Paget's Disease : Diagnoses, Treatments

by Food and Drug Administration (FDA)

(Page 2 of 3)

Research by Frederick Singer, M.D., an endocrinologist with the John Wayne Cancer Institute at Saint John's Hospital and Health Center in Santa Monica, Calif., may eventually yield proof of a genetic role. Studying an Iowa family with a history of Paget's disease, Singer and his colleagues traced a genetic abnormality to chromosome 18. The precise gene has yet to be identified, Singer says, but when it is, genetic tests may be able to predict who will get the disease. "I think that's coming pretty fast," he says.

Many experts, Singer included, also suspect that a slow virus may play a role. The theory is that the virus infects a person early in life, without causing symptoms for many years. This theory is based on studies identifying viral-like particles in osteoclasts from pagetic bone. According to Sakamuri Reddy, Ph.D., assistant professor at the University of Texas Health Science Center at San Antonio, these particles react with antibodies that detect a group of viruses which includes the measles and canine distemper viruses. Reddy and his group also have shown that osteoclasts from patients with Paget's disease contain the measles virus messenger RNA. Osteoclasts of people without Paget's disease do not contain this RNA.

This isn't to say that measles is the cause, though, says Leo Lutwak, M.D., Ph.D., an endocrinologist and medical reviewer in FDA's division of metabolism and endocrine drug products. "The agent may be related to the measles virus," he says.

How do the viral theory and genetics' role fit together? Experts in Paget's disease surmise that heredity may put people at risk for the suspected Paget's virus.

"It may be that some people inherit the tendency to have this virus affect their osteoclasts, while other people are, due to their own genetic makeup, more resistant," Siris writes in the Paget Foundation publication A Patient's Guide to Paget's Disease of Bone.

Accidental Diagnoses

Many patients, especially those with mild cases, first learn they have Paget's disease when a routine blood test reveals an abnormally high blood level of total alkaline phosphatase, an enzyme produced by osteoblasts, as well as cells of the intestine and liver.

When osteoblasts are more numerous or are especially active, the amount of alkaline phosphatase throughout the skeleton is increased. The increased bone alkaline phosphatase spills over into the blood, increasing the serum alkaline phosphatase.

A normal serum alkaline phosphatase ranges from 20 to 141 units per liter (U/L). Patients with severe Paget's disease may have six to 10 times that range. Halstead recalls that at one point his serum alkaline phosphatase rose to nearly 2,000 U/L. Jan Brown of Rockville recalls her alkaline phosphatase was more than 1,000 U/L when she was first diagnosed. "The doctor said he had never seen such a high alkaline phosphatase in as young a person," recalls Brown, who was 52 when diagnosed with Paget's disease.

Sometimes, Paget's patients first learn about their diagnosis when an x-ray taken for other reasons reveals pagetic bone.

Usually, bone pain is the first complaint of patients with symptoms. Bone deformities, arthritic pain, and hearing loss are other complaints that may lead patients to seek medical attention.

Laboratory tests, such as the serum alkaline phosphatase and urinary hydroxyproline (a measure of bone breakdown), may offer evidence of Paget's disease, but x-rays give the definitive diagnosis. Bone scans also may be taken to determine the extent and activity of Paget's disease. Bone scans involve less radiation and are more sensitive than x-rays in detecting areas of pagetic bone.

Treatments

Safe drugs for treating Paget's disease of bone became available only in the last 25 years. FDA approved the first two, calcitonin and Didronel (etidronate disodium), in the mid-1970s.

Salmon calcitonin (Calcimar and Miacalcin) and human calcitonin (Cibacalcin) are synthetic substances similar to the human hormone calcitonin. Synthetic calcitonin preparations help inhibit bone breakdown by decreasing the activity of osteoclasts. Only injectable calcitonin is approved for patients with Paget's disease, although nasal-spray calcitonin, which is approved for other uses, is under study for Paget's disease also, according to the Paget Foundation.

Didronel is taken orally in the middle of a four-hour fast. It is a bisphosphonate, a class of drugs that slows bone turnover.

Two newer bisphosphonates, Aredia (pamidronate disodium for injection) and Fosamax (alendronate sodium tablets), appear to achieve more effective results — as measured by laboratory tests — according to studies, and usually in smaller doses because they are more potent. Aredia, approved by FDA in October 1991, is given intravenously over four hours daily for three consecutive days.

Fosamax, approved by FDA in October 1995, is taken orally. Because this medicine is poorly absorbed, patients should take Fosamax with a glass of water first thing in the morning, then wait at least 30 minutes before taking other medications, eating, or drinking anything other than water. Also, to help prevent esophageal irritation and to ease delivery of the medicine to the stomach, patients should drink a glass of water and not lie down for at least 30 minutes after taking Fosamax.

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