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

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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.

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Most cited references 47

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WNT signaling in bone homeostasis and disease: from human mutations to treatments.

Roland Baron, Michaela Kneissel (2013)

Low bone mass and strength lead to fragility fractures, for example, in elderly individuals affected by osteoporosis or children with osteogenesis imperfecta. A decade ago, rare human mutations affecting bone negatively (osteoporosis-pseudoglioma syndrome) or positively (high-bone mass phenotype, sclerosteosis and Van Buchem disease) have been identified and found to all reside in components of the canonical WNT signaling machinery. Mouse genetics confirmed the importance of canonical Wnt signaling in the regulation of bone homeostasis, with activation of the pathway leading to increased, and inhibition leading to decreased, bone mass and strength. The importance of WNT signaling for bone has also been highlighted since then in the general population in numerous genome-wide association studies. The pathway is now the target for therapeutic intervention to restore bone strength in millions of patients at risk for fracture. This paper reviews our current understanding of the mechanisms by which WNT signalng regulates bone homeostasis.

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Regulation of bone mass by Wnt signaling.

Venkatesh Krishnan, Henry Bryant, Ormond A Macdougald (2006)

Wnt proteins are a family of secreted proteins that regulate many aspects of cell growth, differentiation, function, and death. Considerable progress has been made in our understanding of the molecular links between Wnt signaling and bone development and remodeling since initial reports that mutations in the Wnt coreceptor low-density lipoprotein receptor-related protein 5 (LRP5) are causally linked to alterations in human bone mass. Of the pathways activated by Wnts, it is signaling through the canonical (i.e., Wnt/beta-catenin) pathway that increases bone mass through a number of mechanisms including renewal of stem cells, stimulation of preosteoblast replication, induction of osteoblastogenesis, and inhibition of osteoblast and osteocyte apoptosis. This pathway is an enticing target for developing drugs to battle skeletal diseases as Wnt/beta-catenin signaling is composed of a series of molecular interactions that offer potential places for pharmacological intervention. In considering opportunities for anabolic drug discovery in this area, one must consider multiple factors, including (a) the roles of Wnt signaling for development, remodeling, and pathology of bone; (b) how pharmacological interventions that target this pathway may specifically treat osteoporosis and other aspects of skeletal health; and (c) whether the targets within this pathway are amenable to drug intervention. In this Review we discuss the current understanding of this pathway in terms of bone biology and assess whether targeting this pathway might yield novel therapeutics to treat typical bone disorders.

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Increased incidence of hip fractures in dialysis patients with low serum parathyroid hormone.

M. Coco, H. Rush (2000)

To study the complications of renal osteodystrophy in patients with end-stage renal disease, we reviewed the incidence of hip fractures in our outpatient dialysis population from 1988 to 1998. One thousand two hundred seventy-two patients were treated for a total of 4,039 patient-years; 56 hip fractures were documented during this period. The incidence of hip fractures was many times greater in the dialysis patients than in the general population in each of the age-, race-, and sex-matched subgroups. The 1-year mortality rate from the hip fracture event was nearly two and a half times greater in the dialysis patients compared with the general population. The incidence of hip fractures in the first half of the decade was similar to that observed in the second half. When parathyroid hormone (PTH) levels were evaluated, we determined that patients with lower serum PTH levels were more likely to sustain a hip fracture than patients with higher PTH levels (P: < 0.006). In addition, we determined that patients with lower PTH levels had an earlier mortality than patients with higher PTH levels (P: < 0.03). We conclude that despite more aggressive therapy directed toward bone health in our dialysis patients in recent years, the incidence of hip fractures and their devastating morbidity and mortality remained unchanged over the past decade. Lower PTH levels may predispose to earlier mortality.

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Author and article information

Contributors

Te-Hui Kuo: tk2026@gmail.com

Wei-Hung Lin: dindonwhlin@hotmail.com

Jo-Yen Chao: joyenchao@gmail.com

An-Bang Wu: anbang@mail.ncku.edu.tw

Chin-Chung Tseng: chinchun@mail.ncku.edu.tw

Yu-Tzu Chang: kangxiemperor@gmail.com

Hung-Hsiang Liou: +886-2-22064612 , hh258527@ms23.hinet.net

Ming-Cheng Wang: +886-6-2353535-2594 , wangmc@mail.ncku.edu.tw

Journal

Journal ID (nlm-ta): BMC Nephrol

Journal ID (iso-abbrev): BMC Nephrol

Title: BMC Nephrology

Publisher: BioMed Central (London )

ISSN (Electronic): 1471-2369

Publication date (Electronic): 17 July 2019

Publication date PMC-release: 17 July 2019

Publication date Collection: 2019

Volume: 20

Electronic Location Identifier: 266

Affiliations

[1 ]ISNI 0000 0004 0639 0054, GRID grid.412040.3, Division of Nephrology, Department of Internal Medicine, , National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, ; 138 Shengli Rd., North Dist, Tainan, 704 Taiwan

[2 ]ISNI 0000 0004 0532 3255, GRID grid.64523.36, Department and Graduate Institute of Public Health, College of Medicine, , National Cheng Kung University, ; Tainan, Taiwan

[3 ]ISNI 0000 0004 0639 0054, GRID grid.412040.3, Department of Internal Medicine, , National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, ; Tainan, Taiwan

[4 ]ISNI 0000 0004 0532 3255, GRID grid.64523.36, Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, ; Tainan, Taiwan

[5 ]Division of Nephrology, Department of Internal Medicine, Hsin-Jen Hospital, 395 Zhongzheng Rd., Xinzhuang Dist, New Taipei City, 242 Taiwan

Article

Publisher ID: 1452

DOI: 10.1186/s12882-019-1452-5

PMC ID: 6637583

PubMed ID: 31315601

SO-VID: 3f8f59fc-57bc-4712-b0d2-9ec7b357b700

License:

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

History

Date received : 18 December 2018

Date accepted : 3 July 2019

Funding

Funded by: FundRef http://dx.doi.org/10.13039/501100004844, National Cheng Kung University Hospital;

Award ID: 10406030, 10505030, 10704006

Award Recipient : Te-Hui Kuo

Custom metadata

ScienceOpen disciplines: Nephrology

Keywords: sclerostin,bone mineral density,peritoneal dialysis,chronic kidney disease–mineral and bone disorder (ckd–mbd),wnt pathway

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ScienceOpen disciplines: Nephrology

Keywords: sclerostin, bone mineral density, peritoneal dialysis, chronic kidney disease–mineral and bone disorder (ckd–mbd), wnt pathway

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

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Karger: Nephrology

Most cited references 47

WNT signaling in bone homeostasis and disease: from human mutations to treatments.

Regulation of bone mass by Wnt signaling.

Increased incidence of hip fractures in dialysis patients with low serum parathyroid hormone.

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