Vikram Shanbhogue - Cortical bone microarchitectural, histomorphometric, biomechanical, cellular characteristics and fracture risk in type 2 diabetes mellitus: The Diabetes and Osteoporosis Study (DOS)
Patients with type 2 diabetes mellitus (T2D) have an increased risk of fracture of up to 1.7 in spite of a normal to elevated bone mineral density (BMD). There is currently a gap in our understanding linking the pathophysiological changes at the tissue level with the epidemiological observations of the increased fracture risk in patients with T2D.
Because BMD is normal or elevated, deficits in bone matrix or microarchitecture are implicated in diabetic skeletal fragility. Recently, we have shown that cortical bone deficits in T2D may not be characteristic of all diabetic patients but of a subgroup characterized by the presence of microvascular complications of diabetes.
The overall goal of this study is a comprehensive assessment of the potential underlying mechanisms of diabetic skeletal fragility by acquiring in vitro microCT imaging, microindentation and histomorphometric assessment coupled with in vivo longitudinal clinical, biochemical, densitometric and biomechanical data on intermediate measures of bone strength in patients with T2D.
This proposed study will help elucidate the causes of skeletal fragility in T2D by
a) investigating bone metabolism at the micro- and macroscopic level in patients with T2D with and without microvascular complications,
b) providing a comprehensive assessment of cortical bone tissue properties to better define changes in cortical porosity and establishing the biochemical determinants of these changes, and
c) determining the predictive value of various measures of bone strength in the the assessment of fracture risk among T2D in general and T2D with microvascular complications in particular.
This study will advance our knowledge on bone metabolism in T2D and microvascular disease, and may improve clinical management of diabetic patients who are susceptible to fractures providing a foundation for targeted fracture prevention strategies in T2D.