Osteoprotegerin variant proteins

An osteoprotegerin (OPG) variant protein and conservative substitutions thereof, the variant protein consisting of a modification at residue 115 and one or more additional modifications when compared to wild-type OPG, and wherein the one or more additional modifications occur at one or more residues selected from the group consisting of:

• 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 40, 42, 43, 45, 46, 48, 49, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 63, 64, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 98, 99, 100, 101, 102, 111, 122, 128, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 141, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200 and 201;
• and wherein the OPG variant protein or conservative substitution thereof retains binding affinity for receptor activator of NFκB ligand (RANKL) but exhibits reduced binding affinity for TNF-related apoptosis inducing ligand (TRAIL) when compared to wild-type OPG.

An osteoprotegerin (OPG) variant protein and conservative substitutions thereof, the variant protein consisting of a modification at residue 115 and one or more additional modifications when compared to wild-type OPG, wherein the one or more additional modifications occur at residues selected from the group consisting of:

• 107-154;
• and wherein the OPG variant protein or conservative substitution thereof retains binding affinity for receptor activator of NFκB ligand (RANKL) but exhibits reduced binding affinity for TNF-related apoptosis inducing ligand (TRAIL) when compared to wild-type OPG.