Trabecular bone analysis of loading effects in the same mice showed that of the four trabecular bone parameters analysed, only Tb.Th increased dose responsively in the male WT+/+ mice ( Table 4). Tb.Th in the male Lrp5−/− counterparts did not show a dose–response with loading, though

analysis of the side-to-side differences showed modest but significant Tb.Th loading effects at all 3 load levels in Lrp5−/− males ( Table 2). The magnitude of this response in Tb.Th was similar to that found in male WT+/+ mice. Female WT+/+ and Lrp5−/− mice did not respond dose-responsively to any of the trabecular parameters, the one exception being Tb.Th in Lrp5−/− mice ( Table 3, Fig. 4). However, since the female WT+/+ mice did not respond to loading in a significant dose:responsive manner, the effect in Tb.Th is difficult to interpret. Among the WT+/+ females, Tb.Th in the high load group was the only outcome that learn more produced a significant side-to-side effect ( Table 2). Female Lrp5−/− showed significant side-to-side loading effects

in BV/TV at the medium load, and in Tb.Th in the medium and high loads, but interpretation of this effect is difficult because the WT+/+ controls did not respond for one of the three effects found in Lrp5−/− females. Mechanical loading significantly and dose-responsively PLX4032 increased the cortical bone parameters, % cortical bone area and % total area in WTHBM− and Lrp5HBM+ male and female mice ( Fig. 3, Table 3 and Table 4). A significant dose-responsive reduction in medullary

area was observed in Lrp5HBM+ females, but not in their WT controls ( Table 3). Analysis of side-to-side differences for at individual strain levels indicate that the Lrp5HBM+ mice respond significantly at strains insufficient to induce a similar cortical response in WTHBM− mice, and when WTHBM− mice do show a significant side-to-side effect, the Lrp5HBM+ response is typically significantly greater ( Table 2, Fig. 3). Trabecular bone analysis of loading effects in the same mice showed that mechanical loading significantly and dose-responsively increased BV/TV and Tb.Th in male and female WTHBM− and Lrp5HBM+ mice ( Fig. 4, Table 3 and Table 4). Post-hoc analysis of the strain:response slopes indicated that the Tb.Th response to loading was significantly enhanced in male and female Lrp5HBM+ mice, compared with their respective WTHBM− controls. Analysis of side-to-side differences at individual strain levels indicate that the Lrp5HBM+ mice respond significantly at strains insufficient to induce similar trabecular responses in WTHBM− mice, and when WTHBM− mice do show a significant side-to-side effect, the Lrp5HBM+ response is typically significantly greater ( Table 2). The primary objective of the experiments described in this paper was to establish the role of Lrp5 in bone’s response to mechanical loading.