Advanced Glycation Endproducts May Contribute to Poor Bone Health in Diabetes

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Skeletal abnormalities are common in postmenopausal women with diabetes.
Skeletal abnormalities are common in postmenopausal women with diabetes.

New data indicate that postmenopausal women with type 2 diabetes have impaired bone material properties, with results suggesting a potential role for advanced glycation endproducts (AGEs) in the development of skeletal deterioration.

Skeletal fragility is common in type 2 diabetes and the risk for fracture may be as much as 3-fold higher in these patients, researchers noted in the Journal of Clinical Endocrinology & Metabolism.

“While bone health is frequently eclipsed by more immediate life-threatening complications of type 2 diabetes, fractures in type 2 diabetes can have a devastating effect on quality and length of life,” they wrote. “Yet, we do not understand how diabetes affects the skeleton.”

The accumulation of advanced glycation endproducts is one possible mechanism through which type 2 diabetes adversely affects bone health, explained the researchers. To investigate this association, they conducted a cross-sectional study of 16 postmenopausal women with type 2 diabetes and 19 matched controls to assess whether or not advanced glycation endproducts are related to bone material properties in patients with type 2 diabetes.

For the study, the researchers used the OsteoProbe (Active Life Scientific) to perform microindentation. The hand-held device, which is placed over the tibia at 90 degrees, measures the indentation distance increase from the impact of the test probe through the bone. This is then calculated by software to yield indentation properties (bone material strength index).  

The researchers evaluated advanced glycation endproducts using skin autofluorescence, as measured by the AGE Reader (DiagnOptics Technologies BV), which was calculated based on the wavelength of light emitted from the forearm skin when it was illuminated with an ultraviolet light source.

Results revealed a 9.2% reduction in bone material strength index among patients with type 2 diabetes (P=.02). Bone material strength index also appeared to be inversely linked to duration of disease (r=-0.68, P=.004).

Additionally, the researchers found that increased skin autofluorescence was associated with reduced bone material strength index (r=-0.65, P=.006) and lower bone formation marker procollagen type 1 amino-terminal propeptide (r=-0.63, P=.01) in those with type 2 diabetes.

Data demonstrated no associations in control patients.

Twenty-six percent of the age-adjusted variance in bone material strength index in type 2 diabetes was accounted for by skin autofluorescence (P=.03).

“This report implicates, for the first time, a role for advanced glycation endproducts as a potential mechanism to account for reduced bone material strength in type 2 diabetes,” the researchers wrote. “This study confirms worse bone material strength index in type 2 diabetes, and demonstrates lowest bone material strength in persons with diabetes with greatest advanced glycation endproduct accumulation.”

Despite the findings, the researchers highlighted several limitations, including those pertaining to the technology used. For instance, they noted that it remains unclear how bone material strength index is associated with traditional bone properties, such as toughness and elastic modulus.

“Future studies are necessary to investigate longitudinal changes in bone material strength index in type 2 diabetes and to assess their value at predicting fracture risk,” they concluded. 

Reference

  1. Furst JR, Bandeira LC, Fan W-W, et al. Advanced Glycation Endproducts and Bone Material Strength in Type 2 Diabetes. J Clin Endocrinol Metab. 2016. doi:10.1210/jc.2016-1437.
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