The present invention relates to novel osteoprotegerin variant proteins
(OVPs) that demonstrate reduced binding affinity for their ligand TRAIL
when compared to wild-type osteoprotegerin. Nucleic acids which encode
these OVPs are also provided. Recombinant vectors and host cells
expressing these OVPs are also encompassed as are methods of producing
recombinant OVPs. The present invention also relates to compositions
comprising these OVPs, and to methods of treating bone diseases
characterised by increased bone turnover and/or loss. The OVPs of the
invention are useful for preventing bone resorption and may be used to
treat any condition resulting in abnormal bone turnover or bone loss such
as osteoporosis, hypercalcemia, Paget's disease of bone, multiple
myeloma, bone cancer and bone loss due to rheumatoid arthritis or
osteomyelitis, and the like.