Post-hoc comparison following mixed model analysis was carried out using Bonferroni adjustment. Statistical analysis was performed using SPSS for Windows (version 17.0; SPSS Inc., Chicago, USA) and p < 0.05 was considered to be significant. Initial and final body weight and longitudinal

lengths of the left control and right loaded tibiae are shown in Table 1. There were no significant differences between the body weights or bone lengths of mice treated with vehicle or risedronate at any dose. In trabecular SD-208 bone, treatment with risedronate at a dose of 15 or 150 μg/kg/day resulted in a significantly higher BV/TV of the left non-loaded tibiae than in vehicle-treated controls (Table 2, Fig. 2). This increase was primarily associated with higher trabecular number. In cortical bone, there were no significant differences in bone volume between vehicle-treated Epigenetics inhibitor and risedronate-treated animals at any dose. A dose of 0.15 μg/kg/day induced a lower medullary volume than in vehicle-treated controls, while at a dose of 1.5 μg/kg/day there was a slightly lower periosteally enclosed volume (Table 2, Fig. 2). As has been shown previously [34], [37] and [38], mechanical loading significantly increased both trabecular BV/TV and cortical bone volume (Table 2, Fig. 2). The former effect was primarily due to an increase in

trabecular thickness, while the latter response was mainly associated with an increase in periosteally enclosed volume. Mechanical loading-related increases in trabecular BV/TV and cortical bone volume, as assessed by the difference between the right loaded tibiae and their contra-lateral non-loaded controls, were not significantly influenced by treatment

with risedronate, even when given at a high dose (15 or 150 μg/kg/day) (Fig. 3 and Fig. 4). Consistent with previous reports [34] and [40], the fluorochrome-labeled images supported the inference that such loading-related bone gain was primarily associated with increased osteogenesis all (Fig. 5). The additive effect of risedronate and loading on trabecular BV/TV was found at a dose of 15 or 150 μg/kg/day (Table 2, Fig. 2), while there was no synergistic effect of risedronate and loading on trabecular or cortical bone at any dose (Fig. 3). A slight reduction in the loading-related increase in trabecular thickness was observed with high doses of risedronate, but this only reached statistical significance at a dose of 15 μg/kg/day (Fig. 3). In the present study, vehicle or risedronate at various doses was administered to 17–19 week old female C57BL/6 mice and changes in the structure of the tibiae three-dimensionally analyzed by high-resolution μCT. Although the treatment period was short, high doses of risedronate (15 and 150 μg/kg/day) resulted in higher trabecular BV/TV and trabecular number.