What Is Osteopetrosis?

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Osteopetrosis is a condition that causes high bone density and abnormal bone growth. It also makes bones more vulnerable to fractures (breakage). Osteopetrosis falls within a family of sclerosing bone dysplasias, which are characterized by reduced bone reabsorption.

Researchers have identified several different types of osteopetrosis, and each is distinguished by its severity. Keep reading to learn about osteopetrosis, including its types, symptoms, causes, and more.

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Types of Osteopetrosis

Researchers have identified several types of osteopetrosis, which are classified based on their 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 the most common type of osteopetrosis with an onset during late childhood and adolescence.

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), or septic osteitis (inflammation of the bone).

Autosomal Recessive Osteopetrosis (ARO)

Also called malignant infantile type, ARO develops early in infancy. It is known for fractures, poor growth, sclerosis of the skull base leading to optic nerve compression, facial palsy, and hearing loss. Without treatment, the maximum life span is around 10 years.

ARO is also associated with an absence of bone marrow cavity leading to severe anemia and condition called thrombocytopenia (abnormally low levels of platelets), dental and tooth abnormalities, jaw infection and inflammation, hypocalcemia (low calcium levels), seizures, and too much parathyroid hormone.

Intermediate Autosomal Osteopetrosis (IAO)

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

Adult Delayed-Onset Osteopetrosis

Adult delayed-onset osteopetrosis is a milder type of osteopetrosis that is discovered in adulthood. Adult osteoporosis is sometimes called Albers-Schönberg disease.

People with this type of osteopetrosis have normal bone structure at birth. 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 by X-ray findings of bone abnormalities that were taken for another purpose.

For most adults diagnosed with osteopetrosis, it is was inherited through an autosomal dominant pattern and classified as a type of benign osteopetrosis. In fact, up to 40% of people with adult-onset type, are asymptomatic (without symptoms). Others 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, or abnormal swelling from a build-up of 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 systems that malfunction and cause recurrent infections.

Osteopetrosis Symptoms

Osteopetrosis causes excess bone formation and people with this condition have bones that are more brittle. Mild types of osteopetrosis usually don’t cause symptoms or complications.

Osteopetrosis may cause some very severe signs and symptoms. These may include:

  • Increased fracture risk
  • Stunted growth and deformity
  • Recurrent infections
  • Anemia­: A condition where there aren’t enough healthy red blood cells
  • Bone marrow narrowing from bone expansion
  • Extramedullary hematopoiesis: A state where blood precursor cells typically found inside bone marrow accumulate outside of the bone marrow
  • Blindness, facial paralysis, or deafness from increased pressure on nerves from extra bone
  • Cortisol bone abnormalities: Cortisol generally acts upon bone by blocking calcium which decreases bone cell growth. A disruption in cortisol increases bone resorption (the process where old bone sheds and new bone develops) and leads to reduced bone mass density.
  • Vertebral abnormalities in the spinal column
  • Temperature regulation problems
  • Rib abnormalities
  • Bone pain and osteoarthritis
  • Cranial nerve paralysis: A complete or partial weakness/paralysis of the cranial nerves (the nerves arising directly from the brain)
  • Craniosynostosis: A birth defect where the skull bones of a baby’s skull join together too quickly
  • Hypocalcemia: Lower than normal calcium in the plasma of blood
  • Hydrocephalus­: Fluid on the brain
  • Macrocephaly: Abnormal head enlargement
  • Paralysis or loss of control of facial or eye muscles

Causes

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

Osteopetrosis is inherited in either an autosomal dominant or recessive pattern. In rare cases, osteopetrosis is inherited in an X-linked recessive pattern.

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

Autosomal recessive inheritance means there are copies of a mutated gene in each cell. The parents of a person with the autosomal recessive disease will each carry a copy of the mutated gene, but they don’t show any signs of the condition.

X-linked recessive inheritance refers to genetic diseases linked to X chromosome mutations. These conditions tend to affect mostly males because they carry only one X chromosome. In females who carry two X chromosomes, they carry one gene mutation and an X chromosome that doesn’t contain a defect.

Adult-onset osteoporosis can be inherited either as an autosomal recessive or autosomal dominant genetic trait.

Different gene mutations cause various types of osteopetrosis. But in about 30% of osteopetrosis cases, the cause of the condition is unknown.

Development

The genes involved in the development of osteopetrosis are called osteoclasts. These specialized cells are also involved in the bone remodeling process.

Bone remodeling is a continuous lifelong process of bone breakdown (reabsorption) by osteoclasts. Reabsorption is followed by the formation of new bone tissue by cells called osteoblasts.

With osteopetrosis, there are gene defects that lead to abnormal or missing osteoclasts. Without enough functioning osteoclasts, reabsorption cannot happen even thorough new bone tissue formation still occurs. This is why bones become unusually dense and abnormally structured.  

Diagnosis

Osteopetrosis is usually suspected when X-rays and other imaging reveal bone abnormalities or increases in bone density. A bone biopsy can confirm a diagnosis, but some researchers caution against this method because of marked infection risk.

Additional testing might be done to look for other problems, including those related to vision and hearing, blood composition, and brain abnormalities.

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 osteoporosis includes calcitriol, gamma interferon, erythropoietin, and corticosteroids.

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

Gamma interferon: Treatment with gamma interferon has had long-term benefits, although researchers suggest it should be used with caution in treating infantile type osteopetrosis. Gamma interferon therapy is believed to increase white blood cell function and reduce infection risk. It can also help reduce bone mass volume and increase bone marrow. Combination therapy with calcitriol has been shown to improve patient outcomes.

Erythropoietin: A synthetic form of a hormone produced mainly in the kidneys can be used to correct anemia.

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

Treating autosomal recessive malignant infantile osteopetrosis might also involve hematopoietic stem cell transplantation (HSCT). HSCT allows for the restoration of the bone resorption process through donor-derived osteoclasts.

Adult osteopetrosis does not require treatment and there no specific medical treatments specific to the adult type. However, complications of the disease will need to be treated. Surgery can be used to treat fractures, especially in children and infants.

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. 

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 left 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.

Childhood or 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

Osteoporosis is a rare disorder but 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 calcium and vitamin supplementation for low calcium levels.

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. 

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