Relationship between plasma levels of sclerostin, calcium\u2013phosphate disturbances, established markers of bone turnover, and inflammation in haemodialysis patients

Barbara Pietrzyk,Magdalena Olszanecka-Glinianowicz,Jerzy Chudek,Andrzej Więcek,Aureliusz Kolonko,Katarzyna Wyskida,Joanna Ficek,Rafał Ficek

doi:10.1007/s11255-018-2050-3

Barbara Pietrzyk, Magdalena Olszanecka-Glinianowicz + Show 6 more

Open Access

https://doi.org/10.1007/s11255-018-2050-3

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Abstract

PurposeData concerning the relation between increased levels of circulating sclerostin (a physiological inhibitor of bone formation) and bone turnover in patients with chronic renal failure (CRF) are limited. Therefore, the aim of this study was to evaluate associations between plasma sclerostin levels and calcium–phosphate disturbances, markers of bone turnover as well as inflammation in haemodialysis (HD) patients.MethodsIn plasma samples obtained in 150 stable HD patients (92 men) aged 40–70 years, levels of sclerostin, fibroblast growth factor (cFGF23), osteocalcin, the N-terminal propeptide of type I procollagen, C-terminal telopeptide of the alpha chain of type I collagen (β-CTx), and inflammatory markers (IL-6 and TNF-α) in addition to routine parameters (calcium, phosphorus, parathyroid hormone—iPTH, 25-OH-D, alkaline phosphatase) were measured.ResultsPlasma sclerostin concentrations were significantly higher in HD men than women (2.61 vs. 1.88 ng/mL, p < 0.01). Patients with sclerostin levels above median were characterized by lower iPTH and IL-6, but higher cFGF23 and TNF-α (significantly only in men) concentrations. Plasma sclerostin concentration positively correlated with serum 25-OH-D (τ = 0.204), phosphorus (τ = 0.1482), and TNF-α (τ = 0.183) and inversely with iPTH (τ = − 0.255), alkaline phosphatase (τ = − 0.203), IL-6 (τ =− 0.201), and β-CTx (τ = − 0.099) levels. In multivariate regression analysis, variability of sclerostin levels was explained by sex and 25-OH-D and phosphorus levels.ConclusionsIncreased circulating sclerostin levels seem to reflect slower bone turnover in HD patients. Low levels of sclerostin are associated with vitamin D deficiency and good phosphates alignment.

Highlights

Sclerostin is a protein secreted by osteocytes that prevents excessive bone formation [1]
The sclerostin signal in osteoblasts is further modulated by several other factors, e.g. calcitriol, parathyroid hormone (PTH), glucocorticoids, and tumour necrosis factor-α (TNF-α)
Our study demonstrates a positive relationship between circulating sclerostin levels and both 25-OH-D and phosphates levels, whereas moderate negative correlations were present for only some markers of bone formation: serum ALP activity, and resorption: βCTx

Summary

Introduction

Sclerostin is a protein secreted by osteocytes that prevents excessive bone formation [1]. It activates Wnt pathway that inhibits the differentiation of the mesodermal stem cells towards preosteoblasts and osteoblasts proliferation [2]. Calcitriol induces expression of low-density lipoprotein receptorrelated protein 5 (LRP5) and inhibits bone marrow stromal cells, expression of Dickkopf-related protein 1 (DKK1) and secreted frizzled-related protein 2 (SFRP2)—antagonists of Wnt signalling pathway [3], and transcriptional regulation of key proteins osteoblasts, including non-collagenous. Elevated sclerostin levels have been observed in subjects with a higher bone mineral mass [6]. It suggested that circulating sclerostin level is an important marker of the pool of mature osteocytes. The sclerostin level is considered as a potential biomarker of decreased bone formation

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