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.
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.
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).
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.
Buy single article
Instant access to the full article PDF.
Price excludes VAT (USA)
Tax calculation will be finalised during checkout.
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)
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)
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)
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)
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)
S. Kurra, E. Siris, Diabetes and bone health: the relationship between diabetes and osteoporosis-associated fractures. Diabetes Metab. Res. Rev. 27, 430–435 (2011)
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)
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
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)
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)
E. Lynge, J.L. Sandegaard, M. Rebolj, The Danish National Patient Register. Scand. J. Public Health 39, 30–33 (2011)
K. Helweg-Larsen, The Danish Register of Causes of Death. Scand. J. Public Health 39, 26–29 (2011)
H.W. Kildemoes, H.T. Sørensen, J. Hallas, The Danish National Prescription Registry. Scand. J. Public Health 39, 38–41 (2011)
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
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)
P. Vestergaard, L. Rejnmark, L. Mosekilde, Fracture risk associated with systemic and topical corticosteroids. J. Intern. Med. 257, 374–384 (2005)
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)
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
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)
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
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
The study was approved by relevant review authorities including Statens Serum Institute, the Danish Data Protection Agency and Statistics Denmark.
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.
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.
For this type of study formal consent is not required.
Electronic supplementary material
Rights and permissions
About this article
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
- Fracture risk
- Type II diabetes
- Women’s health
- Secondary osteoporosis