Bone Turnover Markers in Men and Women with Impaired Fasting Glucose and Diabetes

  • Kara L. Holloway-KewEmail author
  • Lelia L. F. De Abreu
  • Mark A. Kotowicz
  • Muhammad A. Sajjad
  • Julie A. Pasco
Original Research


Bone turnover markers (BTMs) are reduced in diabetes, but whether BTM changes occur in impaired fasting glucose (IFG) is unknown. The aim of this study was to investigate whether BTMs are altered in IFG and diabetes compared to normoglycaemia. For men and women (n = 2222) in the Geelong Osteoporosis Study, IFG was defined as fasting plasma glucose (FPG) 5.5–6.9 mmol/L and diabetes as FPG ≥ 7.0 mmol/L, use of antihyperglycemic medication and/or self-report. Serum C-terminal telopeptide (CTx) and procollagen type 1 N-terminal propeptide (P1NP) were measured. After natural log transformation to normalise the data, multivariable regression was used to examine the relationship between glycaemia status and bone turnover markers (BTMs), before and after adjusting for other confounders. There were 643 men and 682 women with normoglycaemia, 355 men and 391 women with IFG and 97 men and 54 women with diabetes. Men with IFG or diabetes had lower adjusted ln(CTx) and ln(P1NP) compared to normoglycaemia (all p < 0.05). Women with IFG or diabetes had lower adjusted ln(CTx) and ln(P1NP) (all p < 0.05) except for ln(P1NP) when comparing diabetes with normoglycaemia, which showed a trend for lower ln(P1NP) (p = 0.053). In both sexes, an age * glycaemia interaction term indicated between-group differences in BTMs diminished with increasing age. No other confounders were identified. Bone turnover was lower in those with either IFG or diabetes compared to normoglycaemia.


Diabetes mellitus Impaired fasting glucose Bone turnover markers 



The Geelong Osteoporosis Study was supported by the Victorian Health Promotion Foundation, National Health and Medical Research Council (NHMRC), Australia (Projects 251638 and 628582) and the Geelong Regional Medical Foundation; however, the funding bodies played no part in either the design or conduct of the study, the collection, management, analysis, and interpretation of the data or the preparation or review of the paper. LFFA and MAS are supported by Postgraduate Scholarships from Deakin University and KLH-K is supported by an Alfred Deakin Postdoctoral Research Fellowship. LLFA, KLH-K, MAS, MAK and JAP have no other conflict of interest to declare.

Compliance with Ethical Standards

Conflict of interest

Kara L. Holloway-Kew, Lelia L. F. De Abreu, Mark A. Kotowicz, Muhammad A. Sajjad, and Julie A. Pasco have no conflicts of interest.

Human and Animal Rights and Informed Consent

All subjects signed informed consent. Ethical approval was obtained from the Barwon Health, Human Research Ethics Committee (ID 92/01 and ID 00/56).


  1. 1.
    International Diabetes Federation (2017) International Diabetes Federation - Facts and Figures. Accessed 23 Jan 2019
  2. 2.
    Evans TC, Capell P (2000) Diabetic nephropathy. Clin Diab 18:7Google Scholar
  3. 3.
    Perlman JA, Wolf PH, Ray R, Lieberknecht G (1988) Cardiovascular risk factors, premature heart disease, and all-cause mortality in a cohort of northern California women. Am J Obstet Gynecol 158:1568–1574CrossRefGoogle Scholar
  4. 4.
    Klein R, Klein BE, Moss SE, Cruickshanks KJ (1998) The wisconsin epidemiologic study of diabetic retinopathy: XVII. The 14-year incidence and progression of diabetic retinopathy and associated risk factors in type 1 diabetes. Ophthalmology 105:1801–1815CrossRefGoogle Scholar
  5. 5.
    de Abreu LLF, Holloway KL, Mohebbi M, Sajjad MA, Kotowicz MA, Pasco JA (2017) All-cause mortality risk in australian women with impaired fasting glucose and diabetes. J Diab Res 2017:8Google Scholar
  6. 6.
    Genuth S, Alberti KG, Bennett P, Buse J, Defronzo R, Kahn R, Kitzmiller J, Knowler WC, Lebovitz H, Lernmark A, Nathan D, Palmer J, Rizza R, Saudek C, Shaw J, Steffes M, Stern M, Tuomilehto J, Zimmet P (2003) Follow-up report on the diagnosis of diabetes mellitus. Diab Care 26:3160–3167CrossRefGoogle Scholar
  7. 7.
    de Abreu L, Holloway KL, Kotowicz MA, Pasco JA (2015) Dysglycaemia and other predictors for progression or regression from impaired fasting glucose to diabetes or normoglycaemia. J Diab Res 2015:373762Google Scholar
  8. 8.
    Sealand R, Razavi C, Adler RA (2013) Diabetes mellitus and osteoporosis. Curr Diab Rep 13:411–418CrossRefGoogle Scholar
  9. 9.
    Strotmeyer ES, Cauley JA, Schwartz AV, Nevitt MC, Resnick HE, Bauer DC, Tylavsky FA, de Rekeneire N, Harris TB, Newman AB (2005) Nontraumatic fracture risk with diabetes mellitus and impaired fasting glucose in older white and black adults: the health, aging, and body composition study. Arch Intern Med 165:1612–1617CrossRefGoogle Scholar
  10. 10.
    Gagnon C, Magliano DJ, Ebeling PR, Dunstan DW, Zimmet PZ, Shaw JE, Daly RM (2010) Association between hyperglycaemia and fracture risk in non-diabetic middle-aged and older Australians: a national, population-based prospective study (AusDiab). Osteoporos Int 21:2067–2074CrossRefGoogle Scholar
  11. 11.
    Starup-Linde J, Vestergaard P (2016) Biochemical bone turnover markers in diabetes mellitus—a systematic review. Bone 82:69–78CrossRefGoogle Scholar
  12. 12.
    Jackuliak P, Payer J (2014) Osteoporosis, fractures, and diabetes. Int J Endocrinol 2014:820615CrossRefGoogle Scholar
  13. 13.
    Hygum K, Starup-Linde J, Harsløf T, Vestergaard P, Langdahl BL (2017) Mechanisms in endocrinology: diabetes mellitus, a state of low bone turnover—a systematic review and meta-analysis. Eur J Endocrinol 176:R137–R157CrossRefGoogle Scholar
  14. 14.
    Starup-Linde J, Eriksen SA, Lykkeboe S, Handberg A, Vestergaard P (2014) Biochemical markers of bone turnover in diabetes patients—a meta-analysis, and a methodological study on the effects of glucose on bone markers. Osteoporos Int 25:1697–1708CrossRefGoogle Scholar
  15. 15.
    Lerchbaum E, Schwetz V, Nauck M, Volzke H, Wallaschofski H, Hannemann A (2015) Lower bone turnover markers in metabolic syndrome and diabetes: the population-based Study of Health in Pomerania. Nutr Metab Cardiovasc Dis 25:458–463CrossRefGoogle Scholar
  16. 16.
    Furst JR, Bandeira LC, Fan WW, Agarwal S, Nishiyama KK, McMahon DJ, Dworakowski E, Jiang H, Silverberg SJ, Rubin MR (2016) Advanced glycation endproducts and bone material strength in type 2 diabetes. J Clin Endocrinol Metab 101:2502–2510CrossRefGoogle Scholar
  17. 17.
    Reyes-García R, Rozas-Moreno P, López-Gallardo G, García-Martín A, Varsavsky M, Avilés-Perez MD, Muñoz-Torres M (2013) Serum levels of bone resorption markers are decreased in patients with type 2 diabetes. Acta Diabetol 50:47–52CrossRefGoogle Scholar
  18. 18.
    Mitchell A, Fall T, Melhus H, Wolk A, Michaëlsson K, Byberg L (2018) Type 2 diabetes in relation to hip bone density, area, and bone turnover in Swedish men and women: a cross-sectional study. Calcif Tissue Int 103:501–511CrossRefGoogle Scholar
  19. 19.
    Jiajue R, Jiang Y, Wang O, Li M, Xing X, Cui L, Yin J, Xu L, Xia W (2014) Suppressed bone turnover was associated with increased osteoporotic fracture risks in non-obese postmenopausal Chinese women with type 2 diabetes mellitus. Osteoporos Int 25:1999–2005CrossRefGoogle Scholar
  20. 20.
    Pasco JA, Nicholson GC, Kotowicz MA (2012) Cohort profile: Geelong osteoporosis study. Int J Epidemiol 41:1565–1575CrossRefGoogle Scholar
  21. 21.
    Jenkins N, Black M, Paul E, Pasco JA, Kotowicz MA, Schneider HG (2013) Age-related reference intervals for bone turnover markers from an Australian reference population. Bone 55:271–276CrossRefGoogle Scholar
  22. 22.
    Giles G, Ireland P (1996) Dietary questionnaire for epidemiological studies (version 2). The Cancer Council Victoria, MelbourneGoogle Scholar
  23. 23.
    Australian Institute of Health and Welfare (2019) Older people overview—Australian Institute of Health and WelfareGoogle Scholar
  24. 24.
    Holloway KL, De Abreu LLF, Hans D, Kotowicz MA, Sajjad MA, Hyde NK, Pasco JA (2018) Trabecular bone score in men and women with impaired fasting glucose and diabetes. Calcif Tissue Int 102:32–40CrossRefGoogle Scholar
  25. 25.
    de Abreu LLF, Holloway-Kew KL, Mohebbi M, Sajjad MA, Kotowicz MA, Pasco JA (2018) Fracture risk in women with dysglycaemia: assessing effects of baseline and time-varying risk factors. Calcif Tissue Int. Google Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Deakin UniversityGeelongAustralia
  2. 2.Department of Medicine–Western CampusThe University of MelbourneSt AlbansAustralia
  3. 3.Barwon HealthGeelongAustralia
  4. 4.Department of Epidemiology and Preventive MedicineMonash UniversityMelbourneAustralia

Personalised recommendations