Paget disease of bone

ALSO KNOWN AS: Osteitis deformans, Paget’s disease

RELATED CONDITIONS: Metabolic and endocrine bone diseases

DEFINITION: Paget's 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 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, but the newly formed bone is structurally unsound. The disease process also results in extensive vascularity (increased blood vessels and blood flow) and increased fibrous connective tissue within the adjacent bone marrow space. Paget's disease can produce a variety of skeletal, neuromuscular, and cardiovascular complications.

Risk factors: Although the exact cause of Paget's 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's 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's disease, the risk is even greater.

Etiology and the disease process: Named after the nineteenth-century English surgeon Sir James Paget, Paget's disease was first described in 1876 as an inflammatory condition affecting 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's is related to a viral infection in the bone cells that may be present for many years before problems emerge.

As living tissue, bone is continually renewed, with old bone removed and replaced by new bone. This process of remodeling is disrupted in Paget's disease. In the initial, or lytic, phase, the old bone starts breaking down faster because of osteoclast cells' erratic and accelerated activity. 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 fracture under stress.

Various tumors and tumor-like conditions develop in the chaotic activity associated with pagetic bone. The most dreaded complication is the development of sarcomas (bone cancer), 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's disease usually follows a relatively benign course.

Incidence: Paget's disease usually begins in the fifth decade of life, becomes progressively more common after that, and has a slight male predominance. Globally, 1.5 to 8.3 percent of individuals over fifty-five may develop Paget's disease. There is a striking variation in prevalence within particular countries. Paget's disease is relatively common in England, Scotland, Austria, regions of Germany, Australia, and Greece. In the United States, Paget's disease occurs in one to three million people over forty-five. Paget's disease is rare before age twenty. The estimated incidence among individuals older than eighty is 10 percent.

Symptoms: Paget's disease affects each person differently. Most people with Paget's 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 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 is responsible for forming new bone, and its serum level is elevated in Paget's disease.
• X-ray: The first indication of Paget's disease is usually an abnormality on an X-ray. X-ray images delineate areas of bone reabsorption, bone enlargement, and bone deformities.
• Bone scan: In some cases, bone scans can pick up Paget's 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: A bone biopsy provides definitive evidence of the disease. Slides of the sectioned tissue show the classic mosaic pattern of bone. The 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 are 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 the extent of bone resorption, provides relief of acute symptoms, and lowers alkaline phosphatase levels) and bisphosphonates, which are the most effective agents in reducing bone resorption.

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

Prognosis, prevention, and outcomes: In most cases, Paget's disease progresses slowly. The condition can be managed effectively in nearly all people and is rarely fatal. A nutritional diet, regular exercise, and healthy weight are essential to any treatment protocol. Certain individuals may require a corset or brace to relieve back pain and provide support. If symptoms become severe, using 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.

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