Paget's Disease of Bone

Definition

Paget's disease of bone, or osteitis deformans, is a chronic (long-lasting) disorder that affects bone growth in localized areas of the skeleton. The disease, which usually strikes the elderly, causes bones to weaken, grow larger, and change shape.

Description

In 1877, Sir James Paget, British surgeon and authority on bone and joint diseases, was the first person to identify Paget's disease of bone. Paget's disease is a metabolic disorder, that is, a disease involving the process by which the body's cells make or use energy. As living tissue, bone is constantly in the process of renewal. Bone cells called osteoclasts dissolve the body's old bone, and bone-building cells called osteoblasts replace the old bone with new bone in a process called remodeling or turnover.

In the remodeling process, bone is usually formed first in what is called woven bone, which forms quickly and is weak in structure. This weak bone is then replaced by lamellar bone—stronger bone that is formed in a series of five layers, or lamellae. The layers contain collagen (a protein that is the main component of connective tissue) fibers in a nearly parallel pattern. This dynamic material then becomes mineralized as tiny crystals grow along the collagen fibers. The collagen fibers of adjacent layers are laid down at an angle or perpendicular to each other, much like plywood, in a process that increases bone strength. Lamellar bone is the most abundant type of bone in humans.

In Paget's disease, however, the bone remodeling process goes awry and becomes overactive. Excessive osteoclast resorption—a process by which bone is destroyed, then absorbed by the body—is followed by osteoblastic bone formation at certain localized sites, leading to a mosaic of woven and lamellar bone. Over time, the deformed bone grows larger, more fragile, and develops more blood vessels than normal bone. This weakened bone fractures more easily, even after a minor injury.

Demographics

The disease primarily affects the elderly and occurs more frequently in the United Kingdom (UK) than anywhere else in the world. In the UK, approximately 750,000 to 1 million are affected with the disease. In the United States, the disease is relatively uncommon in people under 55 years of age. The disorder occurs in 3–4% of people over 55 and in about 10% of people over 80 years old. In addition, Paget's disease is more common among people of Northern European descent.

Causes and symptoms

Although the cause of the disease is unknown, researchers believe that heredity may play a role in about 15–20% of patients. Although when he first identified the disease, Sir James Paget maintained that the disease was caused by an inflammatory process, it was later believed that the disorder could be viral in origin.

Although most people—especially those with mild forms of the disease—do not exhibit symptoms, a variety of symptoms and complications may arise among those with more severe disease. The most common symptom is bone pain and stiffness in the joint areas; this pain, which usually worsens at night, is not related to changes in sleeping position.

In some people, however, as the disease progresses, bones may bow (bend), the skull may enlarge, and the spinal column may curve, causing severe pain or arthritis. These bone deformities may exert pressure on surrounding nerves (and tissues) and result in muscle weakness and gait abnormalities. Bones may break easily, and healing is difficult because the body is not able to form healthy, strong bone.

The skeletal areas most commonly involved are the pelvis (hip), spine, skull, femur (thighbone) and tibia (shinbone). Although the disease is usually localized to one or two bones, numerous active sites are more common in those with a family history of the disease.

When bones of the skull are involved, over time, pressure in the skull may cause a variety of symptoms, such as

• deafness
• dizziness
• headaches
• vision problems
• tinnitus (ringing in the ears)

When large portions of the skeleton are involved (15–35%) and the disease is highly active, cardiovascular complications may occur.

Diagnosis

Individuals without symptoms are sometimes diagnosed with the disease after routine blood testing during a physical examination. An elevated alkaline phosphatase (an enzyme produced mainly by bone and the liver and a marker of bone formation) level may indicate the presence of Paget's disease. An asymptomatic individual may also be diagnosed on discovery of an abnormal finding on an x-ray exam for another condition.

In symptomatic individuals, the alkaline phosphatase blood test is the test of choice for both diagnosing Paget's disease and assessing response to treatment. A high alkaline phosphatase level, especially in combination with a high serum (blood) and urinary hydroxyproline (a marker of bone resorption) level, confirms the presence of Paget's disease in most cases. Other elevated markers of bone resorption, such as urinary N-telopeptide, may also indicate Paget's disease.

In addition to blood tests, a physician may order imaging studies—such as x rays, a computed axial tomography (CT) scan, or a magnetic resonance imaging (MRI) scan—to indicate whether bone enlargement, thickening, or deformity has begun to occur in one or more areas of the body. The particular tests performed may depend on the part of the body affected. If the disease affects the skull, for example, vision and hearing tests may be performed in addition to blood tests and imaging studies.

Treatment

Pharmacologic treatment

The development of effective and potent drugs for Paget's disease has changed the treatment philosophy from treating only those suffering from symptoms of the disease to treating individuals who are at risk for complications but who have no symptoms. Pharmacologic therapy is indicated in the following circumstances:

• To control symptoms caused by active disease, such as bone pain, fracture, headache, or pain from or joint or nerve complications
• To decrease local blood flow and minimize blood loss in patients undergoing surgery
• To reduce the hypercalciuria (urinary loss of calcium) that may occur during immobilization
• To decrease the risk of complications when disease activity is high and when the site of involvement involves weight-bearing bones, areas near major joints, vertebrae, or the skull

Pharmacologic treatment for Paget's disease frequently targets the excess bone resorption or breakdown feature of the disease. The bisphosphonates, a class of drugs most often used to modify osteoclast activity, and thereby reduce bone resorption, include

• Alendronate (Fosamax)
• Etidronate (Didronel)
• Pamidronate (Aredia)
• Risedronate (Actonel)
• Tiludronate (Skelid)
• Zoledronate (Reclast)

In addition, calcitonin (Miacalcin), is also approved to treat Paget's disease. This drug, available by injection (the nasal spray form of the drug is not approved for the treatment of Paget's disease), is a synthetic version of the natural form of calcitonin. In the body, calcitonin is a hormone that is produced by the thyroid gland and that promotes bone formation. This drug is sometimes used if the bisphosphonates are not well-tolerated.

If the symptoms of disease are mild, over-the-counter drugs such as acetaminophen or nonsteroidal anti-inflammatory drugs, such as aspirin or ibuprofen, may alleviate the bone or muscle pain associated with the disorder.

Surgical treatment

If an individual has suffered from bone fracture or severe disability, surgery is often necessary. Joint replacement of the hips or knees or surgery to realign the affected bones (osteotomy) may alleviate the pain in weight-bearing joints. Whether early surgical intervention prevents later complications has not been determined.

Nutrition/Dietetic concerns

Eating a healthy diet , and getting enough calcium, vitamin D , and magnesium is important for those with Paget's disease. Hypocalcemia (low blood calcium) and hyperparathyroidism (the production of excessive parathyroid hormone by the parathyroid glands, resulting in a disturbance of calcium metabolism) may develop in individuals with very active bone formation and insufficient dietary calcium intake. These conditions may be prevented, however, by taking adequate amounts of calcium (500 milligrams three times daily) and vitamin D—preferably vitamin D3—cholecalciferol—(400–800 milligrams daily).

QUESTIONS TO ASK YOUR DOCTOR

• What are my treatment options?
• When is surgery necessary?
• What are some of the possible complications of the disease?
• Should my siblings and children be tested for the disease?
• What kinds of exercise would be safe and useful in my condition?

Therapy

In addition to prescription or over-the-counter medications (nonsteroidal anti-inflammatory drugs) for pain, mild to moderate symptoms may be alleviated by using a heating pad, sleeping on a firm mattress, removing scatter rugs or obstacles to avoid falling or injury, and exercising in moderation under a doctor's supervision.

Prognosis

Although pharmaceutical or surgical treatment may alleviate disease activity and the symptoms of Paget's disease, the disease has no known cure. Symptoms usually progress slowly, however, and most often the disease does not spread to normal bones. In fewer than 1% of people diagnosed with the disease, however, a cancer of the bone called osteosarcoma may develop.

Prevention

Although Paget's disease cannot be prevented, some exercise is necessary to increase bone strength and keep weight under control. Excess weight places additional pressure on already painful joints. It is also helpful to keep joints as flexible as possible.

Caregiver concerns

To avoid further complications of the disease, care givers should be sure that individuals with Paget's disease avoid falls or putting stress on injured or deformed bones. It is important, however, to get physician approval before beginning any exercise program with a person diagnosed with the disease. In addition, kidney stones are more common in people with Paget's disease, so care givers should be sure that the person suffering from the disorder gets enough water every day.

KEY TERMS

Biphosphonates —A class of drugs that bind to the minerals in bone tissue and lessen the amount of bone loss

Osteoblasts —Bone-forming cells

Osteoclasts —Bone-breakdown cells responsible for bone resorption

Parathyroid glands —Two oval-shaped glands located behind the thyroid gland in the neck and responsible for regulating calcium levels in the blood

Resorption —The ongoing process of bone loss as a result of osteoclast activity

Special precautions should be taken to monitor individuals on oral bisphosphonate therapy. These drugs are poorly absorbed and have the potential to produce esophageal ulcers, acid reflux, and although rare, perforation of the esophagus. Therefore, bisphosphonates should be taken first thing in the morning on an empty stomach. Then it is important to maintain an upright posture with no food or drink for 30 to 60 minutes. In addition, other medications, liquids, and food should be avoided for at least 30 to 60 minutes after taking bisphosphonates to maximize absorption.

Resources

BOOKS

Favus, Murray J. Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism. 6th edition. Washington, DC: American Society for Bone and Mineral Research, 2006.

Paget's Disease—A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References San Diego, CA: ICON Health Publications, 2004.

PERIODICALS

Keen R.W. “The current status of Paget's disease of bone.” Hospital Medicine (2003) 64: 230–232.

“Paget's Disease of Bone/Fibrous Dysplasia: Advances and Challenges.” Journal of Bone and Mineral Research (2006) 21(Supp 2).

Tucker, Miriam E. “Watch for adverse effects of bisphosphonates in Paget's.” Internal Medicine News (May 24, 2006).

OTHER

“Paget's disease of bone.” Mayo Clinic. http://www.mayoclinic.com/health/pagets-disease-of-bone/DS00485 (March 1, 2008).

ORGANIZATIONS

The National Association for the Relief of Paget's Disease, 323 Manchester Road, Walkden, Worsley, Manchester, England, M28 3HH, 0161 799 4646 (International +44 161 799 4646), 0161 799 6511, [email protected], http://paget.org.uk.

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Information Clearinghouse, National Institutes of Health, 1 AMS Circle, Bethesda, MD, 20892-3675, (301) 495-4484, (877) -22-NIAMS (226-4267), (301) 718-6366, [email protected], http://www.niams.nih.gov.

NIH Osteoporosis and Related Bone Diseases, National Resource Center, 2 AMS Circle, Bethesda, MD, 20892-3676, (202) 223-0344, (800) 624-BONE, (202) 466-4315, [email protected], http://www.niams.nih.gov/Health_Info/bone/default.asp.

The Paget Foundation, 120 Wall Street, Suite 1602, New York, NY, 10005-4001, (212) 509-5335, (800) 23-PAGET, (212) 509-8492, [email protected], http://www.paget.org.

Genevieve Slomski Ph.D.