Differences in non-enzymatic glycation and collagen cross-links between human cortical and cancellous bone

Abstract

Purpose Accumulation of collagen crosslinks (advanced glycation end products [AGEs]) produced by non-enzymatic glycation deteriorates bone's mechanical properties and fracture resistance. Although a single AGE, pentosidine, is commonly used as a representative marker, it is unclear whether it quantitatively reflects total fluorescent AGEs in bone. The goal of this study was to establish the relationship between pentosidine and total AGEs in cancellous and cortical bone. Methods Pentosidine and total AGEs were quantified in 170 human bone samples. Total fluorescent AGEs were measured in 28 additional cancellous and cortical bone specimens of the same apparent volume that were incubated in control or in vitro glycation solutions. Correlations between pentosidine and total AGEs and differences between cortical and cancellous groups were determined. Results Pentosidine was correlated with total AGEs in cancellous bone (r=0.53, p<0.0001) and weakly correlated in cortical bone (r=0.23, p<0.05). There was more pentosidine (p<0.01) and total AGEs (p<0.001) in cancellous than in cortical bone. The in vitro glycation sub-study showed that cancellous bone accumulated more AGEs than cortical bone (p<0.05). Conclusion The relationship between pentosidine and total AGEs and their magnitude of accumulation differed in cancellous and cortical bone of the same apparent volume, and were dependent on the surface-to-volume ratios of each sample. It is important to consider the bone types as two separate entities, and it is crucial to quantify total AGEs in addition to pentosidine to allow for more comprehensive analysis of the effects of non-enzymatic glycation in bone.

Association between non-enzymatic glycation, resorption, and microdamage in human tibial cortices

“…Unlike previous reports [5, 43, 44], AGEs did not show a positive relationship with age. This difference can be explained by the presence of larger variations in AGE values and smaller samples in our study compared to previous studies.…”

“…A previous study on in vitro ribosylated cancellous bone showed elevated levels of linear microcracks [10]. Cancellous bone has higher levels of non-enzymatic glycation compared to cortical bone [43] which may influence the level of microdamage accumulation in the bone tissue. The absence of a relationship between AGEs and linear microcrack density in this study may also be due to the limited size of the samples used in the correlation analysis between non-enzymatic glycation and microdamage.…”

Bone Material Properties in Osteogenesis Imperfecta

“…(7) Karim also observed variation in the accumulation of nonenzymatic cross-links between cancellous and cortical bone. (8) Enzymatic cross-links are usually regarded as contributing positively to bone strength; nonenzymatic cross-links, by contrast, are widely held to adversely affect bone material properties. (9) The collagen molecules within each microfibril group coil gradually around each other, with specific kinks that create pockets and potential binding sites for other matrix proteins (5) as well as interactions with cells through integrin-binding (Fig.…”

Age-Related Effects of Advanced Glycation End Products (Ages) in Bone Matrix on Osteoclastic Resorption

“…The effects of AGEs on bone are manifested in two aspects: one is the deleterious modification of bone ultrastructure (e.g., non-enzymatic cross linking in collagen), which may directly lead to the reduced toughness of bone [2,[8][9][10]. The other is the negative modulation of cellular activities in bone remodeling process [2], which include abnormal proliferation, differentiation, and apoptosis of bone cells, such as osteoclasts (OCs), osteoblasts, and osteocytes [11][12][13][14][15][16][17].…”