What is Paget disease of bone?

Related conditions:
Metabolic and endocrine bone diseases

Definition:

Paget disease of bone (osteitis deformans) is a bone disorder in which excessive bone resorption is followed by excessive bone formation. The primary disturbance is an exaggeration of activity by a cell called the osteoclast, which is responsible for removing bone in the remodeling process. Frenzied osteoclastic activity results in localized bone loss followed by a period of hectic bone formation. The osteoblast cell responds by regenerating new bone that is primitive (woven), disorganized, and weaker. The resultant effect of this cycle is a net gain in bone mass; however, the newly formed bone is structurally unsound. The disease process also results in extensive vascularity (increased number of blood vessels and blood flow) and increased fibrous connective tissue within the adjacent bone marrow space. Paget disease can produce a variety of skeletal, neuromuscular, and cardiovascular complications.

Risk factors: Although the exact cause of Paget disease remains unknown, being older than forty-five years and having a family history of the disease are the only known risk factors. Of patients with Paget disease, 15 to 30 percent have a family history. Family studies suggest that a person with a first-degree relative has a seven times higher risk of developing this condition. In families with early-onset or severe Paget disease, the risk is even greater.

Etiology and the disease process: Named after the nineteenth-century English surgeon Sir James Paget, Paget disease was first described in 1876 as an inflammatory condition that affects the normal biological processes of bone. The exact cause or mechanism of this disease process remains unknown. Scientists have discovered several genes that appear linked to this disorder. Other investigators believe Paget is related to a viral infection in the bone cells that may be present for many years before problems appear.

As living tissue, bone is engaged in a continual process of renewal; old bone is removed and replaced by new bone. This process of remodeling is disrupted in Paget disease. In the initial, or lytic, phase, old bone starts breaking down faster because of the erratic and accelerated activity of osteoclast cells. The body responds by generating new bone at a faster than normal rate. This mixed phase is devoted to osteoblastic cell activity. In the final osteosclerotic phase, the exhausted cells become quiescent. A mosaic pattern of bone is identifiable. The new bone is coarsely thickened but soft, porous, and lacking structural stability. These microscopic aspects make the bone vulnerable to deformation and to fracture under stress.

A variety of tumors and tumor-like conditions develop in the chaotic activity associated with pagetic bone. The most dreaded complication is the development of sarcomas (bone cancers), which occurs in 5 to 10 percent of patients with severe disease. The prognosis of patients who develop secondary sarcomas is exceedingly poor, but in the absence of malignant transformation, Paget disease usually follows a relatively benign course.

Incidence: Paget disease usually begins in the fifth decade of life, becomes progressively more common thereafter, and has a slight male predominance. There is a striking variation in prevalence both within certain countries and throughout the world. Paget disease is relatively common in England, France, Austria, regions of Germany, Australia, and New Zealand, affecting 5 to 11 percent of the populations in these countries. In the United States, Paget disease is estimated to occur in 1 to 3 percent of people over the age of forty-five. Paget disease is rare before the age of twenty; the estimated incidence among individuals older than eighty is 10 percent. In contrast, Paget disease is rare in the native populations of Scandinavia, China, Japan, and Africa.

Symptoms: Paget disease affects each person differently. Most people with Paget disease have no symptoms. Initial discovery may be the result of a screening X ray for other purposes. When symptoms do occur, they may be widespread but typically arise in the areas affected by the disease, which include bones, joints, and nerves.

The most common bone sites include the spine, pelvis, skull, femur (involved in up to 80 percent of cases), and tibia. Patients will complain of bone pain characterized as constant, aching, deep, and most severe at night. Skull involvement may produce enlargement of the head (frontal bossing). Deafness may result from disease of the temporal bone or ossicles (bones of the middle ear). Involvement at the base of the skull can lead to compression of the brain stem, resulting in symptoms of ataxia (difficulty walking), weakness, or respiratory compromise. Compression fractures of the spine can result in spinal cord injury and spinal deformity.

Hip and knee joints are commonly affected. The cartilage lining the joints near affected bones is damaged. This additional factor coupled with normal wear and tear leads to accelerated osteoarthritis, which may cause joint pain, swelling, and stiffness.

Enlarged bones can compress the spinal cord or the nerves exiting from the brain or spinal cord. Pain resulting from nerve compression is often more severe than bone pain. The location of the pain caused by nerve compression depends on the nerve that is affected. If lumbar nerves from the spine are compromised, this leads to radiating pain from the lower back and into the legs (sciatica). Nerve compression can result in limb weakness, pain, or paralysis. Nerve compression has been implicated in hearing and vision loss along with facial weakness and numbness.

Screening and diagnosis: Diagnosis depends on the following tests:

• Blood test: Specifically, an alkaline phosphatase test. Alkaline phosphatase is a chemical substance produced by bone cells that are responsible for forming new bone, and its serum level is elevated in Paget disease.





• X ray: The first indication of Paget disease usually is an abnormality found on an X ray. X-ray images delineate areas of bone reabsorption, enlargement of bones, and bone deformities.





• Bone scan: In some cases, bone scans can pick up Paget disease before it is seen on an X ray. In a bone scan, radioactive tracers are injected into the body. The tracers are preferentially taken up by areas of the bone that are metabolically active. Areas of pagetoid bone are seen as darker than areas of normal bone.





• Bone biopsy: Biopsy of the bone provides definitive evidence of the disease. Slides of the sectioned tissue show the classic mosaic pattern of bone. Biopsy can also be useful in staging the disease process.

Treatment and therapy: Asymptomatic patients may not need treatment. Treatment is recommended when the disease is active (indicated by elevated serum levels of alkaline phosphatase). Treatment can help alleviate pain and may halt the damage done to the bones. In many cases, treatment can cause a remission of the disease although not a cure. Medications, surgery, and self-care remain the essential elements in most treatment regimens.

Drug therapy incorporates the use of nonsteroidal anti-inflammatory medications, analgesics, and muscle relaxants that lessen pain and discomfort but do not alter the natural course of the disease. The two major pharmaceuticals employed are calcitonin (a hormone that inhibits osteoclast activity and affects extent of bone resorption, provides relief of acute symptom, and lowers alkaline phosphatase levels) and the bisphosphonates, which are the most effective agents in reducing bone resorption.

Surgery, in rare cases, may be required to stabilize a fracture or to replace a damaged joint. If Paget disease affects the spine or skull, decompressive surgery (removal of excess bone) is needed to reduce the pressure on the nerves, thereby restoring normal neurologic function.

Prognosis, prevention, and outcomes: In most cases, Paget disease progresses slowly. The condition can be managed effectively in nearly all people and is rarely fatal. A nutritional diet, regular exercise, and maintaining a healthy weight are important aspects of any treatment protocol. Certain individuals may require a corset or brace to relieve back pain and provide support. If symptoms become severe, the use of analgesics and muscle relaxants is recommended. Medical supervision and examination are necessary since major complications of this disease can include fractures, osteoarthritis, heart failure, and cancer.

Kumar, V., A. Abbas, N. Fausto, and R. Mitchels, eds. Robbins Basic Pathology. 8th ed. Philadelphia: Saunders, 2007. Print.

McDermott, Michael T. Endocrine Secrets. 6th ed. Philadelphia: Elsevier, 2013. Print.

Rosen, Clifford J., R. Bouillon, Juliet Compston, and Vicki Rosen. Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism. Hoboken: Wiley, 2013. Print.

Schwamm, H. A., and C. L. Millward. Histologic Differential Diagnosis of Skeletal Lesions. New York: Igaku-Shoin, 1996. Print.

Singer, F. “Paget’s Disease of the Bone.” In Endocrinology, edited by L. J. DeGroot. Philadelphia: Saunders, 1995. Print.

Waldman, Steven D. Atlas of Uncommon Pain Syndromes. 3rd ed. Philadelphia: Saunder, 2014. Print.