Paget's Disease of Bone

Paget's disease, also known as osteitis deformans, is a condition caused by an initial increase in the breakdown of bone followed by chaotic, atypical creation of replacement bone. Paget's disease is the second most common bone disease following osteoporosis. In the United States, Paget's disease is prevalent in 3 to 4 percent of the general population older than 40 years of age. Globally, Paget's disease is present in approximately 10 percent of the population older than 80 years of age. Overall, Paget's disease is present in males and females with a ratio of 1.8:1. This disease bears resemblance only in name to other diseases named after the 19th century British pathologist Dr. James Paget, such as Paget's disease of the breast.

In a healthy adult, breakdown of bone is balanced with formation of new bone, so that no net increase in bone mass occurs. Paget's disease begins when osteoclasts (the cells that break down bone) become hyperactive, breaking down too much bone, and creating what are called lytic lesions. These lesions are most often found in the axial skeleton, particularly the skull and spine. Generally, the lytic lesions are at specific points in the skeleton and do not become widespread.

After the lytic lesions have formed, the number of osteoblasts (the cells that create new bone) increase in the surrounding bone as a response to the osteoclastic destruction. These osteoblasts secrete new bone matrix, but the replacement bone lacks the organized structure of normal bone. This results in enlargement and significant weakening of the affected bones.

Most patients with Paget's disease are actually asymptomatic. When symptoms do occur, localized skeletal pain is the most common symptom. An affected skull can compress cranial nerves, causing nerve deafness, blindness, or facial pain. If the skull base becomes flattened (known as platybasia), the brainstem is often compressed as it exits the skull. Enlarged facial bones result in disfigurement. Affected vertebrae can compress spinal nerve roots, causing both motor and sensory deficits. Fractures in affected weight-bearing bones are very common as well. Because the increased bone mass requires additional blood supply, some patients also develop high-out-put cardiac failure. In addition, patients with Paget's disease have an increased risk for malignant bone tumors, most common being osteosarcomas occurring in 5 percent of individuals with the disease.

Recent studies and epidemiological data provide strong evidence that a viral infection may trigger Pag-et's disease. Osteoclasts are not only more numerous but also larger and abnormal in appearance. Paget osteoclasts can have as many as 100 nuclei, more than [Page 1320]five times the normal number; also, the nuclei have inclusions that are typical of infection by viruses in the family Paramyxoviridae, which includes the measles virus and the respiratory syncytial virus. Both proteins and genetic markers unique to the measles virus have been discovered in osteoclasts from Paget patients by multiple investigators. Furthermore, the measles virus is known to cause severe encephalitis years after childhood infection, so a similar latent phenomenon may be at work in Paget's disease. However, despite these intriguing discoveries, definitive isolation of a causative virus for this bone disorder remains elusive.

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