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.

Balemans W, Ebeling M, Patel N, Van HE, Olson P, Dioszegi M, Lacza C, Wuyts W, Van Den Ende J, Willems P, Paes-Alves AF, Hill S, Bueno M, Ramos FJ, Tacconi P, Dikkers FG, Stratakis C, Lindpaintner K, Vickery B, Foernzler D, Van HW: Increased bone density in sclerosteosis is due to the deficiency of a novel secreted protein (SOST). Hum Mol Genet 2001;10:537-543.
Brunkow ME, Gardner JC, Van NJ, Paeper BW, Kovacevich BR, Proll S, Skonier JE, Zhao L, Sabo PJ, Fu Y, Alisch RS, Gillett L, Colbert T, Tacconi P, Galas D, Hamersma H, Beighton P, Mulligan J: Bone dysplasia sclerosteosis results from loss of the SOST gene product, a novel cystine knot-containing protein. Am J Hum Genet 2001;68:577-589.
Van Buchem FS, Hadders HN, Hansen JF, Woldring MG: Hyperostosis corticalis generalisata. Report of seven cases. Am J Med 1962;33:387-397.
Semenov M, Tamai K, He X: SOST is a ligand for LRP5/LRP6 and a Wnt signaling inhibitor. J Biol Chem 2005;280:26770-26775.
Joiner DM, Ke J, Zhong Z, Xu HE, Williams BO: LRP5 and LRP6 in development and disease. Trends Endocrinol Metab 2013;24:31-39.
Krishnan V, Bryant HU, Macdougald OA: Regulation of bone mass by Wnt signaling. J Clin Invest 2006;116:1202-1209.
Robling AG, Castillo AB, Turner CH: Biomechanical and molecular regulation of bone remodeling. Annu Rev Biomed Eng 2006;8:455-498.
Cowin SC, Moss-Salentijn L, Moss ML: Candidates for the mechanosensory system in bone. J Biomech Eng 1991;113:191-197.
Robling AG, Niziolek PJ, Baldridge LA, Condon KW, Allen MR, Alam I, Mantila SM, Gluhak-Heinrich J, Bellido TM, Harris SE, Turner CH: Mechanical stimulation of bone in vivo reduces osteocyte expression of SOST/sclerostin. J Biol Chem 2008;283:5866-5875.
Drueke TB, Lafage-Proust MH: Sclerostin: just one more player in renal bone disease? Clin J Am Soc Nephrol 2011;6:700-703.
Jean G, Chazot C: Sclerostin in CKD-MBD: one more paradoxical bone protein? Nephrol Dial Transplant 2013;28:2932-2935.
Padhi D, Jang G, Stouch B, Fang L, Posvar E: Single-dose, placebo-controlled, randomized study of AMG 785, a sclerostin monoclonal antibody. J Bone Miner Res 2011;26:19-26.
McClung MR, Grauer A, Boonen S, Bolognese MA, Brown JP, Diez-Perez A, Langdahl BL, Reginster JY, Zanchetta JR, Wasserman SM, Katz L, Maddox J, Yang YC, Libanati C, Bone HG: Romosozumab in postmenopausal women with low bone mineral density. N Engl J Med 2014;370:412-420.
Delanaye P, Souberbielle JC, Lafage-Proust MH, Jean G, Cavalier E: Can we use circulating biomarkers to monitor bone turnover in CKD haemodialysis patients? Hypotheses and facts. Nephrol Dial Transplant 2014;29:997-1004.
Cejka D, Herberth J, Branscum AJ, Fardo DW, Monier-Faugere MC, Diarra D, Haas M, Malluche HH: Sclerostin and Dickkopf-1 in renal osteodystrophy. Clin J Am Soc Nephrol 2011;6:877-882.
Malluche HH, Davenport DL, Cantor T, Monier-Faugere MC: Bone mineral density and serum biochemical predictors of bone loss in patients with CKD on dialysis. Clin J Am Soc Nephrol 2014;9:1254-1262.
Goodman WG, Goldin J, Kuizon BD, Yoon C, Gales B, Sider D, Wang Y, Chung J, Emerick A, Greaser L, Elashoff RM, Salusky IB: Coronary-artery calcification in young adults with end-stage renal disease who are undergoing dialysis. N Engl J Med 2000;342:1478-1483.
Jean G, Bresson E, Terrat JC, Vanel T, Hurot JM, Lorriaux C, Mayor B, Chazot C: Peripheral vascular calcification in long-haemodialysis patients: associated factors and survival consequences. Nephrol Dial Transplant 2009;24:948-955.
Zhu D, Mackenzie NC, Millan JL, Farquharson C, MacRae VE: The appearance and modulation of osteocyte marker expression during calcification of vascular smooth muscle cells. PLoS One 2011;6:e19595.
Askevold ET, Gullestad L, Aakhus S, Ranheim T, Tonnessen T, Solberg OG, Aukrust P, Ueland T: Secreted Wnt modulators in symptomatic aortic stenosis. J Am Heart Assoc 2012;1:e002261.
Brandenburg VM, Kramann R, Koos R, Kruger T, Schurgers L, Muhlenbruch G, Hubner S, Gladziwa U, Drechsler C, Ketteler M: Relationship between sclerostin and cardiovascular calcification in hemodialysis patients: a cross-sectional study. BMC Nephrol 2013;14:219.
Kramann R, Brandenburg VM, Schurgers LJ, Ketteler M, Westphal S, Leisten I, Bovi M, Jahnen-Dechent W, Knuchel R, Floege J, Schneider RK: Novel insights into osteogenesis and matrix remodelling associated with calcific uraemic arteriolopathy. Nephrol Dial Transplant 2013;28:856-868.
Schlieper G, Kruger T, Djuric Z, Damjanovic T, Markovic N, Schurgers LJ, Brandenburg VM, Westenfeld R, Dimkovic S, Ketteler M, Grootendorst DC, Dekker FW, Floege J, Dimkovic N: Vascular access calcification predicts mortality in hemodialysis patients. Kidney Int 2008;74:1582-1587.
Viaene L, Behets GJ, Claes K, Meijers B, Blocki F, Brandenburg V, Evenepoel P, D'Haese PC: Sclerostin: another bone-related protein related to all-cause mortality in haemodialysis? Nephrol Dial Transplant 2013;28:3024-3030.
Kauppila LI, Polak JF, Cupples LA, Hannan MT, Kiel DP, Wilson PW: New indices to classify location, severity and progression of calcific lesions in the abdominal aorta: a 25-year follow-up study. Atherosclerosis 1997;132:245-250.
Cejka D, Jager-Lansky A, Kieweg H, Weber M, Bieglmayer C, Haider DG, Diarra D, Patsch JM, Kainberger F, Bohle B, Haas M: Sclerostin serum levels correlate positively with bone mineral density and microarchitecture in haemodialysis patients. Nephrol Dial Transplant 2012;27:226-230.
Pelletier S, Dubourg L, Carlier MC, Hadj-Aissa A, Fouque D: The relation between renal function and serum sclerostin in adult patients with CKD. Clin J Am Soc Nephrol 2013;8:819-823.
Bowling CB, Muntner P, Sawyer P, Sanders PW, Kutner N, Kennedy R, Allman RM: Community mobility among older adults with reduced kidney function: a study of life-space. Am J Kidney Dis 2014;63:429-436.
Gaudio A, Pennisi P, Bratengeier C, Torrisi V, Lindner B, Mangiafico RA, Pulvirenti I, Hawa G, Tringali G, Fiore CE: Increased sclerostin serum levels associated with bone formation and resorption markers in patients with immobilization-induced bone loss. J Clin Endocrinol Metab 2010;95:2248-2253.
Spatz JM, Fields EE, Yu EW, Divieti PP, Bouxsein ML, Sibonga JD, Zwart SR, Smith SM: Serum sclerostin increases in healthy adult men during bed rest. J Clin Endocrinol Metab 2012;97:E1736-E1740.
Cejka D, Marculescu R, Kozakowski N, Plischke M, Reiter T, Gessl A, Haas M: Renal elimination of sclerostin increases with declining kidney function. J Clin Endocrinol Metab 2014;99:248-255.
Claes KJ, Viaene L, Heye S, Meijers B, d'Haese P, Evenepoel P: Sclerostin: another vascular calcification inhibitor? J Clin Endocrinol Metab 2013;98:3221-3228.
McNulty M, Singh RJ, Li X, Bergstralh EJ, Kumar R: Determination of serum and plasma sclerostin concentrations by enzyme-linked immunoassays. J Clin Endocrinol Metab 2011;96:E1159-E1162.
Durosier C, van Lierop A, Ferrari S, Chevalley T, Papapoulos S, Rizzoli R: Association of circulating sclerostin with bone mineral mass, microstructure, and turnover biochemical markers in healthy elderly men and women. J Clin Endocrinol Metab 2013;98:3873-3883.
Gennari L, Merlotti D, Valenti R, Ceccarelli E, Ruvio M, Pietrini MG, Capodarca C, Franci MB, Campagna MS, Calabro A, Cataldo D, Stolakis K, Dotta F, Nuti R: Circulating sclerostin levels and bone turnover in type 1 and type 2 diabetes. J Clin Endocrinol Metab 2012;97:1737-1744.
Sheng Z, Tong D, Ou Y, Zhang H, Zhang Z, Li S, Zhou J, Zhang J, Liao E: Serum sclerostin levels were positively correlated with fat mass and bone mineral density in central south Chinese postmenopausal women. Clin Endocrinol (Oxf) 2012;76:797-801.
Urano T, Shiraki M, Ouchi Y, Inoue S: Association of circulating sclerostin levels with fat mass and metabolic disease-related markers in Japanese postmenopausal women. J Clin Endocrinol Metab 2012;97:E1473-E1477.
Keller H, Kneissel M: SOST is a target gene for PTH in bone. Bone 2005;37:148-158.
O'Brien CA, Plotkin LI, Galli C, Goellner JJ, Gortazar AR, Allen MR, Robling AG, Bouxsein M, Schipani E, Turner CH, Jilka RL, Weinstein RS, Manolagas SC, Bellido T: Control of bone mass and remodeling by PTH receptor signaling in osteocytes. PLoS One 2008;3:e2942.
Leupin O, Kramer I, Collette NM, Loots GG, Natt F, Kneissel M, Keller H: Control of the SOST bone enhancer by PTH using MEF2 transcription factors. J Bone Miner Res 2007;22:1957-1967.
Yu EW, Kumbhani R, Siwila-Sackman E, Leder BZ: Acute decline in serum sclerostin in response to PTH infusion in healthy men. J Clin Endocrinol Metab 2011;96:E1848-E1851.
Wang AY, Wai-Kei LC: The diagnostic utility of cardiac biomarkers in dialysis patients. Semin Dial 2012;25:388-396.
Khan NA, Hemmelgarn BR, Tonelli M, Thompson CR, Levin A: Prognostic value of troponin T and I among asymptomatic patients with end-stage renal disease: a meta-analysis. Circulation 2005;112:3088-3096.
Morales-Santana S, Garcia-Fontana B, Garcia-Martin A, Rozas-Moreno P, Garcia-Salcedo JA, Reyes-Garcia R, Munoz-Torres M: Atherosclerotic disease in type 2 diabetes is associated with an increase in sclerostin levels. Diabetes Care 2013;36:1667-1674.
Ferreira JC, Ferrari GO, Neves KR, Cavallari RT, Dominguez WV, dos Reis LM, Graciolli FG, Oliveira EC, Liu S, Sabbagh Y, Jorgetti V, Schiavi S, Moyses RM: Effects of dietary phosphate on adynamic bone disease in rats with chronic kidney disease - role of sclerostin? PLoS One 2013;8:e79721.
Thambiah S, Roplekar R, Manghat P, Fogelman I, Fraser WD, Goldsmith D, Hampson G: Circulating sclerostin and Dickkopf-1 (DKK1) in predialysis chronic kidney disease: relationship with bone density and arterial stiffness. Calcif Tissue Int 2012;90:473-480.
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