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

Abstract

Purpose/Introduction Changes in the quality of bone material contribute significantly to bone fragility. In order to establish a better understanding of the interaction of the different components of bone quality and their influence on bone fragility we investigated the relationship between non-enzymatic glycation, resorption, and microdamage generated in vivo in cortical bone using bone specimens from the same donors. Methods Total fluorescent advanced glycation end-products (AGEs) were measured in 96 human cortical bone samples from 83 donors. Resorption pit density, average resorption pit area, and percent resorption area were quantified in samples from 48 common donors with AGE measurements. Linear microcrack density and diffuse damage were measured in 21 common donors with AGE and resorption measurements. Correlation analyses were performed between all measured variables to establish the relationships among them and their variation with age. Results We found that average resorption pit area and percent resorption area decreased with increasing AGEs independently of age. Resorption pit density and percent resorption area demonstrated negative age-adjusted correlation with diffuse damage. Furthermore, average resorption pit area, resorption pit density, and percent resorption area were found to decrease significantly with age. Conclusions The current study demonstrated the in vivo interrelationship between the organic constituents, remodeling, and damage formation in cortical bone. In addition to the age-related reduction in resorption, there is a negative correlation between AGEs and resorption independent of age. This inverse relationship indicates that AGEs alter the resorption process and/or accumulate in the tissue as a result of reduced resorption and may lead to bone fragility by adversely affecting fracture resistance through altered bone matrix properties.

In Vitro‐Induced High Sugar Environments Deteriorate Human Cortical Bone Elastic Modulus and Fracture Toughness

“…fAGEs were indeed increased by ~81% in ribose‐treated specimens compared with vehicles. The AGE levels in vehicles were like those reported in human cortical bone in vivo in two studies but were higher than those reported by another study (Table ). It is difficult to ascertain why the third study reports much lower AGE values as that study also used human female tibias from a similar age range.…”

“…Moreover, studies using diabetic animals suggest that increased AGEs are associated with lower bone stiffness and are more susceptible to microcrack propagation compared with non‐diabetic controls, but there is little information regarding crack initiation and propagation due to AGEs in human bone . Further, about 12 studies in human bone focused on studying the effect of non‐enzymatic glycation on cancellous bone mechanical behavior, but only six studies report findings on cortical bone, two of which utilize bovine bone . There is some indication that in diabetes (where AGEs are particularly relevant) cortical bone is the primary bone type affected with a reduced quality .…”

Fatigue-induced microdamage in cancellous bone occurs distant from resorption cavities and trabecular surfaces

“…Therefore, the negative spatial correlation between resorption cavities and microdamage in the current study may be a result of more ductile tissue near trabecular surfaces (due to younger local tissue age). However, increased non-enzymatic glycation (a trait associated with increased tissue brittleness [32]) has been shown to impair osteoclastic bone resorption in vitro [40] and is negatively correlated with resorption cavities in cortical bone [41]. If such a negative correlation also exists in cancellous bone it could also explain the negative correlation between microdamage and resorption cavities we observed.…”

Identification and characterization of glycation adducts on osteocalcin

“…AGEs have been implicated in the deterioration of tissue properties in many different tissues, including bone. [11] AGE crosslinking in collagen has been demonstrated to increase bone fragility [12; 13; 14; 15; 16; 17]. …”