Skip to main content

Advertisement

Log in

Effect of liver dysfunction on circulating sclerostin

  • Original Article
  • Published:
Journal of Bone and Mineral Metabolism Aims and scope Submit manuscript

Abstract

Sclerostin is a Wnt inhibitor produced specifically by osteocytes. It decreases bone formation by repressing osteoblast differentiation and proliferation. Whether circulating sclerostin level is affected by liver function is not currently clear. The aim of the study was to evaluate this relationship. Our cross-sectional study included 47 patients with liver cirrhosis and 50 healthy controls. Serum sclerostin level was analyzed by ELISA. Serum sclerostin levels were significantly higher in patients with cirrhosis than in controls (50.8 ± 38.2 vs. 35.1 ± 8.8 pmol/L, p = 0.008). After further adjustment for age, sex, body mass index, serum creatinine, and presence of diabetes, cirrhosis patients had higher sclerostin than controls. Subgroup analysis found that patients with Child–Pugh class B or C had higher sclerostin levels than patients with class A or controls after adjusting for multiple confounding factors. Multiple regression analysis showed that gender (p = 0.022), presence of diabetes (p < 0.001), albumin (p = 0.010), and serum creatinine (p = 0.037) were independent factors for circulating sclerostin level. Circulating sclerostin was higher in patients with advanced liver cirrhosis than in healthy controls or patients with early liver cirrhosis. The elevated sclerostin levels clearly correlated with markers of liver dysfunction such as albumin. The relationship between circulating sclerostin and liver function indicates a possible role of the liver in sclerostin metabolism.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. Collier J (2007) Bone disorders in chronic liver disease. Hepatology 46:1271–1278

    Article  CAS  PubMed  Google Scholar 

  2. Leslie WD, Bernstein CN, Leboff MS, American Gastroenterological Association Clinical Practice Committee (2003) AGA technical review on osteoporosis in hepatic disorders. Gastroenterology 125:941–966

    Article  PubMed  Google Scholar 

  3. Nakchbandi IA, van der Merwe SW (2009) Current understanding of osteoporosis associated with liver disease. Nat Rev Gastroenterol Hepatol 6:660–670

    Article  PubMed  Google Scholar 

  4. Foresta C, Schipilliti M, Ciarleglio FA, Lenzi A, D’Amico D (2008) Male hypogonadism in cirrhosis and after liver transplantation. J Endocrinol Invest 32:470–482

    Article  Google Scholar 

  5. Guañabens N, Parés A, Mariñoso L, Brancós MA, Piera C, Serrano S, Rivera F, Rodés J (1990) Factors influencing the development of metabolic bone disease in primary biliary cirrhosis. Am J Gastroenterol 85:1356–1362

    PubMed  Google Scholar 

  6. Stellon AJ, Webb A, Compston J, Williams R (1987) Low bone turnover state in primary biliary cirrhosis. Hepatology 7:137–142

    Article  CAS  PubMed  Google Scholar 

  7. Poole KE, van Bezooijen RL, Loveridge N, Hamersma H, Papapoulos SE, Löwik CW, Reeve J (2005) Sclerostin is a delayed secreted products of osteocytes that inhibits bone formation. FASEB J 19:1842–1844

    CAS  PubMed  Google Scholar 

  8. Baron R, Rawadi G (2007) Targeting the Wnt/β-catenin pathway to regulate bone formation in the adults skeleton. Endocrinology 148:2635–2643

    Article  CAS  PubMed  Google Scholar 

  9. Li X, Zhang Y, Kang H, Liu W, Liu P, Zhang J, Harris SE, Wu D (2005) Sclerostin binds to LRP5/6 and antagonizes canonical Wnt signaling. J Biol Chem 280:19883–19887

    Article  CAS  PubMed  Google Scholar 

  10. Mödder UI, Hoey KA, Amin S, McCready LK, Achenbach SJ, Riggs BL, Melton LJ 3rd, Khosla S (2011) Relation of age, gender, and bone mass to circulating sclerostin levels in women and men. J Bone Miner Res 26:373–379

    Article  PubMed Central  PubMed  Google Scholar 

  11. Amrein K, Amrein S, Drexler C, Dimai HP, Dobnig H, Pfeifer K, Tomaschitz A, Pieber TR, Fahrleitner-Pammer A (2012) Sclerostin and its association with physical activity, age, gender, body composition, and bone mineral content in healthy adults. J Clin Endocrinol Metab 97:148–154

    Article  CAS  PubMed  Google Scholar 

  12. Gaudio A, Pennisi P, Bratengeier C, Torrisi V, Lindner B, Mangiafico RA, Pulvirenti I, Hawa G, Tringali G, Fiore CE (2010) Increased sclerostin serum levels associated with bone formation and resorption markers in patients with immobilization-induced bone loss. J Clin Endocrinol Metab 95:2248–2253

    Article  CAS  PubMed  Google Scholar 

  13. Pugh RN, Murray-Lyon IM, Dawson JL, Pietroni MC, Williams R (1973) Transection of the esophagus for bleeding esophageal varices. Br J Surg 60:646–649

    Article  CAS  PubMed  Google Scholar 

  14. González-Reimers E, Martín-González C, de la Vega-Prieto MJ, Pelazas-González R, Fernández-Rodríguez C, López-Prieto J, Alvisa-Negrín J, Santolaria-Fernández F (2013) Serum sclerostin in alcoholics: a pilot study. Alcohol Alcohol 48:278–282

    Article  PubMed  Google Scholar 

  15. Mirza FS, Padhi ID, Raisz LG, Lorenzo JA (2010) Serum sclerostin levels negatively correlate with parathyroid hormone levels and free estrogen index in postmenopausal women. J Clin Endocrinol Metab 95:1991–1997

    Article  PubMed Central  PubMed  Google Scholar 

  16. Mödder UI, Clowes JA, Hoey K, Peterson JM, McCready L, Oursler MJ, Riggs BL, Khosla S (2011) Regulation of circulating sclerostin levels by sex steroids in women and in men. J Bone Miner Res 26:27–34

    Article  PubMed Central  PubMed  Google Scholar 

  17. Lapauw B, Vandewalle S, Taes Y, Goemaere S, Zmierczak H, Collette J, Kaufman JM (2013) Serum sclerostin levels in men with idiopathic osteoporosis. Eur J Endocrinol 168:615–620

    Article  CAS  PubMed  Google Scholar 

  18. García-Fontana B, Morales-Santana S, Varsavsky M, García-Martín A, García-Salcedo JA, Reyes-García R, Muñoz-Torres M (2013) Sclerostin serum levels in prostate cancer patients and their relationship with sex steroids. Osteoporos Int [Epub ahead of print] doi 10.1007/s00198-013-2462-y

  19. Bannister P, Losowky MS (1988) Sex hormones and chronic liver disease. J Hepatol 6:258–262

    Article  CAS  PubMed  Google Scholar 

  20. Kaymakoğlu S, Okten A, Cakaloğlu Y, Boztaş G, Beşişik F, Taşçioğlu C, Yalçin S (1995) Hypogonadism is not related to the etiology of liver cirrhosis. J Gastroenterol 30:745–750

    Article  PubMed  Google Scholar 

  21. Galvão-Teles A, Burke CW, Anderson DC, Marshall JC, Corker CS, Bown RL, Clark ML (1973) Biologically active androgens and oestradiol in men with chronic liver disease. Lancet 1:173–177

    Article  PubMed  Google Scholar 

  22. Robling AG, Niziolek PJ, Baldridge LA, Condon KW, Allen MR, Alam I, Mantila SM, Gluhak-Heinrich J, Bellido TM, Harris SE, Turner CH (2008) Mechanical stimulation of bone in vivo reduces osteocytes expression of Sost/sclerostin. J Biol Chem 293:5866–5875

    Google Scholar 

  23. Diamond TH, Stiel D, Lunzer M, McDowall D, Eckstein RP, Posen S (1989) Hepatic osteodystrophy. Static and dynamic bone histomorphometry and serum bone Gla-protein in 80 patients with chronic liver disease. Gastroenterology 96:213–221

    CAS  PubMed  Google Scholar 

  24. Cemborain A, Castilla-Cortázar I, García M, Muguerza B, Delgado G, Díaz-Sánchez M, Picardi A (2000) Effects of IGF-I treatment on osteopenia in rats with advanced liver cirrhosis. J Physiol Biochem 56:91–99

    Article  CAS  PubMed  Google Scholar 

  25. Kawelke N, Bentmann A, Hackl N, Hager HD, Feick P, Geursen A, Singer MV, Nakchbandi IA (2008) Isoform of fibronectin mediates bone loss in patients with primary biliary cirrhosis by suppressing bone formation. J Bone Miner Res 23:1278–1286

    Article  CAS  PubMed  Google Scholar 

  26. Xu G, Niki T, Virtanen I, Rogiers V, De Bleser P, Geerts A (1997) Gene expression and synthesis of fibronectin isoforms in rat hepatic stellate cells. Comparison with liver parenchymal cells and skin fibroblasts. J Pathol 183:90–98

    Article  CAS  PubMed  Google Scholar 

  27. García-Martín A, Rozas-Moreno P, Reyes-García R, Morales-Santana S, García-Fontana B, García-Salcedo JA, Muñoz-Torres M (2012) Circulating levels of sclerostin are increased in patients with type 2 diabetes mellitus. J Clin Endocrinol Metab 97:234–241

    Article  PubMed  Google Scholar 

  28. Gaudio A, Privitera F, Battaglia K, Torrisi V, Sidoti MH, Pulvirenti I, Canzonieri E, Tringali G, Fiore CE (2012) Sclerostin levels associated with inhibition of the Wnt/β-catenin signaling and reduced bone turnover in type 2 diabetes mellitus. J Clin Endocrinol Metab 97:3744–3750

    Article  CAS  PubMed  Google Scholar 

Download references

Conflict of interest

The authors declare no conflict of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Se Hwa Kim.

About this article

Cite this article

Rhee, Y., Kim, W.J., Han, K.J. et al. Effect of liver dysfunction on circulating sclerostin. J Bone Miner Metab 32, 545–549 (2014). https://doi.org/10.1007/s00774-013-0524-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00774-013-0524-z

Keywords

Navigation