INTRODUCTION: Body weight is positively correlated with bone mass and density, and both muscle mass and body fat are thought to play a role in regulating bone metabolism. We examined bone metabolism in calorically restricted mice to determine how alterations in soft tissue mass affect bone mass, density, and strength. MATERIALS AND METHODS: Caloric restriction (CR) was initiated in male mice at 14 wk of age at 10% restriction, increased to 25% restriction at 15 wk, and then increased to 40% restriction at 16 wk, where it was maintained until 24 wk of age when the study was terminated. Control mice were fed ad libitum (AL). Body composition, BMD, and BMC were measured by DXA, BMD and BMC in the femoral metaphysis were measured by pQCT, femora were tested in three-point bending, serum leptin and IGF-1 were measured using immunoassay, and osteoblast and osteoclast numbers were determined using histomorphometry. RESULTS: Body weight, lean mass, fat mass, percent body fat, serum leptin, and serum IGF-1 were all significantly lower in CR mice than AL mice. Whole body BMC and BMD did not differ significantly between the two groups. Femur BMC, BMD, cortical thickness, and fracture strength decreased significantly in CR mice, but trabecular bone volume fraction in the femur did not change with food restriction. Vertebral cortical thickness also decreased with caloric restriction, whereas spine BMC, BMD, and trabecular bone volume fraction were significantly increased with caloric restriction. CONCLUSIONS: Caloric restriction and its related weight reduction are associated with marked decreases in lean mass, fat mass, serum leptin and IGF-1, and cortical bone mass. Consistent with the opposite effects of leptin on cortical and cancellous bone, trabecular bone mass is spared during food restriction.