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Diabetes and Its Complications and Their Relationship with Risk of Fractures in Type 1 and 2 Diabetes

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Abstract

This case–control study sought to assess the effects of diabetes and its complications on the risk of fractures. There were 124,655 fracture cases and 373,962 age- and sex-matched controls. The main exposure was diabetes and its complications, and the main confounders were use of insulin and oral antidiabetic agents, presence of cardiovascular disease, and use of drugs for cardiovascular disease, along with a number of other confounders. In the crude analysis, diabetes and all complications was associated with a statistically significantly increased overall risk of fractures. The increase in risk of fractures was higher in type 1 diabetes (T1D) than in type 2 diabetes (T2D). However, after adjustment for confounders, the difference between T1D and T2D disappeared, and only diabetic kidney disease in T1D retained a significantly increased risk of fractures. There was a time dependency in the risk of fractures with an early increase at <2.5 years after diagnosis. followed by a decrease to the level of the background population from 2.5 to 5 years after diagnosis, and a limited increase in T1D but not T2D at >5 years after diagnosis. We conclude that diabetes, whether T1D or T2D, seems to carry an increased risk of fractures, and complications to diabetes except for diabetic kidney disease add little to the overall risk of fracture, perhaps pointing at a common risk factor linked to the high blood glucose levels, which may weaken bone strength.

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References

  1. Janghorbani M, van Dam R, Willett W et al (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 

  2. 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  PubMed  CAS  Google Scholar 

  3. De Laet C, Kanis JA, Odén A et al (2005) Body mass index as a predictor of fracture risk: a meta-analysis. Osteoporos Int 16:1330–1338

    Article  PubMed  Google Scholar 

  4. McNair P, Madsbad S, Christensen MS et al (1979) Bone mineral loss in insulin-treated diabetes mellitus: studies on pathogenesis. Acta Endocrinol (Copenh) 90:463–472

    CAS  Google Scholar 

  5. McNair P, Christiansen C, Christensen MS et al (1981) Development of bone mineral loss in insulin-treated diabetes: a 1–1/2 years follow-up study in sixty patients. Eur J Clin Invest 11:55–59

    Article  PubMed  CAS  Google Scholar 

  6. Gopalakrishnan V, Vignesh RC, Arunakaran J et al (2006) Effects of glucose and its modulation by insulin and estradiol on BMSC differentiation into osteoblastic lineages. Biochem Cell Biol 84:93–101

    Article  PubMed  CAS  Google Scholar 

  7. McNair P, Christensen MS, Madsbad S et al (1981) Hypoparathyroidism in diabetes mellitus. Acta Endocrinol (Copenh) 96:81–86

    CAS  Google Scholar 

  8. Hein G, Weiss C, Lehmann G et al (2006) Advanced glycation end product modification of bone proteins and bone remodelling: hypothesis and preliminary immunohistochemical findings. Ann Rheum Dis 65:101–104

    Article  PubMed  CAS  Google Scholar 

  9. Saito M, Fujii K, Soshi S et al (2006) Reductions in degree of mineralization and enzymatic collagen cross-links and increases in glycation-induced pentosidine in the femoral neck cortex in cases of femoral neck fracture. Osteoporos Int 17:986–995

    Article  PubMed  CAS  Google Scholar 

  10. Miao J, Brismar K, Nyrén O et al (2005) Elevated hip fracture risk in type 1 diabetic patients: a population-based cohort study in Sweden. Diabetes Care 28:2850–2855

    Article  PubMed  Google Scholar 

  11. Ivers RQ, Cumming RG, Mitchell P et al (2001) Diabetes and risk of fractures—the Blue Mountains Eye Study. Diabetes Care 24:1198–1203

    Article  PubMed  CAS  Google Scholar 

  12. Rix M, Andreassen H, Eskildsen P (1999) Impact of peripheral neuropathy on bone density in patients with type 1 diabetes. Diabetes Care 22:827–831

    Article  PubMed  CAS  Google Scholar 

  13. Mathiassen B, Nielsen S, Johansen JS et al (1990) Long-term bone loss in insulin-dependent diabetic patients with microvascular complications. J Diabet Complications 4:145–149

    Google Scholar 

  14. Clausen P, Feldt-Rasmussen B, Jacobsen P et al (1997) Microalbuminuria as an early indicator of osteopenia in male insulin-dependent diabetic patients. Diabet Med 14:1038–1043

    Article  PubMed  CAS  Google Scholar 

  15. Bouillon R (1991) Diabetic bone disease (editorial). Calcif Tissue Int 49:155–160

    Article  PubMed  CAS  Google Scholar 

  16. Cappuccio F, Meilahn E, Zmuda J et al (1999) High blood pressure and bone-mineral loss in elderly white women: a prospective study. Study of Osteoporotic Fractures Research Group. Lancet 354:971–975

    Article  PubMed  CAS  Google Scholar 

  17. Vestergaard P, Emborg C, Støving RK et al (2002) Fractures in patients with anorexia nervosa, bulimia nervosa, and other eating disorders—a nationwide register study. Int J Eat Disord 32:301–308

    Article  PubMed  Google Scholar 

  18. Andersen TF, Madsen M, Jørgensen J et al (1999) The Danish National Hospital Register. Dan Med Bull 46:263–268

    PubMed  CAS  Google Scholar 

  19. Mosbech J, Jørgensen J, Madsen M et al (1995) The Danish National Patient Register: evaluation of data quality. Ugeskr Laeger 157:3741–3745

    PubMed  CAS  Google Scholar 

  20. Vestergaard P, Rejnmark L, Mosekilde L (2004) Fracture risk associated with use of anti-epileptic drugs. Epilepsia 45:1330–1337

    Article  PubMed  CAS  Google Scholar 

  21. Vestergaard P, Rejnmark L, Mosekilde L (2006) Socioeconomic aspects of fractures within universal public healthcare: a nationwide case–control study from Denmark. Scand J Public Health 34:371–377

    Article  PubMed  Google Scholar 

  22. Kanis JA, Johansson H, Johnell O et al (2005) Alcohol intake as a risk factor for fracture. Osteoporos Int 16:737–742

    Article  PubMed  Google Scholar 

  23. Klotzbuecher CM, Ross PD, Landsman PB et al (2000) Patients with prior fractures have an increased risk of future fractures: a summary of the literature and statistical synthesis. J Bone Miner Res 15:721–739

    Article  PubMed  CAS  Google Scholar 

  24. Munk-Jørgensen P, Mortensen P (1997) The Danish Psychiatric Central Register. Dan Med Bull 44:82–84

    PubMed  Google Scholar 

  25. Vestergaard P, Mosekilde L (2002) Fracture risk in patients with celiac disease, Crohn’s disease, and ulcerative colitis: a nation-wide follow-up study in 16, 416 patients in Denmark. Am J Epidemiol 156:1–10

    Article  PubMed  Google Scholar 

  26. McNair P, Madsbad S, Christiansen C et al (1979) Bone loss in diabetes: effects of metabolic state. Diabetologia 17:283–286

    Article  PubMed  CAS  Google Scholar 

  27. Goliat E, Marusza W, Ostrowski K et al (1998) Microalbuminuria as a risk factor for diabetic osteopathy in patients with IDDM and renal sufficiency. Pol Arch Med Wewn 100:111–118

    PubMed  CAS  Google Scholar 

  28. Vestergaard P, Rejnmark L, Mosekilde L (2005) 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

    Article  PubMed  CAS  Google Scholar 

  29. Rejnmark L, Vestergaard P, Mosekilde L (2005) Reduced fracture risk in users of thiazide diuretics. Calcif Tissue Int 76:167–175

    Article  PubMed  CAS  Google Scholar 

  30. Rejnmark L, Vestergaard P, Mosekilde L (2006) Treatment with beta-blockers, ACE inhibitors, and calcium-channel blockers is associated with a reduced fracture risk: a nationwide case–control study. J Hypertension 24:581–589

    Article  CAS  Google Scholar 

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Acknowledgments

Danmarks Statistik (Statistics Denmark) is acknowledged for help that made this project possible. We thank research librarian Edith Clausen for her help with the references. The Danish Medical Research Council provided financial support (grant 22-04-0495).

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Authors and Affiliations

  1. The Osteoporosis Clinic, Department of Endocrinology and Metabolism C, Aarhus Amtssygehus, Aarhus University Hospital, Tage Hansens Gade 2, 8000, Aarhus C, Denmark

    Peter Vestergaard, Lars Rejnmark & Leif Mosekilde

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  1. Peter Vestergaard
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  2. Lars Rejnmark
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  3. Leif Mosekilde
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Correspondence to Peter Vestergaard.

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Vestergaard, P., Rejnmark, L. & Mosekilde, L. Diabetes and Its Complications and Their Relationship with Risk of Fractures in Type 1 and 2 Diabetes. Calcif Tissue Int 84, 45–55 (2009). https://doi.org/10.1007/s00223-008-9195-5

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  • DOI: https://doi.org/10.1007/s00223-008-9195-5

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