A novel rat model for the study of deficits in bone formation in type-2 diabetes

Background There is evidence to suggest that impairment in bone formation and or turnover is associated with the metabolic abnormalities characteristic of type2 diabetes mellitus. However, bone regeneration repair in type-2 diabetes has not been modeled. Using Zucker Diabetic Fatty (ZDF) rats (a mod...

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Bibliographic Details
Published in:Acta orthopaedica 2007-02, Vol.78 (1), p.46-55
Main Authors: Liu, Zhendong, Aronson, James, Wahl, Elizabeth C, Liu, Lichu, Perrien, Daniel S, Kern, Phillip A, Fowlkes, John L, Thrailkill, Kathryn M, Bunn, Robert C, Cockrell, Gael E, Skinner, Robert A, Lumpkin, Charles K
Format: Article
Language:English
Subjects:
Animals
Bone and Bones - cytology
Bone and Bones - metabolism
Bone and Bones - pathology
Bone Density
Bone Regeneration - physiology
Cell Proliferation
Diabetes Mellitus, Experimental - metabolism
Diabetes Mellitus, Experimental - pathology
Diabetes Mellitus, Experimental - physiopathology
Diabetes Mellitus, Type 2 - metabolism
Diabetes Mellitus, Type 2 - pathology
Diabetes Mellitus, Type 2 - physiopathology
Immunohistochemistry
Models, Biological
Osteogenesis - physiology
Rats
Rats, Zucker
Tibia - cytology
Tibia - metabolism
Tibia - pathology
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Summary:Background There is evidence to suggest that impairment in bone formation and or turnover is associated with the metabolic abnormalities characteristic of type2 diabetes mellitus. However, bone regeneration repair in type-2 diabetes has not been modeled. Using Zucker Diabetic Fatty (ZDF) rats (a model of type-2 diabetes) for tibial distraction osteogenesis (DO), we hypothesized that bone formation within the distraction gap would be impaired. Animals and methods Rats were examined for body weight, glycosuria, and glycosemia to confirm the diabetic condition during the study. The rats received placement of the external fixators and osteotomies on the left tibia. Distraction was initiated the following day at 0.2 mm twice a day and continued for 14 days. The lengthened tibiae were harvested and distraction gaps were examined radiographically and histologically. Results We found significant reduction in new bone formation in the distraction gaps of the ZDF rats, both radiographically and histologically, compared to lean rats. We found a decrease in a marker of cellular proliferation in the distraction gaps and increased adipose volume in adjacent bone marrow of the ZDF rats. Interpretation Our findings suggest that this model might be used to study the contributions of leptin resistance, insulin resistance and or hyperglycemia to impaired osteoblastogenesis in vivo.
ISSN:1745-3674
1745-3682
DOI:10.1080/17453670610013411