Cortical unlike trabecular bone loss is not associated with vascular calcification progression in CKD patients

Costa, Larissa R.; Carvalho, Aluízio Barbosa de; Bittencourt, Amandha L.; Rochitte, Carlos Eduardo; Canziani, María Eugênia Fernandes

doi:10.1186/s12882-020-01756-2

Cited by 11 publications

(11 citation statements)

References 34 publications

(44 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This indicates that cortical bone changes may occur later in CKD, which is consistent with studies correlating decreased trabecular bone density with the progression of vascular calcification before cortical bone loss in early-stage CKD patients. (45) We also note that while PTH was elevated in CKD animals, these values are lower than what we have previously reported in CKD rats at 35 weeks of age. (30,31) PTH levels are correlated with cortical bone porosity in humans with CKD (46) and in our animals.…”

Section: Discussioncontrasting

confidence: 56%

Non‐Additive Effects of Combined NOX1/4 Inhibition and Calcimimetic Treatment on a Rat Model of Chronic Kidney Disease‐Mineral and Bone Disorder (CKD‐MBD)

et al. 2022

View full text Add to dashboard Cite

Chronic kidney disease‐mineral and bone disorder (CKD‐MBD) increases cardiovascular calcification and skeletal fragility in part by increasing systemic oxidative stress and disrupting mineral homeostasis through secondary hyperparathyroidism. We hypothesized that treatments to reduce reactive oxygen species formation and reduce parathyroid hormone (PTH) levels would have additive beneficial effects to prevent cardiovascular calcification and deleterious bone architecture and mechanics before end‐stage kidney disease. To test this hypothesis, we treated a naturally progressive model of CKD‐MBD, the Cy/+ rat, beginning early in CKD with the NADPH oxidase (NOX1/4) inhibitor GKT‐137831 (GKT), the preclinical analogue of the calcimimetic etelcalcetide, KP‐2326 (KP), and their combination. The results demonstrated that CKD animals had elevated blood urea nitrogen, PTH, fibroblast growth factor 23 (FGF23), and phosphorus. Treatment with KP reduced PTH levels compared with CKD animals, whereas GKT treatment increased C‐terminal FGF23 levels without altering intact FGF23. GKT treatment alone reduced aortic calcification and NOX4 expression but did not alter the oxidative stress marker 8‐OHdG in the serum or aorta. KP treatment reduced aortic 8‐OHdG and inhibited the ability for GKT to reduce aortic calcification. Treatments did not alter heart calcification or left ventricular mass. In the skeleton, CKD animals had reduced trabecular bone volume fraction and trabecular number with increased trabecular spacing that were not improved with either treatment. The cortical bone was not altered by CKD or by treatments at this early stage of CKD. These results suggest that GKT reduces aortic calcification while KP reduces aortic oxidative stress and reduces PTH, but the combination was not additive. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

show abstract

Section: Discussioncontrasting

confidence: 56%

Non‐Additive Effects of Combined NOX1/4 Inhibition and Calcimimetic Treatment on a Rat Model of Chronic Kidney Disease‐Mineral and Bone Disorder (CKD‐MBD)

et al. 2022

View full text Add to dashboard Cite

show abstract

“…These studies have demonstrated the association between trabecular bone loss and vascular calcification progression. Reinforcing these findings, we recently showed that cortical, unlike trabecular bone loss, was not associated with vascular calcification progression in CKD patients ( Costa et al, 2020 ). Moreover, an interesting study in end-stage renal disease patients showed that low trabecular bone analyzed by CT was better than DXA in predicting the presence of CAC at baseline and cardiovascular mortality ( Chen et al, 2016 ).…”

Section: Discussionmentioning

confidence: 52%

Bone mass measurement by DXA should be interpreted with caution in the CKD population with vascular calcification

et al. 2022

Self Cite

View full text Add to dashboard Cite

Background KDIGO guidelines suggest the use of dual-energy X-ray absorptiometry (DXA) to assess bone mineral density (BMD) in patients with CKD 3a-5D. Previous studies have demonstrated an association between trabecular bone mass loss and coronary artery calcification (CAC) progression. This study aimed to prospectively investigate the relationship between BMD changes, quantified by DXA, and CAC progression in the non-dialyzed CKD population. Methods In this post hoc study, BMD by DXA was measured at the lumbar spine and total hip at baseline and 12-months. Patients were categorized according to BMD changes into 3 different groups: LOSS, UNCHANGED and GAIN. CAC quantification was obtained by multislice computed tomography at baseline and 12-months. Results 87 patients (55.6 ± 10.7 years, 62% males, 30% diabetic, eGFR = 39.2 ± 18.1 mL/min/1.73m 2 ) were enrolled. CAC was found in 41 (47%) of the patients at baseline and CAC progression in 25 (64%) of them. Considering the lumbar spine and total hip BMD changes together, 24%, 48%, and 25% of the patients were in the LOSS, UNCHANGED and GAIN groups, respectively. Compared to the UNCHANGED or LOSS groups, the GAIN group had an increase in calcium score ( p = 0.04) and a higher proportion of patients with CAC progression ( p = 0.01). In the logistic regression analysis, CAC progression was 4.5 times more likely to be in the GAIN group. Conclusions The association between the increase in BMD values and the progression of vascular calcification was the result of two concomitant processes overlapping, leading to a misinterpretation of DXA results. Thus, the use of DXA for the evaluation of bone mass, especially at the lumbar spine, must be applied with restraint and its results very carefully interpreted in CKD patients.

show abstract

“…Although TBS provides indirect indices of bone trabecular microarchitecture and bone quality, TBS may be associated with osteoporotic fracture risks independent of BMD in patients with CKD [31]. Trabecular bone loss was associated with VC in CKD [32]. In our study, we did not directly analyze the relationship between TBS and VC, but TBS was independently associated with cAIx75 as a marker of vascular stiffness even after correction for age or sex in multiple regression analyses.…”

Section: Discussionmentioning

confidence: 70%

Moderating Effect of the Lean Tissue Index on the Relationship between the Trabecular Bone Score and Augmentation Index in Dialysis Naïve Patients with Stage 5 Chronic Kidney Disease

Han

Pak

Lee

et al. 2022

JCM

View full text Add to dashboard Cite

Osteopenia, sarcopenia, and increased vascular stiffness are common in patients with chronic kidney disease-mineral bone disorder (CKD-MBD) with protein energy wasting and can lead to worse clinical outcomes. We investigated the potential moderating role of the lean tissue index (LTI) in the relationship between bone microarchitecture and vascular stiffness in dialysis naïve patients with stage 5 CKD. Bioimpedance spectroscopy for evaluating LTI, lumbar spine dual energy X-ray absorptiometry for determining the trabecular bone score (TBS), and arterial applanation tonometry measurements for the central augmentation index, at a heart rate of 75 beats/minute (cAIx75), were simultaneously performed in 117 consecutive patients. A hierarchical regression analysis was conducted to assess the moderating effect of LTI on the relationship between TBS and cAIx75 after adjusting for age and sex. The effect of the interaction between LTI and TBS on cAIx75 was statistically significant (p = 0.030), demonstrating that the cAIx75 tends to decrease more, with the joint effect of LTI and TBS. In the separate analyses, the interaction effect was significant only in women (p = 0.048) and the group of diabetes (p = 0.042). Our study suggests that the evaluation of changes in body composition, bone health, and vascular stiffness needs to be performed simultaneously in patients with advanced-stage CKD. Further research in patients with different stages of CKD warranted to generalize and apply our results to patients in other stages.

show abstract

Cortical unlike trabecular bone loss is not associated with vascular calcification progression in CKD patients

Cited by 11 publications

References 34 publications

Non‐Additive Effects of Combined NOX1/4 Inhibition and Calcimimetic Treatment on a Rat Model of Chronic Kidney Disease‐Mineral and Bone Disorder (CKD‐MBD)

Non‐Additive Effects of Combined NOX1/4 Inhibition and Calcimimetic Treatment on a Rat Model of Chronic Kidney Disease‐Mineral and Bone Disorder (CKD‐MBD)

Bone mass measurement by DXA should be interpreted with caution in the CKD population with vascular calcification

Moderating Effect of the Lean Tissue Index on the Relationship between the Trabecular Bone Score and Augmentation Index in Dialysis Naïve Patients with Stage 5 Chronic Kidney Disease

Contact Info

Product

Resources

About