Skip to main content

Fracture risk in women with type II diabetes. Results from a historical cohort with fracture follow-up

Endocrine volume 60, pages 151–158 (2018)Cite this article

Abstract

Purpose

To examine the independent association between type II diabetes and fracture risk in a population of predominantly postmenopausal women referred to a specialist clinic for osteoporosis evaluation.

Methods

Type II diabetes associated fracture risk were evaluated among to 229 patients with type II diabetes in a cohort of 6285 women followed on average (until major osteoporotic fracture (MOF), death or end of study) for 5.8 years. Information of fracture risk factors was obtained from a clinical database and from national registries.

Results

An elevated fracture risk was present. Prevalent fractures (43.7 vs. 33.2%, p = 0.0010) and prevalent MOF (26.2 vs. 20.5% p = 0.038) were more common among patients with type II diabetes. The unadjusted incident fracture risk was increased with a higher relative risk of 42%. An elevated MOF hazard ratio was present (HR = 1.726, p = 0.0006). Adjustment for prevalent osteoporosis and other possible confounders did not change this finding (HR = 1.558, p = 0.0207).

Conclusions

An association between type II diabetes and an increased risk of MOF primarily driven by an increased hip fracture risk was documented. This finding was independent of the presence of osteoporosis. Clinicians need to be aware of and adjust for these findings when evaluating patients with diabetes. Additional research examining pathophysiological mechanisms are needed.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

USD 39.95

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

Fig. 1

References

  1. D.R. Whiting, L. Guariguata, C. Weil, J. Shaw, IDF Diabetes Atlas: Global estimates of the prevalence of diabetes for 2011 and 2030. Diabetes Res Clin. Pract. 94, 311–321 (2011)

    Article  PubMed  Google Scholar 

  2. V.V. Shanbhogue, D.M. Mitchell, C.J. Rosen, M.L. Bouxsein, Type 2 diabetes and the skeleton: new insights into sweet bones. Lancet Diabetes Endocrinol. 8587, 1–15 (2015)

    Google Scholar 

  3. P. Vestergaard, 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 (2007)

    Article  CAS  PubMed  Google Scholar 

  4. P. Vestergaard, L. Rejnmark, L. Mosekilde, Relative fracture risk in patients with diabetes mellitus, and the impact of insulin and oral antidiabetic medication on relative fracture risk. Diabetologia 48, 1292–1299 (2005)

    Article  CAS  PubMed  Google Scholar 

  5. A.V. Schwartz, T.A. Hillier, D.E. Sellmeyer, H.E. Resnick, E. Gregg, K.E. Ensrud, P.J. Schreiner, K.L. Margolis, J.A. Cauley, M.C. Nevitt, D.M. Black, S.R. Cummings, Older women with diabetes have a higher risk of falls: a prospective study. Diabetes Care 25, 1749–1754 (2002)

    Article  PubMed  Google Scholar 

  6. S. Kurra, E. Siris, Diabetes and bone health: the relationship between diabetes and osteoporosis-associated fractures. Diabetes Metab. Res. Rev. 27, 430–435 (2011)

    Article  PubMed  Google Scholar 

  7. W.D. Leslie, M.R. Rubin, A.V. Schwartz, J.A. Kanis, Type 2 diabetes and bone. J. Bone Miner. Res 27, 2231–2237 (2012)

    Article  PubMed  Google Scholar 

  8. S. Epstein, G. Defeudis, S. Manfrini, N. Napoli, P. Pozzilli, Diabetes and disordered bone metabolism (diabetic osteodystrophy): time for recognition. Osteoporos. Int. 27, 1931–1951 (2016). https://doi.org/10.1007/s00198-015-3454-x

    Article  CAS  PubMed  Google Scholar 

  9. M. Saito, K. Marumo, Collagen cross-links as a determinant of bone quality: a possible explanation for bone fragility in aging, osteoporosis, and diabetes mellitus. Osteoporos. Int 21, 195–214 (2010)

    Article  CAS  PubMed  Google Scholar 

  10. A.V. Schwartz, P. Garnero, T.A. Hillier, D.E. Sellmeyer, E.S. Strotmeyer, K.R. Feingold, H.E. Resnick, F.A. Tylavsky, D.M. Black, S.R. Cummings, T.B. Harris, D.C. Bauer, Pentosidine and increased fracture risk in older adults with type 2 diabetes. J. Clin. Endocrinol. Metab. 94, 2380–2386 (2009)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. E. Lynge, J.L. Sandegaard, M. Rebolj, The Danish National Patient Register. Scand. J. Public Health 39, 30–33 (2011)

    Article  PubMed  Google Scholar 

  12. K. Helweg-Larsen, The Danish Register of Causes of Death. Scand. J. Public Health 39, 26–29 (2011)

    Article  PubMed  Google Scholar 

  13. H.W. Kildemoes, H.T. Sørensen, J. Hallas, The Danish National Prescription Registry. Scand. J. Public Health 39, 38–41 (2011)

    Article  PubMed  Google Scholar 

  14. J.P. Holm, L. Hyldstrup, J.-E.B. Jensen, Time trends in osteoporosis risk factor profiles: a comparative analysis of risk factors, comorbidities, and medications over twelve years. Endocrine 54, 241–255 (2016). https://doi.org/10.1007/s12020-016-0987-5

    Article  CAS  PubMed  Google Scholar 

  15. J.P. Holm, A.O.S. Amar, L. Hyldstrup, J.E.B. Jensen, Hyponatremia, a risk factor for osteoporosis and fractures in women. Osteoporos. Int. 27, 989–1001 (2016)

    Article  CAS  PubMed  Google Scholar 

  16. P. Vestergaard, L. Rejnmark, L. Mosekilde, Fracture risk associated with systemic and topical corticosteroids. J. Intern. Med. 257, 374–384 (2005)

    Article  CAS  PubMed  Google Scholar 

  17. J.T. Schousboe, J.A. Shepherd, J.P. Bilezikian, S. Baim, Executive Summary of the 2013 International Society for Clinical Densitometry Position Development Conference on Bone Densitometry. J. Clin. Densitom. 16, 455–466 (2013)

    Article  PubMed  Google Scholar 

  18. S.K. Thygesen, C.F. Christiansen, S. Christensen, T.L. Lash, H.T. Sørensen, The predictive value of ICD-10 diagnostic coding used to assess Charlson comorbidity index conditions in the population-based Danish National Registry of Patients. BMC Med. Res. Methodol. 11, 83 (2011). https://doi.org/10.1186/1471-2288-11-83

    Article  PubMed  PubMed Central  Google Scholar 

  19. M. Janghorbani, R.M. Van Dam, W.C. Willett, F.B. Hu, Systematic review of type 1 and type 2 diabetes mellitus and risk of fracture. Am. J. Epidemiol. 166, 495–505 (2007)

    Article  PubMed  Google Scholar 

  20. Y. Fan, F. Wei, Y. Lang, Y. Liu, Diabetes mellitus and risk of hip fractures: a meta-analysis. Osteoporos. Int. 27, 219–222 (2015). https://doi.org/10.1007/s00198-015-3279-7

    Article  PubMed  Google Scholar 

  21. W.D. Leslie, S.N. Morin, L.M. Lix, S.R. Majumdar, Does diabetes modify the effect of FRAX risk factors for predicting major osteoporotic and hip fracture? Osteoporos. Int. 25, 2817–2824 (2014)

    Article  CAS  PubMed  Google Scholar 

  22. D.E. Bonds, J.C. Larson, A.V. Schwartz, E.S. Strotmeyer, J. Robbins, B.L. Rodriguez, K.C. Johnson, K.L. Margolis, Risk of fracture in women with type 2 diabetes: the Women’s Health Initiative Observational Study. J. Clin. Endocrinol. Metab. 91, 3404–3410 (2006)

    Article  CAS  PubMed  Google Scholar 

  23. W.D. Leslie, L.M. Lix, H.J. Prior, S. Derksen, C. Metge, J.O. Neil, Biphasic fracture risk in diabetes: a population-based study. Bone 40, 1595–1601 (2007)

    Article  PubMed  Google Scholar 

  24. W. Rathmann, K. Kostev, J. Diabetes, Complications fracture risk in patients with newly diagnosed type 2 diabetes: a retrospective database analysis in primary care. J. Diabetes Complicat. 29, 766–770 (2015)

    Article  PubMed  Google Scholar 

  25. A.V. Schwartz, E. Vittinghoff, D.C. Bauer, T.A. Hillier, E.S. Strotmeyer, K.E. Ensrud, M.G. Donaldson, J.A. Cauley, T.B. Harris, A. Koster, C.R. Womack, L. Palermo, D.M. Black, Association of BMD and FRAX score with risk of fracture in older adults with type 2 diabetes. JAMA 305, 2184–2192 (2011)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. L.M. Giangregorio, W.D. Leslie, L.M. Lix, H. Johansson, A. Oden, E. McCloskey, J. a Kanis, FRAX underestimates fracture risk in patients with diabetes. J. Bone Miner. Res. 27, 301–308 (2012)

    Article  PubMed  Google Scholar 

  27. E.W. Yu, M.L. Bouxsein, A.E. Roy, C. Baldwin, A. Cange, R.M. Neer, L.M. Kaplan, J.S. Finkelstein, Bone loss after bariatric surgery: discordant results. J. Bone Miner. Res 29, 542–550 (2014)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. C.I. Li, C.S. Liu, W.Y. Lin, N.H. Meng, C.C. Chen, S.Y. Yang, H.J. Chen, C.C. Lin, T.C. Li, Glycated hemoglobin level and risk of hip fracture in older people with type 2 diabetes: a competing risk analysis of Taiwan Diabetes Cohort Study. J. Bone Min. Res. 30, 1338–1346 (2015)

    Article  CAS  Google Scholar 

  29. W.-P. Koh, R. Wang, L.-W. Ang, D. Heng, J.-M. Yuan, M.C. Yu, Diabetes and risk of hip fracture in the Singapore Chinese Health Study. Diabetes Care 33, 1766–1770 (2010)

    Article  PubMed  PubMed Central  Google Scholar 

  30. V.V. Zhukouskaya, C. Eller-Vainicher, A. Gaudio, E. Cairoli, F.M. Ulivieri, S. Palmieri, V. Morelli, E. Orsi, B. Masserini, A.M. Barbieri, E. Polledri, S. Fustinoni, A. Spada, C.E. Fiore, I. Chiodini, In postmenopausal female subjects with type 2 diabetes mellitus, vertebral fractures are independently associated with cortisol secretion and sensitivity. J. Clin. Endocrinol. Metab. 100, 1417–1425 (2015)

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The study was approved by relevant review authorities including Statens Serum Institute, the Danish Data Protection Agency and Statistics Denmark.

Author information

Authors and Affiliations

  1. Department of Endocrinology, Copenhagen University Hospital Hvidovre, Kettegaards Allé 30, Hvidovre, DK-2650, Denmark

    Jakob Præst Holm, Thomas Jensen, Lars Hyldstrup & Jens-Erik Beck Jensen

Authors
  1. Jakob Præst Holm
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Thomas Jensen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lars Hyldstrup
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jens-Erik Beck Jensen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jakob Præst Holm.

Ethics declarations

Conflict of interest

J.H. has participated as a subinvastigator in studies by Amgen and MSD and received payment for lectures by Amgen. L.H. has been giving lectures sponsored by: Novartis, Lilly, Takeda/Nycomed, Novo-Nordisk, Amgen, GlaxoSmithKline, Servier, MSD, Ferrosan, Pfizer, PharmaVinci and Renapharma. J.E.B.J.: Board membership in Amgen, Eli Lilly, MSD, Novartis, Nycomed. Payment for lectures by Amgen, Eli Lilly and MSD. T.J. declares that he has no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

For this type of study formal consent is not required.

Electronic supplementary material

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Holm, J.P., Jensen, T., Hyldstrup, L. et al. Fracture risk in women with type II diabetes. Results from a historical cohort with fracture follow-up. Endocrine 60, 151–158 (2018). https://doi.org/10.1007/s12020-018-1564-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12020-018-1564-x

Keywords

  • Fracture risk
  • Type II diabetes
  • Women’s health
  • Osteoporosis
  • Secondary osteoporosis