$Unique_ID{BRK04076} $Pretitle{} $Title{Paget's Disease} $Subject{Congenital Hyperphosphatasemia Corticalis Deformans Formans Hyperostosis Corticalis Deformans Hyperphosphatasemia Osteitis deformans Paget's Disease of Bone Osteoporosis Osteoarthritis Engelmann Disease Hypophosphatasia Spinal Stenosis Hyperostosis Frontalis Interna} $Volume{} $Log{} Copyright (C) 1984, 1985, 1987, 1988, 1990, 1991, 1992 National Organization for Rare Disorders, Inc. 11: Paget's Disease ** IMPORTANT ** It is possible that the main title of the article (Paget's Disease) is not the name you expected. Please check the SYNONYMS listing to find the alternate name and disorder subdivisions covered by this article. Synonyms Congenital Hyperphosphatasemia Corticalis Deformans Formans Hyperostosis Corticalis Deformans Hyperphosphatasemia Osteitis deformans Paget's Disease of Bone Pozzi's Information on the following diseases can be found in the Related Disorders section of this report: Osteoporosis Osteoarthritis Engelmann Disease Hypophosphatasia Spinal Stenosis Hyperostosis Frontalis Interna General Discussion ** REMINDER ** The Information contained in the Rare Disease Database is provided for educational purposes only. It should not be used for diagnostic or treatment purposes. If you wish to obtain more information about this disorder, please contact your personal physician and/or the agencies listed in the "Resources" section of this report. Paget's disease of the bone is a chronic, slowly progressive skeletal condition of abnormally rapid bone destruction (osteolytic) and reformation (osteoblastic). The new bone is structurally abnormal, dense and fragile. The bones most frequently affected are in the spine, skull, pelvis and lower legs. Symptoms Early symptoms of Paget's disease include bone pain, joint pain (especially in the back, hips and knees), and headache. Physical signs include enlargement and bowing of the thighs (femurs) and lower legs (tibias), and enlargement of the skull in the area of the forehead. As the disease progresses, other signs and symptoms often appear. These may include further bowing of the affected limbs, a waddling manner of walking (gait), muscle and sensory disturbances, and hearing loss. Congestive heart failure (high-output) may occur. Tumors of the bone (osteogenic sarcoma) are a rare complication. Most cases of Paget's disease are without symptoms (asymptomatic) and are mild. These may be identified through x-rays of the pelvis. When symptoms occur, they are often vague and hard to distinguish from those of many other bone diseases such as lumbar spine diseases or osteoarthritis. Diagnosis is confirmed through blood tests including serum calcium and phosphorus and elevated serum alkaline phosphatase as compared with other inflammatory bone diseases. These other bone conditions usually do not have elevated serum alkaline phosphatase. X-rays showing characteristic lesions on the back of the head (occiput) and thigh bones (femur) are important diagnostic findings. Causes The exact cause of Paget's Disease is not known. Recent scientific research at the National Institutes of Health suggests that Paget's disease may be caused by a slow virus. This type of condition involves a virus which may stay dormant in the body for many years, and then reactivate later in life causing disease symptoms. It is not known whether a person must be genetically predisposed in order to harbor these types of viruses. More research is needed to determine whether genetic and/or slow virus factors are involved in the cause of this disorder. It is possible that Paget's Disease may have a genetic factor. In a few families the disorder appears to have been inherited through a dominant gene on the X chromosome. However, most cases of Paget's disease do not appear to fit this pattern of inheritance. Human traits, including the classic genetic diseases, are the product of the interaction of two genes, one received from the father and one from the mother. In X-linked dominant disorders the female with only one X chromosome affected will develop the disease. However the affected male always has a more severe condition. Affected Population Paget's Disease most frequently occurs in men but it is more severe when it affects women. There may be as many as three million cases in the United States, but it is rarely diagnosed properly. Many people may have symptoms so mild that they do not seek treatment. The symptoms of Paget's disease occur most frequently between the ages of 50 and 70, though it has been known to affect younger adults. Those with a Western European heritage are more likely to have the disease. Related Disorders Symptoms of the following disorders can be similar to those of Paget's Disease. Comparisons may be useful for a differential diagnosis. Osteoporosis is a disorder of the bones that is characterized by a decrease in the density and weight of bones (rarefaction). This can lead to fractures after even minor trauma. Osteoporosis can occur frequently in post-menopausal women or people that are immobile or sedentary. This disorder may cause pain, especially in the lower back, and a variety of deformities. Osteoarthritis is a form of arthritis that causes the degeneration of joints in the body. Initially osteoarthritis is a noninflammatory disease and causes the gradual deterioration of the cartilage of the joints. This is the most common form of arthritis and it usually occurs in older people. Symptoms may include pain and stiffness particularly in the morning or after prolonged rest. Engelmann Disease is a rare genetic bone disorder. Symptoms include muscle weakness, bone pain, an unusual way of walking (gait), extreme fatigue and loss of appetite (anorexia). This may lead to a general appearance of being malnourished. Symptoms usually begin in childhood. Bone pain can be severe especially in the femur. The bones at the base of the skull may be affected. (For more information on this disorder, choose "Engelmann Disease" as your search term in the Rare Disease Database). Hypophosphatasia is a genetic metabolic disorder that is characterized by the loss of bone (demineralization). It can occur in infants, children or adults. In infants, the loss of calcium may be associated with a weakening or bending of the bones. However, in hypophosphatasia there is a low serum alkaline phosphatase as opposed to an elevated level in people with Paget's disease. (For more information on this disorder, choose "Hypophosphatasia" as your search term in the Rare Disease Database). Spinal stenosis is characterized by a constriction or compression of the space within the spinal canal, nerve root canals or vertebrae. This compression may lead to limping and other difficulties with walking, the inability to retain urine (urinary incontinence), temporary paralysis of the legs, and pain or burning sensations in the lower back and legs. Progressive loss of muscle control may also occur. (For more information on this disorder, choose "Spinal Stenosis" as your search term in the Rare Disease Database). Hyperostosis Frontalis Interna is a disorder in which there is an excessive growth or thickening of the frontal bone of the skull. This disorder has been found in connection with other conditions such as obesity, headaches, seizures, diabetes insipidus and disturbances of the sexual glands. Other symptoms may include sudden, uncontrollable electrical discharges of the brain which may cause convulsions or loss of consciousness, decreased vision, and the appearance of secondary male sexual characteristics in women (virilization). There are increased levels of serum alkaline phosphatase and serum calcium in people with Hyperostosis Frontalis Interna. (For more information on this disorder, choose "Hyperostosis Frontalis Interna" as your search term in the Rare Disease Database). Therapies: Standard Treatment for Paget's disease is symptomatic and focuses on relieving pain, preventing deformity, fractures, and the loss of mobility. Diphosphonates are effective medications for the treatment of Paget's disease and are given to people intermittently for periods not exceeding six months. During that time the patient is monitored closely for levels of alkaline phosphatase in the blood. In patients who do not respond to Diphosphonates, Calcitonin and Mithramycin (a cytotoxic antibiotic used with great caution) may help slow down the rate of bone breakdown and bone turnover. Therapies: Investigational Research on Paget's disease is ongoing in the area of bone tissue reformation; how Paget's Disease affects the synthesis of collagen; the role of calcitonin, parathyroid, and other hormones in Paget's patients; and on the development of a method to assess bone turnover in Paget's patients. Research is being conducted on the use of calcitonin on Paget's patients who have not responded to or have had side effects from the use of diphosphonates. Please contact: University of Miami School of Medicine Division of Arthritis (VA111) P.O. Box 016960 Miami, FL 33101 (305) 547-5735 Att: Roy D. Altman, M.D. For research currently investigating the cause of Paget's disease (including viral causes) and for possible clinical studies please contact: Columbia Presbyterian Medical Center Dept. of Medicine 630 W. 168th Street New York, NY (212) 694-3526/5731 Attn: Robert Canfield, M.D., Ethel Siris, M.D., or Thomas Jacobs, M.D. The Food and Drug Administration (FDA) has awarded a research grant to Ethel S. Siris, M.D., Health Sciences, Columbia University College of Physicians & Surgeons, New York, NY, for studies on oral calcium as a treatment for Paget's disease. This disease entry is based upon medical information available through September 1992. Since NORD's resources are limited, it is not possible to keep every entry in the Rare Disease Database completely current and accurate. Please check with the agencies listed in the Resources section for the most current information about this disorder. Resources For more information on Paget's Disease, please contact: National Organization for Rare Disorders (NORD) P.O. Box 8923 New Fairfield, CT 06812-1783 (203) 746-6518 The Paget's Disease Foundation, Inc. (and other diseases of bone resorption) 200 Varick St., Suite 1004 New York, NY 10014-4810 (212) 229-1582 (800) 23-PAGET (212) 229-1582 The National Arthritis and Musculoskeletal and Skin Diseases Information Clearinghouse Box AMS Bethesda, MD 20892 (301) 495-4484 For Genetic Information and Genetic Counseling Referrals: March of Dimes Birth Defects Foundation 1275 Mamaroneck Ave. White Plains, NY 10605 (914) 426-7100 Alliance of Genetic Support Groups 35 Wisconsin Circle, Suite 440 Chevy Chase, MD 20815 (800) 336-GENE (301) 652-5553 References MENDELIAN INHERITANCE IN MAN, 9th Ed.: Victor A. McKusick, Editor: Johns Hopkins University Press, 1990. Pp. 703. CECIL TEXTBOOK OF MEDICINE, 19th Ed.: James B. Wyngaarden, and Lloyd H. Smith, Jr., Editors; W.B. Saunders Co., 1990. Pp. 1431-1433. PAGET'S DISEASE OF BONE, R.L. Merkow and J.M. Lane; Orthop Clin North Am (January, 1990; 21(1)). Pp. 171-189.