Paget's disease of the bone and its management

Paget's disease of bone (PD) is a monostotic or polyostotic non-hormonal osteometabolic disorder.Over a century after the original disease was described by Sir John Paget 1 in 1877, and despite recent intensive studies and widespread interest, its aetiology remains obscure.This review describes the pathomechanism of the structural changes which occur in bone affected with PD, induced by the different dynamic patterns of activity of the disease, and outlines the current methods of treatment. AetiologyThe tendency for sarcomatous transformation, the variability of the appearance of the osteoblasts as regards size, shape and staining, the peculiarity of the osteoclasts with differences in size and up to 100 nuclei, as seen also in giant-cell tumours, and control of the disease by antimitotic agents such as plicamycin, also known as mithramycin, suggest that PD may be a benign neoplasm of the mesenchymal osteoprogenitor cell, as was suggested by Rasmussen and Bordier in 1973.2 It has been postulated that it may be the result of a viral infection.[3][4][5][6] Electron microscopy of osteoclasts has shown the presence of viral intranuclear inclusion structures resembling those of an RNA-type virus related to measles or subacute sclerosing panencephalitis.Immunological studies have indicated the presence of specific viral antigens in osteoclasts and cells grown from Paget's bone.7 A characteristic feature of paramyxoviruses is their ability to persist at very low levels, and to invade the host immune system.Factors which can be activated by the ROS virus, for example, IL-6, C-fos and Bcl-2, are all strongly elevated in PD suggesting that it may be a viral infection.It has been noted that PD is associated with the ownership of birds, dogs, cats or cattle.8,9 Investigations have shown that canine distemper, a paramyxovirus closely related to measles, can contaminate human osteoclast cells, which may contribute to the development of PD. 10,11 Other studies, 12 however, have found no risk factors associated with dogs or cats.Prevalence, distribution and genetic factors PD is found more commonly in people of Anglo-Saxon origin and is rarely encountered in China, Japan, Iran, India, Scandinavia, Africa or the Middle East.13 A survey in Johannesburg, South Africa, revealed a prevalence of 1.3% among the black population and 2.4% among the white, 14 but a recent report on radiological examination of the pelvis 15 showed an estimated overall prevalence in the USA of 1% to 2% with nearly equal distribution between whites and blacks and between sexes.Post-mortem 16,17 and radiological studies 18 indicate that the overall prevalence of PD is 3% to 3.7%, increasing with age.By the age of 90 years, the expected prevalence is about 10%.17Genetic factors play a role in the pathogenesis of PD, which is inherited as an autosomal dominant trait with high penetrance.19,20 It may be seen in more than one member of a family with a prevalence of approximately seven times more in relatives or patients than in control subjects. 21Studies in families with PD have shown linkage to a region of chromosome 18q near the polymorphic locus D18S42, most likely as a result of gene mutation.19,22,23 Genetic heterogeneity is almost certainly present; data from some families with PD suggest the presence of at least one additional locus, which remains to be identified. HistopathologyHistopathological examination shows changes in the structure of bone and fibrosis of the marrow.The bone has a socalled mosaic appearance, the hallmark of a Pagetic lesion, and a peculiar cellularity consisting of variable sizes of osteoblast and large osteoclasts with up to 100 nuclei.