Paget's disease of bone
Paget's disease of bone is a metabolic bone disease that
involves bone destruction and regrowth that results in deformity
Information about Paget's disease
The cause of Paget's disease is unknown. Early viral infection
and genetic causes have been theorized. The disease occurs worldwide, but is more common
in Europe, Australia, and New Zealand where it is seen in up to 5% of the elderly
The disease is characterized by excessive breakdown of bone tissue, followed by
abnormal bone formation. The new bone is structurally enlarged, but weakened and filled
with new blood vessels.
The disease may localize to one or two areas within the skeleton, or become widespread.
Frequently, the pelvis, femur, tibia, vertebrae, clavicle, or humerus are involved. The
skull may enlarge head size and cause hearing loss, if the cranial nerves are damaged by
the bone growth.
Symptoms of Paget's disease
- bone pain (may be severe and persistent)
- joint pain or joint stiffness
- bowing of the legs
- warmth of skin overlying affected bone
- neck pain
- reduced height
- hearing loss
Diagnosis of Paget's disease
- Tests that may indicate Paget's disease include:
- a bone X-ray that shows increased bone density, thickening, bowing, and overgrowth
- a bone scan
- elevated serum alkaline phosphatase
- elevated markers of bone breakdown (e.g., N-telopeptide)
- serum calcium
- ALP (alkaline phosphatase) isoenzyme
Causes of Paget's disease
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.
Paget's disease usually begins without any symptoms. 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 can occur 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 survival time
is within one to three years.
Treatment of Paget's disease
Treatment, given only when symptoms are present, consists of the following types:
Paget's disease is most often treated with drug therapy, with bone pain lessening
within weeks of starting the treatment. While nonsteroidal anti-inflammatory drugs can
reduce bone pain, two additional categories of drugs are used to treat this disease; they
are described below.
The hormone calcitonin, which is made naturally by the thyroid gland, is used to treat
Paget's disease. This compound rapidly decreases the amount of bone breakdown or loss
(resorption). After approximately two to three weeks of treatment with 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.
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.
Bisphosphate drugs suitable for the treatment of Paget's disease are etidronate,
pamidronate, alendronate, clodronate, and tiludronate. Other bisphosphonate drugs are
under development as well. 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).
Surgery for Paget's disease
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. Notably, in addition to the malformation of bone tissue caused by this
condition, there are greater numbers of blood vessels that also form in the diseased bone,
making surgery to bones affected with Paget's disease more difficult.