scholarly journals Molecular Abnormalities Underlying Bone Fragility in Chronic Kidney Disease

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Yoshiko Iwasaki ◽  
Junichiro James Kazama ◽  
Masafumi Fukagawa
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Bone Cells ◽  
Bone Fractures ◽  
Bone Mineralization ◽  
Bone Fragility ◽  
Pathological Process ◽  
Mineral And Bone Disorder ◽  
Molecular Abnormalities ◽  
Skeletal Resistance

Prevention of bone fractures is one goal of therapy for patients with chronic kidney disease-mineral and bone disorder (CKD-MBD), as indicated by the Kidney Disease: Improving Global Outcomes guidelines. CKD patients, including those on hemodialysis, are at higher risk for fractures and fracture-related death compared to people with normal kidney function. However, few clinicians focus on this issue as it is very difficult to estimate bone fragility. Additionally, uremia-related bone fragility has a more complicated pathological process compared to osteoporosis. There are many uremia-associated factors that contribute to bone fragility, including severe secondary hyperparathyroidism, skeletal resistance to parathyroid hormone, and bone mineralization disorders. Uremia also aggravates bone volume loss, disarranges microarchitecture, and increases the deterioration of material properties of bone through abnormal bone cells or excess oxidative stress. In this review, we outline the prevalence of fractures, the interaction of CKD-MBD with osteoporosis in CKD patients, and discuss possible factors that exacerbate the mechanical properties of bone.

scholarly journals The frequency of bone fractures among patients with chronic kidney disease not on dialysis: two-year follow-up

2017 ◽  
Vol 55 (4) ◽  
pp. 222-228 ◽  
Author(s):  
Andreja Figurek ◽  
Vlastimir Vlatkovic ◽  
Dragan Vojvodic ◽  
Branislav Gasic ◽  
Milorad Grujicic
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Bone Fractures ◽  
The Other ◽  
Mineral And Bone Disorder ◽  
Bone Disorder ◽  
The Mean ◽  
Frax Score ◽  
Pth Level

Abstract Introduction. Renal osteodystrophy is a severe complication of chronic kidney disease (CKD) that increases morbidity and mortality in these patients. Mineral and bone disorder starts early in CKD and affects the incidence of bone fractures. The aim of this study was to observe the frequency of diverse bone fractures in patients with CKD not on dialysis. Methods. This cohort study included 68 patients that were followed during the two-year period. The patients were divided into two cohorts: one that developed bone fractures and the other that did not. There were 35 (51.5%) men and 33 (48.5%) women. The mean age of patients ranged 62.88±11.60 years. During follow-up serum values of chronic kidney disease – mineral and bone indicators were measured. The methods of descriptive and analytical statistics were used in order to analyze obtained data. Results. During this two-year follow-up seven patients developed bone fractures. Among them, females dominated (6 patients) compared to males (only 1 patient). The most common were fractures of forearm. The mean level of parathyroid hormone (PTH) at the beginning of the monitoring was higher in the group of patients with bone fractures (165.25 ± 47.69 pg/mL) in regard to another group (103.96 ± 81.55 pg/mL). After two-year follow-up, this difference became statistically significant at the level p < 0.05. Patients that developed bone fractures had higher FRAX (Fracture Risk Assessment) score compared to another group. Conclusion. In our study, about 10% of patients had bone fractures in the two-year follow-up period. Patients who developed fractures had a higher PTH level and FRAX score.

scholarly journals How FGF23 shapes multiple organs in chronic kidney disease

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Maren Leifheit-Nestler ◽  
Dieter Haffner
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Mineral Metabolism ◽  
Bone Mineralization ◽  
Experimental Studies ◽  
Growth Failure ◽  
Short Review ◽  
Mineral And Bone Disorder ◽  
Circulating Levels ◽  
Organ Dysfunctions

AbstractChronic kidney disease (CKD) is associated with distinct alterations in mineral metabolism in children and adults resulting in multiple organ dysfunctions. Children with advanced CKD often suffer from impaired bone mineralization, bone deformities and fractures, growth failure, muscle weakness, and vascular and soft tissue calcification, a complex which was recently termed CKD-mineral and bone disorder (CKD-MBD). The latter is a major contributor to the enhanced cardiovascular disease comorbidity and mortality in these patients. Elevated circulating levels of the endocrine-acting phosphaturic hormone fibroblast growth factor (FGF) 23 are the first detectable alteration of mineral metabolism and thus CKD-MBD. FGF23 is expressed and secreted from osteocytes and osteoblasts and rises, most likely due to increased phosphate load, progressively as kidney function declines in order to maintain phosphate homeostasis. Although not measured in clinical routine yet, CKD-mediated increased circulating levels of FGF23 in children are associated with pathological cardiac remodeling, vascular alterations, and increased cognitive risk. Clinical and experimental studies addressing other FGF23-mediated complications of kidney failure, such as hypertension and impaired bone mineralization, show partly conflicting results, and the causal relationships are not always entirely clear. This short review summarizes regulators of FGF23 synthesis altered in CKD and the main CKD-mediated organ dysfunctions related to high FGF23 levels.

scholarly journals Osteoclast-Released Wnt-10b Underlies Cinacalcet Related Bone Improvement in Chronic Kidney Disease

2019 ◽  
Vol 20 (11) ◽  
pp. 2800 ◽  
Author(s):  
Cai-Mei Zheng ◽  
Yung-Ho Hsu ◽  
Chia-Chao Wu ◽  
Chien-Lin Lu ◽  
Wen-Chih Liu ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Bone Loss ◽  
Bone Fractures ◽  
Bone Mineralization ◽  
Critical Role ◽  
Beta Catenin ◽  
Mineral Density ◽  
High Turnover

Secondary hyperparathyroidism (SHPT) relates to high turnover bone loss and is responsible for most bone fractures among chronic kidney disease (CKD) patients. Changes in the Wingless/beta-catenin signaling (Wnt/β-catenin) pathway and Wnt inhibitors have been found to play a critical role in CKD related bone loss. A calcimimetic agent, cinacalcet, is widely used for SHPT and found to be similarly effective for parathyroidectomy clinically. A significant decrease in hip fracture rates is noted among US hemodialysis Medicare patients since 2004, which is probably related to the cinacalcet era. In our previous clinical study, it was proven that cinacalcet improved the bone mineral density (BMD) even among severe SHPT patients. In this study, the influence of cinacalcet use on bone mass among CKD mice was determined. Cinacalcet significantly reduced the cortical porosity in femoral bones of treated CKD mice. It also improved the whole-bone structural properties through increased stiffness and maximum load. Cinacalcet increased femoral bone wingless 10b (Wnt10b) expression in CKD mice. In vitro studies revealed that cinacalcet decreased osteoclast bone resorption and increased Wnt 10b release from osteoclasts. Cinacalcet increased bone mineralization when culturing the osteoblasts with cinacalcet treated osteoclast supernatant. In conclusion, cinacalcet increased bone quantity and quality in CKD mice, probably through increased bone mineralization related with osteoclast Wnt 10b secretion.

scholarly journals Circulating p-Cresyl Sulfate, Non-Hepatic Alkaline Phosphatase and Risk of Bone Fracture Events in Chronic Kidney Disease-Mineral Bone Disease

Toxins ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 479
Author(s):  
Jia-Feng Chang ◽  
Chih-Yu Hsieh ◽  
Jian-Chiun Liou ◽  
Kuo-Cheng Lu ◽  
Cai-Mei Zheng ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Alkaline Phosphatase ◽  
Kidney Disease ◽  
Bone Fracture ◽  
Bone Cells ◽  
Plasma Concentrations ◽  
Multivariable Analysis ◽  
Surrogate Marker ◽  
P Value ◽  
Mineral And Bone Disorder

Patients with chronic kidney disease (CKD), especially those undergoing hemodialysis, are at a considerably high risk of bone fracture events. Experimental data indicate that uremic toxins intricately involved in bone-related proteins exert multi-faced toxicity on bone cells and tissues, leading to chronic kidney disease–mineral and bone disorder (CKD-MBD). Nonetheless, information regarding the association between p-cresyl sulfate (PCS), non-hepatic alkaline phosphatase (NHALP) and skeletal events remains elusive. We aim to explore the association between PCS, NHALP and risk of bone fracture (BF) in patients with hemodialysis. Plasma concentrations of PCS and NHALP were ascertained at study entry. Cox proportional hazard regression analyses were used to determine unadjusted and adjusted hazard ratios (aHRs) of PCS for BF risk. In multivariable analysis, NHALP was associated with incremental risks of BFs [aHR: 1.06 (95% CI: 1.01–1.11)]. The association between the highest PCS tertile and BF risk remained robust [aHR: 2.87 (95% CI: 1.02–8.09)]. With respect to BF events, the interaction between NHALP and PCS was statistically significant (p value for the interaction term < 0.05). In addition to mineral dysregulation and hyperparathyroidism in hemodialysis patients, higher circulating levels of PCS and NHALP are intricately associated with incremental risk of BF events, indicating that a joint evaluation is more comprehensive than single marker. In light of the extremely high prevalence of CKD-MBD in the hemodialysis population, PCS may act as a pro-osteoporotic toxin and serve as a potential surrogate marker for skeletal events.

scholarly journals A phosphate and calcium-enriched diet promotes progression of 5/6-nephrectomy-induced chronic kidney disease in C57BL/6 mice

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
J. Radloff ◽  
N. Latic ◽  
U. Pfeiffenberger ◽  
C. Schüler ◽  
S. Tangermann ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Calcium Phosphate ◽  
Kidney Disease ◽  
Renal Fibrosis ◽  
Time Course ◽  
Bone Mineralization ◽  
Fibroblast Growth Factor 23 ◽  
Functional Decline ◽  
Left Ventricular ◽  
Normal Diet

AbstractC57BL/6 mice are known to be rather resistant to the induction of experimental chronic kidney disease (CKD) by 5/6-nephrectomy (5/6-Nx). Here, we sought to characterize the development of CKD and its cardiac and skeletal sequelae during the first three months after 5/6-Nx in C57BL/6 mice fed a calcium- and phosphate enriched diet (CPD) with a balanced calcium/phosphate ratio. 5/6-NX mice on CPD showed increased renal fibrosis and a more pronounced decrease in glomerular filtration rate when compared to 5/6-Nx mice on normal diet (ND). Interestingly, despite comparable levels of serum calcium, phosphate, and parathyroid hormone (PTH), circulating intact fibroblast growth factor-23 (FGF23) was 5 times higher in 5/6-Nx mice on CPD, relative to 5/6-Nx mice on ND. A time course experiment revealed that 5/6-Nx mice on CPD developed progressive renal functional decline, renal fibrosis, cortical bone loss, impaired bone mineralization as well as hypertension, but not left ventricular hypertrophy. Collectively, our data show that the resistance of C57BL/6 mice to 5/6-Nx can be partially overcome by feeding the CPD, and that the CPD induces a profound, PTH-independent increase in FGF23 in 5/6-Nx mice, making it an interesting tool to assess the pathophysiological significance of FGF23 in CKD.

MO794EVALUATION OF THE BONE ELASTIC STRUCTURE IN PERSONS WITH AND WITHOUT CHRONIC KIDNEY DISEASE ON DIALYSIS

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Pietro Manuel Ferraro ◽  
Alessandra Nicolosi ◽  
Alessandro Naticchia ◽  
Nicola Panocchia ◽  
Giuseppe Grandaliano ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Linear Regression ◽  
Bone Structure ◽  
Bone Fractures ◽  
Elastic Structure ◽  
Absolute Difference ◽  
P Value ◽  
Non Invasive ◽  
Age And Sex

Abstract Background and Aims Chronic kidney disease is a frequent condition, characterized, especially in its more advanced stages, by an array of derangements in bone structure and density, resulting in a higher rate of bone fractures. Current strategies to monitor the bone status and assess the risk of bone fractures in CKD patients are limited. The Bone Elastic Structure (BES) test is a recently-developed non-invasive tool that measures the elastic characteristics of the trabecular bone by simulating the application of loads on a virtual biopsy obtained from radiographic images of the proximal epiphyses in the patient’s hand fingers. The simulation results are combined to obtain a parameter defined Bone Structure Index (BSI). The aim of our study is to explore whether the BES test could be a useful monitoring tool of bone status in patients with CKD on dialysis by exploring whether such patients have different BSI values compared with persons without CKD. Method The BES test was performed on a sample of 41 patients undergoing chronic hemodialysis (HD) and the BSI compared with a group of 374 persons with normal renal function who had undergone the BES test in previous studies. Differences in BSI and 95% confidence intervals (CIs) between the two groups were obtained and tested for statistical significance with a linear regression model including BSI as the dependent variable and kidney status (HD vs no HD) as the independent variable, adjusted for age and sex. Subgroup effects were explored by including interaction terms (age x kidney status, age x sex, kidney status x sex) in the model. Finally, to further remove the potential confounding by age and sex, each HD patient was individually matched with up to 4 non-HD participants based on sex and age (with a 5-year caliper) and a matched analysis was conducted on BSI values. Results Average (SD) age was 64 (17) years in the HD group and 60 (12) years in the non-HD group, with a prevalence of males of 49% and 16%, respectively. The individual values of BSI divided by kidney status and sex in Figure. The multivariate linear regression model showed that, after adjustment for age and sex, the BSI in the HD group was significantly lower compared with the non-HD group (HD 145, 95% CI 140, 154; non-HD 179, 95% CI 177, 181; absolute difference −32, 95% CI −40, −25; p-value &lt; 0.001). There was no significant interaction between age, sex and kidney status on BSI values (all p-values &gt; 0.05). Individual matching was successful for 36 out of 41 HD patients, who were matched to 127 non-HD participants; matched analysis confirmed the results (absolute difference −31, 95% CI −40, −23; p-value &lt; 0.001). Conclusion The output of a non-invasive tool to determine the bone elastic structure appeared to be strongly associated with kidney function after control for differences in age and sex. Further studies are needed to determine the potential application of the BES test in patients with CKD.

Update on imaging in chronic kidney disease-mineral and bone disorder: promising role of functional imaging

2021 ◽  
Author(s):  
Sharjeel Usmani ◽  
Najeeb Ahmed ◽  
Gopinath Gnanasegaran ◽  
Fahad Marafi ◽  
Tim van den Wyngaert
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Functional Imaging ◽  
Mineral And Bone Disorder ◽  
Bone Disorder
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