Paget's Disease of Bone

Abstract

Paget's disease of bone was first described by Sir James Paget in 1877 as osteitis deformans, a chronic focal skeletal disease that can be monostotic or polyostotic. Paget's disease is the second most common metabolic bone disease and affects between 2 and 3% of the population over the age of 60. The disease is associated with deformity and enlargement of single or multiple bones, among which the skull, clavicles, long bones, and vertebral bodies are the most frequently involved. Patients with Paget's disease are frequently asymptomatic, but approximately 10 to 15% of the patients have severe symptoms including bone pain, fractures, neurological complications due to spinal cord compression, deafness, and dental abnormalities. Paget's disease is a highly localized disease and new lesions rarely develop during the course of the disease. Rather, lesions continue to progress in size unless treated. The primary pathologic abnormality in patients with Paget's disease is increased bone resorption, followed by abundant new bone formation. The bone that is formed is disorganized and of poor quality, resulting in bowing of the bone, stress fractures, and arthritis in joints contiguous to the involved bones. Another interesting feature of Paget's disease is that bones not clinically involved with Paget's disease appear to show increased bone remodeling. This increased bone remodeling in unaffected bones has been ascribed to secondary hyperparathyroidism rather than to subclinical involvement of the bones with Paget's disease. However, less than 20% of patients with Paget's disease have elevated parathyroid hormone levels. A juvenile form of Paget's disease, also called hyperostosis corticalis deformans juvenilis or hereditary hyperphosphatasia, is very different than the adult form of the disease. It is characterized by widespread involvement of the skeleton and has histological and radiological features that distinguish it from Paget's disease of the adults, including the absence of viral-like nuclear inclusions in osteoclasts present in the bone microenvironment.