Increasing Wnt signaling in the bone microenvironment prevents the development of myeloma bone disease. MicroCT analysis of tibiae of 5TGM1-pcDNA and 5TGM1-ΔNTCF4 myeloma–bearing mice demonstrated a significant reduction in trabecular bone volume (A,C) and increase in osteolytic bone lesions (B,D) that was prevented by treatment with LiCl. LiCl also significantly prevented the reduction in bone formation rates associated with the development of myeloma bone disease (E). Data are expressed as means (± SEM). *P < .05 compared with nontumor. **P < .01 compared with nontumor. †P < .05, ††P < .01 compared with untreated.