title: Increasing duration of type 1 diabetes perturbs the strength-structure relationship and increases brittleness of bone.
abstract: Type 1 diabetes (T1DM) increases the likelihood of a fracture. Despite serious complications in the healing of fractures among those with diabetes, the underlying causes are not delineated for the effect of diabetes on the fracture resistance of bone. Therefore, in a mouse model of T1DM, we have investigated the possibility that a prolonged state of diabetes perturbs the relationship between bone strength and structure (i.e., affects tissue properties). At 10, 15, and 18 weeks following injection of streptozotocin to induce diabetes, diabetic male mice and age-matched controls were examined for measures of skeletal integrity. We assessed 1) the moment of inertia (I(MIN)) of the cortical bone within diaphysis, trabecular bone architecture of the metaphysis, and mineralization density of the tissue (TMD) for each compartment of the femur by micro-computed tomography and 2) biomechanical properties by three-point bending test (femur) and nanoindentation (tibia). In the metaphysis, a significant decrease in trabecular bone volume fraction and trabecular TMD was apparent after 10 weeks of diabetes. For cortical bone, type 1 diabetes was associated with decreased cortical TMD, I(MIN), rigidity, and peak moment as well as a lack of normal age-related increases in the biomechanical properties. However, there were only modest differences in material properties between diabetic and normal mice at both whole bone and tissue-levels. As the duration of diabetes increased, bone toughness decreased relative to control. If the sole effect of diabetes on bone strength was due to a reduction in bone size, then I(MIN) would be the only significant variable explaining the variance in the maximum moment. However, general linear modeling found that the relationship between peak moment and I(MIN) depended on whether the bone was from a diabetic mouse and the duration of diabetes. Thus, these findings suggest that the elevated fracture risk among diabetics is impacted by complex changes in tissue properties that ultimately reduce the fracture resistance of bone.
authors.affiliation: Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, TN 27212, USA. jeffry.s.nyman@vanderbilt.edu
authors.forename: Jeffry S
authors.initials: JS
authors.lastname: Nyman
authors.forename: Jesse L
authors.initials: JL
authors.lastname: Even
authors.forename: Chan-Hee
authors.initials: CH
authors.lastname: Jo
authors.forename: Erik G
authors.initials: EG
authors.lastname: Herbert
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Murry
authors.forename: Gael E
authors.initials: GE
authors.lastname: Cockrell
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Wahl
authors.forename: R Clay
authors.initials: RC
authors.lastname: Bunn
authors.forename: Charles K
authors.initials: CK
authors.lastname: Lumpkin
authors.forename: John L
authors.initials: JL
authors.lastname: Fowlkes
authors.forename: Kathryn M
authors.initials: KM
authors.lastname: Thrailkill
mesh_terms: D000818:Animals; D015519:Bone Density; D001842:Bone and Bones / Q000503:physiopathology*; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000503:physiopathology*; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D013311:Streptozocin; D014057:Tomography, X-Ray Computed
chemical_list: D013311:Streptozocin