Osteopetrosis Definition

It is an acute inherited disorder that causes an increase in bone density of sufferers. This is a rare condition.

This condition is also known by many other names like:

  • Albers-Schonberg disease
  • Marble Bone Disease
  • Infantile Osteopetrosis
  • Malignant Osteopetrosis
  • Lethal Osteopetrosis

Osteopetrosis Incidence

This is an extremely rare condition and only 100 cases of it have been reported so far. It is difficult to estimate the overall incidence of this condition. However, Autosomal Recessive Osteopetrosis (ARO) is said to occur in 1 out of 250000 births.

Osteopetrosis Types

The condition is mainly divided into two types:

  • Malignant Osteopetrosis – This affects children and is usually severe in nature. It leads to birth of stillborn children or infants who suffer from anemia. The condition is found to show a poor prognosis.
  • Benign Osteopetrosis – It is found to be present in adults. It is an adult onset form that is generally inherited in a dominant autosomal pattern. Also known as Albers-Schönberg disease, this condition is frequently recognized only incidentally.

Osteopetrosis Symptoms

The condition affects patients as they continue to develop new bone. The overall density of bone increases in such individuals. This makes the additional bone exert pressure on nerves, thereby making patients experience pain in the region surrounding their bones.

In spite of excess bone formation, patients with this condition are found to have bones that are more brittle than usual. Mild cases of this condition may not lead to any symptoms. However, acute forms may result in problems like:

  • Reduced growth
  • Bone deformities
  • Greater likelihood of fractures

Patients may also suffer from disorders such as recurrent infections, Hepatosplenomegaly and anemia due to expansion of bones. This may lead to Extramedullary Hematopoiesis and narrowing of the bone marrow. Heightened pressure on the nerves by the extra bone can also give rise to other problems like:

  • Blindness
  • Deafness
  • Facial paralysis

Due to the brittle bones, many patients of Osteopetrosis often suffer from painful fractures. Fractures are often the first symptom when the condition develops in adults.

Osteopetrosis Causes

Osteopetrosis is usually associated to genetic factors. In healthy individuals, bone growth occurs due to a balance between bone formation and resorption (bone matrix decomposition) by Osteoclasts. In people with Osteopetrosis, the number of osteoclasts may be reduced, increased or even normal. There may also be dysfunction of Osteoclasts that lead to the origin and development of the condition.

It is due to defective or absence of functioning of osteoclasts that the main change over ossification and osteoid tissue calcification occurs. This results in problems like lack of bone in osteogenic and lamellar cells, bone dysplasia and a loss of flexibility. This leads to brittleness of bones.

Osteopetrosis may arise from conditions that intervene in the production of osteoclasts and their capability of bone removal. In most cases, the disorder is associated to a lack of ability of the osteoclasts to manufacture acid on the bone surface. Usually, the cells manufacture the acid within them and later move it outside. This starts the process of bone digestion. Defects in production or movement of the acid have been found to give rise to Osteopetrosis.

Osteopetrosis and Genetics

It is only recently that the genes associated to Osteopetrosis have been described. A “Proton Pump”, only present in Osteoclasts, is the most common genetic defect that is detected in Severe Osteopetrosis. The acid (proton) moves across the cell membrane due to this defect. This gene is known as TCIRG1 or ATP6i. Defects in this gene are found in 50-60% cases of severe cases of this condition.

Defects in another gene, known as ClCN7, are also believed to result in this condition. ClCN7 is a “chloride channel” and is required to shift protons across the cell membrane. Osteopetrosis accounts for approximately 15% of severe Osteopetrosis and is the regarded as the most common causative genetic factor, second only to TCIRG1. Mutations in this gene are also believed to cause less severe cases of the disease.

Osteopetrosis Diagnosis

X-Ray examinations of the bone are quite effective in displaying bone abnormalities caused by this condition. Dense bones can clearly be detected with x ray findings. The family history of the patient may also be considered. In some cases, immunological and biochemical tests along with imaging tests like CT scans may be required for an accurate diagnosis.

Osteopetrosis Differential Diagnosis

The differential diagnosis for Osteopetrosis involves differentiating the disorder from other similar conditions like:

  • Hypervitaminosis D
  • Hypoparathyroidism
  • Paget’s disease
  • Diffuse breast bone metastasis
  • Prostate cancer
  • Fluoride intoxication
  • Lead intoxication
  • Beryllium intoxication

The condition should also be distinguished from hematological disorders such as:

  • Sickle cell disease
  • Leukemia
  • Myelofibrosis

Osteopetrosis Treatment

Presently, no definite treatment for Osteopetrosis is available. However, there are certain ways that can help patients experience more comfort. In case of Osteopetrosis in children, Vitamin D has been found to be an effective cure. Medical research has also found Gamma interferon an effectual way of handling the symptoms. Erythropoetin is also used to cure anemia problems occurring with the disorder. Corticosteroids may be used to provide relief from anemia as well as stimulate bone resorption. Osteomyelitis and fractures can be cured as usual.

Bone marrow transplant is currently regarded to be the only long-lasting cure for Osteopetrosis affecting the Osteoclasts.

Osteopetrosis Prognosis

In as many as 70% cases, children suffering from this condition have poor life expectancy and die within one year of their birth. No patient has been reported to survive over 20 years of age. During survival, patients are found to suffer from one or more problems like:

  • Facial paralysis
  • Anemia
  • Stunted growth
  • Blindness
  • Loss of hearing (deafness)
  • Inability to walk, rise or stand erect
  • Inability to speak

If these symptoms are not properly treated, patients can usually die in their childhood. Death usually occurs due to anemia or infection.

Doctors and family members attending to Osteopetrosis patients must take adequate steps to ensure greater comfort for sufferers. Some doctors use bone marrow transplants for cure, hoping that the bone marrow will help yield more osteoclasts to aid in the decomposition of excess bone.


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