Meeting NewsPerspective

Increased cortical advanced glycation end products contribute to brittle bones in men with type 2 diabetes

Researchers found higher advanced glycation end-product content — associated with decreased bone strength — in the cortical bone of men with vs. without type 2 diabetes, according to data presented at the American Society for Bone and Mineral Research Annual Meeting.

Pablo Palomino, a PhD student in biomedical engineering at Cornell University, and colleagues examined bone samples collected during total hip arthroplasty for osteoarthritis from 33 men with type 2 diabetes (mean age, 64 years; mean preoperative HbA1c, 6.9%) and 32 men without diabetes (mean age, 60 years; mean preoperative HbA1c, 5.5%) to assess initiation and propagation toughness (via variable-pressure scanning electron microscopy), crack tortuosity and cortical morphometric parameters (via micro-CT) and total fluorescent advanced glycation end-product (AGE) content (via fluorescence spectrometry).

The researchers found that men with type 2 diabetes had 19% more AGE content in the cortical bone of the femoral neck compared with those without diabetes (P = .05); AGE content was not corelated with HbA1c. Lower initiation toughness was associated with increased AGE content (P < .03). Bone toughness, crack tortuosity and cortical morphometric parameters did not differ between the two groups.

“Because [type 2 diabetes] is associated with an increase in [total fluorescent AGE content], further analyses are required to discern whether these biochemical changes contribute to the greater hip fracture risk with [type 2 diabetes] clinically.” – by Phil Neuffer

Reference:

Hunt H, et al. Abstract FRI-1039. Presented at: American Society for Bone and Mineral Research Annual Meeting; Sept. 28-Oct. 1, 2018; Montreal.

Disclosure: Palomino reports no relevant financial disclosures.

Researchers found higher advanced glycation end-product content — associated with decreased bone strength — in the cortical bone of men with vs. without type 2 diabetes, according to data presented at the American Society for Bone and Mineral Research Annual Meeting.

Pablo Palomino, a PhD student in biomedical engineering at Cornell University, and colleagues examined bone samples collected during total hip arthroplasty for osteoarthritis from 33 men with type 2 diabetes (mean age, 64 years; mean preoperative HbA1c, 6.9%) and 32 men without diabetes (mean age, 60 years; mean preoperative HbA1c, 5.5%) to assess initiation and propagation toughness (via variable-pressure scanning electron microscopy), crack tortuosity and cortical morphometric parameters (via micro-CT) and total fluorescent advanced glycation end-product (AGE) content (via fluorescence spectrometry).

The researchers found that men with type 2 diabetes had 19% more AGE content in the cortical bone of the femoral neck compared with those without diabetes (P = .05); AGE content was not corelated with HbA1c. Lower initiation toughness was associated with increased AGE content (P < .03). Bone toughness, crack tortuosity and cortical morphometric parameters did not differ between the two groups.

“Because [type 2 diabetes] is associated with an increase in [total fluorescent AGE content], further analyses are required to discern whether these biochemical changes contribute to the greater hip fracture risk with [type 2 diabetes] clinically.” – by Phil Neuffer

Reference:

Hunt H, et al. Abstract FRI-1039. Presented at: American Society for Bone and Mineral Research Annual Meeting; Sept. 28-Oct. 1, 2018; Montreal.

Disclosure: Palomino reports no relevant financial disclosures.

    Perspective

    Mario Skugor

    The increased fracture risk in patients with diabetes is not well understood. Accumulation of advanced glycation end products is one of possible mechanisms for increased bone fragility.

    This study has shown that AGEs are higher in the bone of patients with diabetes and that AGEs are inversely correlated with measures of bone fragility as measured by initiation toughness, and thus, confirming previous findings and further establishing AGEs as possible culprit in bone brittleness.

    However, in this study, the measures of bone fragility were similar in subjects with and without diabetes and cannot be used to explain the differences in the fracture risk. This study is small in terms of the number of subjects studied, and it seems that patients with diabetes were, for the most part, in very good control of their blood glucose levels. So, the difference in HbA1c levels between two groups is small and could obscure the importance of the role of AGEs in the bone fragility. Comparing the poorly controlled patients with higher HbA1c levels with normal controls may offer better opportunity to document importance of the AGEs for bone fragility, if AGEs are really an important factor. Of course, other factors, such as bone geometry, cortical thickness and bone marrow adiposity can play a role, too.

    Another question that needs answering is effect of duration of the diabetes and total glycemic burden (which should be assessed with serial HbA1c measurements) on bone fracture risk and AGEs in the bone.

    This study is interesting as it offers another insight into diabetic bone but, at this point, has no clinical utility. The main takeaway point of the study is that we need data on more patients and controls matched by age, weight and sex and stratified by duration of diabetes and by the quality of disease control over time.

    • Mario Skugor, MD, FACE
    • Endocrine and Metabolic Institute Cleveland Clinic

    Disclosures: Disclosure: Skugor reports no relevant financial disclosures.

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