Osteogenesis Imperfecta (OI) is a genetic bone disorder characterized by fragile bones that break easily. It is also known as “brittle bone disease.” The term literally means “bone that is imperfectly made from the beginning of life.” A person is born with this disorder and is affected throughout his or her life time.
Osteogenesis imperfecta (OI) or Brittle Bone Disease is a
complicated, variable and rare disorder. Its major feature is a fragile
skeleton, but many other body systems are also affected. OI is caused by a
mutation (change) in a gene that affects bone formation, bone strength and the
structure of other tissues. It is a life-long disorder. OI occurs equally among
males and females and in all racial groups. It is estimated that approximately
25,000 to 50,000 people in the U.S. have OI. With good medical management and
supportive care, the majority of people who have OI will lead healthy,
productive lives and can expect an average life span.
People with OI experience frequent broken bones from
infancy through puberty. The frequency typically decreases in the young adult
years but may increase again later in life. Respiratory problems including
asthma are often seen. Other medical characteristics and issues include:
deformity, and bone pain.
joints, ligament laxity and muscle weakness are common.
features of the skull including late closing fontanels, and head circumference
greater than average.
loss may begin in the early 20s and by middle age is present in more than 50%
of people with OI.
teeth (called dentinogenesis imperfecta or DI) are seen in 50% of people who
problems including asthma; may be aggravated by chest wall deformity and/or
problems including myopia and risk for retinal detachment
hyperlaxity; easy bruising.
Invagination a serious neurological problem is seen in some people with the
more severe forms of OI.
blood vessels and internal organs may be fragile.
OI exhibits wide variation in appearance and severity. Severity is described as mild, moderate, or
severe. The most severe forms lead to early death. Clinical features
(observable signs) such as fracture frequency, muscle strength or extraskeletal
problems vary widely not only between types, but within types, and even within
the same family. Some features are age dependent.
Types of OI
Since the 1970’s a list of numbered types has been used
to describe the different forms of OI. The original list featured 4 Types. Today,
as a result of recent research 15 Types of OI have been identified. Many people
with OI do not fit clearly into one of the identified types and not all
characteristics are seen in each person. A description of the more common OI
Types follows. Understanding the individual’s OI Type provides a starting point
for understanding the person’s health care needs. But due to all of the
variable features, care for each person needs to be individualized.
People with Type I OI, the
mildest and most common form, may have only a handful of fractures or as many
as several dozen fractures in a lifetime. They may have few obvious signs of
the disorder. There usually is little or no bone deformity. Height is less
affected than in other types of OI. People with Type I OI are often similar in
height to other family members. Muscle weakness, joint laxity and flat feet are
common. Dislocations and sprains may occur as well as fractures. Life expectancy
appears to be average.
Type II OI is the most severe
form. Infants are quite small and are usually born with multiple fractures, an
unusually soft skull and an unstable neck. Limbs may be disproportionately
small and legs may fall into a frog-like position. The head may be large for
the size of the body. Almost all infants with Type II OI die at or shortly
after birth, often due to respiratory problems. In the newborn period, it can
be difficult to distinguish between Type II and severe Type III OI. This means
that some children diagnosed clinically as Type II at birth may actually have
Type III OI and have a longer life expectancy.
People with Type III OI are born with
fractures. X-rays may reveal healed fractures that occurred before birth. Common signs include short
stature, progressive long bone deformities, spinal curvature, and a barrel-shaped rib
cage. People with Type III OI may have anywhere from several dozen to several hundred
fractures in a lifetime. Surgical correction of long bone bowing and scoliosis is common. Life
expectancy varies. Some people with Type III OI have severe, sometimes fatal, respiratory problems
in infancy or childhood. Some children and adults with severe Type III OI may require
supplemental oxygen. Some individuals succumb to respiratory problems in adulthood due to
progressive rib cage and spine deformities. Other people with Type III OI will have a
near-average life span.
Type IV OI is the moderate type of OI. The
clinical picture can be similar to Type I OI or more like Type III OI. People with this form of OI
may be somewhat shorter than others in their family, have frequent fractures that decrease
after puberty, and have mild to moderate bone deformity. Life expectancy appears to be
Type V is moderate in
severity and is similar to Type IV in appearance and symptoms. Identifying
features include hypertrophic calluses that may form at fracture or surgical
procedure sites and restricted forearm rotation due to calcification of the
membrane between the radius and ulna.
Type VI is another moderate form and is
similar to Type IV in appearance. This is an extremely rare form. It is
distinguished by a characteristic mineralization defect that can be seen in
For additional information on OI Types see the Fact Sheet
section under “About OI/Publications” on this website
How Is OI Inherited?
Osteogenesis imperfecta (OI) is a genetic disorder. Most
cases (90 percent) are caused by a faulty gene that reduces either the amount
or the quality of type 1 collagen throughout the body. These mutations are
inherited in a dominant manner. The other 10 percent of cases are caused by
mutations in other genes that are inherited in either a dominant or a recessive
Children inherit two copies of each gene – one from each
parent. When OI is caused by a dominant mutation only one copy of the OI gene
mutation is necessary for the child to have OI. In the majority of cases, the gene is either inherited from a parent
who has OI or results from a spontaneous new mutation occurring at the time of
conception. In rare cases dominant OI can occur when a parent is mosaic for
an OI mutation. This means that an OI causing mutation is present in a
percentage of one parent’s cells, but does not cause any symptoms in the
parent. For a child to inherit OI in a recessive manner, the gene mutation must
come from both parents. In this situation, the parents do not have OI, but both
carry the mutation in their genes.
A person who has dominant OI has a 50 percent chance of
passing on the disorder to each of his or her children. An affected child will
have the same mutation, and therefore the same type of OI, as the parent.
However, the expression— the degree of severity, or number of fractures— may be
different. Unaffected siblings of a child with dominant OI have no greater risk
of having children with OI than anyone in the general population. Unaffected
siblings of a child with recessive OI have a 67 percent chance of being a
carrier for the recessive gene. Genetic testing is available for siblings.
How is OI Diagnosed?
Broken bones that occur from little or no trauma are
often the first indication that an infant or child may have OI. Babies with moderate
or severe forms of OI are often born with broken bones. Children with milder OI
(Type I) often sustain their first broken bone as a result of normal
activity—during a diaper change, while being lifted or burped, or when they
begin standing and walking. Some very mild cases of OI Type I are not diagnosed
until the teen or adult years.
OI remains primarily a clinical diagnosis. A physician,
usually a geneticist, who is familiar with all types of OI, can often diagnose
the condition based on the presence of fractures and other clinical features. A
family history for the disorder and/or genetic testing can confirm a diagnosis.
Additional blood and urine tests are often used to rule out other disorders
such as Hypophosphatasia or rickets.
The more severe forms of OI can be diagnosed prenatally.
Ultrasound can detect bowing, fractures, shortening or other bone
abnormalities. But even when ultrasound is done by a highly qualified
professional, it may not be possible to pinpoint the type of OI or
differentiate between Type II or Type III.
How is OI Treated?
There is no cure for OI, but there are ways to manage the
symptoms. Despite the obstacles, many people who have OI lead productive and
fulfilling lives well into their adult years. The goal of all treatment is to
minimize fractures, enhance independent function, and promote general health. Medical
care for children and adults who have OI involves an interdisciplinary team.
This can include a primary care doctor, orthopedists, endocrinologists,
geneticists, rehabilitation specialists, neurologists and pulmonologists. Treatment
may include fracture care, physical therapy, surgical procedures, medications,
life style features and mobility aides.
Fracture Care. Casting, splinting and bracing
broken bones can help them heal properly. However long periods of immobility can
further weaken bones and lead to muscle loss, weakness, and more fractures.
Many orthopedists prefer to treat fractures with short term immobilization in
lightweight casts, splints, or braces to allow some movement as soon as
possible after the fracture.
Physical Therapy and Safe
Exercise. Goals for
physical therapy include expanding and maintaining function and promoting
independence. A typical program includes muscle strengthening and aerobic
conditioning. Physical therapy often begins in infancy to counteract the delay
in motor skill development many children experience due to OI related muscle
weakness. Adaptive devices may be needed. Occupational therapy can help with
fine motor skills and selection of adaptive equipment for daily living. As a
child with OI grows older and gains more independence, he or she will benefit
from continued physical activity, such as adapted physical education. Adults
with OI also benefit from safe, regular exercise to maintain bone and muscle mass.
Swimming and water therapy are particularly well-suited for people with OI of
all ages, as they allow independent movement with little fracture risk. Walking
is also excellent exercise for those who are able (with or without mobility aids).
Surgery. Surgery may be needed to repair a
broken bone, correct bone deformities such as bowing, stabilize the spine or
repair tiny bones in the middle ear and improve hearing. Many children with OI
undergo a surgical procedure known as rodding, in which metal rods are inserted
into the long bones to control fractures and improve deformities that interfere
with function. Both non-expandable and expandable rods are available.
Medications. Bisphosphonate drugs, which are currently
approved by the Food and Drug Administration (FDA) to prevent and treat osteoporosis
are used off label to increase bone density in children and adults with
moderate and severe OI. Other drugs that were developed to treat osteoporosis
are also used to prevent age-related bone loss in adults who have OI.
Teriparatide (a drug based on the parathyroid hormone) is one of them. Treatments
under study include growth hormone, and gene therapies. The search continues
for a drug treatment that is specific for OI.
Healthy Lifestyle. People with OI benefit from a
healthy lifestyle that includes safe exercise and a nutritious diet. Adequate intake of nutrients, such
as Vitamin D and calcium is necessary to maintain bone health, however, extra-large
doses of these nutrients are not recommended.
Maintaining a healthy weight is important since extra
weight adds stress to the skeleton, heart and lungs and reduces the ability to
move easily. In addition, people with OI should avoid smoking, second hand
smoke, excessive alcohol or caffeine consumption and steroid medications, all
of which reduce bone density.
Other Treatments that focus on OI related symptoms
for brittle teeth
oxygen for people with breathing problems
aids such as walkers, crutches, canes and wheelchairs
Are There Precautions to
Take When Caring for People with OI?
pull or push on a limb, or bend it into an awkward position not even to take an
caution when inserting IVs, taking blood pressure, or performing other medical
procedures to avoid causing injury.
dose medicines to the size, NOT the age of short statured adults.
a fracture is suspected, minimize handling of the affected limb.
the opinions, advice, or instructions provided by parents, children, and adults
with OI. Based on experience they give good directions for the safest ways to
lift, carry or reposition. Having dealt with dozens of fractures and medical
procedures, even children have a good sense of when a bone is broken even
before x-rays are taken.
babies with extra care.
Lift a baby with OI by placing one
hand under the buttocks and legs, and the other hand under the shoulders, neck
Do not lift the baby from under the
Do not lift by the ankles to change a
diaper; rather slide a hand under the buttocks.
Babies do not need to be kept on a
pillow or soft surface. Encourage babies to explore independent movement.
Supporting infants in a variety of
positions (e.g., side lying, stomach lying) develops muscles that will help
with sitting and standing later on.
There is evidence that OI
has affected people since ancient times. It has been recognized in an Egyptian
mummy of an infant from about 1000 BC. The mummy is currently in the British
Museum in London, England. A Viking leader who lived in the 9th
century, Ivar Ragnarsson “Ivar the Boneless,” probably had OI. He is reported
to have been a very wise leader and a very fierce warrior who had to be carried
into battle on a shield because his legs were so soft. Case studies of people
with fragile bones and hearing loss began appearing in medical literature in
the 1600’s. The term “osteogenesis imperfecta” was used in medical literature
beginning in the 1840’s. Early in the 20th century OI was identified
as a condition people were born with rather than an illness they acquired
later. Today, people who have OI are involved in every walk of life.
article is based on the brochure, Introduction to Osteogenesis Imperfecta: A
Guide for Medical Professionals, Individuals and Families Affected by OI.
See the section of this website – “About OI/Publications” – for fact sheets,
booklets and videos that provide additional information on many topics related
to understanding, treating and living with OI.