Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
BMC Nephrology
Published in: BMC Nephrology 1/2019

Open Access 01-12-2019 | Peritoneal Dialysis | Research article

Serum sclerostin levels are positively related to bone mineral density in peritoneal dialysis patients: a cross-sectional study

Authors: Te-Hui Kuo, Wei-Hung Lin, Jo-Yen Chao, An-Bang Wu, Chin-Chung Tseng, Yu-Tzu Chang, Hung-Hsiang Liou, Ming-Cheng Wang

Published in: BMC Nephrology | Issue 1/2019

Login to get access

Abstract

Background

Sclerostin, an antagonist of the Wingless-type mouse mammary tumor virus integration site (Wnt) pathway that regulates bone metabolism, is a potential contributor of chronic kidney disease (CKD)–mineral and bone disorder (MBD), which has various forms of presentation, from osteoporosis to vascular calcification. The positive association of sclerostin with bone mineral density (BMD) has been demonstrated in CKD and hemodialysis (HD) patients but not in peritoneal dialysis (PD) patients. This study assessed the association between sclerostin and BMD in PD patients.

Methods

Eighty-nine PD patients were enrolled; their sera were collected for measurement of sclerostin and other CKD–MBD-related markers. BMD was also assessed simultaneously. We examined the relationship between sclerostin and each parameter through Spearman correlation analysis and by comparing group data between patients with above- and below-median sclerostin levels. Univariate and multiple logistic regression models were employed to define the most predictive of sclerostin levels in the above-median category.

Results

Bivariate analysis revealed that sclerostin was correlated with spine BMD (r = 0.271, P = 0.011), spine BMD T-score (r = 0.274, P = 0.010), spine BMD Z-score (r = 0.237, P = 0.027), and intact parathyroid hormone (PTH; r = − 0.357, P < 0.001) after adjustments for age and sex. High BMD, old age, male sex, increased weight and height, diabetes, and high osteocalcin and uric acid levels were observed in patients with high serum sclerostin levels and an inverse relation was noticed between PTH and sclerostin. Univariate logistic regression analysis demonstrated that BMD is positively correlated with above-median sclerostin levels (odds ratio [OR] = 65.61, P = 0.002); the correlation was retained even after multivariate adjustment (OR = 121.5, P = 0.007).

Conclusions

For the first time, this study demonstrated a positive association between serum sclerostin levels and BMD in the PD population.
Literature
1.
Moe S, Drueke T, Cunningham J, Goodman W, Martin K, Olgaard K, Ott S, Sprague S, Lameire N, Eknoyan G. Definition, evaluation, and classification of renal osteodystrophy: a position statement from kidney disease: improving global outcomes (KDIGO). Kidney Int. 2006;69:1945–53.CrossRef
2.
Rix M, Andreassen H, Eskildsen P, Langdahl B, Olgaard K. Bone mineral density and biochemical markers of bone turnover in patients with predialysis chronic renal failure. Kidney Int. 1999;56:1084–93.CrossRef
3.
Coco M, Rush H. Increased incidence of hip fractures in dialysis patients with low serum parathyroid hormone. Am J Kidney Dis. 2000;36:1115–21.CrossRef
4.
Cunningham J, Sprague SM, Cannata-Andia J, Coco M, Cohen-Solal M, Fitzpatrick L, Goltzmann D, Lafage-Proust MH, Leonard M, Ott S, et al. Osteoporosis in chronic kidney disease. Am J Kidney Dis. 2004;43:566–71.CrossRef
5.
Krishnan V, Bryant HU, Macdougald OA. Regulation of bone mass by Wnt signaling. J Clin Invest. 2006;116:1202–9.CrossRef
6.
Clevers H. Wnt/beta-catenin signaling in development and disease. Cell. 2006;127:469–80.CrossRef
7.
Johnson ML, Kamel MA. The Wnt signaling pathway and bone metabolism. Curr Opin Rheumatol. 2007;19:376–82.CrossRef
8.
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;6:877–82.CrossRef
9.
Baron R, Kneissel M. WNT signaling in bone homeostasis and disease: from human mutations to treatments. Nat Med. 2013;19:179–92.CrossRef
10.
Ardawi MS, Al-Kadi HA, Rouzi AA, Qari MH. Determinants of serum sclerostin in healthy pre- and postmenopausal women. J Bone Miner Res. 2011;26:2812–22.CrossRef
11.
Modder UI, Hoey KA, Amin S, McCready LK, Achenbach SJ, Riggs BL, Melton LJ 3rd, Khosla S. Relation of age, gender, and bone mass to circulating sclerostin levels in women and men. J Bone Miner Res. 2011;26:373–9.CrossRef
12.
Garcia-Martin A, Rozas-Moreno P, Reyes-Garcia R, Morales-Santana S, Garcia-Fontana B, Garcia-Salcedo JA, Munoz-Torres M. Circulating levels of sclerostin are increased in patients with type 2 diabetes mellitus. J Clin Endocrinol Metab. 2012;97:234–41.CrossRef
13.
Polyzos SA, Anastasilakis AD, Bratengeier C, Woloszczuk W, Papatheodorou A, Terpos E. Serum sclerostin levels positively correlate with lumbar spinal bone mineral density in postmenopausal women--the six-month effect of risedronate and teriparatide. Osteoporos Int. 2012;23:1171–6.CrossRef
14.
van Lierop AH, Witteveen JE, Hamdy NA, Papapoulos SE. Patients with primary hyperparathyroidism have lower circulating sclerostin levels than euparathyroid controls. Eur J Endocrinol. 2010;163:833–7.CrossRef
15.
Jadoul M, Albert JM, Akiba T, Akizawa T, Arab L, Bragg-Gresham JL, Mason N, Prutz KG, Young EW, Pisoni RL. Incidence and risk factors for hip or other bone fractures among hemodialysis patients in the Dialysis outcomes and practice patterns study. Kidney Int. 2006;70:1358–66.CrossRef
16.
Bucur RC, Panjwani DD, Turner L, Rader T, West SL, Jamal SA. Low bone mineral density and fractures in stages 3-5 CKD: an updated systematic review and meta-analysis. Osteoporos Int. 2015;26:449–58.CrossRef
17.
Ketteler M, Block GA, Evenepoel P, Fukagawa M, Herzog CA, McCann L, Moe SM, Shroff R, Tonelli MA, Toussaint ND, et al. Executive summary of the 2017 KDIGO chronic kidney disease-mineral and bone disorder (CKD-MBD) guideline update: what's changed and why it matters. Kidney Int. 2017;92:26–36.CrossRef
18.
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;8:819–23.CrossRef
19.
Kanbay M, Siriopol D, Saglam M, Kurt YG, Gok M, Cetinkaya H, Karaman M, Unal HU, Oguz Y, Sari S, et al. Serum sclerostin and adverse outcomes in nondialyzed chronic kidney disease patients. J Clin Endocrinol Metab. 2014;99:E1854–61.CrossRef
20.
Kazama JJ, Matsuo K, Iwasaki Y, Fukagawa M. Chronic kidney disease and bone metabolism. J Bone Miner Metab. 2015;33:245–52.CrossRef
21.
Cejka D, Jager-Lansky A, Kieweg H, Weber M, Bieglmayer C, Haider DG, Diarra D, Patsch JM, Kainberger F, Bohle B, et al. Sclerostin serum levels correlate positively with bone mineral density and microarchitecture in haemodialysis patients. Nephrol Dial Transplant. 2012;27:226–30.CrossRef
22.
Pelletier S, Confavreux CB, Haesebaert J, Guebre-Egziabher F, Bacchetta J, Carlier MC, Chardon L, Laville M, Chapurlat R, London GM, et al. Serum sclerostin: the missing link in the bone-vessel cross-talk in hemodialysis patients? Osteoporos Int. 2015;26:2165–74.CrossRef
23.
Lee H, Hwang YH, Jung JY, Na KY, Kim HS, Son MJ, Park JY, Cho EJ, Ahn C, Oh KH. Comparison of vascular calcification scoring systems using plain radiographs to predict vascular stiffness in peritoneal dialysis patients. Nephrology (Carlton). 2011;16:656–62.
24.
Ottenbacher KJ, Ottenbacher HR, Tooth L, Ostir GV. A review of two journals found that articles using multivariable logistic regression frequently did not report commonly recommended assumptions. J Clin Epidemiol. 2004;57:1147–52.CrossRef
25.
Hampson G, Edwards S, Conroy S, Blake GM, Fogelman I, Frost ML. The relationship between inhibitors of the Wnt signalling pathway (Dickkopf-1(DKK1) and sclerostin), bone mineral density, vascular calcification and arterial stiffness in post-menopausal women. Bone. 2013;56:42–7.CrossRef
26.
Garnero P, Sornay-Rendu E, Munoz F, Borel O, Chapurlat RD. Association of serum sclerostin with bone mineral density, bone turnover, steroid and parathyroid hormones, and fracture risk in postmenopausal women: the OFELY study. Osteoporos Int. 2013;24:489–94.CrossRef
27.
Lim Y, Kim CH, Lee SY, Kim H, Ahn SH, Lee SH, Koh JM, Rhee Y, Baek KH, Min YK, et al. Decreased plasma levels of Sclerostin but not Dickkopf-1 are associated with an increased prevalence of osteoporotic fracture and lower bone mineral density in postmenopausal Korean women. Calcif Tissue Int. 2016;99:350–9.CrossRef
28.
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 (CKD): relationship with bone density and arterial stiffness. Calcif Tissue Int. 2012;90:473–80.CrossRef
29.
Ishimura E, Okuno S, Ichii M, Norimine K, Yamakawa T, Shoji S, Nishizawa Y, Inaba M. Relationship between serum sclerostin, bone metabolism markers, and bone mineral density in maintenance hemodialysis patients. J Clin Endocrinol Metab. 2014;99:4315–20.CrossRef
30.
Cosman F, Crittenden DB, Adachi JD, Binkley N, Czerwinski E, Ferrari S, Hofbauer LC, Lau E, Lewiecki EM, Miyauchi A, et al. Romosozumab treatment in postmenopausal women with osteoporosis. N Engl J Med. 2016;375:1532–43.CrossRef
31.
Ardawi MS, Rouzi AA, Qari MH. Physical activity in relation to serum sclerostin, insulin-like growth factor-1, and bone turnover markers in healthy premenopausal women: a cross-sectional and a longitudinal study. J Clin Endocrinol Metab. 2012;97:3691–9.CrossRef
32.
Spatz JM, Fields EE, Yu EW, Divieti Pajevic P, Bouxsein ML, Sibonga JD, Zwart SR, Smith SM. Serum sclerostin increases in healthy adult men during bed rest. J Clin Endocrinol Metab. 2012;97:E1736–40.CrossRef
33.
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;28:3024–30.CrossRef
34.
Yamada S, Tsuruya K, Tokumoto M, Yoshida H, Ooboshi H, Kitazono T. Factors associated with serum soluble inhibitors of Wnt-beta-catenin signaling (sclerostin and dickkopf-1) in patients undergoing peritoneal dialysis. Nephrology (Carlton). 2015;20:639–45.CrossRef
35.
Mirza FS, Padhi ID, Raisz LG, Lorenzo JA. Serum sclerostin levels negatively correlate with parathyroid hormone levels and free estrogen index in postmenopausal women. J Clin Endocrinol Metab. 2010;95:1991–7.CrossRef
36.
Jin S, Zhu M, Yan J, Fang Y, Lu R, Zhang W, Zhang Q, Lu J, Qi C, Shao X, et al. Serum sclerostin level might be a potential biomarker for arterial stiffness in prevalent hemodialysis patients. Biomark Med. 2016;10:689–99.CrossRef
37.
Hsu BG, Liou HH, Lee CJ, Chen YC, Ho GJ, Lee MC. Serum Sclerostin as an independent marker of peripheral arterial stiffness in renal transplantation recipients: a cross-sectional study. Medicine (Baltimore). 2016;95:e3300.CrossRef
38.
Wang N, Xue P, Wu X, Ma J, Wang Y, Li Y. Role of sclerostin and dkk1 in bone remodeling in type 2 diabetic patients. Endocr Res. 2018;43:29–38.CrossRef
39.
Gifre L, Ruiz-Gaspa S, Monegal A, Nomdedeu B, Filella X, Guanabens N, Peris P. Effect of glucocorticoid treatment on Wnt signalling antagonists (sclerostin and Dkk-1) and their relationship with bone turnover. Bone. 2013;57:272–6.CrossRef
40.
Balemans W, Piters E, Cleiren E, Ai M, Van Wesenbeeck L, Warman ML, Van Hul W. The binding between sclerostin and LRP5 is altered by DKK1 and by high-bone mass LRP5 mutations. Calcif Tissue Int. 2008;82:445–53.CrossRef
41.
Florio M, Gunasekaran K, Stolina M, Li X, Liu L, Tipton B, Salimi-Moosavi H, Asuncion FJ, Li C, Sun B, et al. A bispecific antibody targeting sclerostin and DKK-1 promotes bone mass accrual and fracture repair. Nat Commun. 2016;7:11505.CrossRef
42.
Isakova T, Cai X, Lee J, Katz R, Cauley JA, Fried LF, Hoofnagle AN, Satterfield S, Harris TB, Shlipak MG, et al. Associations of FGF23 with change in bone mineral density and fracture risk in older individuals. J Bone Miner Res. 2016;31:742–8.CrossRef
43.
Marsell R, Mirza MA, Mallmin H, Karlsson M, Mellstrom D, Orwoll E, Ohlsson C, Jonsson KB, Ljunggren O, Larsson TE. Relation between fibroblast growth factor-23, body weight and bone mineral density in elderly men. Osteoporos Int. 2009;20:1167–73.CrossRef
44.
Imel EA, Liu Z, McQueen AK, Acton D, Acton A, Padgett LR, Peacock M, Econs MJ. Serum fibroblast growth factor 23, serum iron and bone mineral density in premenopausal women. Bone. 2016;86:98–105.CrossRef
45.
Desjardins L, Liabeuf S, Renard C, Lenglet A, Lemke HD, Choukroun G, Drueke TB, Massy ZA. FGF23 is independently associated with vascular calcification but not bone mineral density in patients at various CKD stages. Osteoporos Int. 2012;23:2017–25.CrossRef
46.
Urena Torres P, Friedlander G, de Vernejoul MC, Silve C, Prie D. Bone mass does not correlate with the serum fibroblast growth factor 23 in hemodialysis patients. Kidney Int. 2008;73:102–7.CrossRef
47.
Hlaing TT, Compston JE. Biochemical markers of bone turnover - uses and limitations. Ann Clin Biochem. 2014;51:189–202.CrossRef
48.
Okuno S, Inaba M, Kitatani K, Ishimura E, Yamakawa T, Nishizawa Y. Serum levels of C-terminal telopeptide of type I collagen: a useful new marker of cortical bone loss in hemodialysis patients. Osteoporos Int. 2005;16:501–9.CrossRef
49.
Negri AL, Barone R, Quiroga MA, Bravo M, Marino A, Fradinger E, Bogado CE, Zanchetta JR. Bone mineral density: serum markers of bone turnover and their relationships in peritoneal dialysis. Perit Dial Int. 2004;24:163–8.PubMed
50.
Reichel H, Roth HJ, Schmidt-Gayk H. Evaluation of serum beta-carboxy-terminal cross-linking telopeptide of type I collagen as marker of bone resorption in chronic hemodialysis patients. Nephron Clinical practice. 2004;98:c112–8.CrossRef
51.
Tsuchida T, Ishimura E, Miki T, Matsumoto N, Naka H, Jono S, Inaba M, Nishizawa Y. The clinical significance of serum osteocalcin and N-terminal propeptide of type I collagen in predialysis patients with chronic renal failure. Osteoporos Int. 2005;16:172–9.CrossRef
52.
Hamano T, Tomida K, Mikami S, Matsui I, Fujii N, Imai E, Rakugi H, Isaka Y. Usefulness of bone resorption markers in hemodialysis patients. Bone. 2009;45(Suppl 1):S19–25.CrossRef
53.
Drinka PJ, DeSmet AA, Bauwens SF, Rogot A. The effect of overlying calcification on lumbar bone densitometry. Calcif Tissue Int. 1992;50:507–10.CrossRef
54.
Cherney DD, Laymon MS, McNitt A, Yuly S. A study on the influence of calcified intervertebral disk and aorta in determining bone mineral density. J Clin Densitom. 2002;5:193–8.CrossRef
55.
Toussaint ND, Lau KK, Strauss BJ, Polkinghorne KR, Kerr PG. Associations between vascular calcification, arterial stiffness and bone mineral density in chronic kidney disease. Nephrol Dial Transplant. 2008;23:586–93.CrossRef
56.
Nanjo Y, Morio Y, Nagashima H, Hagino H, Teshima R. Correlation between bone mineral density and intervertebral disk degeneration in pre- and postmenopausal women. J Bone Miner Metab. 2003;21:22–7.CrossRef
57.
Delanaye P, Paquot F, Bouquegneau A, Blocki F, Krzesinski JM, Evenepoel P, Pottel H, Cavalier E. Sclerostin and chronic kidney disease: the assay impacts what we (thought to) know. Nephrol Dial Transplant. 2018;33:1404–10.CrossRef
Metadata
Title
Serum sclerostin levels are positively related to bone mineral density in peritoneal dialysis patients: a cross-sectional study
Authors
Te-Hui Kuo
Wei-Hung Lin
Jo-Yen Chao
An-Bang Wu
Chin-Chung Tseng
Yu-Tzu Chang
Hung-Hsiang Liou
Ming-Cheng Wang
Publication date
01-12-2019
Publisher
BioMed Central
Published in
BMC Nephrology / Issue 1/2019
Electronic ISSN: 1471-2369
DOI
https://doi.org/10.1186/s12882-019-1452-5

Other articles of this Issue 1/2019

BMC Nephrology 1/2019 Go to the issue

Research article

Health related quality of life of dialysis patients in Malaysia: Haemodialysis versus continuous ambulatory peritoneal dialysis

Research article

Derivation and validation of a prediction score for acute kidney injury secondary to acute myocardial infarction in Chinese patients

Research article

Effect of antiplatelet therapy on cardiovascular and kidney outcomes in patients with chronic kidney disease: a systematic review and meta-analysis

Case report

IgG4-related kidney disease (IgG4-RKD) with membranous nephropathy as its initial manifestation: report of one case and literature review

Case report

A case report of recurrent membranoproliferative glomerulonephritis after kidney transplantation due to ventriculoatrial shunt infection

Research article

Outcome of kidney function after ischaemic and zero-ischaemic laparoscopic and open nephron-sparing surgery for renal cell cancer

ACC 2024 Congress Coverage

Heart Failure Video

Year in Review: Heart failure and cardiomyopathies

Watch now

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits