Medical quality assurance by Dr. Albrecht Nonnenmacher, MD at August 31, 2016

Osteopetrosis is a group of rare bone diseases that, when inherited in an autosomal dominant pattern affects about one in every 20,000 people in the United States. The kind that is inherited via an autosomal recessive pattern is rarer and occurs at a rate of about one in every 250,000 people though comprehensive data about this group of conditions is lacking. The disease is sometimes referred to as marble bone disease due to the chalky, opaque appearance of the diseased bone on radiographs.


Definition & Facts

Osteopetrosis is a bone condition in which the bones become exceedingly thick and dense due to abnormal cells. The disease can lead to bone fractures as a result of weakened and malformed bones. Three types of osteopetrosis have been identified.

  • Infantile osteopetrosis, also known as malignant osteopetrosis, is the most severe form and occurs when a genetic mutation is inherited from one parent (autosomal recessive inheritance). Infants born with the disease have severely reduced life expectancy and will likely die of disease-related complications including infection, hemorrhage, and severe anemia that is unresponsive to treatment.
  • Adult osteopetrosis is less severe than infantile malignant osteopetrosis; it is inherited when both parents pass along the mutated gene to the child. The adult form may also result when a gene spontaneously and abnormally mutates during conception. Prognosis is good for people with adult osteopetrosis. This form of the disease is sometimes referred to as Albers-Schönberg disease.
  • Some scientists recognize a third form of the disease called intermediate osteopetrosis that is usually diagnosed in young children, and while not as lethal as the malignant infantile form, it is usually a more severe form than adult onset osteopetrosis.

Symptoms & Complaints

Symptoms of osteopetrosis include easy bruising, bone pain, bones that break easily and heal slowly or improperly, carpal tunnel syndrome, and osteoarthritis.

Depending on the severity of the disease, osteopetrosis can also cause enlargement of certain organs such as the liver (hepatomegaly), spleen (splenomegaly), and lymph nodes and may cause children to appear frail, or be underweight and smaller than normal because of a depressed growth rate.

Those suffering from osteopetrosis may have fluid in the brain (hydrocephalus) or abnormally large heads (macrocephaly) and may suffer from loss of control or paralysis of the facial muscles and eye muscles.

Convulsions, blindness, deafness, sleep apnea, and nerve damage may also occur. Other signs include low platelet counts, anemia, and low white blood cell counts (leukopenia) (a decreased amount of all three types of blood cells is called pancytopenia).

In severe cases of osteopetrosis, nerves can become entrapped between the thickened bones. The immune system can become weakened as a result of osteopetrosis which in turn can make the patient more susceptible to infections. Should the extra bony material disrupt platelet production, hemorrhage can occur.


For bones to grow strong yet remain flexible, a consistent rate of new bone growth coupled with the breakdown and resorption of old bone must occur. Osteoblasts are bone cells that produce the organic material that makes up new bone, while osteoclasts are the bone cells that break down old bone material and cause its resorption into the body for other uses.

People with osteopetrosis may have less, more or normal amounts of osteoclasts, but they do function properly. Therefore, the breakdown and removal of old bone material do not occur as effectively as they should. Since the osteoblasts continue to lay down new material for bone growth and generation, and the osteoclasts are not able to properly remove the old material, the bones become harder and thicker than they should.

There are nine genes whose mutations are implicated in causing osteopetrosis. They include CLCN7, TCIRG1, and IKBKG. 30 percent of cases of osteopetrosis are idiopathic; that is, their cause is unknown.

Diagnosis & Tests

Most often osteopetrosis is diagnosed through X-rays. Adult osteopetrosis can be asymptomatic and may only be discovered when X-rays are taken for a different reason. A bone biopsy can confirm a diagnosis but is not necessary as usually radiographic evidence is enough.

When diagnosing osteopetrosis it is important to rule out congenital disorders with similar symptoms such as hypoparathyroidism, cancers such as leukemia, lead poisoning, or sickle-cell disease.

Treatment & Therapy

Infantile osteopetrosis, which is life-threatening, is usually treated, while adults with the disease (whose cases are less severe) are managed based on symptoms. Treatment for infantile osteopetrosis typically requires a bone marrow transplant, which is the only curative treatment. Two-thirds of those patients diagnosed will likely die before their tenth birthday without the procedure.

A bone marrow transplant comes with its own set of considerations, however. First, a suitable donor must be found. Then drugs must be given which severely suppress the immune system, inviting opportunities for infection in those whose immune systems are already compromised. Finally, the patient must be carefully monitored for signs of transplant rejection after the bone marrow transplant is completed.

Treatment for the infantile form of the disease includes heavy doses of vitamin D to encourage osteoclast activity that can lead to increased bone resorption, combined with a diet that is limited in calcium intake. Patients may be placed on interferon that stimulates the immune system and increases white blood cell and bone marrow production. Interferon is the only drug approved for treatment of osteopetrosis at this time.

When used in combination with vitamin D therapy, patients can vastly improve. Patients may be placed on epoetin alfa in order to stimulate red blood cell production and address anemia. The patient may also be prescribed corticosteroid.

Surgical intervention may be required for both children and adults in severe cases of bone malformation and joint deterioration or for relief in cases where bones are compressed or to relieve cranial nerve compression.

Oral and maxillofacial surgery may be necessary as teeth tend to shift positions, creating complications with eating and the ability to open and close the mouth properly. Occupational therapy, physical therapy, and speech therapy are also recommended to enable patients to live a better quality of life.

Prevention & Prophylaxis

Because osteopetrosis is an inherited disease, it cannot be prevented. Diagnosis during pregnancy can be made if a family history of the disease is known or suspected.