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      Association of Serum Osteoprotegerin Levels with Bone Loss in Chronic Kidney Disease: Insights from the KNOW-CKD Study

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          Abstract

          Osteoprotegerin, a potent osteoclast activation inhibitor, decreases bone resorption and positively affects bone mineral density. This study examined the association between serum osteoprotegerin levels and bone loss in patients with chronic kidney disease, a condition associated with increased risk of mineral and bone disorders. The bone mineral densities of the lumbar spine, total hip, and femur neck were assessed by dual-energy X-ray absorptiometry; serum osteoprotegerin levels were measured at baseline for 1,423 patients enrolled in the prospective KoreaN cohort study for Outcome in patients With Chronic Kidney Disease (KNOW-CKD). Patients aged ≥50 years and with a T-score ≤ –2.5 were diagnosed as having osteoporosis. Multivariable linear regression analysis indicated independent association between serum osteoprotegerin levels and decreased bone mineral density in the lumbar spine (B: –0.489, 95% confidence interval [CI]: –0.883 to –0.095, P = 0.015), and total hip (B: –0.349, 95% CI: –0.672 to –0.027, P = 0.027). However, bone mineral density of the femur neck was not associated with serum osteoprotegerin levels in women. After adjustments, no independent association was found between serum osteoprotegerin levels and bone mineral density in men. In multivariable logistic regression analysis, serum osteoprotegerin levels were associated with increased risk of osteoporosis in women (odds ratio [OR]: 4.72, 95% CI: 1.35 to 16.52, P = 0.015), but not in men (OR: 0.21; 95% CI: 0.04 to 1.31, P = 0.095). To summarize, in female patients with chronic kidney disease, increased serum osteoprotegerin levels were independently associated with decreased bone mineral density in the lumbar spine and total hip, and with increased risk of osteoporosis. Therefore, the measurement of serum osteoprotegerin concentration might be useful as a surrogate marker for determining bone loss in patients with chronic kidney disease, especially for women, although not so much for men.

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          Estimating prevalence of osteoporosis: examples from industrialized countries.

          S Wade, Lucia C Strader, L Fitzpatrick … (2014)
          In nine industrialized countries in North America, Europe, Japan, and Australia, country-specific osteoporosis prevalence (estimated from published data) at the total hip or hip/spine ranged from 9 to 38 % for women and 1 to 8 % for men. In these countries, osteoporosis affects up to 49 million individuals.
          Article 0 comments Cited 126 times – based on 0 reviews     Review now
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            Osteoporosis and sarcopenia in older age.

            M. Edwards, E. Dennison, A Aihie Sayer … (2015)
            Osteoporosis and sarcopenia are common in older age and associated with significant morbidity and mortality. Consequently, they are both attended by a considerable socioeconomic burden. Osteoporosis was defined by the World Health Organisation (WHO) in 1994 as a bone mineral density of less than 2.5 standard deviations below the sex-specific young adult mean and this characterisation has been adopted globally. Subsequently, a further step forward was taken when bone mineral density was incorporated into fracture risk prediction algorithms, such as the Fracture Risk Assessment Tool (FRAX®) also developed by the WHO. In contrast, for sarcopenia there have been several diagnostic criteria suggested, initially relating to low muscle mass alone and more recently low muscle mass and muscle function. However, none of these have been universally accepted. This has led to difficulties in accurately delineating the burden of disease, exploring geographic differences, and recruiting appropriate subjects to clinical trials. There is also uncertainty about how improvement in sarcopenia should be measured in pharmaceutical trials. Reasons for these difficulties include the number of facets of muscle health available, e.g. mass, strength, function, and performance, and the various clinical outcomes to which sarcopenia can be related such as falls, fracture, disability and premature mortality. It is imperative that a universal definition of sarcopenia is reached soon to facilitate greater progress in research into this debilitating condition. This article is part of a Special Issue entitled "Muscle Bone Interactions".
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              Regulation of vascular calcification by osteoclast regulatory factors RANKL and osteoprotegerin.

              Shaun P. Collin (2004)
              Vascular calcification often occurs with advancing age, atherosclerosis, various metabolic disorders such as diabetes mellitus and end-stage renal disease, or in rare genetic diseases, leading to serious clinical consequences. Such mineralization can occur at various sites (cardiac valves, arterial intima or media, capillaries), involve localized or diffuse widespread calcification, and result from numerous causes that provoke active inflammatory and osteogenic processes or disordered mineral homeostasis. Although valuable research has defined many key factors and cell types involved, surprising new insights continue to arise that deepen our understanding and suggest novel research directions or strategies for clinical intervention in calcific vasculopathies. One emerging area in vascular biology involves the RANKL/RANK/OPG system, molecules of the tumor necrosis factor-related family recently discovered to be critical regulators of immune and skeletal biology. Evidence is accumulating that such signals may be expressed, regulated, and function in vascular physiology and pathology in unique ways to promote endothelial cell survival, angiogenesis, monocyte or endothelial cell recruitment, and smooth muscle cell osteogenesis and calcification. Concerted research efforts are greatly needed to understand these potential roles, clarify whether RANKL (receptor activator of nuclear factor kappaB ligand) promotes and osteoprotegerin (OPG) protects against vascular calcification, define how OPG genetic polymorphisms relate to cardiovascular disease, and learn whether elevated serum OPG levels reflect endothelial dysfunction in patients. Overall, the RANKL/RANK/OPG system may mediate important and complex links between the vascular, skeletal, and immune systems. Thus, these molecules may play a central role in regulating the development of vascular calcification coincident with declines in skeletal mineralization with age, osteoporosis, or disease.
              Article 0 comments Cited 106 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Hideharu Abe: Role: Editor
                Journal
                Journal ID (nlm-ta): PLoS One
                Journal ID (iso-abbrev): PLoS ONE
                Journal ID (publisher-id): plos
                Journal ID (pmc): plosone
                Title: PLoS ONE
                Publisher: Public Library of Science (San Francisco, CA USA )
                ISSN (Electronic): 1932-6203
                Publication date (Electronic): 17 November 2016
                Publication date Collection: 2016
                Volume: 11
                Issue: 11
                Electronic Location Identifier: e0166792
                Affiliations
                [1 ]Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea
                [2 ]Depatment of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
                [3 ]Medical Research Collaborating Center, Seoul National University Hospital and Seoul National University College of Medicine, Seoul, Korea
                [4 ]Department of Internal Medicine, Seoul National University, Seoul, Korea
                Tokushima University Graduate School, JAPAN
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                • Conceptualization: CSK SWK.

                • Formal analysis: CSK.

                • Funding acquisition: CSK CA SWK.

                • Investigation: CSK EHB SKM.

                • Project administration: SWK CA.

                • Resources: SHH KHC JL DWC KHO CA.

                • Supervision: CSK SWK.

                • Writing – original draft: CSK.

                • Writing – review & editing: CSK EHB SKM SWK.

                ¶ Membership of the KNOW-CKD Investigator Group is provided in the Acknowledgments.

                Article
                Publisher ID: PONE-D-16-23870
                DOI: 10.1371/journal.pone.0166792
                PMC ID: 5113973
                PubMed ID: 27855207
                SO-VID: c5ecee09-e694-4652-b1b5-b5d7d9ec398f
                Copyright © © 2016 Kim et al
                License:

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                Date received : 14 June 2016
                Date accepted : 3 November 2016
                Page count
                Figures: 2, Tables: 3, Pages: 13
                Funding
                Funded by: Research of Korea Centers for Disease Control and Prevention
                Award ID: 2013E3301600
                Award Recipient :
                Funded by: the Korea Health Industry Development Institute (KHIDI)
                Award ID: HI14C2084
                Award Recipient :
                Funded by: the National Research Foundation of Korea (NRF)
                Award ID: 2016R1A2B4007870
                Award Recipient :
                Funded by: the National Research Foundation of Korea (NRF)
                Award ID: 2015R1C1A1A01051769
                Award Recipient :
                Funded by: Chonnam National University Hospital Institute for Biomedical Science
                Award ID: CRI14008-1
                Award Recipient :
                This research was supported by grants 2011E3300300, 2012E3301100 and 2013E3301600 from Research of Korea Centers for Disease Control and Prevention, by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI14C2084), by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and future Planning (2016R1A2B4007870) and by the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (2015R1C1A1A01051769), Chonnam National University Hospital Institute for Biomedical Science (CRI14008-1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Subject: Research Article
                Subject: Medicine and Health Sciences
                Subject: Nephrology
                Subject: Chronic Kidney Disease
                Subject: Medicine and Health Sciences
                Subject: Rheumatology
                Subject: Connective Tissue Diseases
                Subject: Osteoporosis
                Subject: Biology and Life Sciences
                Subject: Anatomy
                Subject: Bone
                Subject: Bone Density
                Subject: Medicine and Health Sciences
                Subject: Anatomy
                Subject: Bone
                Subject: Bone Density
                Subject: Biology and Life Sciences
                Subject: Anatomy
                Subject: Biological Tissue
                Subject: Connective Tissue
                Subject: Bone
                Subject: Bone Density
                Subject: Medicine and Health Sciences
                Subject: Anatomy
                Subject: Biological Tissue
                Subject: Connective Tissue
                Subject: Bone
                Subject: Bone Density
                Subject: Biology and Life Sciences
                Subject: Anatomy
                Subject: Musculoskeletal System
                Subject: Pelvis
                Subject: Hip
                Subject: Medicine and Health Sciences
                Subject: Anatomy
                Subject: Musculoskeletal System
                Subject: Pelvis
                Subject: Hip
                Subject: Biology and Life Sciences
                Subject: Physiology
                Subject: Physiological Processes
                Subject: Calcification
                Subject: Medicine and Health Sciences
                Subject: Physiology
                Subject: Physiological Processes
                Subject: Calcification
                Subject: Medicine and Health Sciences
                Subject: Vascular Medicine
                Subject: Coronary Heart Disease
                Subject: Medicine and Health Sciences
                Subject: Cardiology
                Subject: Coronary Heart Disease
                Subject: Research and Analysis Methods
                Subject: Research Facilities
                Subject: Research Laboratories
                Subject: Government Laboratories
                Subject: Physical sciences
                Subject: Chemistry
                Subject: Chemical compounds
                Subject: Organic compounds
                Subject: Vitamins
                Subject: Vitamin D
                Subject: Physical sciences
                Subject: Chemistry
                Subject: Organic chemistry
                Subject: Organic compounds
                Subject: Vitamins
                Subject: Vitamin D
                Custom metadata
                Data Availability All relevant data are within the paper and its Supporting Information files.

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