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Lower bone turnover and relative bone deficits in men with metabolic syndrome: a matter of insulin sensitivity? The European Male Ageing Study

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Abstract

Summary

We examined cross-sectional associations of metabolic syndrome and its components with male bone turnover, density and structure. Greater bone mass in men with metabolic syndrome was related to their greater body mass, whereas hyperglycaemia, hypertriglyceridaemia or impaired insulin sensitivity were associated with lower bone turnover and relative bone mass deficits.

Introduction

Metabolic syndrome (MetS) has been associated with lower bone turnover and relative bone mass or strength deficits (i.e. not proportionate to body mass index, BMI), but the relative contributions of MetS components related to insulin sensitivity or obesity to male bone health remain unclear.

Methods

We determined cross-sectional associations of MetS, its components and insulin sensitivity (by homeostatic model assessment-insulin sensitivity (HOMA-S)) using linear regression models adjusted for age, centre, smoking, alcohol, and BMI. Bone turnover markers and heel broadband ultrasound attenuation (BUA) were measured in 3129 men aged 40–79. Two centres measured total hip, femoral neck, and lumbar spine areal bone mineral density (aBMD, n = 527) and performed radius peripheral quantitative computed tomography (pQCT, n = 595).

Results

MetS was present in 975 men (31.2 %). Men with MetS had lower β C-terminal cross-linked telopeptide (β-CTX), N-terminal propeptide of type I procollagen (PINP) and osteocalcin (P < 0.0001) and higher total hip, femoral neck, and lumbar spine aBMD (P ≤ 0.03). Among MetS components, only hypertriglyceridaemia and hyperglycaemia were independently associated with PINP and β-CTX. Hyperglycaemia was negatively associated with BUA, hypertriglyceridaemia with hip aBMD and radius cross-sectional area (CSA) and stress–strain index. HOMA-S was similarly associated with PINP and β-CTX, BUA, and radius CSA in BMI-adjusted models.

Conclusions

Men with MetS have higher aBMD in association with their greater body mass, while their lower bone turnover and relative deficits in heel BUA and radius CSA are mainly related to correlates of insulin sensitivity. Our findings support the hypothesis that underlying metabolic complications may be involved in the bone’s failure to adapt to increasing bodily loads in men with MetS.

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Author information

Author notes

    Authors and Affiliations

    1. Gerontology and Geriatrics, Department of Clinical and Experimental Medicine, KU Leuven, Herestraat 49, PO box 7003, 3000, Leuven, Belgium

      M. R. Laurent & E. Gielen

    2. Molecular Endocrinology Laboratory, Department of Cellular and Molecular Medicine, KU Leuven, Herestraat 49, PO box 901, 3000, Leuven, Belgium

      M. R. Laurent, L. Antonio & F. Claessens

    3. Center for Metabolic Bone Diseases, University Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium

      M. R. Laurent & E. Gielen

    4. Arthritis Research UK Centre for Epidemiology, Institute of Inflammation and Repair, Faculty of Medical and Human Sciences, Manchester Academic Health Science Centre, University of Manchester, Stopford Building, Oxford Road, Manchester, M13 9PT, UK

      M. J. Cook, S. R. Pye & T. W. O’Neill

    5. Elsie Widdowson Laboratory, Medical Research Council Human Nutrition Research, 120 Fulbourn Road, Cambridge, CB1 9NL, UK

      K. A. Ward

    6. Clinical and Experimental Endocrinology, Department of Clinical and Experimental Medicine, KU Leuven, Herestraat 49, PO box 902, 3000, Leuven, Belgium

      L. Antonio, B. Decallonne & D. Vanderschueren

    7. Radiology Department, and Manchester Academic Health Science Centre, Manchester Royal Infirmary, Central Manchester University Hospitals NHS Foundation Trust and University of Manchester, 46 Grafton Street, Manchester, M13 9NT, UK

      J. E. Adams

    8. Department of Obstetrics, Gynecology and Andrology, Albert Szent-György Medical University, Semmelweis u. 1, 6725, Szeged, Hungary

      G. Bartfai

    9. Department of Medicine, Santiago de Compostela University, Complejo Hospitalario Universitario de Santiago, CIBER de Fisiopatología Obesidad y Nutricion, Instituto Salud Carlos III, Travesía de Choupana s/n, 15706, Santiago de Compostela, Spain

      F. F. Casanueva

    10. Andrology Unit, Department of Clinical Physiopathology, University of Florence, Viale Pieraccini 6, 50139, Florence, Italy

      G. Forti

    11. Department of Urology, Scanian Andrology Centre, Malmö University Hospital, University of Lund, Jan Waldenströms gata 35, 20502, Malmö, Sweden

      A. Giwercman

    12. Institute of Reproductive and Developmental Biology, Department of Surgery and Cancer, Imperial College London, Hammersmith Campus, London, W12 0HS, UK

      I. T. Huhtaniemi

    13. Department of Andrology and Reproductive Endocrinology, Medical University of Lodz, Pomorska 45/47, Śródmieście, 90-406, Łódź, Poland

      K. Kula

    14. Department of Human Nutrition, School of Medicine, University of Glasgow, Glasgow Royal Infirmary, Glasgow, G31 2ER, Scotland, UK

      M. E. J. Lean

    15. Cathie Marsh Institute for Social Research, School of Social Sciences, University of Manchester, Humanities Bridgeford Street-G17, Manchester, M13 9PL, UK

      D. M. Lee

    16. School of Community Based Medicine, University of Manchester, Salford Royal NHS Trust, Stott Lane, Salford, M6 8HD, UK

      N. Pendleton

    17. Andrology Unit, United Laboratories of Tartu University Clinics, L. Puusepa 1a, Tartu, Estonia

      M. Punab

    18. Developmental and Regenerative Biomedicine Research Group, Andrology Research Unit, Manchester Academic Health Science Centre, Manchester Royal Infirmary, University of Manchester, Grafton Street, Manchester, M13 9WL, UK

      F. C. W. Wu

    19. NIHR Manchester Musculoskeletal Biomedical Research Unit, 29 Grafton Street, Manchester, M13 9WU, UK

      T. W. O’Neill

    Authors
    1. M. R. Laurent
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    2. M. J. Cook
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    3. E. Gielen
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    4. K. A. Ward
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    5. L. Antonio
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    6. J. E. Adams
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    7. B. Decallonne
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    8. G. Bartfai
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    9. F. F. Casanueva
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    10. G. Forti
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    11. A. Giwercman
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    12. I. T. Huhtaniemi
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    13. K. Kula
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    14. M. E. J. Lean
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    15. D. M. Lee
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    17. M. Punab
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    19. F. C. W. Wu
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    20. D. Vanderschueren
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    22. T. W. O’Neill
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    Consortia

    EMAS Group

    Corresponding author

    Correspondence to M. R. Laurent.

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    Funding

    The European Male Ageing Study was funded by the Commission of the European Communities Fifth Framework Programme, Quality of Life and Management of Living Resources, Grant QLK6-CT-2001-00258, by Arthritis Research UK, by the Research Foundation Flanders grants G.0171.03 and G.0854.13N and KU Leuven grant GOA/15/017. This report includes independent research supported by the UK National Institute for Health Research Biomedical Research Unit Funding Scheme. The views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health. The work of K.A.W. was conducted within the core programme of the MRC Nutrition and Bone Health Group at MRC Human Nutrition Research, funded by the UK Medical Research Council (Programme number U105960371). M.R.L. is a PhD Fellow of the Research Foundation Flanders. D.V. is a senior clinical investigator supported by the Clinical Research Fund of the University Hospitals Leuven, Belgium.

    Conflicts of interest

    All authors have completed the ICMJE uniform disclosure form at http://www.icmje.org/coi_disclosure.pdf and declare the following: Dr. Laurent has received lecture fees from Flanders’ Agricultural Marketing Board (VLAM) and reports consultancy for Novartis and Alexion. Dr. Huhtaniemi has consulted for and/or received research funding from Ferring, Novartis and Takeda. Dr. Wu has consulted for Besins Healthcare and Repros Inc., and received research funding from Besins Healthcare and Bayer Schering. All other authors declare that they have no conflict of interest.

    Additional information

    The European Male Ageing Study (EMAS) Group: The principal investigator of EMAS is Prof. F. C. W. Wu. Participating centres: Florence (Gianni Forti, Luisa Petrone, Giovanni Corona); Leuven (Dirk Vanderschueren, Steven Boonen (deceased), Herman Borghs); Łódź (Krzysztof Kula, Jolanta Slowikowska-Hilczer, Renata Walczak-Jedrzejowska); London (Ilpo Huhtaniemi); Malmö (Aleksander Giwercman); Manchester (Frederick C.W. Wu, Alan J. Silman, Terence W. O’Neill, Joseph D. Finn, Philip Steer, Abdelouahid Tajar, David M. Lee, Stephen R. Pye); Santiago de Compostela (Felipe Casanueva, Mary Lage, Ana I Castro); Szeged (György Bartfai, Imre Földesi, Imre Fejes); Tartu (Margus Punab, Paul Korrovitz); and Turku (Min Jiang)

    M. R. Laurent, M. J. Cook, S. R. Pye and T. W. O’Neill contributed equally to this work.

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    Laurent, M.R., Cook, M.J., Gielen, E. et al. Lower bone turnover and relative bone deficits in men with metabolic syndrome: a matter of insulin sensitivity? The European Male Ageing Study. Osteoporos Int 27, 3227–3237 (2016). https://doi.org/10.1007/s00198-016-3656-x

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