Paget's disease of bone is a chronic disorder of the skeleton in which areas of bone undergo abnormal turnover, resulting in areas of enlarged and softened bone.

• The breakdown and formation of bone increase, resulting in bones that are thicker, but weaker, than normal.
• Symptoms may be absent or may include bone pain, bone deformity, arthritis, and painful nerve compression.
• X-rays show the bone abnormalities.
• Pain and complications are treated, and bisphosphonates may be given.

Paget's disease can affect any bone, but the most commonly affected bones are the pelvis, thighbone (femur), skull, shin (tibia), spine (vertebrae), collarbone (clavicle), and upper arm bone (humerus).

Paget's disease rarely occurs in people younger than 40. In the United States, about 1% of people older than 40 have the disorder, and the prevalence increases with age. However, the prevalence of the disease seems to be decreasing. Men are 50% more likely than women to develop it. Paget's disease is more common in Europe (excluding Scandinavia), Australia, and New Zealand. It is particularly common in England.

Causes

Normally, cells that break down old bone (osteoclasts) and cells that form new bone (osteoblasts) work in balance to maintain bone structure and integrity. In Paget's disease, both osteoclasts and osteoblasts become overactive in some areas of bone, and the rate at which bone is broken down and rebuilt (bone remodeling—see Osteoporosis) in these areas increases tremendously. The overactive areas enlarge but, despite being large, are structurally abnormal and weak.

The cause of Paget's disease is unknown. The disorder tends to run in families, and recent information suggests that a group of genetic defects possibly contributes. Also, some evidence suggests that a virus is involved. Even if a virus is involved, there is no evidence that the disorder is contagious.

Complications: Overgrown bone may compress nerves and other structures passing through small openings. The spinal canal may become narrow and compress the spinal cord. Osteoarthritis (see Joint Disorders: Osteoarthritis (OA)) may develop in joints near the involved bone.

Rarely, heart failure develops because the increased blood flow through the affected bone puts extra stress on the heart. The affected bone becomes cancerous in fewer than 1% of people who have Paget's disease. People whose disease progresses to bone cancer (see Bone and Joint Tumors: Primary Cancerous Bone Tumors) can develop an osteosarcoma, fibrosarcoma, or chondrosarcoma.

High blood levels of calcium (hypercalcemia—see Electrolyte Balance: Hypercalcemia) occasionally occur in bedridden older people with Paget's disease or in anyone with severe Paget's disease who becomes immobilized or dehydrated. These high levels of calcium can result in many problems, such as high blood pressure, muscle weakness, constipation, and stones in the urinary tract.

Symptoms

Paget's disease usually causes no symptoms, although bone pain, bone enlargement, or bone deformity may occur. Bone pain may be deep, aching, and occasionally severe and may worsen at night. The enlarging bones may compress nerves, causing more pain. If osteoarthritis occurs, joints become painful and stiff.

Other symptoms vary depending on which bones are affected. The skull may enlarge, and the brow and forehead may look more prominent. A person may notice this enlargement when a larger hat is needed. Enlarged skull bones may damage the inner ear (cochlea), which can cause hearing loss and dizziness. The enlarged skull bones can compress nerves, which causes headaches. The veins on the scalp may bulge, possibly because of the increased blood flow through the skull bones. The vertebrae may enlarge, weaken, and buckle, resulting in a loss of height and a hunched posture. Damaged vertebrae may pinch the nerves of the spinal cord, causing pain, numbness, tingling, weakness, or, very rarely, even paralysis in the legs. People whose hip or leg bones are affected may have bowed legs and take short, unsteady steps. Affected bones are more likely to break.

Diagnosis

Paget's disease is often discovered accidentally when x-rays or laboratory tests are performed for other reasons. Otherwise, the diagnosis may be based on the symptoms and a physical examination. The diagnosis can be confirmed by x-rays showing abnormalities characteristic of Paget's disease and by a laboratory test measuring blood levels of alkaline phosphatase, an enzyme involved in bone cell formation. A bone scan (a radionuclide test using technetium) shows which bones are affected.

Prognosis

The prognosis for people with Paget's disease is most often very good. However, the few people who develop bone cancer have a poor prognosis. People who develop other complications, such as heart failure or compression of the spinal cord, may also have a poor prognosis, unless treatment of these complications is timely and successful.

Treatment

A person who has Paget's disease needs treatment if the symptoms cause discomfort or if there is a significant risk or suggestion of complications, such as hearing loss, osteoarthritis, and deformity.

Commonly used analgesics such as acetaminophenSome Trade Names
TYLENOL
and nonsteroidal anti-inflammatory drugs (NSAIDs) help reduce bone pain. If one leg becomes bowed and shortened, heel lifts can help make walking easier. Sometimes surgery is needed to relieve pinched nerves or to replace a joint that has become arthritic from Paget's disease.

One of several bisphosphonates—alendronateSome Trade Names
FOSAMAX
, etidronateSome Trade Names
DIDRONEL
, pamidronateSome Trade Names
AREDIA
, risedronateSome Trade Names
ACTONEL
, tiludronateSome Trade Names
SKELID
, or zoledronateSome Trade Names
See Zoledronic acid
—can be used to slow the progression of Paget's disease. Except for pamidronateSome Trade Names
AREDIA
and zoledronateSome Trade Names
See Zoledronic acid
, which are usually given by vein (intravenously), these drugs are given by mouth. These drugs are given for the following:

• Before orthopedic surgery to prevent or reduce bleeding during surgery
• To treat pain caused by Paget's disease
• To prevent or slow the progression of weakness or paralysis in people who cannot have surgery
• To attempt to prevent arthritis, further hearing loss, or further bone deformity
• To people with a blood level of alkaline phosphatase twice the normal level or higher

The newer bisphosphonates (such as zoledronateSome Trade Names
See Zoledronic acid
) seem to slow the progression of Paget's disease for a longer period of time.

CalcitoninSome Trade Names
MIACALCIN
is occasionally injected under the skin or into muscle. It is not as effective as the bisphosphonates and is used only when the other drugs cannot be given.

Bed rest (except for sleeping at night) should be avoided, if possible, to prevent hypercalcemia. If hypercalcemia does develop, intravenous fluids and drugs given to increase the excretion of water (diuretics—such as furosemideSome Trade Names
LASIX
) are given.

Dietary intake of calcium and vitamin D (necessary for calcium absorption) should be sufficient to ensure that the incorporation of calcium into bone (bone mineralization) is adequate, because bone is being remodeled rapidly (see Biology of the Musculoskeletal System: Bones). Otherwise, poor bone mineralization (osteomalacia) may occur.

Last full review/revision December 2007 by Roy D. Altman, MD