The present invention includes compositions and methods that take advantage of MFG-E8s role as a homeostatic regulator of osteoclasts for treating a bone disorder or regulating osteoclast activation. In one aspect, the invention includes a composition comprising an effective amount of milk fat globule-EGF factor 8 (MFG-E8) formulated for local administration and a pharmaceutically acceptable carrier or adjuvant. In another aspect, a method is included for regulating osteoclast activation and inhibiting bone loss at a target site comprising locally administering an effective amount of milk fat globule-EGF factor 8 (MFG-E8) to the target site.
