Skip to main content

Advertisement

Log in

Fracture Risk in Women with Dysglycaemia: Assessing Effects of Baseline and Time-Varying Risk Factors

  • Original Research
  • Published:
Calcified Tissue International Aims and scope Submit manuscript

Abstract

Although individuals with diabetes appear to have a higher fracture risk compared to those without diabetes, fracture risk in impaired fasting glucose (IFG) has not been thoroughly explored. This study determined associations between glycaemia status and fracture risk. Women (n = 575, aged 50 + years) enrolled in the Geelong Osteoporosis Study, were followed from baseline (1993–1997), to date of first fracture, death or December 31, 2010, whichever occurred first (median 13.7 years, IQR 7.4–14.8). Hazard ratios (HRs) for any fracture (excluding fingers, toes, skull/face), as well as major osteoporotic fracture (MOF, clinical spine, hip, proximal humerus, wrist), in diabetes (n = 69), IFG (n = 250) and normoglycaemia (n = 256), were calculated using a Cox proportional hazards model. Normoglycaemia was set as the reference category. A Cox proportional hazards model with time-varying covariates was also used to assess change in baseline risk factors at the 10-year follow-up visit (2004–2008). During follow-up (6433 person-years), 162 women sustained any fracture and 104 had a MOF. Unadjusted fracture risk was higher in diabetes (HR 1.64; 95% CI 1.02–2.63) compared to normoglycaemia, but IFG and normoglycaemia had similar risk (HR 1.06; 95% CI 0.76–1.47). Age- and BMD-adjusted any-fracture risk in diabetes compared to normoglycaemia was greater (HR 1.59; 95% CI 0.98–2.58); IFG was similar to normoglycaemia (HR 1.01; 95% CI 0.72–1.41). For MOF, unadjusted and age- and BMD-adjusted fracture risk in IFG was similar to normoglycaemia HR 1.02; 95% CI 0.74–1.40 and HR 0.95; 95% CI 0.69–1.32, respectively, but diabetes was higher compared to normoglycaemia (unadjusted HR 1.64; 95% CI 1.04–2.60; adjusted HR 1.57; 95% CI 0.98–2.51). In the time-varying model, there was no difference between IFG in either the unadjusted or adjusted models, for both any fracture and MOF (p > 0.05). For diabetes, there was a significant difference between normoglycaemia in the adjusted model for any fracture (p = 0.046), but not for MOF (p = 0.103). An increased risk of fracture for women with diabetes was observed after accounting for time-varying risk factors. There was no difference in fracture risk detected for women with IFG.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Danaei G, Finucane MM, Lu Y, Singh GM, Cowan MJ, Paciorek CJ, Lin JK, Farzadfar F, Khang YH, Stevens GA, Rao M, Ali MK, Riley LM, Robinson CA, Ezzati M (2011) National, regional, and global trends in fasting plasma glucose and diabetes prevalence since 1980: systematic analysis of health examination surveys and epidemiological studies with 370 country-years and 2.7 million participants. Lancet 378:31–40

    Article  CAS  PubMed  Google Scholar 

  2. 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 Diabet Res 2015:373762

    Article  Google Scholar 

  3. 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. Diabet Care 26:3160–3167

    Article  Google Scholar 

  4. Federation ID (2015) IDF diabetes atlas. In: IDF

  5. Australia D (2015) https://www.diabetesaustralia.com.au/diabetes-in-australia. In: Diabetes Australia

  6. Guariguata L, Whiting DR, Hambleton I, Beagley J, Linnenkamp U, Shaw JE (2014) Global estimates of diabetes prevalence for 2013 and projections for 2035. Diabet Res Clin Pract 103:137–149

    Article  CAS  Google Scholar 

  7. Evans TC, Capell P (2000) Diabetic nephropathy. Clin Diabet 18:7

    Google Scholar 

  8. 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 158:1568–1574

    Article  CAS  PubMed  Google Scholar 

  9. 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 105:1801–1815

    Article  CAS  PubMed  Google Scholar 

  10. Harris M, Eastman R, Cowie C (1993) Symptoms of sensory neuropathy in adults with NIDDM in the U.S. population. Diabet Care 16:1446–1452

    Article  CAS  Google Scholar 

  11. Schwartz AV, Sellmeyer DE, Ensrud KE, Cauley JA, Tabor HK, Schreiner PJ, Jamal SA, Black DM, Cummings SR (2001) Older women with diabetes have an increased risk of fracture: a prospective study. J Clin Endocrinol Metab 86:32–38

    Article  CAS  PubMed  Google Scholar 

  12. Munshi M, Grande L, Hayes M, Ayres D, Suhl E, Capelson R, Lin S, Milberg W, Weinger K (2006) Cognitive dysfunction is associated with poor diabetes control in older adults. Diabet Care 29:1794–1799

    Article  Google Scholar 

  13. Hung YC, Lin CC, Chen HJ, Chang MP, Huang KC, Chen YH, Chen CC (2017) Severe hypoglycemia and hip fracture in patients with type 2 diabetes: a nationwide population-based cohort study. Osteoporos Int 28:2053–2060

    Article  CAS  PubMed  Google Scholar 

  14. Trautner C, Haastert B, Giani G, Berger M (1996) Incidence of lower limb amputations and diabetes. Diabet Care 19:1006–1009

    Article  CAS  Google Scholar 

  15. Roglic G, Unwin N (2010) Mortality attributable to diabetes: estimates for the year 2010. Diabet Res Clin Pract 87:15–19

    Article  Google Scholar 

  16. Gu K, Cowie CC, Harris MI (1998) Mortality in adults with and without diabetes in a national cohort of the U.S. population, 1971–1993. Diabet Care 21:1138–1145

    Article  CAS  Google Scholar 

  17. 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 Diabet Res 2017:8

    Article  Google Scholar 

  18. Hanley DA, Brown JP, Tenenhouse A, Olszynski WP, Ioannidis G, Berger C, Prior JC, Pickard L, Murray TM, Anastassiades T, Kirkland S, Joyce C, Joseph L, Papaioannou A, Jackson SA, Poliquin S, Adachi JD (2003) Associations among disease conditions, bone mineral density, and prevalent vertebral deformities in men and women 50 years of age and older: cross-sectional results from the Canadian Multicentre Osteoporosis Study. J Bone Miner Res 18:784–790

    Article  CAS  PubMed  Google Scholar 

  19. de Liefde II, van der Klift M, de Laet CE, van Daele PL, Hofman A, Pols HA (2005) Bone mineral density and fracture risk in type-2 diabetes mellitus: the Rotterdam Study. Osteoporos Int 16:1713–1720

    Article  PubMed  Google Scholar 

  20. Christensen JO, Svendsen OL (1999) Bone mineral in pre- and postmenopausal women with insulin-dependent and non-insulin-dependent diabetes mellitus. Osteoporos Int 10:307–311

    Article  CAS  PubMed  Google Scholar 

  21. van Daele PL, Stolk RP, Burger H, Algra D, Grobbee DE, Hofman A, Birkenhager JC, Pols HA (1995) Bone density in non-insulin-dependent diabetes mellitus Rotterdam Study. Ann Intern Med 122:409–414

    Article  PubMed  Google Scholar 

  22. Lunt M, Masaryk P, Scheidt-Nave C, Nijs J, Poor G, Pols H, Falch JA, Hammermeister G, Reid DM, Benevolenskaya L, Weber K, Cannata J, O’Neill TW, Felsenberg D, Silman AJ, Reeve J (2001) The effects of lifestyle, dietary dairy intake and diabetes on bone density and vertebral deformity prevalence: the EVOS study. Osteoporos Int 12:688–698

    Article  CAS  PubMed  Google Scholar 

  23. Okuno Y, Nishizawa Y, Sekiya K, Hagiwara S, Miki T, Morii H (1991) Total and regional bone mineral content in patients with non-insulin dependent diabetes mellitus. J Nutr Sci Vitaminol 37:S43–S49

    Article  Google Scholar 

  24. Nilsson AG, Sundh D, Johansson L, Nilsson M, Mellstrom D, Rudang R, Zoulakis M, Wallander M, Darelid A, Lorentzon M (2016) Type 2 diabetes mellitus is associated with better bone microarchitecture but lower bone material strength and poorer physical function in elderly women: a population-based study. J Bone Miner Res 32(5):1062–1071

    Google Scholar 

  25. Sosa M, Dominguez M, Navarro MC, Segarra MC, Hernandez D, de Pablos P, Betancor P (1996) Bone mineral metabolism is normal in non-insulin-dependent diabetes mellitus. J Diabet Complications 10:201–205

    Article  CAS  Google Scholar 

  26. 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 165:1612–1617

    Article  PubMed  Google Scholar 

  27. 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 21:2067–2074

    Article  CAS  PubMed  Google Scholar 

  28. Pasco JA, Nicholson GC, Kotowicz MA (2012) Cohort profile: Geelong Osteoporosis Study. Int J Epidemiol 41:1565–1575

    Article  PubMed  Google Scholar 

  29. Pasco JA, Nicholson GC, Henry MJ, Kotowicz MA, Gaudry TM (1999) Identification of incident fractures: the Geelong Osteoporosis Study. Aust N Z J Med 29:203–206

    Article  CAS  PubMed  Google Scholar 

  30. Pasco JA, Lane SE, Brennan-Olsen SL, Holloway KL, Timney EN, Bucki-Smith G, Morse AG, Dobbins AG, Williams LJ, Hyde NK, Kotowicz MA (2015) The epidemiology of incident fracture from cradle to senescence. Calcif Tissue Int 97:568–576

    Article  CAS  PubMed  Google Scholar 

  31. Organization WH (2000) Obesity: preventing and managing the global epidemic. Report of a WHO Consultation on Obesity, Geneva, p 253

  32. (1993) Physical fitness and athletic performance: joint position of the Canadian Dietetic Association and the American Dietetic Association. J Can Diet Assoc 54:81–82

  33. Kunst ADB, Ziegenhorn J (1984) UV-methods with hexokinase and glucose-6-phosphate dehydrogenase. Chemie, Weinheim

    Google Scholar 

  34. WHO (2007) Prevention of cardiovascular disease: pocket guidelines for assessment and management of cardiovascular risk. WHO, Geneva

    Google Scholar 

  35. ABS (2006) An introduction to socio-economic indexes for areas (SEIFA), 2006. ABS Cat. No 2039.0. In, Australia

  36. Bowker SL, Yasui Y, Veugelers P, Johnson JA (2010) Glucose-lowering agents and cancer mortality rates in type 2 diabetes: assessing effects of time-varying exposure. Diabetologia 53:1631–1637

    Article  CAS  PubMed  Google Scholar 

  37. Forsen L, Meyer HE, Midthjell K, Edna TH (1999) Diabetes mellitus and the incidence of hip fracture: results from the Nord-Trondelag Health Survey. Diabetologia 42:920–925

    Article  CAS  PubMed  Google Scholar 

  38. Vestergaard P (2007) Discrepancies in bone mineral density and fracture risk in patients with type 1 and type 2 diabetes—a meta-analysis. Osteoporos Int 18:427–444

    Article  CAS  PubMed  Google Scholar 

  39. Janghorbani M, Van Dam RM, Willett WC, Hu FB (2007) Systematic review of type 1 and type 2 diabetes mellitus and risk of fracture. Am J Epidemiol 166:495–505

    Article  PubMed  Google Scholar 

  40. Holmberg AH, Nilsson PM, Nilsson JA, Akesson K (2008) The association between hyperglycemia and fracture risk in middle age. A prospective, population-based study of 22,444 men and 10,902 women. J Clin Endocrinol Metab 93:815–822

    Article  CAS  PubMed  Google Scholar 

  41. Napoli N, Strotmeyer ES, Ensrud KE, Sellmeyer DE, Bauer DC, Hoffman AR, Dam TT, Barrett-Connor E, Palermo L, Orwoll ES, Cummings SR, Black DM, Schwartz AV (2014) Fracture risk in diabetic elderly men: the MrOS study. Diabetologia 57:2057–2065

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Yamaguchi T, Sugimoto T (2011) Bone metabolism and fracture risk in type 2 diabetes mellitus. Endocr J 58:613–624

    Article  CAS  PubMed  Google Scholar 

  43. Russo GT, Giandalia A (2016) Fracture risk in type 2 diabetes: current perspectives and gender differences. Int J Endocrinol 2016:1615735

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Jiao H, Xiao E, Graves DT (2015) Diabetes and its effect on bone and fracture healing. Curr Osteoporos Rep 13:327–335

    Article  PubMed  PubMed Central  Google Scholar 

  45. Wei J, Karsenty G (2015) An overview of the metabolic functions of osteocalcin. Rev Endocr Metab Disord 16:93–98

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Jackuliak P, Payer J (2014) Osteoporosis, fractures, and diabetes. Int J Endocrinol 2014:820615

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. 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 102:32–40

    Article  CAS  PubMed  Google Scholar 

  48. Wallander M, Axelsson KF, Nilsson AG, Lundh D, Lorentzon M (2017) Type 2 diabetes and risk of hip fractures and non-skeletal fall injuries in the elderly: a study from the fractures and fall injuries in the elderly cohort (FRAILCO). J Bone Miner Res 32:449–460

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors would like to acknowledge Dr Adrienne O’Neil for her role in obtaining the lipid levels in sera, Associate Professor Paul Lewandanski and his laboratory for performing the lipid analyses and the Australian Institute for Health and Welfare (AIHW) for death data. The Geelong Osteoporosis Study was supported by the Victorian Health Promotion Foundation, National Health and Medical Research Council (NHMRC), Australia (Projects 251638 and 628582), 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. KLH-K is supported by an Alfred Deakin Postdoctoral Research Fellowship.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Kara L. Holloway-Kew.

Ethics declarations

Conflict of interest

LLFA, KLH-K, MM, MAS, MAK and JAP have no other conflict of interest to declare.

Human and Animal Rights and Informed Consent

This study was ethically approved by the Human Research and Ethic Committees of Barwon Health (Geelong, Australia) and performed in accordance with the criteria defined by the rules of the committee.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

de Abreu, L.L.F., Holloway-Kew, K.L., Mohebbi, M. et al. Fracture Risk in Women with Dysglycaemia: Assessing Effects of Baseline and Time-Varying Risk Factors. Calcif Tissue Int 104, 262–272 (2019). https://doi.org/10.1007/s00223-018-0498-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00223-018-0498-x

Keywords

Navigation