CD47, also called integrin-associated protein, plays a critical role in the innate immune response and is an atypical memberof the immunoglobulin superfamily that interacts with and activates β3 integrins. β3 integrin–/– mice have defective platelet and osteoclast function and are protected from bone metastasis. The role of CD47 in skeletal homeostasis and bone metastasis has not been described.