Paget disease is a metabolic bone disease characterized by focal abnormalities of increased bone turnover affecting 1 or more sites throughout the skeleton, primarily the axial skeleton. Bone lesions in this disorder show evidence of increased osteoclastic bone ... Paget disease is a metabolic bone disease characterized by focal abnormalities of increased bone turnover affecting 1 or more sites throughout the skeleton, primarily the axial skeleton. Bone lesions in this disorder show evidence of increased osteoclastic bone resorption and disorganized bone structure. Ralston et al. (2008) provided a detailed review of the pathogenesis and current management of the disorder.
Paget disease of bone usually occurs in persons over the age of 40 years (Klein and Norman, 1995) and mainly affects the axial skeleton. Approximately 5% of patients present symptoms requiring treatment, the most frequent complaints being bone ... Paget disease of bone usually occurs in persons over the age of 40 years (Klein and Norman, 1995) and mainly affects the axial skeleton. Approximately 5% of patients present symptoms requiring treatment, the most frequent complaints being bone pain, enlargement, and deformities at the pagetic site (Kanis, 1998). Other manifestations of the disease include increased susceptibility to fractures, deafness, and neurologic complications (Hamdy, 1995). In 5 patients with ancestry in southern Italy, Jacobs et al. (1979) described giant cell tumor as a complication of Paget disease of bone. Three of the patients were related. High doses of dexamethasone resulted in dramatic shrinking of tumors. Wu et al. (1991) reported the cases of 2 sisters and a brother with longstanding (35 years in 1) polyostotic Paget disease. Two of them developed osteogenic sarcoma at sites unrelated to surgical procedures, one in the sacrum and one in the calvaria. Both died shortly after diagnosis of malignancy because of aggressive spread of the tumor. The 3 sibs came from Castallamarre, Italy, which is approximately 10 km from Avellino where the ancestors of the patients of Jacobs et al. (1979) lived.
In 4 families with Paget disease of bone and possible linkage to 18q, Hughes et al. (2000) performed mutation screening and in one of them found a duplication involving bases 75-101 in exon 1 of the TNFRSF11A gene ... In 4 families with Paget disease of bone and possible linkage to 18q, Hughes et al. (2000) performed mutation screening and in one of them found a duplication involving bases 75-101 in exon 1 of the TNFRSF11A gene (603499.0002) that cosegregated with the disease. No TNFRSF11A mutations were found in the other 3 PDB families, or in cDNA prepared from affected bone of 5 patients with sporadic PDB. Laurin et al. (2002) determined that PDB3 is caused by mutation in the SQSTM1 gene (601530). They could show that in a French Canadian population 2 independent mutational events must have caused the mutation, pro392 to leu (P392L; 601530.0001), since the mutation was found on 2 different haplotypes defined by intragenic SNPs. The mutation occurred at a hypermutable CpG dinucleotide, suggesting that it arose by deamination of a methylated cytosine.