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



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.



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).



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 spineaBMD (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 hipaBMD 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.



Men with MetS have higheraBMD 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.
Gerontology and Geriatrics, Department of Clinical and Experimental Medicine, KU Leuven, Herestraat 49, PO box 7003, 3000, Leuven, Belgium. michael.laurent@med.kuleuven.be.|Molecular Endocrinology Laboratory, Department of Cellular and Molecular Medicine, KU Leuven, Herestraat 49, PO box 901, 3000, Leuven, Belgium. michael.laurent@med.kuleuven.be.|Center for Metabolic Bone Diseases, University Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium. michael.laurent@med.kuleuven.be.
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Laurent
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.
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Cook
Gerontology and Geriatrics, Department of Clinical and Experimental Medicine, KU Leuven, Herestraat 49, PO box 7003, 3000, Leuven, Belgium.|Center for Metabolic Bone Diseases, University Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium.
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Gielen
Elsie Widdowson Laboratory, Medical Research Council Human Nutrition Research, 120 Fulbourn Road, Cambridge, CB1 9NL, UK.
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Ward
Molecular Endocrinology Laboratory, Department of Cellular and Molecular Medicine, KU Leuven, Herestraat 49, PO box 901, 3000, Leuven, Belgium.|Clinical and Experimental Endocrinology, Department of Clinical and Experimental Medicine, KU Leuven, Herestraat 49, PO box 902, 3000, Leuven, Belgium.
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Antonio
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.
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Adams
Clinical and Experimental Endocrinology, Department of Clinical and Experimental Medicine, KU Leuven, Herestraat 49, PO box 902, 3000, Leuven, Belgium.
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Decallonne
Department of Obstetrics, Gynecology and Andrology, Albert Szent-György Medical University, Semmelweis u. 1, 6725, Szeged, Hungary.
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Bartfai
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.
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Casanueva
Andrology Unit, Department of Clinical Physiopathology, University of Florence, Viale Pieraccini 6, 50139, Florence, Italy.
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Forti
Department of Urology, Scanian Andrology Centre, Malmö University Hospital, University of Lund, Jan Waldenströms gata 35, 20502, Malmö, Sweden.
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Giwercman
Institute of Reproductive and Developmental Biology, Department of Surgery and Cancer, Imperial College London, Hammersmith Campus, London, W12 0HS, UK.
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Huhtaniemi
Department of Andrology and Reproductive Endocrinology, Medical University of Lodz, Pomorska 45/47, Śródmieście, 90-406, Łódź, Poland.
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Kula
Department of Human Nutrition, School of Medicine, University of Glasgow, Glasgow Royal Infirmary, Glasgow, G31 2ER, Scotland, UK.
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Lean
Cathie Marsh Institute for Social Research, School of Social Sciences, University of Manchester, Humanities Bridgeford Street-G17, Manchester, M13 9PL, UK.
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Lee
School of Community Based Medicine, University of Manchester, Salford Royal NHS Trust, Stott Lane, Salford, M6 8HD, UK.
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Pendleton
Andrology Unit, United Laboratories of Tartu University Clinics, L. Puusepa 1a, Tartu, Estonia.
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Punab
Molecular Endocrinology Laboratory, Department of Cellular and Molecular Medicine, KU Leuven, Herestraat 49, PO box 901, 3000, Leuven, Belgium.
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Claessens
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.
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Wu
Clinical and Experimental Endocrinology, Department of Clinical and Experimental Medicine, KU Leuven, Herestraat 49, PO box 902, 3000, Leuven, Belgium.
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Vanderschueren
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.
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Pye
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.|NIHR Manchester Musculoskeletal Biomedical Research Unit, 29 Grafton Street, Manchester, M13 9WU, UK.
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O'Neill
D000328:Adult; D000368:Aged; D000375:Aging; D015519:Bone Density; D016723:Bone Remodeling; D001842:Bone and Bones / Q000473:pathology*; D003430:Cross-Sectional Studies; D006801:Humans; D006943:Hyperglycemia / Q000150:complications*; D007333:Insulin Resistance; D008297:Male; D024821:Metabolic Syndrome / Q000150:complications*; D008875:Middle Aged
Bone mineral density; Bone turnover; Male; Metabolic syndrome; Obesity; Peripheral quantitative computed tomography