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This Article Full Text Full Text (PDF) All Versions of this Article: 296/4/E765    most recent 90937.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Reinwald, S. Articles by Burr, D. B. Search for Related Content PubMed PubMed Citation Articles by Reinwald, S. Articles by Burr, D. B.

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

¹Department of Anatomy and Cell Biology, Indiana University School of Medicine; and ²PreClinOmics, Inc., Indianapolis, Indiana

Submitted 17 November 2008 ; accepted in final form 18 January 2009

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.

hyperglycemia; leptin; leptin receptor; Zucker diabetic fatty rat; Zucker diabetic Sprague-Dawley rat