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Am J Physiol Endocrinol Metab (January 21, 2009). doi:10.1152/ajpendo.90937.2008
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Submitted on November 17, 2008
Revised on January 13, 2009
Accepted on January 18, 2009

Skeletal Changes Associated with the Onset of Type 2 Diabetes in the ZDF and ZDSD Rodent Models

Susan Reinwald1*, Richard G Peterson2, Matthew R Allen3, and David B. Burr4

1 Indiana University School of Medicine
2 PCO
3 Indiana School of Medicine
4 Indiana University, School of Medicine

* To whom correspondence should be addressed. E-mail: sureinwa{at}iupui.edu.

The incidence and prevalence of type 2 diabetes (T2D) continues 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 due to 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. Bone data were collected after euthanization using dual x-ray absorptiometry, peripheral quantitative tomography and micro-computed tomography imaging modalities and via three-point bending or compression mechanical testing methods. ZDF and ZDSD diabetic rats exhibited lower bone mineral densities that coincided with declines in structural strength and increased fragility at the femoral midshaft and the fourth lumbar 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. The metabolic origin of the T2D-like state that develops in the ZDSD rat strain is highly relevant to adult-onset diabetes and makes this strain a particularly attractive novel model for future preclinical research.







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