Abstract: The invention provides a novel method for down-regulating the biological activity of osteoprotegerin ligand (OPGL, TRANCE) thereby rendering possible the treatment/amelioration of diseases characterized by excessive loss of bone mass, e.g. osteoporosis. Down-regulation is effected by inducing an immune response against OPGL in an individual in need thereof. Immune responses can be raised by classical immunization with immunogenic variants of OPGL or by nucleic acid immunization where the nucleic acids encode the OPGL variant. The invention also pertains to compositions, polypeptides and nucleic acids useful in the invention, as well as to vectors and transformed host cells useful in the preparation thereof.