A therapeutic composition is described that can be used for treating or prevention of diseases association with bone resorption, particularly of a metastatic carcinoma. In certain aspects, the composition is based on a polypeptide which includes the leading 215 amino acids of the human osteoprotegerin followed by the Fc portion of the human IgGl protein. DNA expression vectors and expression systems for overproducing the polypeptide in mammalian cells are also provided for.