Skeletal changes associated with the onset of type 2 diabetes in the ZDF and ZDSD rodent models

Susan Reinwald, Richard G. Peterson, Matthew Allen, David Burr

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

The incidence and prevalence of type 2 diabetes (T2D) continue to escalate at an unprecedented rate in the United States, particularly among populations with high rates of obesity. The impact of T2D on bone mass, geometry, architecture, strength, and resistance to fracture has yet to be incontrovertibly characterized because of the complex and heterogeneous nature of this disease. This study utilized skeletally mature male diabetic rats of the commonly used Zucker diabetic fatty (ZDF) and Zucker diabetic Sprague-Dawley (ZDSD) strains as surrogate models to assess alterations in bone attributable to T2D-like states. After the animals were euthanized, bone data were collected using dual-energy X-ray absorptiometry, peripheral quantitative tomography, and micro-CT imaging modalities and via three-point bending or compression mechanical testing methods. ZDF and ZDSD diabetic rats exhibited lower bone mineral densities, which coincided with declines in structural strength and increased fragility at the femoral midshaft and the L4 vertebral body in response to monotonic loading. Vertebral trabecular morphology was compromised in both diabetic rodent strains, and ZDSD diabetic rats exhibited additional phenotypic impairments to bone material properties at the spine. Because the metabolic origin of the T2D-like state that develops in the ZDSD rat strain is highly relevant to adult-onset diabetes, it is a particularly attractive novel model for future preclinical research.

Original languageEnglish
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume296
Issue number4
DOIs
StatePublished - Apr 2009

Fingerprint

Type 2 Diabetes Mellitus
Rodentia
Sprague Dawley Rats
Bone and Bones
Photon Absorptiometry
Thigh
Bone Density
Spine
Obesity
Tomography
Incidence
Research
Population

Keywords

  • Hyperglycemia
  • Leptin
  • Leptin receptor
  • Zucker diabetic fatty rat
  • Zucker diabetic sprague-dawley rat

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Endocrinology, Diabetes and Metabolism

Cite this

Skeletal changes associated with the onset of type 2 diabetes in the ZDF and ZDSD rodent models. / Reinwald, Susan; Peterson, Richard G.; Allen, Matthew; Burr, David.

In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 296, No. 4, 04.2009.

Research output: Contribution to journalArticle

@article{d00d8a989a9a4bde8ba9ab84a07562fe,
title = "Skeletal changes associated with the onset of type 2 diabetes in the ZDF and ZDSD rodent models",
abstract = "The incidence and prevalence of type 2 diabetes (T2D) continue to escalate at an unprecedented rate in the United States, particularly among populations with high rates of obesity. The impact of T2D on bone mass, geometry, architecture, strength, and resistance to fracture has yet to be incontrovertibly characterized because of the complex and heterogeneous nature of this disease. This study utilized skeletally mature male diabetic rats of the commonly used Zucker diabetic fatty (ZDF) and Zucker diabetic Sprague-Dawley (ZDSD) strains as surrogate models to assess alterations in bone attributable to T2D-like states. After the animals were euthanized, bone data were collected using dual-energy X-ray absorptiometry, peripheral quantitative tomography, and micro-CT imaging modalities and via three-point bending or compression mechanical testing methods. ZDF and ZDSD diabetic rats exhibited lower bone mineral densities, which coincided with declines in structural strength and increased fragility at the femoral midshaft and the L4 vertebral body in response to monotonic loading. Vertebral trabecular morphology was compromised in both diabetic rodent strains, and ZDSD diabetic rats exhibited additional phenotypic impairments to bone material properties at the spine. Because the metabolic origin of the T2D-like state that develops in the ZDSD rat strain is highly relevant to adult-onset diabetes, it is a particularly attractive novel model for future preclinical research.",
keywords = "Hyperglycemia, Leptin, Leptin receptor, Zucker diabetic fatty rat, Zucker diabetic sprague-dawley rat",
author = "Susan Reinwald and Peterson, {Richard G.} and Matthew Allen and David Burr",
year = "2009",
month = "4",
doi = "10.1152/ajpendo.90937.2008",
language = "English",
volume = "296",
journal = "American Journal of Physiology",
issn = "0193-1857",
publisher = "American Physiological Society",
number = "4",

}

TY - JOUR

T1 - Skeletal changes associated with the onset of type 2 diabetes in the ZDF and ZDSD rodent models

AU - Reinwald, Susan

AU - Peterson, Richard G.

AU - Allen, Matthew

AU - Burr, David

PY - 2009/4

Y1 - 2009/4

N2 - The incidence and prevalence of type 2 diabetes (T2D) continue to escalate at an unprecedented rate in the United States, particularly among populations with high rates of obesity. The impact of T2D on bone mass, geometry, architecture, strength, and resistance to fracture has yet to be incontrovertibly characterized because of the complex and heterogeneous nature of this disease. This study utilized skeletally mature male diabetic rats of the commonly used Zucker diabetic fatty (ZDF) and Zucker diabetic Sprague-Dawley (ZDSD) strains as surrogate models to assess alterations in bone attributable to T2D-like states. After the animals were euthanized, bone data were collected using dual-energy X-ray absorptiometry, peripheral quantitative tomography, and micro-CT imaging modalities and via three-point bending or compression mechanical testing methods. ZDF and ZDSD diabetic rats exhibited lower bone mineral densities, which coincided with declines in structural strength and increased fragility at the femoral midshaft and the L4 vertebral body in response to monotonic loading. Vertebral trabecular morphology was compromised in both diabetic rodent strains, and ZDSD diabetic rats exhibited additional phenotypic impairments to bone material properties at the spine. Because the metabolic origin of the T2D-like state that develops in the ZDSD rat strain is highly relevant to adult-onset diabetes, it is a particularly attractive novel model for future preclinical research.

AB - The incidence and prevalence of type 2 diabetes (T2D) continue to escalate at an unprecedented rate in the United States, particularly among populations with high rates of obesity. The impact of T2D on bone mass, geometry, architecture, strength, and resistance to fracture has yet to be incontrovertibly characterized because of the complex and heterogeneous nature of this disease. This study utilized skeletally mature male diabetic rats of the commonly used Zucker diabetic fatty (ZDF) and Zucker diabetic Sprague-Dawley (ZDSD) strains as surrogate models to assess alterations in bone attributable to T2D-like states. After the animals were euthanized, bone data were collected using dual-energy X-ray absorptiometry, peripheral quantitative tomography, and micro-CT imaging modalities and via three-point bending or compression mechanical testing methods. ZDF and ZDSD diabetic rats exhibited lower bone mineral densities, which coincided with declines in structural strength and increased fragility at the femoral midshaft and the L4 vertebral body in response to monotonic loading. Vertebral trabecular morphology was compromised in both diabetic rodent strains, and ZDSD diabetic rats exhibited additional phenotypic impairments to bone material properties at the spine. Because the metabolic origin of the T2D-like state that develops in the ZDSD rat strain is highly relevant to adult-onset diabetes, it is a particularly attractive novel model for future preclinical research.

KW - Hyperglycemia

KW - Leptin

KW - Leptin receptor

KW - Zucker diabetic fatty rat

KW - Zucker diabetic sprague-dawley rat

UR - http://www.scopus.com/inward/record.url?scp=65649135477&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=65649135477&partnerID=8YFLogxK

U2 - 10.1152/ajpendo.90937.2008

DO - 10.1152/ajpendo.90937.2008

M3 - Article

C2 - 19158319

AN - SCOPUS:65649135477

VL - 296

JO - American Journal of Physiology

JF - American Journal of Physiology

SN - 0193-1857

IS - 4

ER -