Figure 4.

Intermittent ligand activation of Rs1 by RS67333 does not overtly alter the whole skeleton or diaphyseal cortical bone. A, Whole-body microCT images of control and ColI/Rs1–late (ColI/Rs1–late^Int) mice treated with RS67333 show no major skeletal changes after 10 wk of intermittent agonist treatment. Scale bars, 5 mm. B, Representative microCT midfemur cross-sectional images show no increase in trabecular bone in 13 of 14 ColI/Rs1–late^Int mice. However, one of the 14 mice (C) showed trabecular bone formation similar to that seen in the ColI/Rs1–late^Con mice. Scale bars, 1 mm. D–F, MicroCT quantitation of the 50 midfemur slices for TV, BV, and cortical thickness. n = 9 controls + vehicle; 11 controls + RS67333; 11 ColI/Rs1–late + vehicle; 13 ColI/Rs1–late^Int mice. Error bars, mean ± 1 sd. G, Serum alkaline phosphatase levels in the ColI/Rs1–late mice treated with vehicle or RS67333. n = 6 ColI/Rs1–late + vehicle; 6 ColI/Rs1–late^Int mice. Error bars, mean ± 1 sd. *, P < 0.05. H, P1NP levels in the ColI/Rs1–late mice treated with vehicle or RS67333. n =5 ColI/Rs1–late + vehicle; 7 ColI/Rs1–late^Int mice. Error bars, mean ± 1 sd. ***, P < 0.001.