Skip to main content

Advertisement

SpringerLink
Log in

Associations between the levels of sclerostin, phosphate, and fibroblast growth factor-23 and treatment with vitamin D in hemodialysis patients with low intact PTH level

  • Original Article
  • Published:
Osteoporosis International Aims and scope Submit manuscript

Abstract

Summary

Serum sclerostin levels could be closely associated with serum phosphate and fibroblast growth factor-23 levels in hemodialysis patients with low intact parathyroid hormone (PTH) levels. Further study is required to indicate whether these close associations are present in patients with spontaneously low PTH levels without any vitamin D treatment.

Introduction

Intact parathyroid hormone (iPTH) is involved in the interaction between sclerostin and phosphate/fibroblast growth factor-23 (FGF23) in animal models. However, their relationship in patients on hemodialysis (HD) is unclear.

Methods

Data of 102 HD patients were collected regarding clinical and laboratory parameters and mineral bone disorder medications. The patients were divided into subgroups according to the iPTH level (A, <70 pg/mL; B, 70–150 pg/mL; C, 150–300 pg/mL; and D, ≥300 pg/mL).

Results

The sclerostin level was significantly and positively correlated with phosphate and log of FGF23 levels in subgroups A, B, and combined A and B. Multiple linear regression analysis in the combined A and B subgroup revealed that male sex (t = 3.24, P = 0.01; 95 % confidence interval [CI] 11.78 to 50.43) and phosphate level (t = 2.13, P = 0.04; 95 % CI, 1.08 to 36.91) were independent factors for serum sclerostin level. The log of serum FGF23 level (t = 1.90, P = 0.06, 95 % CI −1.85 to 63.50) appeared to be an important factor for serum sclerostin level. The frequency of patients using vitamin D treatment was not significantly different among subgroups A (93.1 %), B (88.0 %), C (85.2 %), and D (90.5 %).

Conclusion

Serum sclerostin levels were associated with serum phosphate and FGF23 levels in patients with low iPTH levels. Further study is required to indicate whether these close associations are present in patients with spontaneously low iPTH levels without vitamin D treatment.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Bonewald LF (2011) The amazing osteocyte. J Bone Miner Res 26(2):229–238

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  2. Bonewald LF, Johnson ML (2008) Osteocytes, mechanosensing and Wnt signaling. Bone 42(4):606–615

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  3. Baron R, Rawadi G (2007) Wnt signaling and the regulation of bone mass. Curr Osteoporos Rep 5(2):73–80

    Article  PubMed  Google Scholar 

  4. Moester MJ, Papapoulos SE, Löwik CW, van Bezooijen RL (2010) Sclerostin: current knowledge and future perspectives. Calcif Tissue Int 87(2):99–107

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  5. Atkins GJ, Findlay DM (2012) Osteocyte regulation of bone mineral: a little give and take. Osteoporos Int 23(8):2067–2079

    Article  CAS  PubMed  Google Scholar 

  6. Wijenayaka AR, Kogawa M, Lim HP, Bonewald LF, Findlay DM, Atkins GJ (2011) Sclerostin stimulates osteocyte support of osteoclast activity by a RANKL-dependent pathway. PLoS One 6(10):e25900

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  7. Atkins GJ, Rowe PS, Lim HP, Welldon KJ, Ormsby R, Wijenayaka AR, Zelenchuk L, Evdokiou A, Findlay DM (2011) Sclerostin is a locally acting regulator of late-osteoblast/preosteocyte differentiation and regulates mineralization through a MEPE-ASARM-dependent mechanism. J Bone Miner Res 26(7):1425–1436

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  8. Kogawa M, Wijenayaka AR, Ormsby RT, Thomas GP, Anderson PH, Bonewald LF, Findlay DM, Atkins GJ (2013) Sclerostin regulates release of bone mineral by osteocytes by induction of carbonic anhydrase 2. J Bone Miner Res 28(12):2436–2448

    Article  CAS  PubMed  Google Scholar 

  9. Ryan ZC, Ketha H, McNulty MS, McGee-Lawrence M, Craig TA, Grande JP, Westendorf JJ, Singh RJ, Kumar R (2013) Sclerostin alters serum vitamin D metabolite and fibroblast growth factor 23 concentrations and the urinary excretion of calcium. Proc Natl Acad Sci U S A 110(15):6199–6204

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  10. Dawson-Hughes B, Harris SS, Ceglia L, Palermo NJ (2014) Effect of supplemental vitamin D and calcium on serum sclerostin levels. Eur J Endocrinol 170(4):645–650

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  11. Keller H, Kneissel M (2005) SOST is a target gene for PTH in bone. Bone 37(2):148–158

    Article  CAS  PubMed  Google Scholar 

  12. Bellido T, Ali AA, Gubrij I, Plotkin LI, Fu Q, O’Brien CA, Manolagas SC, Jilka RL (2005) Chronic elevation of parathyroid hormone in mice reduces expression of sclerostin by osteocytes: a novel mechanism for hormonal control of osteoblastogenesis. Endocrinology 146(11):4577–4583

    Article  CAS  PubMed  Google Scholar 

  13. 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(4):1991–1997

    Article  PubMed Central  PubMed  Google Scholar 

  14. Sabbagh Y, Graciolli FG, O’Brien S, Tang W, dos Reis LM, Ryan S, Phillips L, Boulanger J, Song W, Bracken C, Liu S, Ledbetter S, Dechow P, Canziani ME, Carvalho AB, Jorgetti V, Moyses RM, Schiavi SC (2012) Repression of osteocyte Wnt/β-catenin signaling is an early event in the progression of renal osteodystrophy. J Bone Miner Res 27(8):1757–1772

    Article  CAS  PubMed  Google Scholar 

  15. Cejka D, Herberth J, Branscum AJ, Fardo DW, Monier-Faugere MC, Diarra D, Haas M, Malluche HH (2011) Sclerostin and Dickkopf-1 in renal osteodystrophy. Clin J Am Soc Nephrol 6(4):877–882

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  16. Jean G, Chazot C (2013) Sclerostin in CKD-MBD: one more paradoxical bone protein? Nephrol Dial Transplant 28(12):2932–2935

    Article  PubMed  Google Scholar 

  17. Pereira RC, Juppner H, Azucena-Serrano CE, Yadin O, Salusky IB, Wesseling-Perry K (2009) Patterns of FGF-23, DMP1, and MEPE expression in patients with chronic kidney disease. Bone 45(6):1161–1168

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  18. Isakova T, Wahl P, Vargas GS, Gutiérrez OM, Scialla J, Xie H, Appleby D, Nessel L, Bellovich K, Chen J, Hamm L, Gadegbeku C, Horwitz E, Townsend RR, Anderson CA, Lash JP, Hsu CY, Leonard MB, Wolf M (2011) Fibroblast growth factor 23 is elevated before parathyroid hormone and phosphate in chronic kidney disease. Kidney Int 79(12):1370–1378

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. Gutiérrez OM, Mannstadt M, Isakova T, Rauh-Hain JA, Tamez H, Shah A, Smith K, Lee H, Thadhani R, Jüppner H, Wolf M (2008) Fibroblast growth factor 23 and mortality among patients undergoing hemodialysis. N Engl J Med 359(6):584–592

    Article  PubMed Central  PubMed  Google Scholar 

  20. National Kidney Foundation (2003) K/DOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease. Am J Kidney Dis 42(4) (Suppl 3):S1-S201

  21. Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Work Group (2009) KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of chronic kidney disease-mineral and bone disorder (CKD-MBD). Kidney Int Suppl 113:S1–S130

    Google Scholar 

  22. Guideline Working Group, Japanese Society for Dialysis Therapy (2008) Clinical practice guideline for the management of secondary hyperparathyroidism in chronic dialysis patients. Ther Apher Dial 12(6):514–525

    Article  Google Scholar 

  23. Fukagawa M, Yokoyama K, Koiwa F, Taniguchi M, Shoji T, Kazama JJ, Komaba H, Ando R, Kakuta T, Fujii H, Nakayama M, Shibagaki Y, Fukumoto S, Fujii N, Hattori M, Ashida A, Iseki K, Shigematsu T, Tsukamoto Y, Tsubakihara Y, Tomo T, Hirakata H, Akizawa T (2013) CKD-MBD guideline working group; Japanese society for dialysis therapy. Clinical practice guideline for the management of chronic kidney disease-mineral and bone disorder. Ther Apher Dial 17(3):247–288

    Article  PubMed  Google Scholar 

  24. 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, Moysés RM (2013) Effects of dietary phosphate on adynamic bone disease in rats with chronic kidney disease-role of sclerostin? PLoS One 8(11):e79721

    Article  PubMed Central  PubMed  Google Scholar 

  25. Inaba M, Terada M, Nishizawa Y, Shioi A, Ishimura E, Otani S, Morii H (1999) Protective effect of an aldose reductase inhibitor against bone loss in galactose-fed rats: possible involvement of the polyol pathway in bone metabolism. Metabolism 48(7):904–909

    Article  CAS  PubMed  Google Scholar 

  26. Shidara K, Inaba M, Okuno S, Yamada S, Kumeda Y, Imanishi Y, Yamakawa T, Ishimura E, Nishizawa Y (2008) Serum levels of TRAP5b, a new bone resorption marker unaffected by renal dysfunction, as a useful marker of cortical bone loss in hemodialysis patients. Calcif Tissue Int 82(4):278–287

    Article  CAS  PubMed  Google Scholar 

  27. Polyzos SA, Anastasilakis AD, Bratengeier C, Woloszczuk W, Papatheodorou A, Terpos E (2012) Serum sclerostin levels positively correlate with lumbar spinal bone mineral density in postmenopausal women—the six-month effect of risedronate and teriparatide. Osteoporos Int 23(3):1171–1176

    Article  CAS  PubMed  Google Scholar 

  28. Yamashita H, Yamazaki Y, Hasegawa H, Yamashita T, Fukumoto S, Shigematsu T, Kazama JJ, Fukagawa M, Noguchi S (2005) Fibroblast growth factor-23 in patients with Graves’ disease before and after antithyroid therapy: its important role in serum phosphate regulation. J Clin Endocrinol Metab 90(7):4211–4215

    Article  CAS  PubMed  Google Scholar 

  29. Pelletier S, Dubourg L, Carlier MC, Hadj-Aissa A, Fouque D (2013) The relation between renal function and serum sclerostin in adult patients with CKD. Clin J Am Soc Nephrol 8(5):819–823

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  30. Fukagawa M, Komaba H, Onishi Y, Fukuhara S, Akizawa T, Kurokawa K; MBD-5D Study Group (2011) Mineral metabolism management in hemodialysis patients with secondary hyperparathyroidism in Japan: baseline data from the MBD-5D. Am J Nephrol 33(5):427–437

    Article  Google Scholar 

  31. Devarajan-Ketha H, Craig TA, Madden BJ, Robert Bergen H 3rd, Kumar R (2012) The sclerostin-bone protein interactome. Biochem Biophys Res Commun 417(2):830–835

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  32. Rowe PS (2012) Regulation of bone-renal mineral and energy metabolism: the PHEX, FGF23, DMP1, MEPE ASARM pathway. Crit Rev Eukaryot Gene Expr 22(1):61–86

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  33. Quarles LD (2008) Endocrine functions of bone in mineral metabolism regulation. J Clin Invest 118(12):3820–3828

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  34. Rowe PS (2012) The chicken or the egg: PHEX, FGF23 and SIBLINGs unscrambled. Cell Biochem Funct 30(5):355–375

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  35. de Oliveira RB, Graciolli FG, dos Reis LM, Cancela AL, Cuppari L, Canziani ME, Carvalho AB, Jorgetti V, Moysés RM (2013) Disturbances of Wnt/β-catenin pathway and energy metabolism in early CKD: effect of phosphate binders. Nephrol Dial Transplant 28(10):2510–2517

    Article  PubMed  Google Scholar 

  36. 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(5):2248–2253

    Article  CAS  PubMed  Google Scholar 

  37. Padhi D, Jang G, Stouch B, Fang L, Posvar E (2011) Single-dose, placebo-controlled, randomized study of AMG 785, a sclerostin monoclonal antibody. J Bone Miner Res 26(1):19–26

    Article  CAS  PubMed  Google Scholar 

  38. 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 (2014) Romosozumab in postmenopausal women with low bone mineral density. N Engl J Med 370(5):412–420

    Article  CAS  PubMed  Google Scholar 

  39. 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(2):373–379

    Article  PubMed Central  PubMed  Google Scholar 

  40. Cejka D, Jäger-Lansky A, Kieweg H, Weber M, Bieglmayer C, Haider DG, Diarra D, Patsch JM, Kainberger F, Bohle B, Haas M (2012) Sclerostin serum levels correlate positively with bone mineral density and microarchitecture in haemodialysis patients. Nephrol Dial Transplant 27(1):226–230

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We thank Mr. Tsutomu Ishizuka for his technical support in the measurement of serum sclerostin and serum FGF23 levels.

Conflicts of interest

Yukari Asamiya, Aiji Yajima, Satoru Shimizu, Shigeru Otsubo, Ken Tsuchiya, and Kosaku Nitta declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Medicine, Kidney Center, Tokyo Women’s Medical University, 8-1 Kawada-chou, Shinjuku-ku, Tokyo, 162-8666, Japan

    Y. Asamiya, A. Yajima, K. Tsuchiya & K. Nitta

  2. Department of Medicine, Division of Nephrology, Otsuki Municipal Central Hospital, 1225 Otsukimachihanasaki, Otsuki, Yamanashi, 401-0015, Japan

    A. Yajima

  3. Department of Developmental Biology of Hard Tissue, Graduate School of Dental Medicine, Hokkaido University, Kita 13 Nishi 7 kita-ku, Sapporo, 060-8586, Japan

    A. Yajima

  4. Medical Research Institute, Tokyo Women’s Medical University, 8-1 Kawada-chou, Shinjuku-ku, Tokyo, 162-8666, Japan

    S. Shimizu

  5. Department of Blood Purification, Sangenjaya Hospital, 1-25-5 Sangenjaya, Setagaya-ku, Tokyo, 154-0024, Japan

    S. Otsubo

  6. Department of Blood Purification, Kidney Center, Tokyo Women’s Medical University, 8-1 Kawada-chou, Shinjuku-ku, Tokyo, 162-8666, Japan

    K. Tsuchiya

Authors
  1. Y. Asamiya
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. Yajima
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S. Shimizu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. S. Otsubo
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. K. Tsuchiya
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. K. Nitta
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Y. Asamiya.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Asamiya, Y., Yajima, A., Shimizu, S. et al. Associations between the levels of sclerostin, phosphate, and fibroblast growth factor-23 and treatment with vitamin D in hemodialysis patients with low intact PTH level. Osteoporos Int 26, 1017–1028 (2015). https://doi.org/10.1007/s00198-014-2934-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00198-014-2934-8

Keywords

Search

Navigation