Increasing duration of type 1 diabetes perturbs the strength-structure relationship and increases brittleness of bone

Jeffry S. Nyman, Jesse L. Even, Chan Hee Jo, Erik G. Herbert, Matthew R. Murry, Gael E. Cockrell, Elizabeth C. Wahl, R. Clay Bunn, Charles K. Lumpkin, John L. Fowlkes, Kathryn M. Thrailkill

Research output: Contribution to journalArticlepeer-review

77 Scopus citations

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 18weeks 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 (IMIN) 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 10weeks of diabetes. For cortical bone, type 1 diabetes was associated with decreased cortical TMD, IMIN, 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 IMIN 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 IMIN 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.

Original languageEnglish
Pages (from-to)733-740
Number of pages8
JournalBone
Volume48
Issue number4
DOIs
StatePublished - Apr 1 2011

Bibliographical note

Funding Information:
We thank Professor George Pharr for access to the nanoindenter. This work was supported by a grant from the Children's University Medical Group fund of the Arkansas Children's Hospital Research Institute (to K.M.T.), the Martha Ann Pugh Diabetes Research Fund (to K.M.T.), the Arkansas Biosciences Institute (to J.L.F.), and in part by National Institutes of Health Grants R01DK055653 (to J.L.F.), R01AA012223 (to C.K.L.), and C06RR16517 (to Arkansas Children's Hospital Research Institute).

Keywords

  • Biomechanics
  • Bone density
  • Bone toughness
  • Diabetes
  • Nanoindentation

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Histology
  • Physiology

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