Paget's Disease

Paget's disease - also known as osteitis deformans­is a slowly progressive metabolic bone disease characterized by an initial phase of excessive bone resorption (osteoclastic phase) followed by a reactive phase of excessive abnormal bone formation (osteoblastic phase). The new bone structure, which is chaotic, fragile, and weak, causes painful deformities of the external contour and the internal structures.

Paget's disease usually affects one or several skeletal areas (most commonly the spine, pelvis, femur, and skull). Occasionally, a patient has widely distributed skeletal deformity. In about 5% of patients, the involved bone undergoes malignant changes.

The disease can be fatal, particularly when associated with heart failure (widespread disease creates a continuous need for high cardiac output), bone sarcoma, or giant cell tumors.

Causes

At present, the cause of Paget's disease of bone is unknown. Because of the racial and geographical pattern we have just mentioned, some doctors have concluded that the disease may be inherited. It is certainly true that in some families several people are affected, but this is quite rare. However, it has been suggested that Paget's may be caused by a 'slow virus' infection of bone cells. It is called 'slow' because the virus may settle in the bone cells early in life and only cause the disease many years later.

Signs and Symptoms

Many people with Paget's disease have no symptoms and only find out they have the disease by chance when having an x-ray. When symptoms do occur they may include:

• bone and joint pain
• leg bowing, skull enlargement or curvature of the spine
• muscle weakness due to bones pressing on nerves
• bone fractures resulting from minor injury
• arthritis
• deafness, vision disturbance, dizziness and tinnitus because of skull enlargement pressure.

Diagnostic tests

X-ray studies performed before overt symptoms develop show bone expansion and increased bone density.

Bone scans (more sensitive than X-rays) clearly show early pagetic lesions (the radioisotope concentrates in areas of active disease).

Bone biopsy may show bone tissue that has a characteristic mosaic pattern.

Red blood cell count indicates anemia.

Serum alkaline phosphatase level- an index of osteoblastic activity and bone formation - is elevated.

A 24-hour urinalysis demonstrates elevated hydroxyproline levels. Hydroxyproline, an amino acid excreted by the kidneys, provides an index of osteoblastic hyperactivity.

Treatment

If the patient is asymptomatic, treatment isn't needed. The patient with symptoms requires drug therapy.

The hormone calcitonin may be given subcutaneously or intramuscularly. The patient requires longterm maintenance therapy with calcitonin; noticeable improvement occurs after the first few weeks of treatment. The patient also may receive oral etidronate to retard bone resorption (and relieve bone lesions) and to reduce serum alkaline phosphatase and urinary hydroxyproline excretion. Etidronate produces improvement after 1 to 3 months.

Mithramycin (a cytotoxic antibiotic used to decrease serum calcium, urinary hydroxyproline, and serum alkaline phosphatase levels) produces remission of symptoms within 2 weeks and biochemically detectable improvement in 1 to 2 months. Mithramycin can destroy platelets or compromise renal function, so it's usually given only to patients who have severe disease, require rapid relief, or don't respond to other treatment.

Self-administration of calcitonin and etidronate helps patients with Paget's disease lead nearly normal lives. Even so, these patients may need surgery to reduce or prevent pathologic fractures, correct secondary deformities, and relieve neurologic impairment. To decrease the risk of excessive bleeding caused by hypervascular bone, drug therapy with calcitonin and etidronate or mithramycin must precede surgery. Joint replacement is difficult because polymethylmethacrylate (a gluelike bonding material) doesn't set properly on bone affected by Paget's disease. Other treatments vary according to symptoms. Aspirin, indomethacin, or ibuprofen typically controls pain.