Paget Paget
Paget Paget
General   Information about Paget's Disease
Paget's Disease and Other Medical Conditions
Diet and Exercise
Treatment
 
General Information about Paget's Disease
 
 

1. Q.† What is Pagetís disease of bone?

A.     Pagetís disease of bone is a chronic, treatable disease.† Though there is no cure,

several effectivedrugs are available to treat the disease. The disease typically results in enlarged and deformed bones in one or more regions of the skeleton. In Pagetís disease, the two bone cells the osteoclast (the cell that resorbs or breaks bone down) and the osteoblast (the cell that forms new bone) do not interact normally. When this happens, excessive bone breakdown and formation can produce bone that is weak. As a result, bone pain, osteoarthritis, noticeable deformities, and fractures can occur.

 

2. Q.† What causes Pagetís disease?

A.     The cause/s of Pagetís disease are still not clearly defined. Research suggests that Pagetís disease may be caused by a ďslow virusĒ infection of bone, a condition that is present for many years before symptoms appear. There is also a hereditary factor since the disease sometimes is present in more than one member of a family. This hereditary factor may be the reason that members of a family who have Pagetís disease are susceptible to the suspected virus. One gene that predisposes individuals to develop Pagetís disease, the sequestosome 1 gene, has been discovered. Two other genes, RANK and the VCP gene, are also associated with Pagetís disease. Alterations in the RANK gene cause a disease named familial expansile osteolysis (FEO) that has some similarities to Pagetís disease. Also, RANK has been found in one family where a family member developed Pagetís disease at a younger age than most Pagetís disease patients.† The final gene associated with Pagetís disease is the VCP gene, a gene that is found in Pagetís disease patients who also have a muscle weakness disease and dementia. In summary, it is likely that environmental factors such as viruses and genetic factors may both be involved in the development of Pagetís disease.

 

3. Q.† Which groups of people are usually affected by Pagetís disease, and how

common is the disease?

A.     Pagetís disease is rarely diagnosed in people under 40.† The prevalence ranges from 1.5 percent to 8 percent in older adults depending on the personís age and area of the world where he or she lives. Familial Pagetís disease ranges from 10 percent to 40 percent in different parts of the world. Men and women are affected almost equally.

 

4. Q.† How is Pagetís disease usually diagnosed?

A.† Pagetís disease may be discovered by x-ray examination, blood tests or by bone scans. Because bones affected with Pagetís disease have a distinct appearance in x-rays, x-ray is the main means of diagnosing Pagetís disease.† Rarely, a bone biopsy is necessary for diagnosis when the x-ray result is inconclusive. The patientís doctor may be alerted to the possibility of Pagetís disease when a blood test reveals an elevated level of serum alkaline phosphatase (SAP), an enzyme that is produced by bone cells called osteoblasts. (In Pagetís disease, too much SAP is produced).†† Another test which may detect Pagetís disease is a bone scan. A bone scan is done by injecting a safe amount of a radioactive substance which circulates through the bloodstream and localizes to areas where there is Pagetís disease. Bone scans are useful in determining the extent andactivity of the disease. If a bone scan suggests Pagetís disease, the affected bone/bones should be x-rayed to confirm the diagnosis.

 

Urinary markers of bone resorption such as N- telopeptide are also used to determine disease activity.

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†††††††††††

5. Q. Should siblings or children of patients with Pagetís disease ask their physicians for any special diagnostic tests?

A.     After the age of 40, siblings and children of a patient with Pagetís disease should have a SAP blood test every 2 or 3 years. Though the levels of SAP vary in different laboratories, 125 is often the upper limit of normal.†

 

6. Q.† What are the symptoms?

†A.†† In many cases, there may be no symptoms.

 

When symptoms do occur, they can include:

Bone pain.† This can occur in any bone affected by Pagetís disease. Pain is often felt in joints near the affected bone/s, reflecting the common presence of degenerative arthritis.

Back Pain. This can occur from vertebral fractures or degenerative changes in the spine, as well as from bone pain due to Pagetís disease.

 

Headaches.† These may occur when Pagetís disease occurs in the skull.

 

Hearing loss.† This can result from Pagetís disease in the skull.

 

Bone deformities. These deformities, such as increased head size, bowing of a limb or curvature of the spine, are caused by enlargement and/or weakening of the affected bones and occur in advanced cases.†

 

Fractures.† Bones weakened by Pagetís disease can break more easily than healthy bones. Most fractures that occur in Pagetís disease are in the long bones of the lower extremity.

 

Osteoarthritis.†This is a common occurrence that leads to joint pain due to damage to the cartilage of joints adjacent to affected bone or bones.

 

Back and leg pain.† These problems may occur when Pagetís disease irritates nerves in the spine.

 

7. Q. Do all people who have Pagetís disease know that they have it?

A.† No. Many patients who have Pagetís disease do not know they have it since the disease may be so mild that it is not diagnosed. Sometimes the patientís symptoms are confused with arthritis or other disorders. In other cases, the diagnosis is made only after complications have developed.

 

8. Q. Which bones can be affected by Pagetís disease?

A.† Any bone can be affected in Pagetís disease. Pagetís disease occurs most frequently in the spine, skull, pelvis and bones of the lower extremities (thighs and lower legs.)† Some patients will have only one affected bone, while others may have two, three, or more affected bones.

9. Q. What is the prognosis for patients with Pagetís disease?

A.† The course of Pagetís disease varies greatly and may range from completely stable to rapid progression. In general, symptoms progress slowly in affected bones, and there is usually no spread to normal bones. The outlook for patients with Pagetís disease is generally good, particularly if treatment is given before major complications occur. Treatment can control Pagetís disease and lessen symptoms but is not a cure. When untreated, Pagetís disease can cause serious complications, depending on which bones are affected and how long the disease is present.

 

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10. Q. Is Pagetís disease a fatal disease and is there a relationship between pagetís disease and cancer?

A.       Pagetís disease is rarely fatal. Sarcoma, a form of bone cancer, is an extremely rare complication that occurs in less than one percent of all Pagetís disease patients. When a patient has a sudden onset of severe pain or worsening of previous pain that is not due to a fracture, sarcoma should be considered. However, in most cases sarcoma is not the cause of the increased pain.†

 

Pagetís Disease and Other Medical Conditions

 

11. Q. What is the relationship between osteoarthritis and Pagetís disease?

A.     Pagetís disease can cause osteoarthritis by changing bones around joints:(1) longbones such as the thigh and leg bones may become bowed and distort the normal alignment and pressures within the adjacent joints; (2) bone with Pagetís disease may become enlarged, causing the joint surfaces to undergo excessive wear and tear. Osteoarthritis is a common cause of pain in Pagetís disease, but the disease itself also causes bone pain. In many patients, the pain may be due to a combination of Pagetís disease and osteoarthritis.†

 

12. Q. What is the relationship between Pagetís disease and the bone disease osteoporosis?

A.     There is no relationship except that both diseases affect the bones and some drugs are used to treat both diseases. Osteoporosis is a condition of generalized loss of bone mass, often found in the elderly, which can lead to fractures. Although Pagetís disease and osteoporosis can occur in the same patient, they are completely different diseases with different causes.† The appropriate doses of the drugs that are used to treat Pagetís disease and osteoporosis are different for Pagetís disease than for osteoporosis. ††

 

The drug teriparatide (Forteoģ) was approved for the treatment of osteoporosis, particularly for men and postmenopausal women who have a high risk of fracture.† Because some people with Pagetís disease may develop sarcomas, Pagetís patients should not take Forteoģ because some animals in studies wherehigh doses of Forteoģ were used developed sarcomas.†

 

13. Q. Is there a relationship between Pagetís disease and heart disease?

A.† In patients with extensive Pagetís disease, the heart may have to work harder to pump extra blood to affected bones. This usually does not result in heart failure except in some people who already have heart disease such as arteriosclerosis (hardening) of the arteries of the heart.

 

14. Q. Is there a relationship between Pagetís disease and kidney problems?

A. There is no direct relationship between Pagetís disease and kidney problems. However, kidney stones may be more common in patients with Pagetís disease.

 

15. Q. What causes pain in Pagetís disease?

A.     Pain is the most common symptom that brings a patient with Pagetís disease to a

physician. Since many patients with painful symptoms of Pagetís disease do not have obvious deformities, they may not receive the correct diagnosis.† The types of pain associated with Pagetís disease can include: bone pain, osteoarthritic pain, headaches, muscular pain and sciatica, a pain down a leg resulting from irritation of the sciatic nerve.

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16. Q. Why do some Pagetís disease patients experience loss of hearing? Can anything be done to remedy this condition?

A.     When Pagetís disease affects the skull, severe and progressive loss of hearing may occur. This may involve both sides or one side predominantly. If the loss of hearing is progressive and due to Pagetís disease, treating the Pagetís disease may slow or stop the progression of the hearing loss. Hearing aids often may help improve hearing.

 

17. Q. Can Pagetís disease affect vision?

A.† Yes. When the skull is involved, the nerves to the eye may be affected and cause some loss of vision. This complication is quite rare.

 

18. Q. How does Pagetís disease affect the teeth?

A.     When Pagetís disease affects the facial bones, the teeth may be affected and become

loose.† Disturbance of the chewing mechanism may occur. Patients may also be prone to developing infections after dental procedures.

 

Diet and Exercise

 

19. Q. Is there a relationship between diet and Pagetís disease? Specifically, is there a relationship between calcium and/or vitamin d and Pagetís disease?

A.† No. There is no relationship between diet and Pagetís disease. In general, all people including Pagetís disease patients should receive the nutritionally proper amount of calcium (1000-1500 mg daily), adequate sunshine, and at least 400 units of vitamin Ddaily to maintain a healthy skeleton. A Pagetís disease patient with a history of kidney stones should discuss the use of calcium and vitamin D intake with his or her physician. Adequate calcium and vitamin D are especially important for patients being treated with bisphosphonates.

 

20. Q. what role does exercise play in managing pagetís disease?

A.† Exercise is very important in maintaining skeletal health, avoiding weight gain and maintaining mobility of the joints.† However, before beginning any exercise program, a Pagetís disease patient should discuss the exercise program with his or her physician since undue stress on bones affected with Pagetís disease should be avoided.

 

Treatment

 

21. Q. Which types of physicians are specialists in Pagetís disease?

A.† Endocrinologists (physicians who specialize in hormonal and metabolism disorders) and rheumatologists (physicians who specialize in joint and muscle disorders) are internists who are generally knowledgeable about treating Pagetís disease. Also, orthopedic surgeons, neurologists, and otolaryngologists (physicians who specialize in ear, nose, and throat disorders) may be called upon to evaluate specific symptoms or complications in Pagetís disease of bone.

 

22. Q. What is the goal of treatment and what treatments are available in the u.s.?

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A.† The goal of treatment is to relieve bone pain and prevent the progression of the disease. In general, the therapies of choice are the three more potent bisphosphonates: Actonelģ, Fosamaxģ and Arediaģ. Didronelģ, Skelidģ or Miacalcinģ may be appropriate therapies for selected patients, but are seldom used. Information about all therapies approved by the U.S. Food and Drug Administration (FDA) for the treatment of Pagetís disease follows.

Bisphosphonates. Five bisphosphonates are currently available. Four are in tablet form and one is in intravenous form. As a rule, bisphosphonate tablets should be taken on an empty stomach. Specific instructions for taking each drug are included in the chart that follows. Also, an adequate dietary calcium intake (1000-1500 mg daily) and vitamin D intake (400 units) are recommended during bisphosphonate use, except if there is a history of kidney stones that contain calcium. Patients who receive Arediaģ should have serum creatinine (a measure of kidney function) tested before each treatment, since kidney function can be impaired when Arediaģ is used in high doses or when it is given too rapidly.

 

The recommended dosages that follow are those approved by the FDA. However, experienced physicians may sometimes prescribe different doses. None of these drugs should be used by people with severe kidney disease.

 

Calcitonin.† Miacalcinģ is a brand of synthetic salmon calcitonin that is taken by injection. The dose may vary from 50 units to 100 units, taken daily or three times a week for 6 to 18 months. Repeat courses can be given after brief rest periods. The nasal spray form of this drug is not approved or recommended for Pagetís disease.

 

The chart that follows includes information regarding the administration and dosage of drugs approved in the U.S. for the treatment of Pagetís disease:

 

 


I. Bisphosphonates

Administration and Dosage

Risedronate Sodium

Trade Name:

Actonelģ

(Procter & Gamble/ Aventis)

Approved by FDA 1998

30 mg tablet taken once daily for 2 months

Must be taken on an empty stomach, with 6-8 oz tap water, in the morning

Patients should wait at least 30 minutes after taking Actonelģ before eating any food, drinking anything other than tap water, or taking any medication

Should not lie down for at least 30 minutes after taking Actonelģ (Patient may sit)

Alendronate Sodium

Trade Name: Fosamaxģ

(Merck)

 

Approved by FDA 1995

40 mg tablet taken once daily for 6 months

Must be taken on an empty stomach, with 6-8 oz of tap water, in

the morning

Same instructions as for Actonelģ

Fosamaxģ is only available by mail order through Merckís Paget Patient Support Program which is administered by CVS ProCare,

Tel. 888-900-3232.

Tiludronate Disodium

Trade Name: Skelidģ

(Sanofi-Synthelabo)

 

Approved by FDA 1997

400 mg (two 200 mg tablets) taken once daily for 3 months

Must be taken on an empty stomach with 6-8 oz of tap water

Skelidģ may be taken any time of day, as long as there is a period of 2 hours before and after eating food, drinking anything other than tap water, or taking any medication

Pamidronate Disodium

Trade Name: Arediaģ

(Novartis)

 

Approved by FDA 1994

Generic pamidronate, Pamidronate Disodium for Injection (Bedford Laboratories), is also available.

Intravenous

The FDA approved regimen is a 30 mg intravenous infusion given over 4 hours on 3 consecutive days.

-          A single infusion of 60-90 mg given over 2-4 hours is effective in mild disease.

-          For more severe disease, 60 mg infusions given over 2-4 hours for 2 or more consecutive or non-consecutive days may be administered.

A course of pamidronate may be readministered at intervals as needed.

Serum creatinine (a measure of kidney function) should be tested before each pamidronate treatment

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Etidronate Disodium

Trade Name: Didronelģ

(Procter & Gamble/ Aventis)

 

Approved by FDA 1977

200 to 400 mg taken once daily for 6 months

Though the approved regimen is 200-400 mg once daily for 6 months, the higher dose (400 mg) is preferred

Didronelģ may be taken any time of day, as long as there is a period of 2 hours before and after eating food, drinking anything other than tap water, or taking any medication.

A course of Didronelģ should not exceed 6 months

Repeat courses can be given after rest periods of at least 6 months duration

Fosamaxģ, Skelidģ, and Actonelģ should be used with caution by patients who have disorders affecting the esophagus or the stomach.

 

 

II. Calcitonin
Administration and Dosage

Trade Name: Miacalcinģ

(Novartis)

 

Approved by FDA 1990

Injection

50 to 100 units daily or 3 times per week for 6-18 months

 

 

 

The cost of these drugs varies depending on where a patient

lives and his or her insurance coverage.

 

Other Treatments

 

Analgesics and nonsteroidal anti-inflammatory agents may be helpful to relieve pain in bone and adjacent joints.† Walking aids, shoe lifts, canes and physical therapy may be recommended when a patient experiences difficulty walking due to bowing of leg/s.

 

23.Q. After treatment with the bisphosphonate drugs, actonelģ, fosamaxģ, didronelģ, skelidģ and arediaģ, when should the patient follow up with his or her physician?

A.† For the oral drugs, Actonelģ, Fosamaxģ, Didronelģ and Skelidģ, SAP should be checked at the end of the treatment period and again in three months. Then the SAP can be checked every six months to one year, depending on whether the SAP was in the normal range after the treatment. For the intravenous drug Arediaģ, the SAP should be checked three months after the last infusion and then every three to six months.

24.Q. how is a patientís response to treatment monitored?††

A.† Measurement of serum alkaline phosphatase is used to monitor response to treatment.†† If a patientís SAP was above the normal range when treatment was initiated and is in the normal range after the treatment, this means that the treatment has been successful. In some cases urinary markers of bone resorption such as N-telopeptide are also used to monitor the response to treatment.

 

25. †Q. When is surgery recommended for Pagetís disease?

A.† There are generally three major complications of Pagetís disease for which surgery

may be recommended. The first complication is fractures in bone affected with Pagetís disease. Surgical repair of fractures in bones with Pagetís disease may help the fractures heal in a better position. When needed, metal rods may stabilize the bone.

 

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The second complication is severe degenerative arthritis. If medication and physical therapy are no longer helpful and if disability is severe, joint replacement of the hips and knees may be considered. The third complication involves bone deformity, especially of the tibia. The surgical cutting and realignment of a bone with Pagetís disease† (osteotomy) may help painful weight-bearing joints, especially the knees.

 

If it is possible, a patient having surgery on a bone with Pagetís disease, should have medical therapy such as Arediaģ, Actonelģ or Fosamaxģfor several months prior to surgery. This therapy helps decrease bleeding and prevent other complications. The patient having surgery should discuss pre-treatment with his or her physician.† There are two complications for which neurosurgery can be helpful:† enlargement of the skull that causes the back of the skull to deform and injure the nervous system or bone; and overgrowth of the spine that compresses the spinal cord and spinal nerves. However, if medical therapy corrects the symptoms surgery may be avoided.


 


The Paget Foundation for Pagetís Disease of Bone and Related Disorders provides information and programs for consumers and health professionals on several bone disorders including Pagetís disease of bone, primary hyperparathyroidism, fibrous dysplasia, osteopetrosis, and the complications of certain cancers on the skeleton.

 

 

 

Foundation programs and services include:

Patient Education and Assistance, Professional Education, Public Education,

Research & Advocacy

 

A copy of the Foundationís annual report is available by writing to the Foundation office or the Office of the Attorney General, Charities Bureau, 120 Broadway, New York, NY 10271.


120 Wall Street, Suite 1602, New York, NY 10005-4001

Toll-free: 800-23-PAGET††††††††††† Phone: 212-509-5335†††††††††††† Fax: 212-509-8492

 

Website: http://www.paget.org††††††††††† E-mail: PagetFdn@aol.com

Copyright, The Paget Foundation, 2004

 
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