Top

Osteoporosis International

Published in:

01-03-2015 | Original Article

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

Authors: Y. Asamiya, A. Yajima, S. Shimizu, S. Otsubo, K. Tsuchiya, K. Nitta

Published in: Osteoporosis International | Issue 3/2015

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.

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

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

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

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

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

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):e25900CrossRefPubMedCentralPubMed

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):1425–1436CrossRefPubMedCentralPubMed

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):2436–2448CrossRefPubMed

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):6199–6204CrossRefPubMedCentralPubMed

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):645–650CrossRefPubMedCentralPubMed

11.

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

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):4577–4583CrossRefPubMed

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):1991–1997CrossRefPubMedCentralPubMed

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):1757–1772CrossRefPubMed

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):877–882CrossRefPubMedCentralPubMed

16.

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

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):1161–1168CrossRefPubMedCentralPubMed

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):1370–1378CrossRefPubMedCentralPubMed

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):584–592CrossRefPubMedCentralPubMed

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

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):514–525CrossRef

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):247–288CrossRefPubMed

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):e79721CrossRefPubMedCentralPubMed

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):904–909CrossRefPubMed

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):278–287CrossRefPubMed

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):1171–1176CrossRefPubMed

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):4211–4215CrossRefPubMed

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):819–823CrossRefPubMedCentralPubMed

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):427–437CrossRef

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):830–835CrossRefPubMedCentralPubMed

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):61–86CrossRefPubMedCentralPubMed

33.

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

34.

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

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):2510–2517CrossRefPubMed

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):2248–2253CrossRefPubMed

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):19–26CrossRefPubMed

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):412–420CrossRefPubMed

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):373–379CrossRefPubMedCentralPubMed

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):226–230CrossRefPubMed

Title: 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
Authors: Y. Asamiya
A. Yajima
S. Shimizu
S. Otsubo
K. Tsuchiya
K. Nitta
Publication date: 01-03-2015
Publisher: Springer London
Published in: Osteoporosis International / Issue 3/2015
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI: https://doi.org/10.1007/s00198-014-2934-8

At a glance: The STEP trials

Springer Medicine

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

Abstract

Summary

Introduction

Methods

Results

Conclusion

At a glance: The STEP trials

Springer Medicine

Abstract

Summary

Introduction

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 3/2015

Hyponatremia and osteoporosis: insights from the Danish National Patient Registry

Nonunion of osteoporotic vertebral compression fracture with a severe spinal stenosis treated in minimally invasive manner: a case report

Teriparatide treatment patterns in osteoporosis and subsequent fracture events: a US claims analysis

Response to Hotta: High prevalence of vitamin D insufficiency and deficiency among patients with anorexia nervosa in Japan

Mediating effects on health-related quality of life in adults with osteoporosis: a structural equation modeling

Local renin-angiotensin system is associated with bone mineral density of glucocorticoid-induced osteoporosis patients