Paget disease of bone

Other Names: osseous Paget's disease osteitis deformans Paget disease, bone Paget's disease of bone PDB

Paget disease of bone is a disorder that causes bones to grow larger and weaker than normal. Affected bones may be misshapen and easily broken (fractured).

The classic form of Paget disease of bone typically appears in middle age or later. It usually occurs in one or a few bones and does not spread from one bone to another. Any bones can be affected, although the disease most commonly affects bones in the spine, pelvis, skull, or legs. Bones with Paget disease may break more easily, and the disease can lead to other health problems.

Epidemiology

Classic Paget disease of bone occurs in approximately 1 percent of people older than 40 in the United States. Scientists estimate that about 1 million people in this country have the disease. It is most common in people of western European heritage. Early-onset Paget disease of bone is much rarer. This form of the disorder has been reported in only a few families.

Cause

A combination of genetic and environmental factors likely play a role in causing Paget disease of bone. Researchers have identified changes in several genes that increase the risk of the disorder. Other factors, including infections with certain viruses, may be involved in triggering the disease in people who are at risk. However, the influence of genetic and environmental factors on the development of Paget disease of bone remains unclear.

Researchers have identified variations in three genes that are associated with Paget disease of bone: SQSTM1, TNFRSF11A, and TNFRSF11B. Mutations in the SQSTM1 gene are the most common genetic cause of classic Paget disease of bone, accounting for 10 to 50 percent of cases that run in families and 5 to 30 percent of cases in which there is no family history of the disease. Variations in the TNFRSF11B gene also appear to increase the risk of the classic form of the disorder, particularly in women. TNFRSF11A mutations cause the early-onset form of Paget disease of bone.

The SQSTM1, TNFRSF11A, and TNFRSF11B genes are involved in bone remodeling, a normal process in which old bone is broken down and new bone is created to replace it. Bones are constantly being remodeled, and the process is carefully controlled to ensure that bones stay strong and healthy. Paget disease of bone disrupts the bone remodeling process. Affected bone is broken down abnormally and then replaced much faster than usual. When the new bone tissue grows, it is larger, weaker, and less organized than normal bone. It is unclear why these problems with bone remodeling affect some bones but not others in people with this disease.

Researchers are looking for additional genes that may influence a person's chances of developing Paget disease of bone. Studies suggest that genetic variations in certain regions of chromosome 2, chromosome 5, and chromosome 10 appear to contribute to disease risk. However, the associated genes on these chromosomes have not been identified.

Inheritance

Autosomal dominant pattern, a 50/50 chance.

In 15 to 40 percent of all cases of classic Paget disease of bone, the disorder has an autosomal dominant pattern of inheritance. Autosomal dominant inheritance means that having one copy of an altered gene in each cell is sufficient to cause the disorder.

In the remaining cases, the inheritance pattern of classic Paget disease of bone is unclear. Many affected people have no family history of the disease, although it sometimes clusters in families. Studies suggest that close relatives of people with classic Paget disease of bone are 7 to 10 times more likely to develop the disease than people without an affected relative.

Early-onset Paget disease of bone is inherited in an autosomal dominant pattern. In people with this form of the disorder, having one altered copy of the TNFRSF11A gene in each cell is sufficient to cause the disease.

Symptoms

Most people with the condition have no symptoms. Paget disease is often diagnosed when an x-ray is done for another reason. It may also be discovered when trying to find the cause of high blood calcium levels. If they do occur, symptoms may include:

• Bone pain, joint pain or stiffness, and neck pain (the pain may be severe and be present most of the time)
• Bowing of the legs and other visible deformities
• Enlarged head and skull deformities
• Fracture
• Headache
• Hearing loss
• Reduced height
• Warm skin over the affected bone

Diagnosis

Tests that may indicate Paget disease include: Bone scan Bone x-ray Elevated markers of bone breakdown (for example, N-telopeptide)

This disease may also affect the results of the following tests: Alkaline phosphatase (ALP), bone specific isoenzyme Serum calcium.

Treatment

Not all people with Paget disease need to be treated. People who may not need treatment include those who: Only have mildly abnormal blood tests Have no symptoms and no evidence of active disease

Paget disease is commonly treated when: Certain bones, such as weight-bearing bones, are involved and the risk of fracture is higher. Bony changes are getting worse quickly (treatment can reduce the risk of fractures). Bony deformities are present. A person has pain or other symptoms. The skull is affected. (This is to prevent hearing loss.) The calcium levels are elevated and causing symptoms. Drug therapy helps prevent further bone breakdown and formation. Currently, there are several classes of drugs used to treat Paget disease. These include:

Bisphosphonates: These drugs are the first treatment, and they help decrease bone remodeling. Medicines are commonly taken by mouth, but can also be given through a vein (intravenously). Calcitonin: This hormone is involved in bone metabolism. It may be given as a nasal spray (Miacalcin), or as an injection under the skin (Calcimar or Mithracin). Acetaminophen (Tylenol) or nonsteroidal anti-inflammatory drugs (NSAIDs) may also be given for pain. In severe cases, orthopedic surgery may be needed to correct a deformity or fracture. The medication(s) listed below have been approved by the Food and Drug Administration (FDA) as orphan products for treatment of this condition. Calcitonin human for injection (Brand name: Cibacalcin)Treatment of symptomatic Paget's disease (osteitis deformans).

Prognosis

Most of the time, the condition can be controlled with medicines. A small number of people may develop a cancer of the bone called osteosarcoma. Some people will need joint replacement surgery.

NIH genetic and rare disease info

• NIH info on Paget disease of bone

Paget disease of bone is a rare disease.

Paget disease of bone Resources
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