Overview of Osteogenesis Imperfecta

Osteogenesis imperfecta (OI) is a genetic or heritable disease in which bones fracture (break) easily, often with no obvious cause or minimal injury. OI is also known as brittle bone disease, and the symptoms can range from mild with only a few fractures to severe with many medical complications.

What Happens in OI?

For most people, a change or defect in the genes that carry the instructions for making type I collagen causes OI. Type I collagen is a material in bones that helps make them strong. The defect in the genes causes the body to make collagen incorrectly or not make enough, leading to weak bones that break more easily. There is no way to prevent the disease. Type I collagen is also in other connective tissues such as tendon, ligament, lung, and skin, and these tissues can sometimes be affected.

Who Gets Osteogenesis Imperfecta?

Though anyone can be born with OI, people with a family history of the disease are at greater risk of inheriting the disease through an abnormal gene that is passed on from one or both parents. Genetic counselors can help you better understand the genetics of OI.

Types of Osteogenesis Imperfecta

There are several types of OI, and different classifications are used based on the severity of the disease or on the nature of the underlying gene defect. Type I is the mildest and most common form of OI. Type II is the most severe form of OI. Other types of OI have symptoms that fall between Type I and Type II. Following is an overview of the types most often diagnosed. The remaining types are rare and still being studied.

Type I

Bones likely to break from mild to moderate trauma, with most broken bones occurring before puberty.
No change or only slight changes to stature with aging.
Loose joints and muscle weakness.
Blue, purple, or gray tint to sclera (whites of the eyes).
Triangular face.
Curved spine with potential for compression of the vertebrae (spine bones) with aging.
Mild or no bone deformity.
Possible changes to the strength and color of teeth.
Possible hearing loss.
Normal collagen structure, but less than the normal amount is produced.

Type II

Causes death at birth or shortly after, because of the inability to breathe.
Numerous broken bones that develop before birth while the baby is still in the womb.
Severe bone deformities.
Very small stature.
Underdeveloped lungs.
Blue, purple, or gray tint to sclera.
Improperly formed collagen.

Type III

Most severe type among those who survive the neonatal period and usually results in the greatest number of physical disabilities.
Easily broken bones with very little trauma over a lifetime. (Broken bones are often present at birth, and x-rays may reveal healed bone breaks that occurred before birth.)
Moderate to severe bone deformity.
Small stature.
Blue, purple, or gray tint to sclera.
Loose joints.
Poor muscle development in arms and legs.
Barrel-shaped rib cage.
Triangular face.
Curved spine and compression or collapse of vertebrae.
Possible lung problems that worsen with age.
Often severe bone deformity.
Possible changes to the strength and color of teeth with tooth fracture.
Possible malocclusion of the teeth, meaning they are not aligned properly.
Possible changes to the strength and color of teeth.
Possible hearing loss.
Improperly formed collagen.

Type IV

Bones break easily, sometimes before birth, with most broken bones occurring before puberty.
Smaller than average stature.
White or blue tint to sclera.
Mild bone deformity.
Vertebra compression or collapse.
Barrel-shaped rib cage.
Triangular face.
Possible changes to strength and color of teeth.
Possible hearing loss.
Improperly formed collagen.

Type V

Clinically similar to Type IV OI in appearance and symptoms.
A dense band seen on x-rays by the cartilage growth plate of the long bones.
Unusually large calluses, called hypertrophic calluses, at the sites of fractures or surgical procedures. (A callus is an area of new bone that is laid down at the fracture site as part of the healing process.)
Calcification of the membrane between the radius and ulna (the bones of the forearm), which results in restricted arm movement.
Possible loose joints.
White sclera.
No changes to teeth.
\u201cMesh-like\u201d appearance to bone when viewed under the microscope.
Changes in the mineralization of bone.

Type VI

Resembles Type IV OI in appearance and symptoms.
Not always diagnosed at birth, and symptoms progress over time.
\u201cFish-scale\u201d appearance to bone when viewed under the microscope.
Curved spine.
Diagnosed by bone biopsy or genetic studies.
Changes in the mineralization of bone.

Type VII

Resembles Type II and Type III OI in appearance and symptoms.
White sclera.
Small stature.
Short humerus (upper arm bone) and short femur (upper leg bone).
Possible smaller head size.
Changes in the process of forming collagen.

Type VIII

Resembles Type II and Type III OI in appearance and symptoms.
White sclera.
Small stature.
Short humerus (upper arm bone) and short femur (upper leg bone).
Possible smaller head size.
Changes in the process of forming collagen.

There are rarer types of the disease, and in general they are moderately severe forms. These types are similar to OI types III or IV. Some of these rare forms do not affect the structure of collagen but instead affect the function of bone-forming cells.

Symptoms of Osteogenesis Imperfecta

All people with OI have weak, brittle bones. Some people with OI may have only a few broken bones over their lifetime. Others may have hundreds of broken bones in their lifetime, including broken bones that occur before birth.

People with OI may have other symptoms, which can range from mild to severe and vary from person to person. These include:

Malformed or bowing of long bones.
Small stature.
Skin that bruises easily.
Loose joints.
Weak muscles.
Whites of the eyes (sclera) that look blue, purple, or gray.
A face shaped like a triangle.
A rib cage shaped like a barrel.
A curved spine.
Collapse or compression of the vertebrae in the spine.
Brittle, misshapen, or discolored teeth.
Malocclusion of teeth, meaning they are not aligned properly.
Hearing loss.
Breathing problems.
A deformed hip joint in which the neck of the femur is bent downward, a condition called coxa vara.
Joint contractures (a joint stays in a permanently bent or straightened position).

Causes of Osteogenesis Imperfecta

A mutation or change in a gene causes OI. Genes carry information that determines which features are passed to you from your parents. We have two copies of most of our genes, one from each parent.

In the most common forms, people with OI have a gene that carries incorrect instructions in one copy of the gene for making collagen, a substance that makes bones strong. The gene causes the body to not make enough collagen or the collagen does not work properly. This leads to weak bones that break easily.

Most people with OI inherit this gene from one parent or they occur for the first time in the person. In other forms, the child has to inherit a mutation in a gene from both parents. Parents do not have to have OI to pass on the gene that causes it. Sometimes, neither parent passes on the gene. Instead, the gene stops working properly on its own before the child is born.

Dominant OI

Most people with OI have a dominant form. This means they carry one normal copy and one copy of the gene that causes OI. The abnormal copy of the gene is stronger or \u201cdominant\u201d over the normal copy of the gene. This causes a person to have OI. A person with a dominant mutation has a 50-percent chance (1 in 2) of passing on the disorder to each of his or her children. Some children with the dominant form of OI inherit a gene that causes OI from a parent. While others are born with the dominant form of OI even though there is no family history of the disorder and the mutation occurs in their genome for the first time in the family.

Recessive OI

Some people with OI have a recessive form of the disease. People with recessive OI have parents who do not have OI but who both have an abnormal gene that causes the disease and one normal gene that protects them from symptoms. When both parents carry the recessive gene for OI, there is a 25% chance (1 out of 4) per pregnancy of having a child with the disease. Unaffected or asymptomatic siblings of a person with recessive OI have a two-thirds chance (2 out of 3) of carrying an abnormal gene that causes OI and a normal copy, making them carriers of the disease like their parents. If one parent has OI because they carry two copies of a recessive mutation, all of their children will carry an abnormal gene that causes OI but will not necessarily have OI, unless in the usually very rare situation when the affected parent has children with a carrier of mutation in the same disease gene.

Diagnosis of Osteogenesis Imperfecta

Doctors may diagnose OI by:

Asking about family and medical history.
Completing a physical exam.
Ordering x-rays and bone density tests.

In addition, doctors can also diagnose OI and identify the type of OI with a genetic blood test that detects the change in the inherited gene. These tests can detect OI in most people who have it. Sometimes, additional genetic testing may be necessary. People who have genetic testing should see a specialist or genetic counselor to help them understand the test results. A negative genetic test does not rule out an OI diagnosis.

Treatment of Osteogenesis Imperfecta

There is no cure for OI. The goal of treatment, depending on the type of OI, is to prevent or control symptoms, increase bone mass and muscle strength, and maximize a person\u2019s ability to be independent. These treatments include:

Physical or Occupational Therapy

People with OI may benefit from physical or occupational therapy, which can help the person:

Build muscle strength; improve joint movement, mobility, and gross motor skills; and prevent broken bones.
Learn how to avoid injuries.
Safely perform activities of daily living.
Recover from broken bones.

Therapists and doctors also may recommend swimming to condition and build strength.

Medicines

Although there are no medicines approved by the U.S. Food and Drug Administration to treat OI, your doctor may recommend a therapy approved for a related condition. Your doctor may prescribe:

Bone strengthening medicines approved to treat other bone diseases can help slow bone loss and reduce the frequency and seriousness of broken bones.
Pain medicines to treat pain caused by broken bones and chronic bone pain.

In addition, some medicines are currently being studied to help prevent the complications of or to treat OI in adults and children. Talk to your primary care provider or your child\u2019s pediatrician about the using these medicines or participating in studies.

Bone Care

An orthopaedic specialist can treat broken bones with a cast, splint, or brace. Sometimes people need surgery to repair a broken bone.

In addition, doctors perform surgery to support or correct bones that are curved or bowed, including the spine. Many children with OI have rodding surgery, in which a metal rod is placed into a bone. Rodding surgery is performed to support the bone and prevent the bone from breaking. Some of these rods are \u201ctelescoping\u201d and can be adjusted to lengthen as a child with OI grows.

Mobility Aids

Using a mobility aid may help people safely perform daily activities and reduce injuries. These aids include:

Walkers.
Canes and crutches.
Braces or prosthetics.
Wheelchairs.

Oral and Dental Care

Some people with OI have:

Teeth that easily chip or break.
Changes in tooth color and shape.
Tooth decay.
Small jaw size.
Incorrect position of teeth.

Regular dental check-ups and care are important to prevent dental symptoms and improve bite, alignment and appearance of teeth. In addition, some people need to see:

Oral-maxillofacial surgeon, who specializes in oral and jaw surgery.
Orthodontist, who treats tooth alignment and jaw position.

Hearing

Doctors recommend hearing testing beginning in childhood, with regular testing throughout the person\u2019s life. It\u2019s important to see an audiologist who specializes in caring for people with OI. Treatment can include:

Hearing aids, small electronic devices worn outside the ear that make sound louder.
Cochlear implants, small electronic devices that have two pieces, one outside behind the ear and another under the skin.
Surgery called stapedectomy, when a surgeon places a prosthetic or artificial device into the middle ear, allowing sound waves to reach the inner ear.

Who Treats Osteogenesis Imperfecta?

People with OI usually require a health care team of several doctors and health care providers. Your health care team may include:

Primary care physicians, who diagnose and treat adults.
Pediatricians, who diagnose and treat children.
Clinical geneticists, who diagnose and treat children and adults with genetic disorders.
Endocrinologists, who specialize in treating bone disorders.
Orthopaedists, who treat and perform surgery for bone and joint diseases, and have experience treating people with OI.
Occupational therapists, who teach how to safely perform activities of daily living.
Physical therapists, who teach ways to build muscle strength, recover from broken bones, and prevent broken bones.
Dental providers such as orthodontists and oral-maxillofacial surgeons.

Living With Osteogenesis Imperfecta

Certain activities can help people with OI stay healthy and prevent broken bones.

Follow a nutritious diet with enough calcium and vitamin D.
Exercise as much as possible. Regular physical activity can help strengthen muscles and bones. Swimming and water therapy are common choices for people with OI because exercising in water has little risk for causing broken bones. Talk with your doctor or physical therapist to discuss appropriate and safe exercise.
Keep a healthy weight. Being overweight increases the risk for many health problems, such as diabetes and heart disease. Extra weight also adds stress to the bones, which is especially unhealthy for people with OI.
Don\u2019t smoke, and avoid secondhand smoke, because smoking can also weaken bones.
Do not drink a lot of alcohol or caffeine because they may weaken your bones.
Seek counseling or talk to a health care professional if you feel depressed or anxious about OI and its symptoms.

Research Progress Related to Osteogenesis Imperfecta

Research is underway to help people with OI, including:

Continuing to understand the genetic underpinnings of OI.
Studying medicines to help manage and control symptoms of OI.
Studying how bones form to find ways to increase bone mass.
Using bone marrow or stem cells to treat OI.
Studying oral health and its impact on the quality of life in people with OI.
Studying how connective tissues in other parts of the body may be affected in people with OI.

For More Info

Genetic and Rare Diseases Information Center
Website: https://rarediseases.info.nih.gov/diseases/1017/osteogenesis-imperfecta

Genetics Home Reference
Website: https://ghr.nlm.nih.gov/condition/osteogenesis-imperfecta

U.S. Food and Drug Administration
Toll free: 888-INFO-FDA (888-463-6332)
Website: https://www.fda.gov

Drugs@FDA at https://www.accessdata.fda.gov/scripts/cder/daf Drugs@FDA is a searchable catalog of FDA-approved drug products.

Centers for Disease Control and Prevention, National Center for Health Statistics
Website: https://www.cdc.gov/nchs

Osteogenesis Imperfecta Foundation
Website: https://www.oif.org

The NIAMS gratefully acknowledges the assistance of the following individuals in the review of this information: Brendan Lee, M.D., Ph.D., Baylor College of Medicine; and Deborah Krakow, M.D., University of California, Los Angeles.

If you need more information about available resources in your language or other languages, please visit the webpages below or contact the NIAMS Information Clearinghouse at [email protected]. You can also find a variety of information from organizations that are NIAMS Coalition Members.