The 82nd Annual Meeting of the American Association of Physical Anthropologists (2013)

Severely impaired skeletal acquisition in a mouse model of adolescent Type 2 diabetes


1Anthropology, University of Michigan, 2Center for Advanced Orthopaedic Studies, Beth Israel Deaconess Medical Center, 3Orthopaedic Surgery, Harvard Medical School

Thursday 8:00-8:15, Ballroom B Add to calendar

The rise in adolescent onset type 2 diabetes (T2D) is of concern for bone health since diabetes is known to impair skeletal acquisition and increase fracture risk. Here we test the hypothesis that adolescent T2D impairs peak bone mass acquisition using the TALLYHO/JngJ mouse, a model of early onset polygenic T2D. We compared skeletal acquisition in male TALLYHO/JngJ and SWR/J controls (N=8-10/grp) starting at 4 wks of age. Outcomes at 8 and 17 wks of age included body mass, %body fat, glucose tolerance, whole body bone mineral densitometry by pDXA, cortical and trabecular microarchitecture by ┬ÁCT, femoral strength by three-point bending, and cortical bone tissue material properties by microindentation. Tallyho were obese and glucose intolerant, developing T2D (fasting glucose >250 mg/dl) by 8 wks of age. Tallyho had ~2-fold higher leptin and %body fat, with severe deficits in distal femur trabecular bone volume fraction (-54%), trabecular number (-27%) and connectivity density (-82%) vs. SWR (p<0.03 for all). Tallyho had higher midshaft femur cortical bone area fraction, cortical thickness, total cross-sectional area, and polar moment of inertia vs. SWR (p<0.05 for all), reflecting their higher body mass. Three-point bending of the diaphysis showed Tallyho had lower post-yield displacement than SWR, indicating brittleness (p<0.01 for both). Microindentation showed higher indentation distances in Tallyho (p<0.05), signifying impaired cortical bone tissue properties. The Tallyho mouse has pronounced deficits in bone mineral content, trabecular microarchitecture, cortical bone material properties, and bone brittleness, suggesting adolescent T2D may be deleterious to bone health in humans.

Funding for this project was provided by NIH RC1AR058389 and F32HD060419.

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