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Title page for ETD etd-07182018-171913


Type of Document Dissertation
Author Creecy, Amy
Author's Email Address amycreecy@gmail.com
URN etd-07182018-171913
Title Age- and Diabetes-Related Changes in the Matrix and Fracture Resistance of Bone
Degree PhD
Department Biomedical Engineering
Advisory Committee
Advisor Name Title
Jeffry Nyman, Ph.D. Committee Chair
David Merryman, Ph.D. Committee Member
Jeffery Davidson, Ph.D. Committee Member
Julie Sterling, Ph.D. Committee Member
Maureen Gannon, Ph.D. Committee Member
Michael Miga, Ph.D. Committee Member
Keywords
  • bone
  • extracellular matrix
  • mechanics
  • age
  • type 2 diabetes
Date of Defense 2018-06-15
Availability restricted
Abstract
Fracture resistance of bone depends on the hierarchical organization of its constituents, primarily the organic matrix, mineral, and water, and as such, requires characterization at multiple length-scales. The extracellular matrix of bone influences fracture resistance by promoting energy dissipation prior to breaking and inhibiting crack propagation. Aging and type 2 diabetes reduce bone quality independently of bone quantity, possibly through an accumulation of advanced glycation end-products (AGEs). However, it is not known how aging and type 2 diabetes affect bone matrix. Towards this goal, we have analyzed bone’s fracture resistance and matrix from preclinical models of type 2 diabetes and aging. Type 2 diabetes increased brittleness of cortical bone in a preclinical model. Higher tissue mineralization density and changes to the secondary structure of collagen could have resulted in the brittling of cortical bone. However, the brittleness phenotype did not progressively worsen with duration of diabetes. Aging lowered strength, toughness, and fracture toughness of cortical bone in a preclinical model. The bone matrix of older mice had higher mineralization density, altered collagen structure, higher enzymatic and non-enzymatic AGEs crosslinks, and lower bound water, all of which could have deleteriously affected fracture resistance. Furthermore, when analyzing proteins for post-translational modifications at specific sites, AGEs were found to be higher on specific residues of proteins from the matrix of older mice. Overall, matrix changes occur with aging and type 2 diabetes in preclinical models that have lower fracture resistance.
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