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

doi:10.1016/j.bone.2010.12.016

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 journal › Article › peer-review

88 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 (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 10weeks 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.

Original language	English
Pages (from-to)	733-740
Number of pages	8
Journal	Bone
Volume	48
Issue number	4
DOIs	https://doi.org/10.1016/j.bone.2010.12.016
State	Published - 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
Physiology
Histology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.bone.2010.12.016

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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 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.",

keywords = "Biomechanics, Bone density, Bone toughness, Diabetes, Nanoindentation",

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

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). ",

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T1 - Increasing duration of type 1 diabetes perturbs the strength-structure relationship and increases brittleness of bone

AU - Nyman, Jeffry S.

AU - Even, Jesse L.

AU - Jo, Chan Hee

AU - Herbert, Erik G.

AU - Murry, Matthew R.

AU - Cockrell, Gael E.

AU - Wahl, Elizabeth C.

AU - Bunn, R. Clay

AU - Lumpkin, Charles K.

AU - Fowlkes, John L.

AU - Thrailkill, Kathryn M.

N1 - 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).

PY - 2011/4/1

Y1 - 2011/4/1

N2 - 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.

AB - 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.

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KW - Nanoindentation

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

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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