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.

 
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