Short summary

Although type 2 diabetes mellitus is associated with an increased risk of fracture, the underlying pathophysiological mechanisms responsible for structural alterations and bone fragility remain unclear. The current study is a large scale comprehensive prospective study assessing structural components of skeletal integrity, including the microarchitecture of trabecular and cortical bone, bone mineralization and bone turnover, and identification of potential structural determinants of incident fractures in patients with type 2 diabetes. We anticipate that this study will advance our knowledge and may improve clinical management of diabetic patients who are susceptible to fractures providing a foundation for targeted fracture prevention strategies.  

Rationale

Patients with type 2 diabetes have increased fracture risks despite a normal to elevated bone mineral density. This has prompted a number of high resolution 3D imaging studies investigating the hypothesis that diabetes-associated alterations in bone microarchitecture increase skeletal fragility independent of traditional BMD measurements used clinically for fracture prediction. In our centre, we observed that deficits in bone microarchitecture are not characteristic of all diabetics but of a subgroup characterized by the presence of microvascular complications of diabetes (i.e. long-term complications of diabetes affecting the vascular beds of the eye, kidney, nerves and presumably of the bone).

The overall objective of this study is a comprehensive assessment of the potential underlying mechanisms of diabetic skeletal fragility by acquiring longitudinal clinical, biochemical, densitometric and biomechanical data on intermediate measures of bone strength in patients with type 2 diabetes in general and diabetics with microvascular complications in particular.

Description of the cohort

This three-year large prospective, cohort study will include 500 women and men with type 2 diabetes mellitus recruited during routine medical evaluation from the diabetic outpatient clinic at the endocrinology department at the Odense University Hospital and from "Fyn Diabetes Database".

Data and biological material

At baseline and at the three-year follow-up visit, the following data will be collected:

• Clinical data- questionnaire-based full medical, diabetic, fracture and fall history; and examination data including anthropometry and assessment of diabetic complications.
• Radiological data- regional and whole body DXA, Vertebral Fracture Assessment, and HR-pQCT at the distal radius and tibia.
• Biological material-blood investigation results

Collaborating researchers and departments

Department of Endocrinology, Odense University Hospital

• Jan Erik Henriksen, 
• Morten Frost