Part of “CHAPTER 65 – PAGET DISEASE OF BONE“

The precise etiology of Paget disease remains unknown; genetic and environmental—specifically viral—factors play a role. Geographic and ethnic epidemiologic data document the common occurrence of Paget disease in some parts of the world and its rarity in others. Earlier studies had indicated that Paget disease was present in 4% to 5% of older Britons.1 A focus of the disorder occurred in the Lancashire area, where as many as 8% of the older population showed radiographic evidence of this condition.2 Interestingly, more recent epidemiologic studies from the United Kingdom and New Zealand suggest both a decreasing frequency and decreasing severity of the disease.2a,2b Nonetheless, it is relatively common in those countries, as well as in Australia and throughout western Europe (with the exception of Scandinavia, where it is infrequently seen).3 The disorder is uncommon in both southern Asia (i.e., the Indian subcontinent), eastern Asia (i.e., China, Japan), and sub-Saharan Africa. In the United States, it occurs primarily in people of Anglo-Saxon or European descent but is seen in blacks, although apparently to a smaller degree than in whites.4

Paget disease is often present in more than one member of a family; this is noted in up to 40% of cases.5,6 and 7 This value may be an underestimate, because many patients with the condition never know they have it. Early studies analyzing pedigrees of several affected kindreds suggest autosomal dominant inheritance.8 Familial aggregation studies in the United States indicate that first-degree relatives of patients with Paget disease have seven times the risk of developing it than do persons without such a family history. The risk increases if the affected relative had deforming disease or was younger than 50 years old when the disease was diagnosed.9 Linkage of Paget disease to HLA is not conclusive.10,11,12 and 13 Specific susceptibility loci for Paget disease may occur on chromosome 18q, the apparent site of the gene responsible for a similar but rare bone dysplasia called familial expansile osteolysis.14 Studies have reported some families with
Paget disease that display genetic linkage to this site,15,16 but such linkage has not been found in others.16 Genetic heterogeneity is very likely.