7) but not in the distal femur (Fig. 6). The trabecular BMD of the distal Ku-0059436 price femur (Fig. 6C) as well as the L3 vertebrae (Fig. 7C) was significantly improved

upon diet correction in both age groups, after adjusting to lean controls. The mean trabecular BVF in the distal femur of mature HFD:LFD mice was equivalent to the age-matched LFD:LFD controls; however, a relative deficit with no improvement persisted in the normalized BVF of immature mice (Fig. 6D). A trend towards improved cortical thickness (Fig. 6F) and significant relative improvements in SMI (Fig. 6E) as well as Tb.Th (Fig. 6H) was observed in the femurs of both age groups after diet correction (HFD:LFD). However,

all other trabecular structure metrics remained inferior to age-matched lean controls in the distal femur (Table S2). In the L3 vertebrae, relative improvements were observed with diet correction in the trabecular BVF, total cross-sectional bone area, and Tb.Th in both age groups (Figs. 7D,E,H). Interestingly, the vertebral Tb.Th of HFD-fed mice significantly exceeds that of age-matched LFD:LFD controls in both age groups after diet correction (Table S3). Further, the cortical shell thickness of the vertebral bodies is significantly improved after diet correction in the mature, but not immature, mice (Fig. 7F). In accordance with the recovered BVF and cortical thickness, as well as the increasing Tb.Th, INCB024360 in vivo the total cross-sectional bone area was significantly improved with diet correction in both age groups (Fig. 7E). The vertebral bone area was equivalent to age-matched LFD:LFD controls in the immature group and tended to exceed those of LFD:LFD controls in the mature group

(Table S3). The compressive strength of the L3 vertebral bodies followed the relative improvements aminophylline of bone structure after transitioning the HFD-fed mice to a lean diet. The maximum force, yield force and stiffness were significantly increased with the diet correction (HFD:LFD), after normalizing to age-matched LFD controls, in both age groups (Figs. 8C–E). Interestingly, while the strength of immature HFD:LFD mouse vertebrae was equivalent to that of lean controls, the strength of mature HFD:LFD mouse vertebrae tended to exceed that of their respective lean controls (Table S4). The effect of diet correction and trends in improvement remain significant after normalizing the compressive loads by the total cross-sectional bone areas (Figs. 8G–I). This result suggests that apparent bone tissue quality may be improved with diet correction, in relation to that of lean controls, particularly in mature mice.