Paget's disease of bone

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Paget's Disease of Bone

 

Definition

Paget's disease of bone (osteitis deformans) is the abnormal formation of bone tissue that results in weakened and deformed bones.

Description

Named for Sir James Paget (1814–1899), this disease affects 1-3% of people over 50 years of age, but affects over 10% of people over 80 years of age. Paget's disease can affect one or more bones in the body. Most often, the pelvis, bones in the skull, the long bones (the large bones that make up the arms and legs), and the collarbones are affected by Paget's disease. In addition, the joints between bones (the knees or elbows, for example) can develop arthritis because of this condition.
Paget's disease is characterized by changes in the normal mechanism of bone formation. Bone is a living material made by the body through the continual processes of formation and breakdown (resorption). The combination of these two actions is called remodeling and is used by the body to build bone tissue that is strong and healthy. Strong bones are formed when bone tissue is made up of plate-shaped crystals of minerals called hydroxyapatite. Normal wear and tear on the skeletal system is repaired throughout life by the ongoing process of remodeling. In fact, the entire human skeleton is remodeled every five years.
Healthy bone tissue has an ordered structure that gives the bone its strength. Bones affected by Paget's disease, however, have a structure that is disorganized. This disorganized structure weakens the diseased bone and makes people suffering from this disease more likely to have fractures. These fractures are slow to heal.
Paget's disease of bone is most commonly found in Europe, England, Australia, New Zealand, and North America. In these areas, up to 3% of all people over 55 years of age are affected with the disease. It is interesting to note that Paget's disease is rare in Asia, possibly showing that this disease may affect some ethnic groups and geographic areas more than others.

Causes and symptoms

The cause of Paget's disease is not known. Various viruses have been suggested to be involved in this disease, but the relationship between viral infections and Paget's disease remains uncertain. There also may to be a genetic component to this disease since it may appear in more than one person within the same family.
Paget's disease usually begins without any symptoms. And, in its early stages, the symptoms that do occur are often confused with symptoms of arthritis. However, as the disease progresses, bone and joint pain develop. A unique feature of Paget's disease is the enlargement of areas of affected bone. This type of enlargement is clearly identifiable on an x ray.
If the bones of the skull are affected by Paget's disease, enlargement of the skull can occur and may result in a loss of hearing. When the long bones in the legs are affected, they can become bent under the body's weight because of their weakness. Little or no injury to a bone can cause fractures in the weakened bones. Fractures that occur when no traumatic injury is present are known as spontaneous fractures.
Although rare, bone cancer occurs in less than 1% of patients with Paget's disease. Such cancer is often accompanied by an abrupt increase in the intensity of pain at the diseased site. Unfortunately, this type of cancer has a poor prognosis; the average survival time from the onset of symptoms is generally one to three years.

Diagnosis

Paget's disease is often found when an individual is having x rays taken for medical reasons unrelated to this bone disease. A diagnosis of Paget's disease can also be made when higher than normal levels of a chemical called alkaline phosphatase are found in the blood. Alkaline phosphatase is a substance involved in the bone formation process, so if its levels are abnormally high this indicates that the balance between bone formation and resorption is upset.

Treatment

Treatment, given only when symptoms are present, consists of the following types:

Drugs

Paget's disease is most often treated with drug therapy, with bone pain lessening within weeks of starting the treatment. While non-steroidal anti-inflammatory drugs can reduce bone pain, two additional categories of drugs are used to treat this disease.
HORMONE TREATMENT. Calcitonin, a hormone which is made naturally by the thyroid gland, is used to treat Paget's disease. This chemical rapidly decreases the amount of bone breakdown or loss (resorption). After approximately two to three weeks of treatment with extra calcitonin, bone pain lessens and new bone tissue forms. Calcitonin is commonly given as daily injections for one month, followed by three injections each week for several additional months. The total dose of calcitonin given to an individual depends upon the amount of disease present and how well the individual's condition responds to the treatment.
Although calcitonin is effective in slowing the progression of Paget's disease, the favorable effects of the drug do not continue for very long once administration of the drug is stopped. In addition, some temporary side effects can occur with this drug. Nausea and flushing are the most common side effects and have been found in 20-30% of individuals taking calcitonin. Vomiting, diarrhea, and abdominal pain can also occur, but these effects are also temporary. A form of calcitonin taken nasally causes fewer side effects, but requires higher doses because less of the drug reaches the diseased bone.
BISPHOSPHONATES. The bisphosphonate group of drugs are drugs that bind directly to bone minerals because of their specific chemical structure. Once bound to the bone, these drugs inhibit bone loss by reducing the action of bone cells that normally degrade bone during the remodeling process. Unlike treatment with calcitonin, the positive effects of increased bone formation and reduced pain can continue for many months or even years after bisphosphonate treatment is stopped. Bisphosphonates are considered the treatment of choice for Paget's disease and are usually given for 3-6 months at a time.
Bisphosphonate drugs suitable for the treatment of Paget's disease are alendronate, clodronate, etidronate, pamidronate, risedronate, and tiludronate. The main side effects of these drugs include a flu-like reaction (pamidronate), gastrointestinal disturbances (alendronate, clodronate), and abnormal bone formation (etidronate, when taken in high doses). Risedronate is the newest of these drugs. It is about 1,000 times more potent than etidronate and 3 to 5 times more potent than alendronate. Because of the greater potency of this drug, lower doses and a shorter duration of treatment are required. This leads to fewer side effects with similar, or better, clinical results in the patient.

Surgery

Treatment of Paget's disease usually begins with drug therapy. However, various surgical treatments can also be used to treat skeletal conditions that occur in patients with Paget's disease.
In patients with severe arthritis of the hip or knee, a joint replacement operation can be beneficial. However, in addition to the malformation of bone tissue caused by this condition, there are greater numbers of blood vessels that form in the diseased bone relative to a healthy bone. This makes surgery on bones affected with Paget's disease more difficult.

Prognosis

There is no cure for Paget's disease. However, the development of potent bisphosphonate drugs like risedronate has resulted in the ability to slow the progress of the disease.

Key terms

Bisphosphonate — A class of drugs used to treat Paget's disease. These drugs bind to the minerals in bone tissue and lessen the amount of bone loss associated with Paget's disease.
Calcitonin — A naturally occurring hormone made by the thyroid gland that can be used as a drug to treat Paget's disease.
Remodeling — The ongoing process of bone formation and breakdown that results in healthy bone development.

Paget's disease of bone

Osteitis deformans An idiopathic bone-remodeling disorder of older Northern European ♂ especially of lumbosacral spine, pelvis, skull, affecting ±10% of those > age 80 Clinical Often asymptomatic; or pain, deformity, pathologic fracture, neural compression Imaging Moth-eaten destruction of trabecular bone, endosteal scalloping, cortical penetration, soft tissue masses Lab ↑ Serum alk phos Complications Heart failure due to AV shunting; osteosarcoma, or other sarcomas in 1-25% Treatment Biphosphonate, calcitonin, mitrimycin, surgery for decompressing critical cranial structures, or joint replacement. See Mosaic bone.
References in periodicals archive ?
In a preliminary clinical evaluation, serum concentrations of circulating BSP were also determined in healthy controls ages 20-80 years (n = 90), and in patients with Paget disease of bone (n = 24), primary hyperparathyroidism (PHPT; n = 11), renal secondary hyperparathyroidism (SHPT; n = 25), chronic renal failure without SHPT (RF; n = 26), and alcoholic liver cirrhosis (LC; n = 35).
In patients with Paget disease of bone, serum BSP concentrations were 32.
Highest concentrations were seen in subjects with active Paget disease of bone and in individuals with secondary renal hyperparathyroidism.