L-4F prevents myeloma bone disease and increases bone volume and bone formation in non–tumor-bearing mice. (A) KaLwRij mice were treated with L-4F for 28 days before inoculation of 5TGM1 myeloma cells. Treatment was continued for a further 25 days, at which point mice were killed. Representative images of tibiae of vehicle and L-4F treated are shown. Osteolytic lesions through cortical bone were quantitated after micro-CT analysis. Vehicle, n = 9; L-4F, n = 10. (B) Bone formation rates in myeloma-bearing control and L-4F–treated mice were quantitated by dynamic histomorphometry. (C) KaLwRij mice were treated with L-4F for 28 days. Micro-CT analysis demonstrated a significant increase in trabecular bone volume. N = 5 per group. (D) Osteoblast number in control and L-4F–treated mice was quantitated by histomorphometry. (E) Adiponectin-deficient mice (KO) or WT controls were treated with L-4F for 28 days before inoculation of 5TGM1 myeloma cells. Treatment was continued for a further 25 days, at which point mice were killed. Trabecular bone volume was quantitated by micro-CT analysis, and rates of bone formation were quantitated by dynamic histomorphometry (F). (E-F) Data are presented as percentage change in response to treatment with L-4F. Data are mean ± SEM. *P < .05 and ***P < .001, compared with vehicle. #P < .05, compared with WT.