Osteopetrosis (marble bone disease): symptoms, causes, and treatment

Definition of osteopetrosis

What is marble bone disease?

Osteopetrosis is a disease in which bones become abnormally dense and break easily. This disease is quite rare and runs in families, and is also known as marble bone disease or Albers-Schönberg disease.

This musculoskeletal disorder occurs due to abnormalities in osteoclasts that play a role in the process of re-absorption of substances in bone.

This causes buildup and thickening of the bones, but with an abnormal bone structure that can cause fractures easily.

Types of osteopetrosis

Apart from being classified based on the method of inheritance, marble bone disease is also grouped into several types according to the severity of the signs and symptoms, namely:

Autosomal dominant osteopetrosis (ADO)

This type is also known as osteopetrosis of the tarda. This is the mildest bone disorder that appears late in childhood to adulthood. People with this condition generally have no symptoms, but when the disease develops symptoms will appear.

Autosomal recessive osteopetrosis (ARO)

This type is quite severe that began to appear in infancy. Children with this condition will experience slow growth. In severe cases, this bone disorder can be life-threatening because it causes bone marrow abnormalities.

Intermediate autosomal osteopetrosis (IAO)

This type of disorder has a combined pattern of ADO and ARO. Symptoms appear in childhood and usually do not cause life-threatening bone marrow abnormalities.

Osteopetrosis X-linked recessive (XLO)

This form of the disorder is very rare, but very severe when it occurs in a person. Apart from causing the common symptoms of osteopetrosis, people with this condition also often experience inflammation.

How common is this disease?

Osteopetrosis (marble bone disease or Albers-Schönberg disease) is a rare bone disease.

There is an estimated 1 case of ADO in 20,000 people and 1 case of ARO out of 250,000 people in the world, according to the Medline Plus website. This disease generally affects newborns, children and young adults.

Signs & symptoms of osteopetrosis

Symptoms of abnormalities in this bone are very diverse, considering that this disease is categorized into several types. More clearly, the symptoms of osteopetrosis (marble bone disease) based on the types are:

Symptoms of autosomal dominant osteopetrosis (ADO)

People with this type of bone disorder usually don't cause symptoms in the early stages. Symptoms will appear when childhood ends or when entering adolescence. Symptoms include:

• Have a broken bone.
• Experiencing inflammation of the joints in the hips.
• There is a change in the curvature of the spine that is not normal, such as scoliosis, kyphosis, or lordosis.
• Experiencing an infection in the bone called osteomyelitis.

Symptoms of autosomal recessive osteopetrosis (ARO)

Babies born with this condition may experience several symptoms, such as:

• It is easy to fracture a bone even though the impact or injury is quite light.
• Dense, abnormal skull bones can pinch the nerves in the head and face, causing hearing loss, or paralysis of the facial muscles. The child's eye condition can also protrude, squint, or even be blind.
• Bone marrow function will also be damaged and the production of new blood cells and immune system cells will be impaired. As a result, the baby can experience abnormal bleeding, anemia (lack of red blood cells), and bone infections.
• Experiencing slow growth, short stature, dental abnormalities, enlarged liver and spleen (hepatosplenomegaly).
• Intellectual disabilities, brain disorders, and recurrent seizures can also occur. Some have chronic inflammation of the mucous membranes in the nose, making it difficult to eat.
• Babies have an abnormally large head and shape that is a sign of macrocephaly or hydrocephalus.

Intermediate autosomal osteopetrosis (IAO) symptoms

Children with this condition usually experience the following symptoms:

• It is easy to have broken bones and develop anemia.
• There are abnormal calcium deposits in the brain.
• Intellectual disability.
• Experiencing kidney disease, such as renal tubular acidosis.

Symptoms of X-linked recessive osteopetrosis (XLO)

People with this type of XLO bone disorder may experience the following symptoms:

• Abnormal swelling due to fluid buildup (lymphedema).
• Have anhydrotic ectodermal dysplasia that affects your skin, hair, teeth, and sweat glands.
• Continue to have repeated infections, because the immune system is not functioning properly.

When to see a doctor?

This disease can affect newborns, children and adolescents. Therefore, if you find your baby showing the signs and symptoms mentioned above, immediately check the child's health to the doctor.

Causes of osteopetrosis

The main cause of osteopetrosis is a basic defect in bone reabsorption, that is, the osteoclast cell is not functioning properly.

These cells are responsible for the process of re-absorption by bone and maintaining healthy bones, which depends on the balance of osteoclast function itself and the function of osteoblasts in forming bone.

It can be concluded that osteoclasts play an important role in the replacement of old bone with new bone, remodeling, and repairing micro fractures. Thus, when there is bone reabsorption defect, osteopetrosis (marble bone disease) can occur.

After doing the research, there are several genes that cause various types of osteopetrosis, namely:

• Mutations in the CLCN7 gene cause about 75% of cases of ADO type bone disorders and 10-15% of cases of ARO type bone disorders.
• TCIRG1 gene mutations cause about 50% of cases of ARO type bone deformities.
• The mutation of the IKBKG gene causes bone abnormality type IAO.
• Mutations in the OSTM1 gene can also cause osteopetrosis.

Risk factors for osteopetrosis

It is not known exactly what factors increase the risk of osteopetrosis (marble bone disease). Even so, experts believe that this is closely related to the presence of certain genetic copies that are passed on in families.

The risk of passing an abnormal copy of the ADO-related gene from the parent to the offspring is 50% with each pregnancy.

Meanwhile, both parents who have an abnormal copy of the ARO-related gene have a 25% risk of a child with this bone disorder in each pregnancy.

Then, the child who carries this abnormal gene has a 50% risk of giving birth to a baby with the same bone abnormality in each pregnancy.

Diagnosis and treatment of osteopetrosis

The information provided is not a substitute for medical advice. ALWAYS consult your doctor.

Diagnosis for osteopetrosis (marble bone disease) is made by a series of medical tests, such as:

• Examine the patient and family medical history in detail.
• Have X-ray imaging tests and increased bone mass density measurements to look for any abnormal bone conditions.
• Biochemical discovery tests, such as increased concentrations of isoenzyme BB creatinine kinase and tartrate-resistant acid phosphatase (TRAP) can also help make the diagnosis.
• Genetic testing can show a gene mutation in more than 90% of cases. This test can help doctors determine the type of osteopetrosis you have and the complications that occur.
• A bone biopsy is sometimes performed to confirm a diagnosis, but it is not performed routinely because it is an invasive procedure with an irresistible risk.

Once the diagnosis has been made, blood tests will be carried out. This test can measure various levels of substances in the body which include serum calcium, parathyroid hormone, phosphorus, creatinine, 25-hydroxyvitamin D, BB isozyme from creatine kinase, and lactate dehydrogenase.

The purpose of this medical test is to help doctors refer patients to specialists as needed. Then, a brain-based magnetic resonance imaging (MRI) test is also performed to detect the presence of cranial nerves, hydrocephalus, and vascular abnormalities occurring in the patient.

What are the ways to treat osteopetrosis (marble bone disease)?

Several types of effective treatment for osteopetrosis include:

Hematopoietic stem cell transplant

Currently, the only treatment considered effective for osteopetrosis (marble bone disease) in infants is hematopoietic stem cell transplantation (HSCT). This medical procedure enables the restoration of bone resorption by osteoclasts obtained from donors.

However, doctors must carefully consider the treatment of HSCT. This is because the possibility of rejection, severe infection, or very high levels of calcium in the blood can cause death in the patient.

In addition, in some cases HSCT is not possible. Especially if the cause is a mutation of the OSTM1 gene and two mutations of the CLCN7 gene. The reason is, the gene mutation causes a decrease in nerve function which is not effectively treated with HSCT.

Use of drugs

Until now, health professionals are still researching the effectiveness of corticosteroids as a cure for marble bone disease that cannot be treated with HSCT.

The use of the drug Gamma-1b (Actimmune) has been approved by the FDA, which is an agency similar to the Food and Drug Administration in America. The goal is to delay the progression of disease severity.

Use of vitamin supplements

Nutritional fulfillment is also very important for marble bone disease patients, for example the use of calcium and vitamin D supplements if calcium levels in the blood are low.

Other treatments that are symptomatic (reduce complaints of symptoms) and supportive (support the patient in improving the quality of life) may also be recommended by the doctor.

Home treatment for osteopetrosis

There are no home remedies, such as using herbal medicines to treat osteopetrosis (marble bone disease).

Treatment is focused on medical procedures recommended by doctors and guidance on care for parents or caregivers to treat symptoms that appear in infants and children.

Prevention of osteopetrosis

Osteopetrosis (marble bone disease) is closely related to the abnormal gene inherited from parents. Therefore, there are no precautions you can take.

If you, your family members, or friends have a history of these health problems, you should consult and counsel with specialists, especially those who are planning to have a child.