The effect of aminoguanidine (AG) and pyridoxamine (PM) on ageing human cortical bone.

OBJECTIVES

Advanced glycation end-products (AGEs) are a post-translational modification of collagen that form spontaneously in the skeletal matrix due to the presence of reducing sugars, such as glucose. The accumulation of AGEs leads to collagen cross-linking, which adversely affects bone quality and has been shown to play a major role in fracture risk. Thus, intervening in the formation and accumulation of AGEs may be a viable means of protecting bone quality.

METHODS

An model was used to examine the efficacy of two AGE-inhibitors, aminoguanidine (AG) and pyridoxamine (PM), on ageing human cortical bone. Mid-diaphyseal tibial cortical bone segments were obtained from female cadavers (n = 20, age range: 57 years to 97 years) and randomly subjected to one of four treatments: control; glucose only; glucose and AG; or glucose and PM. Following treatment, each specimen underwent mechanical testing under physiological conditions via reference point indentation, and AGEs were quantified by fluorescence.

RESULTS

Treatment with AG and PM showed a significant decrease in AGE content control groups, as well as a significant decrease in the change in indentation distance, a reliable parameter for analyzing bone strength, via two-way analysis of variance (ANOVA) (p < 0.05).

CONCLUSIONS

The data suggest that AG and PM prevent AGE formation and subsequent biomechanical degradation . Modulation of AGEs may help to identify novel therapeutic targets to mitigate bone quality deterioration, especially deterioration due to ageing and in AGE-susceptible populations (e.g. diabetics).: 2018;7:105-110.