Osteogenesis imperfecta (OI) is a genetic disorder characterized by fragile bones that break easily. It is also known as “brittle bone disease.” A person is born with this disorder and is affected throughout his or her life time.
In addition to fractures people with OI often have muscle weakness, hearing loss, fatigue, joint laxity, curved bones, scoliosis, blue sclerae, dentinogenesis imperfecta (brittle teeth), and short stature. Restrictive pulmonary disease occurs in more severely affected people.
OI is caused by an error called a mutation on a gene that affects the body’s production of the collagen found in bones, and other tissues. It is not caused by too little calcium or poor nutrition.
OI is variable with 8 different types described in medical literature.
The types range in severity from a lethal form to a milder form with few visible symptoms.
The specific medical problems a person will encounter will depend on the degree of severity.
A person with mild OI may experience a few fractures while those with the severe forms may have hundreds in a lifetime.
The number of Americans affected with OI is thought to be 25,000-50,000.
The range is so wide because mild OI often goes undiagnosed.
The majority of cases are caused by a dominant mutation to type 1 collagen (COL1A1 or COL1A2) genes
Other types are caused by mutations of the cartilage-associated protein (CRTAP) gene or the LEPRE1 gene. This type of mutation is inherited in a recessive manner.
OI occurs with equal frequency among males and females and among all racial and ethnic groups.
Approximately 35% of children with OI are born into a family with no family history of OI. Most often this is due to a new mutation to a gene and not by anything the parents did before or during pregnancy.
Testing and Diagnosis
Diagnosis for OI is primarily based on signs seen in a doctor’s examination. When there is uncertainty about the diagnosis, it is best to consult a physician who is familiar with OI. Genetic testing is available to confirm a diagnosis of OI through collagen or gene analysis—a skin sample or a blood sample are used to study the amount of Type I collagen or to do a DNA analysis.
Since 1979, OI has been classified by type according to a system based on mode of inheritance, clinical picture, and information from x-rays. 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. Not all characteristics are evident in each person. The OI type descriptions provide general information about how severe the symptoms probably will be. Health issues frequently seen in children and adults who have OI include:
Weak tissues, fragile skin, muscle weakness, and loose joints
Bleeding, easy bruising, frequent nosebleeds and in a small number of people heavy bleeding from injuries
Hearing loss may begin in childhood and affects approximately 50% of adults
Breathing problems, higher incidence of asthma plus risk for other lung problems
Doctors who see children and adults with OI include primary care physicians, orthopedists, endocrinologists, geneticists and physiatrists (rehabilitation specialists). Other specialists such as a neurologist may be needed.
Treatments focuses on minimizing fractures, maximizing mobility, maximizing independent function and general health
Physical therapy and safe exercise including swimming
Casts, splints or wraps for broken bones
Braces to support legs, ankles, knees and wrists as needed
Orthopedic surgery, often including implanting rods to support the long bones in arms or legs
Medications to strengthen bones
Mobility aids such as canes, walkers, or wheelchairs and other equipment or aids for independence may be needed to compensate for weakness or short stature.
The prognosis for a person with OI varies greatly depending on the number and severity of symptoms.
Life expectancy is not affected in people with mild or moderate symptoms.
Life expectancy may be shortened for those with more severe symptoms.
The most severe forms result in death at birth or during infancy. Respiratory failure is the most frequent cause of death for people with OI, followed by accidental trauma.
Despite the challenges of managing OI, most adults and children who have OI lead productive and successful lives. They attend school, develop friendships and other relationships, have careers, raise families, participate in sports and other recreational activities and are active members of their communities.
Techniques for safe handling, protective positioning and safe movement are taught to parents
Infancy, early childhood and the pre-teen years are often challenging
Growth and hormonal changes can affect the frequency of fractures
Children and youth learn which activities to avoid and how to practice energy conservation
The number of fractures usually decreases in adulthood
Following a healthy lifestyle including not smoking, and maintaining a healthy weight is beneficial
History of OI in Medical Literature
There is evidence that OI has affected people throughout history. OI has been recognized in an Egyptian mummy dating from 1000 BC. It has also been identified as the medical condition suffered by Ivan the Boneless who lived in 9th century Denmark. Prince Ivan, according to legend, was carried into battle on a shield because he was unable to walk on his soft legs.
Case studies of fragile bones and hearing loss have appeared in the medical literature since the 1600s.The term “osteogenesis imperfecta” was originated by W. Vrolik in 1849, and the condition was loosely divided into “congenita” and “tarda” by E. Looser in 1906. Van der Hoeve in 1918 described the occurrence of fragile bones, in combination with blue sclera and early deafness as a distinct inherited syndrome.
In the 1970s, Dr. David Sillence and his team of researchers in Australia developed the system of categorization using “Types” that is currently in use. His original four classifications (Type I, Type II, Type III and Type IV) combine clinical symptoms with genetic components. This listing is based on the number of people in the study who had similar symptoms. The types do not go from mildest to most severe. This classification system has been generally accepted world wide since 1979 but continues to evolve as new information is discovered. In recent years, evidence from bone biopsies and other research led to the addition of Types V, VI, VII and VIII.
For more detailed information on these topics and others related to understanding and living with OI see the Resources section of this website.