What Is Osteopetrosis?

Osteopetrosis is a condition in which abnormal bone growth and high bone density can lead to a vulnerability to bone fractures and other effects, such as bleeding. Osteopetrosis falls within a family of sclerosing bone dysplasias, which are characterized by an impairment of normal bone reabsorption (bone remodeling).

Researchers have identified several different types of osteopetrosis, with varying degrees of severity. Keep reading to learn about osteopetrosis, including its types, symptoms, causes, and more.

Types of Osteopetrosis

Osteopetrosis is classified based on symptoms, age of onset, and inheritance patterns. The most common types are autosomal dominant, autosomal recessive, intermediate autosomal osteopetrosis, and adult delayed-onset osteopetrosis.

Autosomal Dominant Osteopetrosis

Autosomal dominant osteopetrosis, Albers-Schönberg disease, is the most common type of osteopetrosis, with an onset during adolescence or adulthood.

This type is associated with fractures of the long bones (bones that are longer than they are wide) or the posterior part of the vertebrae (bones of the spinal column). It may also lead to scoliosis, hip osteoarthritis, osteomyelitis of the mandible (bone infection of the lower jawbone), anemia (low red blood cells, RBCs), and/or septic osteitis (infection of the bone).

Autosomal Recessive Osteopetrosis (ARO)

Also called malignant infantile type, ARO develops early in infancy. It is known for fractures, impaired growth, thickening of the skull base leading to optic nerve compression, facial palsy, and hearing loss. 

ARO is also associated with an absence of bone marrow cavity, leading to severe anemia, thrombocytopenia (a deficiency of platelets that leads to abnormal bleeding), recurrent infections, dental and tooth abnormalities, jaw infection and inflammation, hypocalcemia (low calcium levels), seizures, and too much parathyroid hormone.

Without treatment, the maximum life span is around 10 years.

Intermediate Autosomal Osteopetrosis (IAO)

IAO onset is during childhood. Characteristics of IOA include predisposition to fractures after minor trauma, skeletal changes, mild anemia, and visual impairment from optic nerve compression. Life expectancy is not affected by IOA.

Adult Delayed-Onset Osteopetrosis

Adult delayed-onset osteopetrosis is a milder type of autosomal dominant osteopetrosis that begins during adulthood.

People with this type of osteopetrosis have normal bone structure at birth. Adult delayed-onset osteopetrosis is classified as benign. In fact, up to 40% of people with adult-onset type are asymptomatic (without symptoms).

Bone mass will increase with age, but symptoms generally do not appear to affect health, brain function, or lifespan. A diagnosis of adult osteopetrosis is usually made based on bone abnormalities noted on imaging studies that are done for another purpose. Some people are diagnosed after developing osteomyelitis of the jaw.

Additional symptoms associated with adult-onset osteopetrosis include bone pain, fractures, back pain, and degenerative arthritis.

X-Linked Osteopetrosis

In rare cases, osteopetrosis has an X-linked inheritance pattern. X-linked osteopetrosis is characterized by lymphedema (abnormal swelling of the extremities from a build-up of lymphatic fluid) and anhidrotic ectodermal dysplasia, a condition that causes abnormal development of skin, hair, teeth, and sweat glands.

People affected by X-linked osteopetrosis have immune system impairment that leads to recurrent infections.

Osteopetrosis Symptoms

Osteopetrosis causes excess bone formation and brittle bones. Mild types of osteopetrosis usually don’t cause symptoms or complications, but severe types can cause a number of signs and symptoms.

These may include:

• Increased fracture risk
• Stunted growth
• Bone deformities, including bones of the extremities, ribs, and spinal column
• Recurrent infections
• Bone marrow narrowing from bone expansion, which leads to anemia, thrombocytopenia, and leukopenia (low amounts of white blood cells, WBCs)
• Extramedullary hematopoiesis: A state where blood precursor cells that are typically found inside bone marrow accumulate outside of the bone marrow
• Blindness, facial paralysis, or deafness from increased bony pressure on the corresponding cranial nerves
• Cortisol bone abnormalities: Cortisol generally blocks calcium, which decreases bone cell growth
• Temperature regulation problems
• Bone pain and osteoarthritis
• Craniosynostosis: A birth defect where the bones of a baby’s skull join together too quickly
• Hypocalcemia: Lower than normal blood calcium
• Hydrocephalus­: Fluid accumulation around the brain
• Macrocephaly: Abnormal head enlargement

Causes

Autosomal dominant type osteopetrosis affects approximately 1 in 20,000 people, while autosomal recessive types affect approximately 1 in 250,000 people. Other types of osteopetrosis are rare and have been referenced in the medical literature.

Autosomal dominant inheritance occurs when only one copy of a mutated gene is necessary to cause the disorder. With this type of osteopetrosis, you inherit the condition from one affected parent.

Autosomal recessive inheritance means that two copies of a mutated gene are needed to cause the disorder. The parents of a person with the autosomal recessive disease will each carry at least one copy of the mutated gene. A parent of a person with a recessive disease can have the disease if they have 2 copies of the mutated gene—but parents with only one copy of the mutated gene wouldn't show any signs of the condition.

X-linked recessive inheritance refers to hereditary diseases linked to X chromosome mutations. These conditions tend to affect mostly genetic males because they carry only one X chromosome. In genetic females, who carry two X chromosomes—if they carry the gene mutation on only one X chromosome but not the other X chromosome, they would not show signs of a recessive X-linked disorder.

In about 30% of osteopetrosis cases, the cause of the condition is unknown.

Development

Osteoclasts are cells that are involved in the bone remodeling process, and they play a role in osteopetrosis.

Gene defects associated with osteopetrosis can lead to deficiency or dysfunction of osteoclasts. Without enough functioning osteoclasts, reabsorption is impaired, even as new bone tissue formation occurs. This is why bones become unusually dense and abnormally structured.  

Diagnosis

Osteopetrosis is usually suspected when X-rays or other imaging reveals bone abnormalities or increased bone density. Additional testing might be done to look for other problems, including those related to vision and hearing, blood composition, and brain abnormalities.

A bone biopsy can confirm a diagnosis, but this procedure is associated with a risk of infection.

Genetic testing can be done to confirm a diagnosis and determine the type of osteopetrosis. Genetic testing can also be helpful in determining prognosis, treatment response, and recurrence risks.

Treatment

Treatment for infant and childhood types of osteopetrosis includes medications that affect bone formation and medications that treat various effects of the condition.

Calcitriol: This is a synthetic form of vitamin D3 that can be helpful in stimulating dormant osteoclasts to stimulate bone reabsorption.

Gamma interferon: Gamma interferon therapy is believed to increase WBC function and reduce infection risk. It can also help reduce bone mass volume and increase the size of the bone marrow. Combination therapy with calcitriol has been shown to improve long-term outcomes, but it is used with caution for treatment of infantile-type osteopetrosis.

Erythropoietin: A synthetic form of a hormone produced mainly in the kidneys can be used to increase the production of RBCs.

Corticosteroids: Corticosteroid therapy can help treat anemia and stimulate bone absorption.

Adult osteopetrosis does not usually require treatment, although complications of the disease need to be treated.

Procedures

• Treatment of autosomal recessive malignant infantile osteopetrosis might also involve hematopoietic stem cell transplantation (HSCT). HSCT promotes restoration of the bone resorption process through donor-derived osteoclasts.
• Bone marrow transplantation has been proven to be successful in treating severe infantile osteopetrosis. It can resolve bone marrow failure and improve the chance of survival from infantile osteopetrosis. 
• Surgery may be needed to treat fractures.

Prognosis

Long-term outlook with osteopetrosis depends on the type and severity of the condition. Infantile types of osteopetrosis are associated with a shortened life expectancy, especially if untreated.

Bone marrow transplantation can cure some infants of the condition, thereby improving life expectancy. But the long-term prognosis after bone marrow transplant for osteopetrosis is unknown.

The prognosis of childhood and adolescent-onset osteopetrosis will depend on symptoms, including the fragility of bones and fracture risk.

Life expectancy in adult type osteoporosis is generally unaffected.

A Word From Verywell

Osteopetrosis is a rare disorder. For many people, the condition causes mild or no symptoms. When it affects infants, children, and teens, parents should be aware of the possible complications of the disease and how to prevent such complications.

Good nutrition is important for children and adults with osteopetrosis, including adequate calcium and vitamin D supplementation.

Genetic counseling is an option for families affected by osteopetrosis. It can help address family planning, early diagnosis, and providing action towards the prevention of disease complications.