Journal
JOURNAL OF ORTHOPAEDIC RESEARCH
Volume 38, Issue 5, Pages 972-983Publisher
WILEY
DOI: 10.1002/jor.24543
Keywords
advanced glycation end-products; non-enzymatic glycation; microindentation; fracture toughness; bone
Categories
Funding
- Office of the Provost at the University of Massachusetts Dartmouth
- National Science Foundation [1726239]
- National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health [K01AR069685]
- American Society for Bone and Mineral Research Rising Star Award
- Directorate For Engineering
- Div Of Chem, Bioeng, Env, & Transp Sys [1726239] Funding Source: National Science Foundation
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Advanced glycation end-products (AGEs) have been suggested to contribute to bone fragility in type 2 diabetes (T2D). AGEs can be induced through in vitro sugar incubations but there is limited data on the effect of total fluorescent AGEs on mechanical properties of human cortical bone, which may have altered characteristics in T2D. Thus, to examine the effect of AGEs on bone directly in T2D patients with uncontrolled sugar levels, it is essential to first understand the fundamental mechanisms by studying the effects of controlled in vitro-induced AGEs on cortical bone mechanical behavior. Here, human cortical bone specimens from female cadaveric tibias (ages 57-87) were incubated in an in vitro 0.6 M ribose or vehicle solution (n = 20/group) for 10 days at 37 degrees C, their mechanical properties were assessed by microindentation and fracture toughness tests, and induced AGE levels were quantified through a fluorometric assay. Results indicated that ribose-incubated bone had significantly more AGEs (+81%, p <= 0.005), lower elastic modulus assessed by traditional microindentation, and lower fracture toughness compared with vehicle controls. Furthermore, based on pooled data, increased AGEs were significantly correlated with deteriorated mechanical properties. The findings presented here show that the accumulation of AGEs allows for lower stiffness and increased ability to initiate a crack in human cortical bone. Statement of clinical significance: High sugar levels as in T2D results in deteriorated bone quality via AGE accumulation with a consequent weakening in bone's mechanical integrity. (c) 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res
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