Understanding Osteopetrosis

Osteoporosis and Related Bone Diseases~National Resource Center
1150 17th St., NW, Suite 500, Washington DC 20036
202-223-0344 or 800-624-BONE
TTY (202) 466-4315
E-Mail: orbdnrc@nof.org

One of the less common metabolic bone disorders is osteopetrosis. Osteopetrosis is an inherited disease caused by a defect in bone resorption--the process in which old bone is broken down and removed so that new bone can be added to the skeleton. Osteoclasts are the cells responsible for bone resorption. In osteopetrosis the osteoclasts do not perform normally, either because there are too few of them or because they are ineffective in removing bone. This flaw in bone resorption results in bones that are abnormally dense, yet are easily broken. Men and women are equally affected by the disease.

The increased bone mass in individuals with osteopetrosis can limit the amount of available bone marrow space. Since the bone marrow is responsible for the production of blood cells, impaired bone marrow function can produce several clinical problems. For example, interference with red blood cell production can lead to anemia. Impairment of white blood cell production can limit the body's ability to fight infection. When platelet production is suppressed, individuals are prone to bleeding since platelets are essential for clotting blood. Anemia, infection, and bleeding are just some of the symptoms that individuals with osteopetrosis can experience--blindness, deafness and even stroke can occur when the skeletonis so dense that blood vessels and nerves cannot pass through the bones.

Three major types of osteopetrosis have been identified in humans:

Malignant infantile form. This type of osteopetrosis is usually discoveredin the first months of life. In addition to having many of the above symptoms of the disease, children with this condition often have significant delays in psychomotor and tooth development. The malignant infantile form of the disease can be severe and frequently results in death from infection or bleeding. In fact, thirty percent of children with this form of the disease will die during the first ten years of life. This form of the disease is inherited as an autosomal recessive trait—there by affecting some brothers and sisters.

Adult form. The adult form of osteopetrosis is milder than the infantile form. This type of the disease is benign and generally does not alter life expectancy. Many of the individuals with the adult form of osteopetrosis have few or no symptoms. It is inherited from generation to generation as an autosomal dominant trait.

Intermediate form. This type of the disease is found in children younger than ten years of age. It tends to be less severe than the malign antinfantile form, but more severe than the adult form. Individuals with this type of osteopetrosis generally do not have a reduced life expectancy.

The diagnosis of osteopetrosis is usually made when dense bones are discovered on x-rays. A bone biopsy can confirm the presence of the disease, while supplemental tests are usually performed to evaluate any potential complications. Confirming the specific subtype of the disease is important so that individuals can receive the most appropriate treatment.

Various therapies have been used in the treatment of osteopetrosis. Bone marrow transplantation (BMT) allows the abnormal osteoclasts to be replaced with normal cells. BMT is the only approach that has resulted in a cure of the malignant infantile form of the disease. Because of its high failure rate and because of its side-effects, BMT tends to be reserved for only the most severe cases of osteopetrosis. According to the Paget Foundation, survival rates after BMT in children with osteopetrosis range from 40-70%.

High doses of calcitrol (the active form of vitamin D) have been used tostimulate osteoclast function in individuals with osteopetrosis. Calcitrolhas been shown to significantly reduce symptoms in people who have mild or severe forms of the disease, though it is not approved by the Food and Drug. Administration for this purpose. Similarly, experimental use of interferon gamma 1-b treatment has been reported to decrease infection rate and improve blood abnormalities in severely affected patients. Another type of medication that may be used to treat patients with osteopetrosis are glucocorticoids. Large doses of glucocorticoid drugs (such as prednisone) may be given for short periods of time to patients with impaired red blood cell or platelet production.

Research efforts are underway in an attempt to identify the gene defects that cause osteopetrosis.

Two documents on osteopetrosis have recently been developed by the Resource Center and the Paget Foundation: a patient information brochure and an annotated bibliography for professionals. For further information on these educational resources, please contact the ORBD~NRC at 202-223-0344.