Advanced Glycation End Products and Bone Quality in Diabetes

Advanced Glycation End Products (AGEs) arise from non-enzymatic reactions between reducing sugars and amino groups on proteins, accumulating in long-lived collagen within the skeletal matrix. In diabetes, chronic hyperglycaemia accelerates AGE formation, resulting in stiffening of collagen fibres, impaired bone remodelling and compromised material properties that are not reflected by bone mineral density alone. The cross-linking and accumulation of AGEs such as pentosidine increase collagen brittleness and interfere with osteoblastic and osteoclastic activity, while interactions with the receptor for AGEs (RAGE) exacerbate local inflammation and oxidative stress. Collectively, these processes undermine bone quality at multiple hierarchical levels—from nanoscale fibrils through microarchitecture to whole-bone performance—leading to an elevated risk of fragility fractures in diabetic individuals.

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Advanced Glycation End Products and Bone Quality in Diabetes publication trend

The graph below shows the total number of articles in advanced glycation end products and bone quality in diabetes across all publications each year (not limited to Nature Index journals).

Technical terms

Advanced Glycation End Products (AGEs): Diverse compounds formed by non-enzymatic reactions between reducing sugars and proteins, leading to cross-links that stiffen collagen.

Bone Mineral Density (BMD): A measure of mineral content in bone, typically assessed by dual-energy X-ray absorptiometry, reflecting bone quantity rather than material quality.

Collagen Cross-links: Chemical bonds between collagen molecules; beneficial enzymatic cross-links reinforce strength, whereas non-enzymatic cross-links such as pentosidine increase brittleness.

Receptor for Advanced Glycation End Products (RAGE): A cell-surface receptor that binds AGEs and triggers inflammatory and catabolic pathways affecting bone cells.

Oxidative Stress: An imbalance between reactive oxygen species production and antioxidant defences, promoting AGE formation and tissue damage.

References

1. Multiscale and multidisciplinary analysis of aging processes in bone. npj Aging (2024).
2. Role of Advanced Glycation End-Products and Oxidative Stress in Type-2-Diabetes-Induced Bone Fragility and Implications on Fracture Risk Stratification. Antioxidants (2023).
3. Advanced Glycation End Products, Diabetes, and Bone Strength. Current Osteoporosis Reports (2016).
4. Non-enzymatic Glycation of Bone Collagen Modifies Osteoclastic Activity and Differentiation*. Journal of Biological Chemistry (2006).
5. Non-enzymatic glycosylation of a type I collagen matrix: effects on osteoblastic development and oxidative stress. BMC Molecular and Cell Biology (2001).
6. Skin Autofluorescence, a Noninvasive Biomarker for Advanced Glycation End‐Products, Is Associated With Prevalent Vertebral and Major Osteoporotic Fractures: The Rotterdam Study. Journal of Bone and Mineral Research (2020).