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

Liu Z, Aronson J, Wahl EC, Liu L, Perrien DS, Kern PA, Fowlkes JL, Thrailkill KM, Bunn RC, Cockrell GE, Skinner RA, Lumpkin CK
Acta Orthop. 2007 78 (1): 46-55

PMID: 17453392 · DOI:10.1080/17453670610013411

BACKGROUND - There is evidence to suggest that impairment in bone formation and/or turnover is associated with the metabolic abnormalities characteristic of type-2 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.

MeSH Terms (13)

Animals Bone and Bones Bone Density Bone Regeneration Cell Proliferation Diabetes Mellitus, Experimental Diabetes Mellitus, Type 2 Immunohistochemistry Models, Biological Osteogenesis Rats Rats, Zucker Tibia

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