calcium score changes was observed (p =?0.001), there was no correlation between cortical bone and calcium score changes (p =?0.34). CONCLUSION:CKD patients experience either cortical or trabecular bone loss over time, but these changes do not take place simultaneously in all patients. Cortical, unlike trabecular bone loss, is not associated with vascular calcification progression in these patients.

Dataset Information

Low Turnover Renal Osteodystrophy With Abnormal Bone Quality and Vascular Calcification in Patients With Mild-to-Moderate CKD.

Introduction

Methods

Results

Conclusion

Publications

Low Turnover Renal Osteodystrophy With Abnormal Bone Quality and Vascular Calcification in Patients With Mild-to-Moderate CKD.

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