4
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

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

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          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.

          Related collections

          Most cited references24

          • Record: found
          • Abstract: found
          • Article: not found

          Fibroblast growth factor 23 is elevated before parathyroid hormone and phosphate in chronic kidney disease.

          Fibroblast growth factor 23 (FGF23) regulates phosphorus metabolism and is a strong predictor of mortality in dialysis patients. FGF23 is thought to be an early biomarker of disordered phosphorus metabolism in the initial stages of chronic kidney disease (CKD). We measured FGF23 in baseline samples from 3879 patients in the Chronic Renal Insufficiency Cohort study, which is a diverse cohort of patients with CKD stage 2-4. Mean serum phosphate and median parathyroid hormone (PTH) levels were in the normal range, but median FGF23 was markedly greater than in healthy populations, and increased significantly with decreasing estimated glomerular filtration rate (eGFR). High levels of FGF23, defined as being above 100 RU/ml, were more common than secondary hyperparathyroidism and hyperphosphatemia in all strata of eGFR. The threshold of eGFR at which the slope of FGF23 increased was significantly higher than the corresponding threshold for PTH based on non-overlapping 95% confidence intervals. Thus, increased FGF23 is a common manifestation of CKD that develops earlier than increased phosphate or PTH. Hence, FGF23 measurements may be a sensitive early biomarker of disordered phosphorus metabolism in patients with CKD and normal serum phosphate levels.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            SOST is a target gene for PTH in bone.

            Intermittent parathyroid hormone (PTH) application is an established pharmacological principle to stimulate bone formation. Yet, the molecular mechanisms underlying this bone anabolic action are not fully understood. Recently, SOST (sclerostin) was identified as a potent osteocyte expressed negative regulator of bone formation in vitro, in murine models and in patients with the bone overgrowth disorders Sclerosteosis and Van Buchem disease. Therefore, we have studied the impact of PTH on SOST regulation. First, we analyzed SOST expression during PTH-induced bone formation in a classical model of local bone formation. 8-month-old mice received intermittently 100 nM hPTH(1-34) or vehicle onto the calvaria for 5 days. PTH stimulated bone formation as assessed by fluorochrome-marker-based histomorphometry. SOST expression was reduced in PTH-treated calvariae 4 h after the last administration as evaluated by real-time quantitative PCR. Next, we observed a decrease of SOST expression in femoral cortical bone of 6-month-old rats following single subcutaneous systemic administration of 80 microg/kg PTH(1-34). Finally, we studied SOST mRNA expression in bone of 11-month-old osteopenic estrogen-deprived (OVX) rats following 8-week systemic intermittent administration of 5 microg/kg PTH(1-34). PTH-treated animals displayed increases in bone mineral density as detected by pQCT, while SOST mRNA levels were decreased compared to vehicle-treated OVX and SHAM controls. PTH decreased SOST expression also in vitro. 100 nM PTH(1-34) inhibited expression in mouse calvaria organ cultures and in osteoblastic UMR-106 cells within 6 h by 95%. An IC50 of 1 nM was determined for PTH(1-34) in UMR-106 cells, whereas the PTH antagonist (d-Trp12,Tyr34)-bPTH(7-34) did not efficiently reduce SOST expression. Furthermore, SOST inhibition by PTH was not blocked by the protein synthesis inhibitor cycloheximide, indicating direct regulation, and PTH did not influence SOST mRNA degradation, implying transcriptional regulation. Finally, we observed full suppression of SOST by the cAMP inducer forskolin, partial inhibition by ionomycin, and no effect with PMA, indicating that PTH action is mainly mediated via the cAMP/PKA pathway. In summary, we have shown that PTH directly inhibits SOST transcription in vivo and in vitro, suggesting that SOST regulation may play a role in mediating PTH action in bone.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Building bone to reverse osteoporosis and repair fractures.

              An important, unfilled clinical need is the development of new approaches to improve fracture healing and to treat osteoporosis by increasing bone mass. Recombinant forms of bone morphogenetic protein 2 (BMP2) and BMP7 are FDA approved to promote spinal fusion and fracture healing, respectively, and the first FDA-approved anabolic drug for osteoporosis, parathyroid hormone, increases bone mass when administered intermittently but can only be given to patients in the US for two years. As we discuss here, the tremendous explosion over the last two decades in our fundamental understanding of the mechanisms of bone remodeling has led to the prospect of mechanism-based anabolic therapies for bone disorders.
                Bookmark

                Author and article information

                Contributors
                chj@poczta.fm
                Journal
                Int Urol Nephrol
                Int Urol Nephrol
                International Urology and Nephrology
                Springer Netherlands (Dordrecht )
                0301-1623
                1573-2584
                24 December 2018
                24 December 2018
                2019
                : 51
                : 3
                : 519-526
                Affiliations
                [1 ]ISNI 0000 0001 2198 0923, GRID grid.411728.9, Pathophysiology Unit, Department of Pathophysiology, , Medical University of Silesia, ; Katowice, Poland
                [2 ]ISNI 0000 0001 2198 0923, GRID grid.411728.9, Health Promotion and Obesity Management Unit, Department of Pathophysiology, , Medical University of Silesia, ; Katowice, Poland
                [3 ]ISNI 0000 0001 2198 0923, GRID grid.411728.9, Department of Nephrology, Transplantation and Internal Medicine, , Medical University of Silesia, ; Katowice, Poland
                [4 ]ISNI 0000 0001 2198 0923, GRID grid.411728.9, Department of Internal Medicine and Oncological Chemotherapy, School of Medicine in Katowice, , Medical University of Silesia in Katowice, ; 40-752 Katowice, Poland
                Article
                2050
                10.1007/s11255-018-2050-3
                6424932
                30584645
                ab72ae27-60f1-4d66-ab58-08eda07f62c7
                © The Author(s) 2018

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                : 27 September 2018
                : 7 December 2018
                Funding
                Funded by: Medical University of Silesia in Katowice
                Award ID: KNW-1-004/N/7/0
                Award Recipient :
                Categories
                Nephrology - Original Paper
                Custom metadata
                © Springer Nature B.V. 2019

                Nephrology
                chronic kidney disease-mineral and bone disorder (ckd-mbd),sclerostin,renal osteodystrophy (rod),calcium–phosphate disturbances,haemodialysis patients

                Comments

                Comment on this article