Definition

Osteogenesis imperfecta (OI) is a genetic disorder characterized by bones that break easily, often from little or no apparent cause. There are at least four recognized forms of the disorder, representing extreme variation in severity from one individual to another. For example, a person may have just a few or as many as several hundred fractures in a lifetime.

Prevalence

While the number of people affected with OI in the United States is unknown, the best estimate suggests a minimum of 20,000 and possibly as many as 50,000.

Diagnosis

OI is caused by a genetic defect that affects the body’s production of collagen. Collagen is the major protein of the body's connective tissue and can be likened to the framework around which a building is constructed. In OI, a person has either less collagen than normal, or a poorer quality of collagen than normal—leading to weak bones that fracture easily.
It is often, though not always, possible to diagnose OI based solely on clinical features (see chart). Clinical geneticists can also perform biochemical (collagen) or molecular (DNA) tests that can help confirm a diagnosis of OI in some situations. These tests generally require several weeks before results are known, and approximately 10 to 15 percent of individuals with mild OI who have collagen testing, and approximately 5 percent of those who have genetic testing, test negative for OI despite having the disorder.

Clinical Features

The characteristic features of OI vary greatly from person to person—even among people with the same type of OI, and even within the same family—and not all characteristics are evident in each case. The general features of the four recognized types of OI, which vary in characteristics and severity, are as follows:

• Type I
  • Most common and mildest type of OI.
  • Bones predisposed to fracture. Most fractures occur before puberty.
  • Normal or near-normal stature.
  • Loose joints and low muscle tone.
  • Sclera (whites of the eyes) usually have a blue, purple, or gray tint.
  • Triangular face.
  • Tendency toward spinal curvature.
  • Bone deformity absent or minimal.
  • Brittle teeth possible.
  • Hearing loss possible, often beginning in early 20s or 30s.
  • Collagen structure is normal, but the amount is less than normal.
• Type II
  • Most severe form.
  • Frequently lethal at or shortly after birth, often due to respiratory problems. In recent years, some people with Type II have lived into young adulthood.
  • Numerous fractures and severe bone deformity.
  • Small stature with underdeveloped lungs.
  • Collagen is improperly formed.
• Type III
  • Bones fracture easily. Fractures often present at birth, and x-rays may reveal healed fractures that occurred before birth.
  • Short stature.
  • Sclera have a blue, purple, or gray tint.
  • Loose joints and poor muscle development in arms and legs.
  • Barrel-shaped rib cage.
  • Triangular face.
  • Spinal curvature.
  • Respiratory problems possible.
  • Bone deformity, often severe.
  • Brittle teeth possible.
  • Hearing loss possible.
  • Collagen is improperly formed.
• Type IV
  • Between Type I and Type III in severity.
  • Bones fracture easily, most before puberty.
  • Shorter than average stature.
  • Sclera are white or near-white (i.e., normal in color).
  • Mild to moderate bone deformity.
  • Tendency toward spinal curvature.
  • Barrel-shaped rib cage.
  • Triangular face.
  • Brittle teeth possible.
  • Hearing loss possible.
  • Collagen is improperly formed.

Inheritance Factors

Most cases of OI are caused by a dominant genetic defect. Some children with OI inherit the disorder from a parent. Other children are born with OI even though there is no family history of the disorder. In these children, the genetic defect occurred as a spontaneous mutation.
Because the defect—whether inherited or due to a spontaneous mutation—is usually dominant, a person with OI has a 50 percent chance of passing on the disorder to each of his or her children. Genetic counselors can help people with OI and their family members further understand OI genetics and the possibility of recurrence, and assist in prenatal diagnosis for those who wish to exercise that option. For more information on OI inheritance, see the OI Foundation fact sheet titled “Genetics.”

Treatment

There is not yet a cure for OI. Treatment is directed toward preventing or controlling the symptoms, maximizing independent mobility, and developing optimal bone mass and muscle strength. Care of fractures, extensive surgical and dental procedures, and physical therapy are often recommended for people with OI. Use of wheelchairs, braces, and other mobility aids is common, particularly (although not exclusively) among people with more severe types of OI.

A surgical procedure called “rodding” is frequently considered for individuals with OI. This treatment involves inserting metal rods through the length of the long bones to strengthen them and prevent and/or correct deformities. For more information, see the OI Foundation’s fact sheet on “Rodding Surgery.”

Several medications and other treatments are being explored for their potential use to treat OI. The OI Foundation can provide current information on research studies and experimental treatments for OI, as well as information to help individuals decide whether to participate in clinical trials.
People with OI are encouraged to exercise as much as possible to promote muscle and bone strength, which can help prevent fractures. Swimming and water therapy are common exercise choices for people with OI, as water allows independent movement with little risk of fracture. For those who are able, walking (with or without mobility aids) is excellent exercise. Individuals with OI should consult their physician and/or physical therapist to discuss appropriate and safe exercise.

Children and adults with OI will also benefit from maintaining a healthy weight, eating a nutritious diet, and avoiding activities such as smoking, excessive alcohol and caffeine consumption, and taking steroid medications—all of which may deplete bone and exacerbate bone fragility. For more information on nutrition, see the OI Foundation fact sheet titled “Nutrition.”

Prognosis

The prognosis for an individual with OI varies greatly depending on the number and severity of symptoms. Despite numerous fractures, restricted activity, and short stature, most adults and children with OI lead productive and successful lives.

The NIH Osteoporosis and Related Bone Diseases ~ National Resource Center acknowledges the assistance of the Osteogenesis Imperfecta Foundation in the preparation of this publication.

For more information about Osteogenesis Imperfecta, contact:
Osteogenesis Imperfecta Foundation
804 West Diamond Avenue, Suite 210
Gaithersburg, MD 20878
(800) 981-BONE (2663) or (301) 947-0083
Fax: (301) 947-0456
E-mail: bonelink@oif.org
Internet: www.oif.org

Revision Date: 4/2002

The NIH Osteoporosis and Related Bone Diseases ~ National Resource Center is supported by the
National Institute of Arthritis and Musculoskeletal and Skin Diseases
with contributions from the National Institute of Child Health and Human Development, National Institute of
Dental and Craniofacial Research, National Institute of Diabetes and Digestive and Kidney Diseases,
NIH Office of Research on Women's Health, DHHS Office on Women's Health, and National Institute on Aging.