Osteoprotegerin and sclerostin in chronic kidney disease prior to dialysis: potential partners in vascular calcifications

Moréna, Marion; Jaussent, Isabelle; Dupuy, Anne‐Marie; Bargnoux, Anne-Sophie; Kuster, Nils; Chénine, Leïla; Leray‐Moragues, Hélène; Klouche, Kada; Vernhet, Hélène; Canaud, Bernard; Cristol, Jean‐Paul

doi:10.1093/ndt/gfv081

Cited by 122 publications

(108 citation statements)

References 42 publications

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“…62 The decrease in GFR and concomitant reduction of sclerostin biodegradation is potentially the main cause of the increased concentrations of this protein in circulation, despite increases in the fraction excreted into urine with the progression of CKD. 63,64 As with subjects having normal renal function, higher concentrations of sclerostin occurs in men, which can be explained by a higher bone mass and indirectly a greater number of osteocytes. 65 The relationship between the concentration of phosphorus and sclerostin (independent from GFR) indicates its potential contribution to the regulation of its secretion by osteocytes.…”

Section: Sclerostin In Chronic Kidney Diseasementioning

confidence: 99%

Sclerostin: Intracellular mechanisms of action and its role in the pathogenesis of skeletal and vascular disorders

Pietrzyk¹,

Smertka²,

Chudek³

2017

Adv Clin Exp Med

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Sclerostin is a glycoprotein involved in the regulation of bone metabolism, exclusively secreted by osteocytes. It affects the activity of bone morphogenetic proteins (BMPs) and is an inhibitor of the Wnt/β-catenin metabolic pathway in bone cells. Osteocytes reduce the release of sclerostin in response to mechanical stimuli acting on bone, and thus promote the activation of osteogenic pathway Wnt/β-catenin in osteoblasts. This signaling pathway plays a key role in osteogenesis and bone turnover. Loss of sclerostin gene function is related to 3 different craniotubular hyperostosis processes: sclerosteosis, craniodiaphyseal dysplasia, and van Buchem disease. Additionally, experimental and clinical studies suggest that sclerostin may promote vascular calcification. Antibodies directed against sclerostin stimulate bone formation and represent a new therapeutic option in the treatment of diseases with increased bone resorption, such as osteoporosis and inflammatory diseases where there is generalized bone loss, periarticular osteoporosis, and cartilage damage, such as rheumatoid arthritis (RA), ankylosing spondylitis (AS), and glucocorticoid-induced osteoporosis (GIO). Antibody use has the potential to offer new therapeutic approaches in the therapy of mineral and bone disorders resulting from chronic kidney disease (CKD-MBD) and vascular calcifications.

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Section: Sclerostin In Chronic Kidney Diseasementioning

confidence: 99%

Sclerostin: Intracellular mechanisms of action and its role in the pathogenesis of skeletal and vascular disorders

Pietrzyk¹,

Smertka²,

Chudek³

2017

Adv Clin Exp Med

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“…High osteoprotegerin values have also been linked to poor glycemic control58, 59 and severity of diabetic nephropathy 60, 61. In patients with chronic renal failure, levels of osteoprotegerin are higher compared with healthy controls,62 are inversely correlated with glomerular filtration rate,63 and correlate with time on maintenance hemodialysis in patients with end‐stage renal disease 64. Third, associations of osteoprotegerin may be attenuated because of the dominance of other factors more relevant to CVD risk in high‐risk patients, including highly prevalent traditional CVD risk factors as well as factors related to quality of clinical care, treatment response, or medication adherence 65.…”

Section: Discussionmentioning

confidence: 99%

Osteoprotegerin and Cardiovascular Events in High‐Risk Populations: Meta‐Analysis of 19 Prospective Studies Involving 27 450 Participants

Tschiderer

Klingenschmid

Nagrani

et al. 2018

JAHA

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BackgroundOsteoprotegerin is a cytokine involved in bone metabolism as well as vascular calcification and atherogenesis. Although circulating osteoprotegerin levels are robustly associated with incident cardiovascular disease (CVD) in the general population, its relevance as a biomarker among populations at high CVD risk is less clear.Methods and ResultsThree independent reviewers systematically searched PubMed, EMBASE, and Web of Science to identify prospective studies that had recruited participants on the basis of having conditions related to high CVD risk. A total of 19 studies were eligible for inclusion, reporting on 27 450 patients with diabetes mellitus (2 studies), kidney disease (7 studies), preexisting heart disease (5 studies), or recent acute coronary syndromes (5 studies) at baseline. Over a mean follow‐up of 4.2 years, 4066 CVD events were recorded. In a random‐effects meta‐analysis, the pooled risk ratio for CVD events comparing people in the top versus the bottom tertile of osteoprotegerin concentration was 1.30 (95% confidence interval, 1.12–1.50; P<0.001; I2=68.3%). There was evidence for presence of publication bias (P value from Egger's test=0.013). Correction for publication bias using the trim‐and‐fill method reduced the risk ratio to 1.21 (95% confidence interval, 1.03–1.42; P<0.001). The risk ratios did not vary significantly by population type, geographical region, statistical adjustment, sample or assay type, age, sex, or length of follow‐up.ConclusionsIn populations at high CVD risk, elevated circulating osteoprotegerin levels are associated with a higher risk for future CVD events. The magnitude of association appears weaker than in the general population.

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“…Specifically, sclerostin is an endogenous inhibitor of the canonical Wnt/β-catenin pathway specific to the bone. In the presence of sclerostin, osteoblast precursors are unexposed to a Wnt signal, leading to β-catenin degradation with the cessation of osteoblast differentiation and recruitment [10,11]. …”

Section: Introductionmentioning

confidence: 99%

Clearance of Sclerostin, Osteocalcin, Fibroblast Growth Factor 23, and Osteoprotegerin by Dialysis

Carlson¹,

Mortensen²,

Axelsen³

et al. 2017

Blood Purif

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Introduction: Fibroblast growth factor (FGF23), sclerostin, osteocalcin, and osteoprotegerin are important factors that control mineral bone metabolism. End-stage renal disease is associated with the pronounced dysregulation of mineral bone metabolism; however, the impact and clearance of mineral bone metabolism factors during dialysis remain largely undescribed. Methods: In a cross-sectional study, 10 chronic hemodialysis patients were treated with hemodialysis for 8 h using a high-flux filter and a dialysate bath of 50% calculated total body water continuously recycled at a rate of 500 mL/min. Plasma and dialysate concentrations of FGF23, sclerostin, osteoprotegerin, and osteocalcin were measured at 1, 2, 4, 6, and 8 h permitting the estimation of dialysis clearance. Results: Clearance of FGF23 was 7.7 mL/min, of sclerostin was 7.6 mL/min, of osteoprotegerin was 1.2 mL/min, and of osteocalcin was 19.7 mL/min. Clearance of FGF23 was correlated to sclerostin and osteoprotegerin clearance and also to the ultrafiltration rate. Although, osteocalcin blood concentrations decreased during dialysis, they rebounded within 6 h. Overall, no significant changes in blood concentrations of the measure mineral bone metabolism factors were observed. Conclusions: The intradialytic clearance of osteocalcin, FGF23, sclerostin, and osteoprotegerin occurs; however, only clearance of FGF23 is directly correlated with the ultrafiltration rate. The effects of dialytic clearance on mineral bone metabolism are, however, uncertain and intradialytic plasma concentrations of the studied substrates remained largely unchanged.

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Osteoprotegerin and sclerostin in chronic kidney disease prior to dialysis: potential partners in vascular calcifications

Abstract: Our results strongly suggest that bone turnover inhibitors, OPG and sclerostin, are independently associated with CAC with potential additive effects in ND-CKD patients.

Cited by 122 publications

References 42 publications

Sclerostin: Intracellular mechanisms of action and its role in the pathogenesis of skeletal and vascular disorders

Sclerostin: Intracellular mechanisms of action and its role in the pathogenesis of skeletal and vascular disorders

Osteoprotegerin and Cardiovascular Events in High‐Risk Populations: Meta‐Analysis of 19 Prospective Studies Involving 27 450 Participants

Clearance of Sclerostin, Osteocalcin, Fibroblast Growth Factor 23, and Osteoprotegerin by Dialysis

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