Non-enzymatic glycation alters microdamage formation in human cancellous bone

S. Y. Tang, D. Vashishth

Research output: Contribution to journalArticlepeer-review

99 Scopus citations

Abstract

Introduction: The accumulation of advanced glycation end-products (AGEs) in bone has been suggested to adversely affect the fracture resistance of bone with aging, diabetes, and pharmacological treatments. The formation of AGEs increases crosslinking in the organic matrix of bone but it is unknown how elevated levels of AGEs affect the mechanisms of fracture resistance such as microdamage formation. Methods: Human tibial cancellous bone cores were subjected to non-enzymatic glycation (NEG) by in vitro ribosylation and were mechanically loaded to pre- (0.6%) and post- (1.1%) yield apparent level strains. Loaded specimens were stained with lead-uranyl acetate and subjected to microCT-based 3D quantification and characterization of microdamage as either diffuse damage and linear microcracks. Damaged volume per bone volume (DV/BV) and damaged surface per damaged volume (DS/DV) ratios were used to quantify the volume and morphology of the detected microdamage, respectively. Results: In vitro ribosylation increased the microdamage morphology parameter (DS/DV) under both pre- (p < 0.05; + 51%) and post-yield loading (p < 0.001; + 38%), indicating that the alteration of bone matrix by NEG caused the formation of crack-like microdamage morphologies. Under post-yield loading, the NEG-mediated increase in DS/DV was coupled with the reductions in microdamage formation (DV/BV; p < 0.001) and toughness (p < 0.001). Discussion: Using a novel microCT technique to characterize and quantify microdamage, this study shows that the accumulation of AGEs in the bone matrix significantly alters the quantity and morphology of microdamage production and results in reduced fracture resistance.

Original languageEnglish
Pages (from-to)148-154
Number of pages7
JournalBone
Volume46
Issue number1
DOIs
StatePublished - Jan 2010

Keywords

  • Advanced glycation end-products
  • Biomechanics
  • Bone
  • Diabetes
  • Microdamage
  • Non-enzymatic glycation
  • microCT

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