Clinical and Biological Determinants of Sclerostin Plasma Concentration in Hemodialysis Patients

Abstract

Background: Sclerostin is a potent inhibitor of bone formation, but the meaning of its serum levels remains undetermined. We evaluated the association between sclerostin levels and clinical or biological data in hemodialyzed patients (HD), notably parathormone (PTH), biomarkers of bone turnover, vascular calcifications and mortality after 2 years. Methods: 164 HD patients were included in this observational study. The calcification score was assessed with the Kauppila method. Patients were followed for 2 years. Results: Median sclerostin levels were significantly (p < 0.0001) higher in HD versus healthy subjects (n = 94) (1,375 vs. 565 pg/ml, respectively). In univariate analysis a significant association (p < 0.05) was found between sclerostin and age, height, dialysis vintage, albumin, troponin, homocysteine, PTH, C-terminal telopeptide of collagen type I, bone-specific alkaline phosphatase and osteoprotegerin, but not with the calcification score. In a multivariate model, the association remained with age, height, dialysis vintage, troponin, homocysteine, phosphate, PTH, but also with vascular calcifications. Association was positive for all variables, except PTH and vascular calcifications. The baseline sclerostin concentration was not different in survivors and non-survivors. Conclusions: We confirm a higher concentration of sclerostin in HD patients, a positive association with age and a negative association with PTH. A positive association with phosphate, homocysteine and troponin calls for additional research. The clinical interest of sclerostin to assess vascular calcifications in HD is limited and no association was found between sclerostin and mortality.

High Serum Sclerostin Levels Are Associated with a Better Outcome in Haemodialysis Patients

“…Recently, Drechsler et al [12] reported an association between high serum sclerostin levels and better survival rate in HD patients. The same association has been reported by Viaene et al [13], but not confirmed by Delanaye et al [43]. Using the same sclerostin assay as Drechsler et al [12], Viaene et al [13] and Delanaye et al [43], we confirmed the apparent protective effect of high serum sclerostin levels with better outcome in our studied population.…”

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

“…61 Some studies show no association between sclerostin and mortality. 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.…”

“…67 Delanaye et al confirmed the presence of higher concentrations of sclerostin in hemodialyzed patients (HD), a positive association with age and a negative association with PTH. 62 Logically, the accumulation of sclerostin in circulation should lead to a stronger inhibition of osteoblasts and lower level of bone formation. However, lower bone turnover and increased bone resorption was observed.…”

Association Between Risk Factors Including Bone-Derived Biomarkers and Aortic Arch Calcification in Maintenance Hemodialysis Patients

“…However, the relationship between sclerostin and vascular calcification is controversial when considering ESRD patients. Delanaye et al found no association between sclerostin and the aortic calcification grade in HD patients [34], whereas Pelletier el al. reported that sclerostin levels correlated with aortic calcification severity [35].…”