1. Q.  What is Paget’s disease of bone?

A.     Paget’s 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 Paget’s 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 Paget’s disease?

A.     The cause/s of Paget’s disease are still not clearly defined. Research suggests that Paget’s disease may be caused by a “slow virus” 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 Paget’s disease are susceptible to the suspected virus. One gene that predisposes individuals to develop Paget’s disease, the sequestosome 1 gene, has been discovered. Two other genes, RANK and the VCP gene, are also associated with Paget’s disease. Alterations in the RANK gene cause a disease named familial expansile osteolysis (FEO) that has some similarities to Paget’s disease. Also, RANK has been found in one family where a family member developed Paget’s disease at a younger age than most Paget’s disease patients.  The final gene associated with Paget’s disease is the VCP gene, a gene that is found in Paget’s 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 Paget’s disease.

3. Q.  Which groups of people are usually affected by Paget’s disease, and how

common is the disease?

A.     Paget’s disease is rarely diagnosed in people under 40.  The prevalence ranges from 1.5 percent to 8 percent in older adults depending on the person’s age and area of the world where he or she lives. Familial Paget’s 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 Paget’s disease usually diagnosed?

A.  Paget’s disease may be discovered by x-ray examination, blood tests or by bone scans. Because bones affected with Paget’s disease have a distinct appearance in x-rays, x-ray is the main means of diagnosing Paget’s disease.  Rarely, a bone biopsy is necessary for diagnosis when the x-ray result is inconclusive. The patient’s doctor may be alerted to the possibility of Paget’s 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 Paget’s disease, too much SAP is produced).   Another test which may detect Paget’s 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 Paget’s disease. Bone scans are useful in determining the extent andactivity of the disease. If a bone scan suggests Paget’s 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 Paget’s disease ask their physicians for any special diagnostic tests?

A.     After the age of 40, siblings and children of a patient with Paget’s 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 Paget’s 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 Paget’s disease.

Headaches.  These may occur when Paget’s disease occurs in the skull.

Hearing loss.  This can result from Paget’s 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 Paget’s disease can break more easily than healthy bones. Most fractures that occur in Paget’s 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 Paget’s disease irritates nerves in the spine.

7. Q. Do all people who have Paget’s disease know that they have it?

A.  No. Many patients who have Paget’s disease do not know they have it since the disease may be so mild that it is not diagnosed. Sometimes the patient’s 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 Paget’s disease?

A.  Any bone can be affected in Paget’s disease. Paget’s 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 Paget’s disease?

A.  The course of Paget’s 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 Paget’s disease is generally good, particularly if treatment is given before major complications occur. Treatment can control Paget’s disease and lessen symptoms but is not a cure. When untreated, Paget’s 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 Paget’s disease a fatal disease and is there a relationship between paget’s disease and cancer?

A.       Paget’s disease is rarely fatal. Sarcoma, a form of bone cancer, is an extremely rare complication that occurs in less than one percent of all Paget’s 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. 

Paget’s Disease and Other Medical Conditions

11. Q. What is the relationship between osteoarthritis and Paget’s disease?

A.     Paget’s 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 Paget’s disease may become enlarged, causing the joint surfaces to undergo excessive wear and tear. Osteoarthritis is a common cause of pain in Paget’s disease, but the disease itself also causes bone pain. In many patients, the pain may be due to a combination of Paget’s disease and osteoarthritis. 

12. Q. What is the relationship between Paget’s 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 Paget’s 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 Paget’s disease and osteoporosis are different for Paget’s disease than for osteoporosis.   

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

13. Q. Is there a relationship between Paget’s disease and heart disease?

A.  In patients with extensive Paget’s 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 Paget’s disease and kidney problems?

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

15. Q. What causes pain in Paget’s disease?

A.     Pain is the most common symptom that brings a patient with Paget’s disease to a

physician. Since many patients with painful symptoms of Paget’s disease do not have obvious deformities, they may not receive the correct diagnosis.  The types of pain associated with Paget’s 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 Paget’s disease patients experience loss of hearing? Can anything be done to remedy this condition?

A.     When Paget’s 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 Paget’s disease, treating the Paget’s disease may slow or stop the progression of the hearing loss. Hearing aids often may help improve hearing.

17. Q. Can Paget’s 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 Paget’s disease affect the teeth?

A.     When Paget’s 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 Paget’s disease? Specifically, is there a relationship between calcium and/or vitamin d and Paget’s disease?

A.  No. There is no relationship between diet and Paget’s disease. In general, all people including Paget’s 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 Paget’s 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 paget’s 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 Paget’s disease patient should discuss the exercise program with his or her physician since undue stress on bones affected with Paget’s disease should be avoided.

Treatment

21. Q. Which types of physicians are specialists in Paget’s 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 Paget’s 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 Paget’s 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: Actonel^®, Fosamax^® and Aredia^®. Didronel^®, Skelid^® or Miacalcin^® 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 Paget’s 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 Aredia^® should have serum creatinine (a measure of kidney function) tested before each treatment, since kidney function can be impaired when Aredia^® 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.  Miacalcin^® 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 Paget’s disease.

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

Fosamax^®, Skelid^®, and Actonel^® should be used with caution by patients who have disorders affecting the esophagus or the stomach.

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, actonel^®, fosamax^®, didronel^®, skelid^® and aredia^®, when should the patient follow up with his or her physician?

A.  For the oral drugs, Actonel^®, Fosamax^®, Didronel^® and Skelid^®, 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 Aredia^®, the SAP should be checked three months after the last infusion and then every three to six months.

24.Q. how is a patient’s response to treatment monitored?  

A.  Measurement of serum alkaline phosphatase is used to monitor response to treatment.   If a patient’s 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 Paget’s disease?

A.  There are generally three major complications of Paget’s disease for which surgery

may be recommended. The first complication is fractures in bone affected with Paget’s disease. Surgical repair of fractures in bones with Paget’s 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 Paget’s disease  (osteotomy) may help painful weight-bearing joints, especially the knees.

If it is possible, a patient having surgery on a bone with Paget’s disease, should have medical therapy such as Aredia^®, Actonel^® or Fosamax^®for 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.