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Article Excerpt
After completing this article, the reader should be able to:
* Discuss the etiology of Paget disease of bone.
* Identify the clinical characteristics of the disease.
* Recognize the radiological manifestations of Paget disease of bone.
* Describe the treatment for Paget disease of bone.
On January 11, 1814, a man was born who would influence the science of medicine like Leonardo da Vinci influenced Renaissance art. This man, Sir James Paget, is considered to be one of the founders of modern pathology and one of the surgical "greats" of 19th century England (see Figure 1). Paget began his apprenticeship in medicine at the age of 16. At the age of 20, he began his medical studies at St. Bartholomew's Hospital in London. (1) Paget had not even graduated from medical school when he made his first important medical discovery: the pathogen for trichinosis. Trichinosis is a parasitic disease caused by minuscule roundworms that infest the muscles of the human body and usually is contracted by eating infected pork. When describing how he discovered this pathogen, Trichina spiralis, he said, "All the men in the dissecting rooms, teachers included, 'saw' the little white specks in the muscles, but I believe I alone 'looked at' them and 'observed' them." (2)
Paget wrote several important works, including Lectures on Tumors and Lectures on Surgical Pathology. He received many rewards and achieved knighthood in 1871. He also was the first to describe osteochondritis dessicans, also known as Osgood-Schlatter disease, and the first to recognize that the median nerve could be compressed at the wrist, which was confirmed in the early 20th century. Additionally, Paget was the first to describe several nonrheumatologic conditions, including Paget disease of the nipple, extramammary Paget disease, maxillary vein thrombosis and recurrent abscesses (Paget residual abscesses). (1) However, he is best known for his description of osteitis deformans, or Paget disease of bone, the clinical symptoms of which include enlarged bones, progressive deafness, bowed legs and chronically inflamed bone (see Figure 2). (2)
[FIGURE 1 OMITTED]
Paget disease of bone is a localized disorder of bone remodeling, with both active and inactive phases, that results in large and deformed bones in various parts of the skeleton. (3) Paget first described the disease in 1877 in reference to a small group of patients. These patients were described as having overly large heads and enlarged or deformed extremities with a higher likelihood of fracture. (3) Dr. Paget believed it was a new disease; however, today abundant evidence indicates that it was not a new development in 1877. This has been confirmed by histologic and radiographic studies of ancient skeletal remains. (1)
Skeletons unearthed in medieval burial grounds in England showed radiographic and histopathologic evidence of Paget disease. (4) Skeletons unearthed in a cemetery in Torre de Palma, Portugal, a Roman villa established in the late 1st century AD, also showed signs of Paget disease. The report of this exhumation and research, presented in 2002 to the Paleopathology Association by Drs Cook and Powell stated, "This adult male skeleton showed extensive new bone formation on the medial and lateral surfaces of the right ilium. There is no remaining normal bone cortex, and the underlying trabecular bone is coarsened. There is fine, new nodular bone on the recovered acetabulum. Radiographic and histologic analysis helps to differentiate between Paget disease of bone, fibrous dysplasia, and metastatic carcinoma in this interesting specimen." (5) It even has been suggested by some that the painting of a grotesque old woman with an enlarged head, hanging in the National Gallery in London, suggests Paget disease of the skull. (1)
Etiology
The exact cause of Paget disease remains uncertain. (6) However, genetic factors certainly are involved, and viral factors are suspected. (7) Research from several different areas of investigation provides useful hypotheses. One hypothesis, although still controversial, proposes that changes in bone remodeling occur due to a viral infection in the bone. These viruses include the measles virus, the canine distemper virus and the respiratory syncytial virus. (3)
A case-control study with dog owners indicated the risk of Paget disease was nearly 3 times higher in owners of unvaccinated dogs compared with those who owned dogs vaccinated against the distemper virus. (8) Additionally, a study of 13 patients with Paget disease found that the osteoclasts and peripheral blood mononuclear cells from 9 of these patients expressed measles virus transcripts, but none of the 10 control patients expressed any measles virus at all. In 1 patient, a novel mutation that converted lysine to glutamic acid in the measles virus transcript was identified. (9)
[FIGURE 2 OMITTED]
No theory about the cause of Paget disease has been proven definitively, and all remain controversial; however, studies suggest that Paget disease could result from a virus in the osteoclasts of genetically susceptible people. The belief is that the viral infection lies dormant for many years in the person, then an unknown trigger causes activation of the osteoclast, which in turn forms the pagetic osteoclasts. The bone then remodels until it appears characteristic of Paget disease. (10) This theory is supported by the fact that giant osteoclasts are present during the active phase of Paget disease, and giant osteoclasts also are found in viral infections such as measles. (3)
Paget disease of bone has a genetic predisposition and is inherited in an autodominant way. (11) This is called familial Paget disease. (3) One study that used bone scans to evaluate the presence of Paget disease reported that at least 40% of patients had at least 1 family member who also was affected. (12) Additionally, studies done to investigate the extent to which the disorder occurs in families reported that the risk of developing Paget disease was 7 times higher in individuals with relatives who had Paget disease than those who did not. (11)
Several studies also have reported a possible connection between Paget disease and the human leukocyte antigen, but the reports remain inconclusive. (13) Another study mapped the susceptibility for Paget disease to the gene located on chromosome 18q21-22. (14) This gene had been mapped first to a rare disease called familial expansile osteolysis, which has some of the same clinical characteristics as Paget disease. This same gene also was mapped in certain other families with Paget disease. Not all families with Paget disease have a linkage to chromosome 18q21-22, a factor which indicates genetic heterogeneity. (12,14)
Further research has uncovered several other genes related to Paget disease. One of these is the gene sequestesome 1, which can cause predisposition for Paget disease when altered. This altered gene was discovered by scientists first in families with histories of Paget disease in Canada, which in turn led to the same discoveries in other parts of the world, including the United States. (3) When Paget disease occurs without any family history, it is called sporadic Paget disease. (6)
Incidence
Although the exact reason is not known, Paget disease of bone is believed to be more common in some parts of the world than others. Radiographic surveys in Europe of hospitalized patients who were older than 55 years found the highest percentages of Paget disease in England (4.6%) and France (2.4%). Slightly less prevalence was reported in Ireland (0.7% to 1.7%), Spain and West Germany (both 1.3%) and Italy (0.5%). Additionally, there is an especially high incidence (6.3% to 8.3%) of Paget disease in Lancashire, England, in people older than 55 years. Paget disease is rare in China, India and Malaysia; however, occasional cases of Paget disease in Indians living in the United States have been reported. (6) The prevalence also is high in Australia and New Zealand, with about 3% to 4% of the population being affected....
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