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  A Nurseís Guide to Pagetís Disease of Bone  
 

A Nurse's Guide to Paget's Disease of Bone

Paget's disease of bone is the second most common bone disease in the US, after osteoporosis. Prevalence in the population ranges from 1.5% to 8%, depending on the patient's age and where he or she lives. During the last eight years, several effective therapies for Paget's disease have been approved in the US.† However, many patients still have difficulty finding appropriate treatment.

To address this problem, The Paget Foundation for Paget's Disease of Bone and Related Disorders with support from the NIH Osteoporosis and Related Bone Diseases~National Resource Center launched an educational outreach project for health professionals. The first publication in this project was a publication for physicians, The Management of Paget's Disease of Bone. (This publication is available on the Paget Foundation website at www.paget.org and the NIH Osteoporosis and Related Bone Diseases ~ National Resource Center website at www.osteo.org.)

The Paget Foundation acknowledges editorial contributions by Betsy Love McClung, M.N., R. N., Associate Director, Oregon Osteoporosis Center, Portland OR and Linda Pachuki-Hyde, MS. R.N., C.D.E., Coordinator, Osteoporosis and Metabolic Bone Disease Program, Midwest Endocrinology Associates, Milwaukee, WI and manuscript review by Joan Terita, R.N., Staff Nurse, Saint John's Health Center and Rebecca Crane-Okada, Ph.D., R.N. AOCN, Clinical Nurse Researcher, John Wayne Cancer Center at Saint John's Health Center, Santa Monica, CA.

The opinions and recommendations in A Nurse's Guide to Paget's Disease of Bone are those of The Paget Foundation and do not necessarily reflect the views of the National Institutes of Health.


NIH ORBD~NRC National Institutes of Health Osteoporosis and Related Bone Diseases ~ National Resource Center

1232 22nd St., NW
Washington, DC 20037-1292
(202) 223-0344, (800) 624-BONE
Fax (202) 293-2356, TTY (202) 466-4315
E-mail - orbdnrc@nof.org Internet - www.osteo.org

Paget Foundation Logo The Paget Foundation for Paget's Disease of Bone and Related Disorders

120 Wall Street, Suite 1602
New York, NY 10005-4001
(212) 509-5335, (800) 23-PAGET
Fax (212) 509-8492
E-mail - pagetfdn@aol.com Internet - www.paget.org

The National Resource Center is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases with contributions from the National Institute of Child Health and Human Development, National Institute of Dental and Craniofacial Research, National Institute of Environmental Health Sciences, NIH Office of Research of Women's Health, DHHS Office on Women's Health, and the National Institute on Aging.

The Resource Center is operated by the National Osteoporosis Foundation, in collaboration with The Paget Foundation and the Osteogenesis Imperfecta Foundation.


Introduction

Although Paget's disease is the second most common bone disease in the US, it often goes unrecognized and untreated until its course has advanced.† Nurses, radiologists and other health care professionals who work in hospital emergency rooms, nursing homes and family clinics should be aware of Paget's disease and its symptoms, in order to identify patients as early as possible and utilize the effective treatments that are available to manage the disease

In one typical diagnostic scenario, an elderly person suffers a broken bone in an accident and a radiologist recognizes Paget's lesions in the x-rays.† Other patients, assuming that they have arthritis, treat Paget-related bone pain with increasing amounts of over-the-counter medications.† They do not learn that the source of the pain is Paget's disease until they receive a proper diagnosis, sometimes years after the pain began.

Nurses, on the front-line of health care, need to know what to look for and what questions to ask in order to find Paget's disease early in the disease's progression.† The earlier a diagnosis is made, the more effective the treatment, and the less devastating the impact on the individual patient.

What is Paget's Disease of Bone?

First described by the eminent British surgeon Sir James Paget in 1877, Paget's disease of bone is a disorder of bone remodeling in which there is excessive bone resorption followed by excessive bone formation that results in bone that is architecturally unsound. The disease occurs in both males and females, affecting 1.5 to 8% of the population over 50 years of age in many countries.† It is much less common in people of Asian, Indian and Scandinavian ancestry.

Paget's disease may be found in multiple family members due to mutations in several genes.† There is also evidence of measles virus in bone lesions in Paget's disease, but the relevance of this is still under investigation.

Paget's disease may cause the enlargement and deformity of a single bone or multiple bones.† As a result, bone pain, arthritis, noticeable skeletal deformities and fractures can occur. While any bone can be affected, the most common sites are the femur, tibia, pelvis, vertebrae and skull. Long bones in the leg tend to bow, and the skin over the Pagetic lesion is frequently warm

due to the increased blood flow to the site. The skull can become enlarged and lead to headaches or hearing loss when the disease affects the temporal bone. The spine may develop curvature in advanced cases.† In the spine, the increased bone volume may compress the spinal cord or nerve roots, causing severe pain and impaired neurological functioning. Hip pain is a common complaint when the pelvis or thighbone is involved. Clinical signs and symptoms will vary from one patient to the next, depending on the number and location of affected skeletal sites, as well as on the rapidity of the abnormal bone turnover. Long-term observation of Paget's disease patients indicates that the disease does not spread from one bone to another.

The most devastating complication of Paget's disease is a transformation of the bone that becomes cancerous.† Fortunately, osteosarcoma or other types of sarcoma occur in less than 1 percent of patients with Paget's disease, but this is a significantly higher rate than in non-affected individuals.† In patients with Paget's disease, osteosarcoma is often fatal.

Guidelines for Evaluation

It is likely that many patients have the disorder for a long period before any diagnosis is made, especially because Paget's disease is often asyptomatic and the diagnosis may be an incidental finding.††

Biochemical Tests

Elevated levels of the enzyme serum alkaline phosphatase (SAP) detected in routine serum chemistry profiles can be the first indication that an individual has Paget's disease and not arthritis or another disorder.† Alkaline phosphatase, an enzyme produced by bone cells and a marker for bone formation, is over-produced by Pagetic bones.† A mild over-production might indicate a healing fracture, but a SAP level two or more times higher than normal strongly suggests Paget's disease, provided there is no evidence of liver disease or renal failure.

Biochemical tests that serve as markers of bone resorption and disease activity may support the diagnosis of Paget's disease. These tests include urinary hydroxyproline, pyridinoline/deoxypyridinoline, N-telopeptide and C-telopeptide.

Radiographic Testing

Bones affected by Paget's disease have a characteristic appearance on x-rays.† These characteristic changes include the presence of osteolytic lesions and enlarged bones with a chaotic sclerotic appearance. A decrease in joint space is an indication of degenerative arthritis, a common disorder in people with Paget's disease.

Radionuclide Bone Scan

A radionuclide bone scan is the most sensitive means of detecting Paget's disease in the skeleton.† A radiolabeled bisphosphonate is injected intravenously and circulates through the blood stream.† This substance then localizes in Pagetic areas of bone where there is increased blood flow and high levels of bone formation.† This test is used primarily to establish the full extent of Paget's activity. It is not generally used to monitor the effects of treatment.

Medical History

The diagnosis of Paget's disease for patients in clinical settings begins with obtaining a careful medical history.† This history includes documentation of family members who have been diagnosed with the disease. Specific symptoms related to Paget's disease should be sought including pain (onset, location, severity), deformity and increased warmth over an extremity. General history taking includes documentation of current and previous medical conditions, fractures, surgeries, medications, height (maximum and current) and weight. Patients who come for a second opinion regarding a previous diagnosis of Paget's disease should be queried regarding the following:

  • Date of diagnosis
  • How the diagnosis was made
  • Skeletal site/s affected
  • Date of diagnostic test (bone scan, x-ray, lab test)
  • Serum alkaline phosphatase level
  • Current/previous Paget's medications
  • Symptoms
  • Previous fractures
  • Physical function limitations
    • a. Activities of daily living
    • b. Mobility
    • c. Balance
    • d. Hearing.

A compete medical history, physical examination and interpretation of laboratory test results contribute to making an accurate diagnosis and identifying the appropriate management strategy.

Objectives for Management of Paget's Disease

The three major objectives for the management of patients with Paget's disease are:

Minimize symptoms

Improve the patient's physical function

Help slow the disease process and prevent complications

The nurse plays a major role in helping the patient accomplish each of these objectives by providing the patient and family members with education and professional support and by encouraging the patient's adherence to therapy.

Indications for Treatment

Treatment for Paget's disease is based on antiresorptive therapy.† There are four general indications for treatment of Paget's disease:

  1. Symptoms due to metabolically active Paget's disease warrant treatment, including bone pain related to a pagetic site or fatigue fracture, headache resulting from an affected skull, back pain from affected pagetic vertebrae or other neurological syndromes associated with Pagetic changes.
  1. Treatment is warranted in a patient planning to undergo elective surgery on a pagetic site, such as hip replacement, in an attempt to minimize the operative blood loss due to hypervascularity present in active Pagetic bone.
  2. Treatment is indicated in the management of hypercalcemia, a rare occurrence when a patient with multiple bones affected by Paget's disease and a highly elevated serum alkaline phosphatase level undergoes prolonged immobilization.
  1. Many Paget's disease specialists believe that treatment is indicated as an attempt to decrease local progression and reduce the risk of future complications – even in asymptomatic patients whose sites of disease and degree of metabolic activity place them at risk of progression and complications.† This group of patients includes individuals who may be at risk for: a. bowing deformities in their long bones; b. hearing loss because of skull enlargement; c. neurological complications due to Pagetic changes in their vertebrae; d. secondary arthritis as a complication of Paget's disease located next to major joints.

Though there is no direct evidence that aggressive treatment of Paget's disease is associated with prevention of progression or reduction in risk of future complications, investigators have looked to indirect evidence to suggest this possibility.† This indirect evidence includes the assumptions that:

Failure to treat Paget's disease is associated with the further extension of the osteolytic lesions in a bone and the progression of bone deformities.

Successful treatment of Paget's disease is associated with restoration of normal patterns of new bone deposition.

Improvement of facial and skull deformities may be observed after successful treatment. (Shown in one study.)

Therefore, specialists conclude that it is good clinical practice to treat both symptomatic patients whose symptoms may improve after a reduction in abnormal bone turnover and asymptomatic patients who have active Paget's disease in areas of the skeleton that might be expected to produce future complications of clinical significance.

Adherence to Therapy

Increasing concern about skeletal health, risk of complications and safety of drug therapy are major concerns that can produce stress and anxiety in individuals who have been diagnosed with Paget's disease.† Counseling patients can promote implementation of new behaviors to optimize skeletal health, reduce further consequences and enhance quality of life. The targets of such counseling are:† a. behaviors related to adherence to medical therapy, b. injury prevention and c. physical therapy when indicated.† Continuous collaboration between nurses and patients can help improve adherence. It is important for the nurse to understand the following patient issues to help the patient make appropriate changes in health behaviors:

  • Individual health beliefs
  • Motivation to change and level of commitment
  • Presence or absence of denial of risk or severity of disease.

Counseling techniques to promote and maintain new health behaviors include:
  • Providing specific individual information regarding risks and benefits of medical†therapy, including side effects, duration of treatment and cost
  • Setting mutual goals
  • Providing feedback regarding response to therapy
  • Encouraging long-term follow-up.

Therapy Options

Four main methods of treatment exist for a patient with Paget's disease:

  • Non-pharmacological therapy (focusing mainly on physical therapy as a means of improving muscle strength to help control some types of pain)
  • Pharmacological therapy using either bisphosphonates or calcitonin
  • Pain management using analgesics
  • Surgery.

Pharmacological Treatment

Bisphosphonates

Bisphosphonates suppress or reduce bone resorption by osteoclasts. They do this both directly by hindering the recruitment and function of osteoclasts and perhaps indirectly by stimulating osteoblasts to produce an inhibitor of osteoclast formation.† There is now a reasonable understanding of how these drugs work, and the differences between the various types of bisphosphonates are better understood.

Currently, five bisphosphonates are approved by the US Food and Drug Administration (FDA) for the treatment of Paget's disease.† These include pamidronate, which is given intravenously, and etidronate, tiludronate, alendronate and risedronate, which are taken orally.

A mild form of Paget's disease can be suppressed with one or two 60mg infusions of pamidronate, while a more severe manifestation of the disease may require several infusions of 60-90 mg of pamidronate on a weekly or twice-weekly basis.† Serum alkaline phosphatase testing should occur approximately two to three months after the appropriate number of infusions is administered.† Oral calcium and vitamin D supplementation are recommended for patients using pamidronate to lessen hypocalcemia.

Both alendronate and risedronate have been shown to reduce the biochemical indices of bone turnover, often into the normal range, in patients with moderate-to-severe Paget's disease.

Alendronate is taken as a daily 40mg tablet for six months; risedronate is taken as a daily 30mg tablet for two to three months.† These drugs are generally taken at least 30 minutes before breakfast with water only.

Etidronate and tiludronate are less potent than alendronate and risedronate.† They are both taken as daily 400 mg tablets.† Etidronate – the original bisphosphonate used to treat Paget's disease – is taken for six months, while tiludronate is taken for three months.† With both of these bisphosphonates, calcium supplements and food and beverages should not be taken for several hours before or following taking the drugs.

Investigators have recognized that secondary resistance to individual bisphosphonates (etidronate and pamidronate) can occur.† Therefore, it may be necessary for a patient to switch from one bisphosphonate to another in long-term treatment.† Due to the generally poor absorption of the bisphosphonates, it is vital that patients take oral bisphosphonates in the prescribed manner to avoid incomplete absorption of the drugs.

Bisphosphonates are generally well tolerated. The main problem can be irritation of the esophagus.

Calcitonin

Subcutaneous injection of salmon calcitonin was the first widely utilized therapy for Paget's disease.† Salmon calcitonin has been shown to reduce elevated indices of bone turnover by 50%, decrease symptoms of bone pain, reduce warmth over affected bones, improve some neurological complications and promote healing of lytic lesions.† Today, the use of calcitonin is limited mostly to patients who do not tolerate bisphosphonates.† In the case of secondary resistance to salmon calcitonin, a switch to bisphosphonate therapy is necessary.

The therapies most widely used by Paget's disease medical specialists are the three more potent bisphosphonates: risedronate, alendronate and pamidronate.

Pain Management: Analgesics

Pain directly attributable to Paget's disease is generally relieved through anti-osteoclast treatment as described above.† Some pain may be the result of muscle spasm associated with either bone deformity or arthritic or neurological complications.† In this case, acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDS) or the new cox-2 inhibitors may be helpful for the management of nonskeletal pain in addition to the main pagetic therapy chosen.†

Surgery

Different orthopedic interventions that may be necessary in pagetic patients include:

  • Fixing a complete fracture through Pagetic bone;
  • Realigning the knee through tibial osteotomy to decrease mechanical pain, particularly if medical therapy is unsuccessful in managing severe pain symptoms; and/or
  • Replacing the hip and/or knee through total joint arthroplasty for patients unresponsive to anti-osteoclast treatment and therapy for the osteoarthritis.

When repairing a pagetic fracture, total immobilization of that site should be avoided if possible. In all cases of surgical intervention, pre-treatment with a potent bisphosphonate is very important.† Since hypervascularity is a feature of active Paget's disease, this may lead to serious bleeding during an operation.† Pre-treatment with a bisphosphonate will reduce the hypervascularity and reduce the risk of greater-than-normal operative blood loss.

THE COST OF THESE DRUGS VARIES IN DIFFERENT AREAS
AND ACCORDING TO A PATIENT'S INSURANCE COVERAGE.

Bisphosphonates Approved for Paget's disease of bone

(Listed in Chronological Order of FDA Approval)††††††††††††††††††††††††††

I. Bisphosphonates

Administration and Dosage

Cost
Etidronate

Trade Name:

Didronel®

(Procter & Gamble)

FDA approval: 1977

Tablet

200 to 400 mg once daily for 6 months

200-400 mg dose is approved; 400 mg dose is preferred

Must be taken with 6-8 ounces of water on an empty stomach (no food, beverages, or medications for 2 hours before and after dose).

Course of Didronel® should not exceed 6 months.

Repeat courses can be given after rest periods of 3-6 months duration.

Average cost:

$763.35 for

6-month dose of 400 mg tablets

Pamidronate

Trade Name:

Aredia®

(Novartis)

FDA approval: 1994

Intravenous

Approved regimen is 30 mg intravenous infusion over 4 hours on 3 consecutive days

A more commonly used regimen is a 60 mg or 90 mg intravenous infusion over 2-4 hours and repeated as clinically indicated.

A single infusion is sometimes effective in mild disease; 2-3 or more infusions may be required in more severe disease.†

A course of Aredia® may be readministered at intervals as needed.†

Average cost:

$222.11 for one 30 mg vial, $888.45 for a box of four vials

Additional fees charged by the hospital or clinic for administration of the drug

Alendronate

Trade Name:

Fosamax®

(Merck)

FDA approval: 1995

Tablet

40 mg once daily for 6 months

Must be taken on an empty stomach, with 6-8 ounces of water, in the morning.

Wait at least 30 minutes after taking Fosamax® before eating any food, drinking anything other than tap water, or taking any medication.

Do not lie down for at least 30 minutes after taking Fosamax®. (Patient may sit.)

Average cost:

$1,061.52 for 6-month dose of 40 mg tablets.

40 mg Fosamax® is only available by mail order through the Paget's Patient Support Program, administered by CVS ProCare. Up to 6 months of additional treatment will be provided at no charge if, after completing 6 months of therapy, further therapy is needed.† For information, call 1-888-900-3232.


 

Bisphosphonates

Administration and Dosage

Cost

Tiludronate

Trade Name:

Skelid®

(Sanofi-Synthelabo, Inc.)

FDA approval: 1997

Tablet

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

Must be taken on an empty stomach with 6-8 ounces of water.

Skelid® may be taken any time of day, as long as there is a period of 2 hours before and after resuming food, beverages, and medications.

Average cost:

$1,352.86 for 3-month dose of 400 mg (two 200 mg tablets)

Risedronate

Trade Name:

Actonel®

(Procter & Gamble/Aventis)

FDA approval: 1998

Tablet

30 mg once daily for 2 months

Must be taken on an empty stomach, with 6-8 ounces of water in the morning.

Wait at least 30 minutes after taking Actonel® before eating any food, drinking anything other than water, or taking any medication.

Do not lie down for at least 30 minutes after taking Actonel®. (Patient may sit.)

Average cost:

$772.80 for 2-month dose of 30 mg tablets


 

II. Calcitonin

Administration and Dosage

Cost

Trade Name:

Miacalcin®

(Novartis)

Approved by FDA 1990

Injection

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

Average cost:
Injection: $1,468.35 for 100 units/day taken daily for 6 months

Summary

Drugs Approved for Paget's Disease in the US

Two types of drugs, bisphosphonates and calcitonin, are approved by the US Federal Drug Administration (FDA) to treat Paget's disease.† Two bisphosphonates, Actonel® and Fosamax®, and the calcitonin drug Miacalcin® are also approved to treat osteoporosis.

The doses of these drugs used to treat Paget's disease and osteoporosis are different.

Bisphosphonates

Actonel® – Paget's disease dose is a 30 mg tablet taken once daily for two months.

Osteoporosis doses are 5 and 35 mg tablets taken for as long as the physician recommends.

Fosamax® – Paget's disease dose is a 40 mg tablet taken once daily for six months.

Osteoporosis doses are 5, 10, 35 and 70 mg tablets taken for as long as the physician recommends.

(40mg Fosamax® is not available in retail pharmacies. It can only be purchased from CVS ProCare Direct Pharmacy Paget's Patient Support Program, 600 Penn Center Blvd, Pittsburgh, PA 15235 Tel (888) 900-3232 Fax (888) 776-5722. Physicians can prescribe Fosamax® 40mg by mail, fax or telephone.

Aredia® is an intravenous drug that can be administered in several ways. The approved regimen for Paget's disease is 30 mg given over 4 hours on 3 consecutive or non-consecutive days for a total of 90mg of the drug.† A more commonly used regimen is a 60 mg infusion given over 2-4 hours for 2 or more consecutive or non-consecutive days for a total of 120mg of the drug.

Skelid® – 400 mg (two 200 mg tablets) taken once daily for 3 months.

Didronel® – 200 to 400 mg taken once daily for 6 months. (The higher dose is preferred).

Calcitonin

The only calcitonin approved for Paget's disease is Miacalcin® that is an injection taken daily or three times per week. The suggested dose is 50 to 100 units daily or 3 times a week for 6-18 months. Miacalcin® nasal spray is approved for treating osteoporosis, but is not approved or recommended for treating Paget's disease.

©Copyright, The Paget Foundation, 2002

 
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