Type 2 diabetes (T2D) incidence in adolescents is rising, and may interfere with peak bone mass acquisition. We tested the effects of early onset T2D on bone mass, microarchitecture and strength in the TALLYHO/JngJ mouse, which develops T2D by 8 wks of age. We assessed metabolism and skeletal acquisition in male TALLYHO/JngJ and SWR/J controls (N=8-10/group) from 4 wks to 8 and 17 wks of age. Tallyho mice were obese; had ∼2-fold higher leptin and %body fat; and had lower BMD vs. SWR at all time points (p<0.03 for all). Tallyho had severe deficits in distal femur trabecular (Tb) bone volume fraction (BV/TV) (-54%), Tb number (-27%), and connectivity density (Conn.D) (-82%) (p<0.01 for all). Bone formation was higher in Tallyho mice at 8 wks but lower by 17 wks of age vs. SWR despite similar numbers of osteoblasts. Bone marrow adiposity was 7- to 50-fold higher in Tallyho vs. SWR. In vitro, primary bone marrow stromal cell differentiation into osteoblast and adipocyte lineages was similar in SWR and Tallyho, suggesting skeletal deficits were not due to intrinsic defects in Tallyho bone-forming cells. These data suggest the Tallyho mouse might be a useful model to study the skeletal effects of adolescent T2D.
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