Osteogenesis Imperfecta

Osteogenesis imperfecta is a genetic disorder that causes bones to break easily, often from little or no force. While some people experience only a few fractures in their lifetime, others may face hundreds of breaks, along with additional health challenges affecting the teeth, hearing, spine, and breathing.

Table of contents

• What is osteogenesis imperfecta?
• Types of osteogenesis imperfecta
• Signs and symptoms
• Causes and inheritance
• Possible complications
• How doctors diagnose the condition
• Treatment approaches
• Living with osteogenesis imperfecta

What is osteogenesis imperfecta?

Osteogenesis imperfecta, also known as brittle bone disease, is a group of genetic disorders that mainly affect the bones. The term means “imperfect bone formation.” People with this condition have bones that are much weaker and thinner than they should be, making them break very easily^[1][4].

Osteogenesis imperfecta is a connective tissue disease, which means it affects the body’s ability to make collagen properly. Collagen is a protein that acts as a major building block for bones, skin, muscles, and tendons. When collagen doesn’t form correctly or there isn’t enough of it, the result is fragile bones that break easily, often with little or no force^[2].

The condition affects approximately 1 in 10,000 to 20,000 people worldwide. An estimated 25,000 to 50,000 people in the United States live with osteogenesis imperfecta^[4].

brittle bone disease, Lobstein syndrome, fragilitas ossium, Vrolik disease, osteopsathyrosis idiopathica

Types of osteogenesis imperfecta

Healthcare providers classify osteogenesis imperfecta into at least 19 recognized forms. Types I through IV are the most common, and several types are distinguished by their signs and symptoms^[1][4].

People with type I have lower amounts of normal collagen than they should. People with types II, III, and IV have improperly formed collagen, which causes more severe symptoms^[1].

Type I

This is the most common and mildest form of osteogenesis imperfecta. People with type I break bones more easily than usual, but most broken bones happen before puberty. Fractures occur less frequently in adulthood. The condition doesn’t cause bone deformity. People with type I typically have a blue or grey tint to the whites of their eyes, and about half develop hearing loss as adults. Unlike more severely affected individuals, people with type I are usually of normal or near normal height^[1][4][5].

Type II

Type II is the most serious form of osteogenesis imperfecta. Babies with type II are usually born with many fractures and are very small. This type causes fatal complications like underdeveloped lungs, serious bone deformities, and multiple broken bones before birth. Most infants with type II die at or shortly after birth due to these severe problems^[1][4][5].

Type III

Type III is the second most severe form. It causes dangerous bone deformities that make bones very fragile. Babies with type III are often born with broken bones. People with this type live with physical disabilities and may have frequent bone breaks throughout their lives. They are usually shorter than other people their age, and mobility can be reduced. Some individuals may use a walker or wheelchair^[1][4][5].

Type IV

Type IV is more severe than type I but less severe than type III. Bones are more fragile than usual, but they won’t break as often as with type III. Signs and symptoms fall somewhere between the mild and severe forms^[1][4].

Signs and symptoms

The symptoms of osteogenesis imperfecta can vary greatly from person to person, even among people with the same type of the condition and within the same family. The range of symptoms may be mild to severe^[3][4].

Bone-related symptoms

The main bone issues include:

• Weak bones that break easily, often from mild trauma or with no apparent cause
• Multiple fractures throughout a person’s lifetime
• Bone deformities, such as bowed legs
• Bone pain
• Barrel-shaped rib cage
• Curved spine, called scoliosis or kyphosis
• Small stature or short height
• Triangular face shape

^[1][2][6]

Other symptoms

People with osteogenesis imperfecta might also experience:

• The whites of the eyes looking blue or gray
• Weak, brittle, or discolored teeth
• Teeth that don’t align properly, a condition called dentinogenesis imperfecta
• Hearing loss, especially in adulthood
• Difficulty breathing or breathing problems
• Bruising easily
• Loose joints or joint hypermobility
• Muscle weakness

^[1][2][4]

In many children with osteogenesis imperfecta, the number of times their bones fracture decreases significantly as they mature. However, the condition may become active again after menopause in women or after the age of 60 in men^[6].

• Bones
• Skin
• Muscles
• Tendons
• Teeth
• Spine
• Lungs
• Eyes (sclera)
• Ears

Causes and inheritance

Osteogenesis imperfecta is caused by a genetic change or mutation. In the majority of cases, mutations in the COL1A1 and COL1A2 genes cause the condition. These genes provide instructions for making proteins that are used to assemble type I collagen. Mutations in these two genes cause approximately 90 percent of all cases^[1][2][4].

Type I osteogenesis imperfecta is caused by mutations that reduce the amount of type I collagen produced in the body, though the collagen molecules that are produced are normal. A reduction in type I collagen causes bones to be brittle and to fracture easily^[4].

The mutations that cause types II, III, and IV typically alter the structure of type I collagen molecules, resulting in abnormal collagen. A defect in the structure of type I collagen weakens connective tissues, particularly bone, resulting in the more severe features of these forms^[4].

Mutations in other genes cause rarer forms of osteogenesis imperfecta. More recently, diverse mutations related to the condition have been identified^[2][4].

How the condition is inherited

The genetic changes that cause osteogenesis imperfecta can be random. In these cases, neither parent has the condition, and the change happens early in pregnancy when the baby is first forming. This is called a spontaneous mutation^[5][14].

You may also inherit the genetic changes from your biological parents. You’re more likely to have osteogenesis imperfecta if someone else in your biological family has it. You can inherit the gene change from one parent (called dominant inheritance) or both parents (called recessive inheritance), depending on the type of the condition^[1][2].

Some people have the genetic variation but never develop osteogenesis imperfecta^[1].

Possible complications

Osteogenesis imperfecta can cause various complications beyond frequent fractures:

• Heart disease, including heart failure
• Frequent pneumonia
• Respiratory issues, including respiratory failure
• Nervous system issues

^[1]

There are also reports of heart valve problems and widening of the aortic root, which is the main blood vessel leaving the heart^[2].

The most severe forms of osteogenesis imperfecta, particularly type II, can include an abnormally small, fragile rib cage and underdeveloped lungs. Infants with these abnormalities may have life-threatening problems with breathing^[4].

How doctors diagnose the condition

Healthcare providers usually diagnose brittle bone disease in childhood. Diagnosis typically involves genetic testing to identify mutations in the genes responsible for collagen production^[1][4].

When a baby is four weeks old or younger and has multiple fractures, doctors will order a more extensive series of X-rays that can reveal broken bones. Genetic testing follows to confirm the diagnosis^[14].

Increasingly, genetic causes are used to define rarer forms of osteogenesis imperfecta. Several types are distinguished by their signs and symptoms, although their characteristic features overlap^[4].

Treatment approaches

Because osteogenesis imperfecta is a genetic condition, it has no cure. Treatment focuses on managing symptoms, preventing fractures, and helping broken bones heal properly^[5][8].

Managing broken bones

Positioning devices such as splints and casts are used to hold a fractured bone in place so it can heal properly. Larger bones, such as those in the legs and arms, are usually fitted with a plaster or fiberglass cast. A splint may be used to stabilize smaller bones, such as those in fingers and toes. Sometimes, an orthopedist recommends using a brace, which permits movement in joints while maintaining proper alignment^[12].

Broken bones in people with osteogenesis imperfecta can heal at a normal rate, even though they break easily^[6].

Medications

Bisphosphonates are medications that increase bone formation and can improve bone density. They are commonly used to help prevent new fractures. These medications inhibit the breakdown of bone on the inside surface, resulting in an increase in the thickness of the bone’s outer layer. Cyclic intravenous pamidronate is commonly given at regular intervals. Current evidence supports the use of intravenous bisphosphonates, and they have been shown to reduce the number of fractures and increase bone mineral density, while reducing pain and increasing energy levels^[8][12].

Bisphosphonates can be effective in babies and can be used to relieve pain in severe cases. However, current evidence does not support the use of oral bisphosphonates in patients with osteogenesis imperfecta^[8].

Surgery

Surgery remains an important part of treatment for patients with osteogenesis imperfecta, but it should be performed only if it is likely to improve function. Surgical interventions include placing metal rods through the long bones to support them and prevent fractures. This procedure is called rodding. The rods are inserted into the center of long bones to provide internal support and stability^[8][10][14].

Surgery may also be used to correct curvature of the spine and to manage other specific problems^[8].

Physical therapy and assistive devices

Physical therapy plays an important role in treatment. Therapists can teach strengthening exercises to help build muscle and bone strength. Occupational therapists can teach patients and families how to perform everyday activities while wearing positioning devices or managing the condition^[12].

Assistive devices such as crutches, walkers, or wheelchairs may help with mobility. Some people with osteogenesis imperfecta need these devices temporarily after fractures, while others may use them long-term depending on the severity of their condition^[12][14].

Other treatments

Treatment may also focus on managing specific symptoms:

• Dental care for weak or discolored teeth
• Hearing aids for hearing loss
• Breathing support for respiratory problems
• Pain management

^[7][8]

For children with the mildest form of osteogenesis imperfecta, doctors may recommend using nonsurgical therapies to strengthen bones during growth. After a child stops growing, treatment focuses on protecting bones and preventing bone loss^[12].

Living with osteogenesis imperfecta

The outlook for people with osteogenesis imperfecta varies greatly depending on the type and severity of the condition. The most common form causes mild symptoms, and many people with type I lead relatively normal lives with proper care^[1].

People with milder forms may experience only a few fractures over their lifetime, particularly during childhood. In many children, the number of fractures decreases significantly as they mature, though the condition may become active again later in life^[4][6].

Learning to adapt and take calculated risks is an important part of living with the condition. Families and individuals must decide for themselves what risks they believe are worth taking, whether that’s pursuing physical activities, educational goals, or other life experiences. Throughout life, people with osteogenesis imperfecta often go through several major surgeries to repair fractures, spending weeks in recovery each time^[13].

Support from healthcare teams, including orthopedic surgeons, physical therapists, and other specialists, is essential. Regular clinic assessments and home visits are important, particularly in the first few years of life. Close follow-up after surgery is vital to ensure fracture healing and restoration of function^[8][14].

With proper treatment and care, many people with osteogenesis imperfecta can reach their full potential and lead fulfilling lives^[5].