<P> There is a hereditary factor in the development of Paget's disease of bone . Two genes, SQSTM1 and RANK, and specific regions of chromosome 5 and 6 are associated with Paget's disease of bone . Genetic causes may or may not involve a family history of Paget's disease . </P> <P> About 40--50% of people with the inherited version of Paget's disease have a mutation in the gene SQSTM1, which encodes a protein, called p62, that is involved in regulating the function of osteoclasts (bone cells). However, about 10 - 15 percent of people that develop the disease without any family history also have a mutation in the SQSTM1 gene . </P> <P> Paget's disease of bone is associated with mutations in RANK . Receptor Activator of Nuclear Factor κ B (RANK), which is a type I membrane protein that is expressed on the surface of osteoclasts and is involved in their activation upon ligand binding Additional genetic associations include: </P> <Table> <Tr> <Th> Name </Th> <Th> OMIM </Th> <Th> Locus </Th> <Th> Gene </Th> </Tr> <Tr> <Td> PDB1 </Td> <Td> 167250 </Td> <Td> 6p </Td> <Td>? </Td> </Tr> <Tr> <Td> PDB2 </Td> <Td> </Td> <Td> 18q22. 1 </Td> <Td> RANK </Td> </Tr> <Tr> <Td> PDB3 </Td> <Td> </Td> <Td> 5q35 </Td> <Td> SQSTM1 </Td> </Tr> <Tr> <Td> PDB4 </Td> <Td> 606263 </Td> <Td> 5q31 </Td> <Td>? </Td> </Tr> </Table>

Pagets disease often leads to which of the following