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

Int Urol Nephrol. 2019 Mar;51(3):519-526. doi: 10.1007/s11255-018-2050-3. Epub 2018 Dec 24.

Abstract

Purpose: Data 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.

Methods: In 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.

Results: Plasma 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.

Conclusions: Increased 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.

Keywords: Calcium–phosphate disturbances; Chronic kidney disease-mineral and bone disorder (CKD-MBD); Haemodialysis patients; Renal osteodystrophy (ROD); Sclerostin.

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Adult
  • Aged
  • Alkaline Phosphatase / blood
  • Bone Morphogenetic Proteins / blood*
  • Bone Remodeling*
  • Calcium / blood
  • Chronic Kidney Disease-Mineral and Bone Disorder / blood*
  • Chronic Kidney Disease-Mineral and Bone Disorder / etiology
  • Chronic Kidney Disease-Mineral and Bone Disorder / physiopathology
  • Collagen Type I / blood
  • Female
  • Fibroblast Growth Factor-23
  • Fibroblast Growth Factors / blood
  • Genetic Markers
  • Humans
  • Inflammation / blood
  • Interleukin-6 / blood
  • Kidney Failure, Chronic / blood*
  • Kidney Failure, Chronic / complications
  • Kidney Failure, Chronic / physiopathology
  • Kidney Failure, Chronic / therapy*
  • Male
  • Middle Aged
  • Osteocalcin / blood
  • Parathyroid Hormone / blood
  • Peptides / blood
  • Phosphates / blood
  • Phosphorus / blood
  • Renal Dialysis
  • Sex Factors
  • Tumor Necrosis Factor-alpha / blood
  • Vitamin D / analogs & derivatives
  • Vitamin D / blood

Substances

  • Adaptor Proteins, Signal Transducing
  • Bone Morphogenetic Proteins
  • Collagen Type I
  • Genetic Markers
  • IL6 protein, human
  • Interleukin-6
  • Parathyroid Hormone
  • Peptides
  • Phosphates
  • SOST protein, human
  • Tumor Necrosis Factor-alpha
  • collagen type I trimeric cross-linked peptide
  • Osteocalcin
  • Vitamin D
  • Phosphorus
  • Fibroblast Growth Factors
  • Fibroblast Growth Factor-23
  • 25-hydroxyvitamin D
  • Alkaline Phosphatase
  • Calcium