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Effect of Diabetes on the Fracture Resistance of Bone

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Abstract

Diabetes increases the likelihood of suffering a fracture, and in the case of type 2 diabetes mellitus (T2D), low bone mass does not explain this loss in fracture resistance. Insulin contributes to the accrual of bone mass. As such, the elevated fracture risk among those with type 1 diabetes (T1D) could be due to a deficit in bone structure, especially if the diabetes is poorly controlled. Clinical studies involving computed tomography scans do suggest that low moment of inertia and low cross-sectional area of cortical bone accompany T1D. However, low bone mass does not typically accompany T2D, and fracture resistance arises from all the hierarchical levels comprising the organization of bone’s constituents. One consequence of diabetes, hyperglycemia, causes an increase in non-enzymatic collagen crosslinks, also known as advanced glycation end products (AGEs). Increases in AGEs within the bone matrix are strongly correlated with the age-related decrease in the ability of bone to dissipate energy during failure (toughness and fracture toughness). While elevated AGEs are associated with higher incidence of fracture, the mechanism by which non-enzymatic crosslinking lowers fracture resistance is not fully delineated. The general concept is that increases in AGEs within the matrix cause the collagen phase to become brittle, reducing the capacity of the tissue to resist the formation and propagation of microdamage. While certainly more research into the diabetic effects on fracture resistance is necessary before clear therapeutic options are identified, diabetes should be considered a problem of bone brittleness, not just one of low bone strength.

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Acknowledgments

The author thanks Dr. John Fowlkes for insightful comments on earlier versions of the present paper. Also, he thanks Dr. Colm Morrissey for providing the histological image of trabecular bone.

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Correspondence to Jeffry S. Nyman.

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Nyman, J.S. Effect of Diabetes on the Fracture Resistance of Bone. Clinic Rev Bone Miner Metab 11, 38–48 (2013). https://doi.org/10.1007/s12018-012-9124-z

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