Investigation of Mechanical, Material, and Compositional Determinants of Human Trabecular Bone Quality in Type 2 Diabetes

J Clin Endocrinol Metab. 2021 Apr 23;106(5):e2271-e2289. doi: 10.1210/clinem/dgab027.

Abstract

Context: Increased bone fragility and reduced energy absorption to fracture associated with type 2 diabetes (T2D) cannot be explained by bone mineral density alone. This study, for the first time, reports on alterations in bone tissue's material properties obtained from individuals with diabetes and known fragility fracture status.

Objective: To investigate the role of T2D in altering biomechanical, microstructural, and compositional properties of bone in individuals with fragility fracture.

Methods: Femoral head bone tissue specimens were collected from patients who underwent replacement surgery for fragility hip fracture. Trabecular bone quality parameters were compared in samples of 2 groups, nondiabetic (n = 40) and diabetic (n = 30), with a mean duration of disease 7.5 ± 2.8 years.

Results: No significant difference was observed in aBMD between the groups. Bone volume fraction (BV/TV) was lower in the diabetic group due to fewer and thinner trabeculae. The apparent-level toughness and postyield energy were lower in those with diabetes. Tissue-level (nanoindentation) modulus and hardness were lower in this group. Compositional differences in the diabetic group included lower mineral:matrix, wider mineral crystals, and bone collagen modifications-higher total fluorescent advanced glycation end-products (fAGEs), higher nonenzymatic cross-link ratio (NE-xLR), and altered secondary structure (amide bands). There was a strong inverse correlation between NE-xLR and postyield strain, fAGEs and postyield energy, and fAGEs and toughness.

Conclusion: The current study is novel in examining bone tissue in T2D following first hip fragility fracture. Our findings provide evidence of hyperglycemia's detrimental effects on trabecular bone quality at multiple scales leading to lower energy absorption and toughness indicative of increased propensity to bone fragility.

Keywords: AGEs; bone quality; bone toughness; diabetes; fragility fracture; trabecular bone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biomechanical Phenomena / physiology
  • Bone Density / physiology
  • Bone and Bones / chemistry
  • Bone and Bones / pathology
  • Bone and Bones / physiology*
  • Bone and Bones / ultrastructure
  • Cancellous Bone / physiology
  • Cancellous Bone / ultrastructure
  • Case-Control Studies
  • Collagen / analysis
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetes Mellitus, Type 2 / pathology
  • Diabetes Mellitus, Type 2 / physiopathology*
  • Female
  • Flexural Strength / physiology*
  • Glycation End Products, Advanced / analysis
  • Hip Fractures / complications
  • Hip Fractures / metabolism
  • Hip Fractures / pathology
  • Hip Fractures / physiopathology
  • Humans
  • India
  • Male
  • Middle Aged
  • Minerals / analysis

Substances

  • Glycation End Products, Advanced
  • Minerals
  • Collagen