Ovariectomy (OVX)-induced estrogen withdrawal resulted in both bone loss and an increase in fat. We observed elevated osteoclast (OC) formation by bone marrow-derived macrophages treated with medium conditioned by fats from OVX mice, but not from sham-operated mice. Fats from OVX mice expressed and secreted higher levels of monocyte chemoattractant protein-1 (MCP-1) than those from sham-operated mice. Increased fat resulting from estrogen deficiency is thus responsible for bone loss due to enhanced OC formation, which is, at least partly, a consequence of elevated MCP-1 production.