PAGETS DISEASE

INTRODUCTION

Paget's (PAJ-ets) disease is a condition in which bone formation is 
speeded up, changing the strength and shape of the bone. The bones most 
often affected include the pelvis, lumbar spine (lower back), sacrum 
(tailbone), skull, and the femur or the tibia (long bones in the legs). 
(See Figure 1.) Paget's disease usually centers in one or more of these 
areas. Once established, however, it rarely spreads to other areas. With 
early diagnosis and treatment, most people who have Paget's disease are 
able to lead active, independent lives.

HOW DOES PAGET'S DISEASE AFFECT PEOPLE?

To understand what happens in Paget's disease, it is helpful to 
understand the difference between normal bone cell activity and Pagetic 
bone cell activity. Bone is active and living tissue that constantly is 
being remodeled in a three-stage process. First, old bone is resorbed
 (broken down) by cells called osteoclasts (OS-te-o-klasts) to make way 
for new bone. Next, cells called osteoblasts (OS-te-o-blasts) lay down 
an orderly framework for new bony tissue. Finally, the bone hardens when
calcium is added to the framework laid down by the osteoblasts.

Normal bone cell activity is a very controlled process that is necessary
for bone development and repair throughout life. The bone turnover
process slows somewhat after puberty and continues at a slower rate
through adult life. (This is why an older person's bones break more
easily.)

Bone affected by Paget's disease is broken down faster than usual. 
Consequently, new bone formation increases. Because the new bone forms 
so rapidly, its structure becomes jumbled and disorganized. Extra blood 
vessels appear, and the new formation becomes bulky and somewhat softer 
than normal bone. This can result in joints near the affected area 
developing arthritis.

Because the bones are weaker than normal, they may break or fracture 
more easily. The thigh or leg can become bowed. If the vertebrae (bones 
of the spine) are involved, they may collapse, making the spine curve 
forward.

A person may experience other forms of discomfort as well. The increased 
flow of blood through the bone may cause a feeling of warmth over the 
affected areas. Thickened bones in some locations can pinch nerves. For 
example, pinched nerves in the spine may cause sciatica (si-AT-i-kah), a 
syndrome of radiating pain from the back into the buttocks and down the 
legs. Paget's disease of the bones inside the ears also can cause 
ringing or a decrease in hearing.

Eventually, the rapid bone breakdown and disorganized bone formation 
slows down, and Paget's disease appears to "burn out. " Symptoms may 
come and go. However, any bone enlargement or bowing that has occurred 
will remain.

WHAT ARE THE SYMPTOMS?

Most people with Paget's disease have no symptoms. The condition often 
is diagnosed only after an x-ray of the bone or the results of a routine 
blood test indicate that Paget's disease may be present. However, some 
people do experience symptoms, the most common of which is mild pain 
(sometimes described as "deep bone" pain). Another symptom is a feeling 
of warmth over the affected area. And if the skull is affected, the 
person may experience headaches.

WHO GETS PAGET'S DISEASE?

Paget's disease is slightly more common in men than in women and often 
begins between the ages of 50 and 70. No definite evidence exists 
indicating that Paget's disease is hereditary. However, in some
instances, it tends to run in families.

The disease affects mostly Caucasians of northwestern European ancestry. 
In the United States, Paget's disease is also seen occasionally in 
African-Americans.

WHAT CAUSES PAGET'S DISEASE?

The cause of Paget's disease is unknown. One of the most accepted 
theories points to an early viral infection of the bone. It is thought 
that this infection lies inactive for many years, only to surface later 
in life as Paget's disease.

HOW IS PAGET'S DISEASE DIAGNOSED?

Although there is no way to prevent Paget's disease, it can be detected 
before it becomes a serious problem. Diagnosis can be made by x-rays of 
the affected bones. A bone scan often helps to determine the location 
and extent of bone involvement. 

Blood tests may be run to determine the presence of increased amounts of 
alkaline phosphatase (a product of bone-forming cells). Urine tests 
(such as a 24-hour urine collection) may be run to determine the 
presence of an increased amount of hydroxyproline (another product of 
bone breakdown). A bone biopsy is rarely needed to ensure the accuracy 
of the diagnosis.

HOW IS PAGET'S DISEASE TREATED?

With or without symptoms, if the disease seems to be active, most 
doctors will prescribe treatment. Treatment usually focuses on pain 
relief and prevention of bone deformities, fractures, hearing loss, and 
loss of mobility.

Medications

Aspirin, other nonsteroidal anti-inflammatory medications (NSAIDs), and 
non-narcotic analgesics (pain relievers) help reduce pain that might be 
associated with Paget's disease. Anti-Pagetic treatment includes 
medications that slow down or block the rate of bone breakdown and
formation. Medications most often prescribed include calcitonin S
 (Calcimar, Miacalcin, or Cibacalcin) or bisphosphonates (Didronel). A 
third medication, plicamycin (Mithracin) - previously called mithramycin 
- is prescribed in rare instances where there is serious and extensive 
disease activity.

Calcitonin is a natural hormone that reduces the breakdown of bone. 
Calcitonin must be injected to be used as a treatment (a person can 
learn self-injection). Initial treatment usually involves a daily 
injection, but over time some people find that two or three injections 
per week are sufficient. Improvement of some symptoms may be seen within 
the first two weeks to two months. However, it often takes three to six 
months to see evidence of the anti-Pagetic effects.

Bisphosphonates, especially etidronate (Didronel), are oral medications 
that slow down both the breakdown and formation of bone. Etidronate is 
best absorbed when the stomach is empty. (Don't take the tablets with 
milk, vitamins, or calcium, all of which may block absorption.) 
Etidronate should never be used longer than six months at a time and is 
most effective when the person waits another six months before resuming
the medication.

Other, newer bisphosphonates are being studied. A new bisphosphonate 
pamidronate (Aredia) - has been approved by the U.S. Food and Drug 
Administration for use in treating other calcium disorders in an 
intravenous form, but specialists in the field of Paget's disease are 
also occasionally using it for that condition as well.

Plicamycin is administered by intravenous injection. Plicamycin can slow 
down the activity of cells that make and remove bone in Paget's disease. 
Because the drug can produce serious side effects to bone marrow, the 
liver, and the kidneys, its use in Paget's disease is still quite 
limited. 

Each of these medications requires close supervision by a doctor and 
must be taken exactly as prescribed. Regular blood and urine tests are 
required to determine whether or not the medication is producing the 
desired effect.

Surgery

For some people who have Paget's disease near the hip or knee joint, 
joint replacement surgery can help to relieve pain and improve function. 
In some situations, surgery may also help correct leg or thigh bowing or 
hearing loss due to Paget's disease.

Other Measures

A healthy diet can help a person with Paget's disease maintain normal 
weight. Extra weight can put too much stress on certain bones or joints 
that already are weak from Paget's disease.

If Paget's disease affects your ability to do your daily activities, 
your doctor may refer you to an occupational or physical therapist. For 
example, if bowing of a leg bone interferes with walking, a shoe lift 
may help. Canes may also help. Your doctor or a physical therapist can 
give you an exercise program that will help you maintain flexibility and 
strength. If your hearing has been affected, a special hearing aid may 
help.

COPING WITH PAGET'S DISEASE

Understanding the disease is the first step in self-help. Just because 
you have Paget's disease does not mean that you will have pain, 
fractures, or deformity. For those people with these problems, it may be 
difficult to cope. It is usually easier to adjust if you can talk about 
your feelings with a friend or someone who also has the disease.