What Is Osteopetrosis?

Overview

Osteopetrosis, also known as marble bone disease or Albers-Schönberg disease, is a rare genetic disorder that affects bone development and metabolism. Osteoporosis causes the bones to become overly dense and brittle, making them prone to breaking (fracturing). 

Additionally, abnormally dense bones can cause various serious complications in the body, including bone pain, nerve compression, vision loss, paralysis of the facial muscles, and even loss of hearing capabilities.

Causes of osteopetrosis

Osteopetrosis is caused by mutations in genes that are involved in the formation and function of osteoclasts, which are the type of bone cells that break down and remodel bone tissue. In osteopetrosis, the osteoclasts are dysfunctional or absent, leading to an imbalance between bone formation and resorption and resulting in the accumulation of dense and brittle bone.

There are several types of osteopetrosis, which vary in severity and age of onset. The most severe form is diagnosed in infancy and early childhood and can lead to life-threatening complications such as bone marrow failure and hydrocephalus (excessive accumulation of cerebrospinal fluid in the brain). The milder forms may not be diagnosed until later in life and may cause less severe symptoms.

There are three major types of osteopetrosis that can be classified depending on their hereditary mode: 

• Autosomal dominant osteopetrosis (ADA): This is the most common form of osteopetrosis, which is usually mild and diagnosed in late childhood to adulthood. Individuals with this type may experience frequent bone fractures without proper healing. Bone infections, degenerative arthritis, pain, and headaches are more prominent in this form. 
• Autosomal recessive osteopetrosis (ARO): It is also known as malignant infantile osteopetrosis. This type is usually apparent right after birth and has a short term life expectancy. Infants with this type have severely brittle bones, which can be fractured easily. Children can also develop anaemia, a low platelet count in the blood, and compressions on the optic nerve, which may lead to visual or hearing impairments.
• X-linked recessive: This type of osteopetrosis is extremely rare and is linked to and passed through the X chromosome. Only a few cases have been reported for this form.

According to a study, around six out of eight highlighted genes are associated with the malignant autosomal recessive type of the disease.¹

Signs and symptoms of osteopetrosis

The symptoms of osteopetrosis can vary widely depending on the severity and type of the disease. However, following are a few common symptoms which may include:

• Bone pain
• Fractures that occur easily or spontaneously
• Abnormally dense bones that are visible on X-rays
• Dental abnormalities, such as delayed tooth eruption or overcrowding
• Nerve compression - which may cause numbness, tingling, weakness, or even paralysis
• Anaemia due to bone marrow failure
• Vision and hearing problems due to cranial nerve compression
• Infections due to impaired immune function

In severe cases of osteopetrosis, symptoms may lead to:

• Failure to thrive
• Developmental delays
• Hydrocephalus. (a neurological disorder caused by a fluid buildup within the cavities of the brain)
• Osteomyelitis (a bone infection)
• Blindness

Management and treatment for osteopetrosis

Doctors and researchers have been investigating several treatment options for enhanced recovery from osteopetrosis. Doctors may advise treatment and management options depending on the condition's type and severity. The treatment for osteopetrosis may include:

• Actimmmune injections (interferon gamma-1b) are a drug that is designed to delay the progression of the autosomal recessive form
• A bone marrow transplant provides a cure for specific cases of osteopetrosis. The transplant may impose several risks, though it can provide high benefits in enhancing an individual's survival over the long term
• Physical and occupational therapies are important for developing motor skills, especially in children
• Bone care and management, which may include splints, casts, or surgical measures to correct fractured bones
• Specific nutrition plans and exercises to manage symptoms according to the type of osteopetrosis you have
• Corticosteroids may be prescribed to improve blood cell levels
• Prenatal testing can also be performed to identify osteopetrosis in a developing foetus if there is a known family history of the disease or if the parents are carriers of the disease-causing mutations. In some cases, prenatal diagnosis may allow for early intervention and treatment

A study showed that several children with osteopetrosis were treated with an active form of vitamin D to ensure the resorption of bone by the non resorbing osteoclasts. Though there were no clinical improvements, certain bone biopsy results showed improved bone resorption by the osteoclasts. However, this therapy is still under further experimentation.²

FAQs

How is osteopetrosis diagnosed?

Generally, doctors diagnose osteopetrosis by taking several evaluative tests, which may include:

• Asking for a family or medical history
• Ordering X-rays to determine bone structure, dense, and misshapen bones
• Genetic testing to evaluate the type and cause of osteopetrosis
• Imaging testing, including magnetic resonance imaging (MRI) or computerised axial tomography (CAT) scans, is used to check for alterations in the skull and bone marrow space
• Laboratory blood tests include checking the blood cell count, vitamins, minerals, and hormonal levels in the body

How can I prevent osteopetrosis?

Osteopetrosis is a genetic disorder that is caused by mutations in some specific genes. Currently, there is no known way to prevent its development in individuals who are genetically predisposed to it.

However, genetic counselling and testing can be offered to individuals who have a family history of osteopetrosis or who are at increased risk of carrying the mutations associated with the disease. This can help identify carriers of the disease-causing genes and provide them with information about their risk of passing the condition on to their offspring.

Who is at risk of osteopetrosis?

Individuals with a family history of this disease tend to be at higher risk of developing it or passing it on to their children. This usually happens when an abnormal gene is inherited from either one or both parents. 

Osteopetrosis can affect people of all races and ethnicities, and both males and females can develop the condition. It is important to note that not all individuals who are at risk of developing osteoporosis will develop the condition, and not all cases of osteopetrosis are inherited. Some cases of the disease are caused by spontaneous mutations that occur during foetal development.

How common is osteopetrosis?

Osteopetrosis is a rare disease, and its exact prevalence is not well established. However, it is estimated that the incidence of osteopetrosis ranges from 1 in 20,000 to 1 in 250,000 births, depending on the type of osteopetrosis.¹

The autosomal recessive form (also called the infantile malignant form) is the most severe and rarest type of osteopetrosis, accounting for about 10% of all cases.

When should I see a doctor?

If a person has been diagnosed with osteopetrosis then it is recommended that they receive regular monitoring and treatment from a team of healthcare professionals, including orthopaedic specialists, haematologists, and endocrinologists. This can help manage symptoms, prevent complications, and improve outcomes.

It is important to consult your doctor so they may help evaluate your symptoms, determine their severity, and prescribe the right course of treatment.

Summary

Osteopetrosis is a rare hereditary disorder that affects the bones. It is caused by mutations in specific genes that impair the normal process of bone remodelling, leading to abnormally dense and brittle bones. The condition can cause a range of symptoms, including bone pain, frequent fractures, dental problems, and vision or hearing problems.

Osteopetrosis can be inherited in an autosomal recessive or dominant pattern, and it can affect people of all races and ethnicities. Treatment for osteopetrosis is focused on managing symptoms and preventing complications and may include medications, surgical interventions, and bone marrow transplantation. Genetic counselling and testing can be offered to individuals who have a family history of the disease or who are at increased risk of carrying the mutations associated with the disease. Early diagnosis and treatment can improve outcomes for individuals with osteopetrosis and reduce the risk of complications.