Reviews in Endocrine & Metabolic Disorders 2001;2:195±201 # 2001 Kluwer Academic Publishers. Manufactured in The Netherlands. Paget's Disease of Bone: A Disease of the Osteoclast Sakamuri V. Reddy, Noriyoshi Kurihara, Cheikh Menaa, and G. David Roodman Department of Medicine, Division of Hematology, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX, and the Audie L. Murphy Veterans Administration Hospital, 7400 Merton Minter Boulevard, San Antonio, TX Key Words. Paget's disease, osteoclast, measles virus, bisphos- phonates Introduction Paget's disease of bone was ®rst described by Sir James Paget over 100 years ago, and its clinical description has changed little since that time [1]. Paget's disease is a disease of the elderly and usually occurs in patients over the age of 55, although younger patients have been reported. Paget's disease is the second most common metabolic bone disease and affects between 2±3% of the population over the age of 60. It has an even higher incidence in patients over the age of 75. The incidence of Paget's disease appears to be decreasing over the last several decades [2±4], but the basis for this decrease in the incidence of Paget's disease is unknown. Paget's disease can cause deformity or enlargement of single or multiple bones. Although any bone in the body can be involved with Paget's disease, the skull, long bones, and vertebral bodies are the most frequently affected bones. Patients with Paget's disease are frequently asympto- matic, but approximately 10±15% of the patients have severe symptoms including bone pain, fractures, neuro- logical complications due to spinal cord compression or nerve entrapment syndromes, deafness, and dental abnormalities. Paget's disease is a highly localized disease, and new lesions rarely, if ever, develop during the course of the disease. Rather, lesions continue to progress in size if untreated. 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. Siris et al. [5] and Meunier et al. [6] have ascribed this increased bone remodeling in unaffected bones 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 (PTH) levels, and even these PTH levels are modestly increased at best. Thus, the increased bone remodeling in bones not involved with Paget's disease in these patients cannot be explained solely on the basis of secondary hyperparathyroidism. A juvenile form of Paget's disease occurs, although it 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 [7], including the absence of viral-like nuclear inclusions. Epidemiology As noted above, Paget's disease affects a signi®cant percentage of the population over the age of 50, with 1 to 3 million patients affected with Paget's disease in the United States. Paget's disease has a very unusual geographic distribution, with an increased incidence in Caucasians from the British Isles, Australia, North America, and Western Europe, rarely occurring in the Orient or Scandinavia. Interestingly, even within Britain there is a marked geographic variation in the incidence of Paget's disease, with an increased incidence in the Western portion of England and a much lower incidence in the Southern portion of England (8% vs. 4%) [8]. This unusual geographic distribution for the incidence of Paget's disease is not attributable to geographic, environmental or industrial exposures in these areas and currently cannot be explained. Address correspondence to: G. David Roodman, Research Service (151), Audie Murphy Veterans Administration Hospital, 7400 Merton Minter Boulevard, San Antonio, TX 78284. E-mail: roodman@uthscsa.edu 195