Type 2 diabetes mellitus (T2DM) is an enormous, and growing, public health problem. While patients with T2DM are at significant risk for premature morbidity and mortality due to macrovascular disease, retinopathy, nephropathy, and neuropathy, it is also clear that T2DM patients are at increased risk for fragility fractures. As efforts to understand the underlying pathogenesis of skeletal abnormalities in T2DM have primarily focused on rodent models, major gaps in our understanding of diabetic bone disease in humans remain. Nonetheless, mounting evidence now suggests that fragility fractures in T2DM may result from compromised bone “quality” (i.e., altered bone material properties and/or bone microarchitecture) rather than reduced bone mineral density. Consistent with this, recent work has demonstrated, using in vivo microindentation technology, that bone material properties are compromised in patients with T2DM compared to nondiabetic controls, and that, in patients with T2DM, poor chronic glycemic control is associated with worse bone material properties. Thus, our current understanding of the pathogenesis of skeletal fragility in diabetes suggests that poor glucose control in patients with T2DM leads to increases in advanced glycation end products (AGEs) that have negative effects on osteoblasts, which in turn causes a reduction in bone formation. This defect in bone formation subsequently results in low bone turnover in T2DM patients, which prolongs the lifespan of type I collagen in bone, thereby leaving it particularly vulnerable to damage from increased AGEs. Ultimately, this creates a “vicious cycle” that may contribute to reduced bone qulity and increased fracture risk in patients with T2DM.
|Original language||English (US)|
|Title of host publication||Diabetic Bone Disease: Basic and Translational Research and Clinical Applications|
|Publisher||Springer International Publishing|
|Number of pages||14|
|ISBN (Print)||9783319164021, 9783319164014|
|State||Published - Jan 1 2016|
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