Osteogenesis imperfecta


Osteogenesis imperfecta (OI) is a group of genetic diseases in which the bones are formed improperly, making them fragile and prone to breaking.


Collagen is a fibrous protein material that serves as the structural foundation of skin, bone, cartilage, and ligaments. In osteogenesis imperfecta, the collagen produced is abnormal and disorganized, which results in a number of abnormalities throughout the body, the most notable being fragile, easily broken bones.

There are four forms of OI, types I through IV. Of these, type II is the most severe and is usually fatal within a short time after birth. Types I, III, and IV have some overlapping and some distinctive symptoms, with the hallmark symptom being fragile bones.

OI is usually inherited as an autosomal dominant condition. In autosomal dominant inheritance, a single abnormal gene on one of the autosomal chromosomes (one of the first 22 non-sex chromosomes) from either parent can cause the disease. Only one parent needs to be a carrier in order for the child to inherit the disease. The parent affected by OI will have one abnormal gene and one normal gene. A child who has one parent with the disease therefore has a 50 percent chance of also inheriting the disease.

If both parents have OI caused by an autosomal dominant gene change, there is a 75 percent chance that the child will inherit one or both OI genes. In other words, there is a 25 percent chance of inheriting a faulty gene from the mother and a normal gene from the father, a 25 percent chance of inheriting a normal gene from the mother and a faulty gene from the father, a 25 percent chance of inheriting faulty genes from both parents, and a 25 percent chance of inheriting normal genes from both parents. It is difficult to predict the severity of OI in a child who has inherited two copies of the faulty gene because of its rarity.

There is no family history of OI in about 25 percent of children born with the disease. This occurs as a result of a spontaneous mutation of the gene in either the sperm or egg. The cause of such mutations is not known. Called new dominant mutation, the affected child subsequently has a 50 percent of passing the abnormal gene to his or her children. The risk of normal parents having a second child with OI, or of normal siblings going on to have affected children, does not appear to be greater than that of the general population.

In studies of families into which infants with OI type II were born, most of the babies had a new dominant mutation in a collagen gene. In some of these families, however, more than one infant was born with OI. Previously, researchers had seen this recurrence as evidence of recessive inheritance of OI type II. Subsequently, however, researchers concluded that the rare recurrence of OI to a couple with a child with autosomal dominant OI is more likely due to gonadal mosaicism. Instead of mutation occurring in an individual sperm or egg, it occurs in a percentage of the cells that give rise to a parent's multiple sperm or eggs. This mutation, present in a percentage of his or her reproductive cells, can result in more than one affected child without affecting the parent with the disorder. An estimated 2 percent to 4 percent of families into which an infant with OI type II is born are at risk of having another affected child because of gonadal mosaicism.


OI affects equal numbers of males and females. It occurs in about one of every 20,000 births.

Causes and symptoms

Evidence suggests that OI results from abnormalities in the collagen gene COL1A1 or COL1A2 and possibly abnormalities in other genes. In OI, the genetic abnormality causes one of two things to occur. It may direct cells to make an altered collagen protein and the presence of this altered collagen causes OI type II, III, or IV. Alternately, the dominant altered gene may fail to direct cells to make any collagen protein. Although some collagen is produced by instructions from the normal gene, an overall decrease in the total amount of collagen produced results in OI type I.

Type I

OI type I is the most common and mildest type. Among the common features of type I are the following:

  • Bones are predisposed to fracture, with most fractures occurring before puberty ; people with OI type I typically have about 20 to 40 fractures before puberty.
  • Stature is normal or near-normal.
  • Joints are loose and muscle tone is low.
  • Sclerae (whites of the eyes) have blue, purple, or gray tint.
  • Face shape is triangular.
  • Tendency toward scoliosis (a curvature of the spine) is present.
  • Bone deformity is absent or minimal.
  • Dentinogenesis imperfecta may occur, causing brittle teeth.
  • Hearing loss is a possible symptom, often beginning in early 20s or 30s.
  • Structure of collagen is normal but the amount is lower than normal.

Type II

Sometimes called the lethal form, type II is the most severe form of OI. Among the common features of type II are the following:

  • Frequently, OI type II is lethal at or shortly after birth, often as a result of respiratory problems.
  • Fractures are numerous and bone deformity is severe.
  • Stature is small with underdeveloped lungs.
  • Collagen is formed improperly.

Type III

Among the common features of type III are the following:

  • Bones fracture easily (Fractures are often present at birth, and x rays may reveal healed fractures that occurred before birth; people with OI type III may have more than 100 fractures before puberty.)
  • Stature is significantly shorter than normal.
  • Sclerae have blue, purple, or gray tint.
  • Joints are loose and muscle development is poor in arms and legs.
  • Rib cage is barrel-shaped.
  • Face shape is triangular.
  • Scoliosis (a curvature of the spine) is present.
  • Respiratory problems are possible.
  • Bones are deformed and deformity is often severe.
  • Dentinogenesis imperfecta may occur.
  • Hearing loss is possible.
  • Collagen is formed improperly.

Type IV

OI type IV falls between type I and type III in severity. Among the common features of type IV are the following:

  • Bones fracture easily, with most fractures occurring before puberty.
  • Stature is shorter than average.
  • Sclerae are normal in color, appearing white or near-white.
  • Bone deformity is mild to moderate.
  • Scoliosis (curvature of the spine) is likely.
  • Rib cage is barrel-shaped.
  • Face is triangular.
  • Dentinogenesis imperfecta may occur.
  • Hearing loss is possible.
  • Collagen is formed improperly.

When to call the doctor

Parents should contact a healthcare professional if their child exhibits any of the symptoms of OI, particularly a tendency to fracture bones easily.


It is often possible to diagnose OI solely on clinical features and x-ray findings. Collagen or DNA tests may help confirm a diagnosis of OI; test results may take several weeks to confirm. 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.

Diagnosis is usually suspected when a baby has bone fractures after having suffered no apparent injury. Another indication is small, irregular, isolated bones in the sutures between the bones of the skull (wormian bones). Sometimes the bluish sclerae serve as a diagnostic clue. Unfortunately, because of the unusual nature of the fractures occurring in a baby who is not yet mobile, some parents have been accused of child abuse before the actual diagnosis of osteogenesis imperfecta was reached.

Prenatal diagnosis

Testing is available to assist in prenatal diagnosis. Women with OI who become pregnant or women who conceive a child with a man who has OI may wish to explore prenatal diagnosis. Because of the relatively small risk (2–4%) of recurrence of OI type II in a family, families may opt for ultrasound studies to determine if a developing fetus has the disorder.

Ultrasound is the least invasive procedure for prenatal diagnosis and carries the least risk. Using ultrasound, a doctor can examine the fetus's skeleton for bowing of the leg or arm bones, fractures, shortening, or other bone abnormalities that may indicate OI. Different forms of OI may be detected by ultrasound in the second trimester. When OI occurs as a new dominant mutation and is found inadvertently on ultrasound, it may be difficult to confirm the diagnosis until after delivery since other genetic conditions can cause bowing and/or fractures prenatally.

Chorionic villus sampling is a procedure that obtains a sampling of cells from the placenta for testing. Examination of fetal collagen proteins in the tissue can reveal information about the quantitative or qualitative collagen defects that leads to OI. When a parent has OI, it is necessary for the affected parent to have the results of his or her own collagen test available. Chorionic villus sampling can be performed at ten to 12 weeks of pregnancy.

Amniocentesis is a procedure that involves inserting a thin needle into the uterus, into the amniotic sac, and withdrawing a small amount of amniotic fluid. Genetic material can be extracted from the fetal cells contained in the amniotic fluid and tested for the specific mutation known to cause OI in that family. This technique is useful only when the mutation causing OI in a particular family has been identified through previous genetic testing of affected family members, including previous pregnancies involving a baby with OI. Amniocentesis is performed at 16 to 18 weeks of pregnancy.


There are no treatments available to cure OI, nor to prevent most of its complications. Most treatments are aimed at treating the fractures and bone deformities caused by OI. Splints, casts, braces, and rods are all used. Rodding is a surgical procedure in which a metal rod is implanted within a bone (usually the long bones of the thigh and leg). This surgery is performed when bowing or repeated fractures of these bones has interfered with a child's ability to walk.

Other treatments include hearing aids and early capping of teeth. Patients may require the use of a walker or wheelchair. Pain may be treated with a variety of medications. Exercise is encouraged as a means to promote muscle and bone strength. Swimming is a form of exercise that puts a minimal amount of strain on muscles, joints, and bones. Walking is encouraged for those who are able.

Alternative treatment

Alternative treatment such as acupuncture, naturopathic therapies, hypnosis, relaxation training, visual imagery, and biofeedback have all been used to try to decrease the constant pain of fractures.

Nutritional concerns

Smoking , excessive alcohol and caffeine consumption, and steroid medications may deplete bone and exacerbate bone fragility.


The lifespan of people with OI types I, III, and IV is not generally shortened. The prognosis for people with these types of OI is quite variable, depending on the severity of the disorder and the number and severity of the fractures and bony deformities.

Fifty percent of all babies with OI type II are stillborn. The rest of these babies usually die within a very short time after birth. In the early 2000s, some people with type II have lived into young adulthood.


As a congenital birth defect, OI cannot be prevented. Individuals at risk of having a child with OI should be encouraged to undergo genetic counseling to more accurately determine their chances of having a child with OI. The risk of fractures can be minimized with bone- and muscle-strengthening exercises, rehabilitative therapy, and use of leg braces.

Nutritional concerns

Because the symptoms of OI are caused by collagen abnormalities and not a calcium deficiency (such as in osteoporosis), supplementation of vitamins or minerals will not cure the disease. To prevent bone loss related to calcium deficiency, which could exacerbate the fragility of bones, it is important that children with OI consume an adequate amount of calcium (generally 500 mg for children ages one to three, 800 mg for children ages four to eight, and 1,300 mg a day for preteens and teenagers).

Parental concerns

In cases in which OI is not diagnosed at birth, a child may experience numerous fractures of seemingly unexplained cause, leading healthcare providers to suspect the child is being abused. Once a child has been diagnosed, it may be helpful for parents to carry with them a letter from the child's healthcare provider detailing the diagnosis in order to facilitate care in an emergency.


Chromosome —A microscopic thread-like structure found within each cell of the human body and consisting of a complex of proteins and DNA. Humans have 46 chromosomes arranged into 23 pairs. Chromosomes contain the genetic information necessary to direct the development and functioning of all cells and systems in the body. They pass on hereditary traits from parents to child (like eye color) and determine whether the child will be male or female.

Collagen —The main supportive protein of cartilage, connective tissue, tendon, skin, and bone.

Ligament —A type of tough, fibrous tissue that connects bones or cartilage and provides support and strength to joints.

Mutation —A permanent change in the genetic material that may alter a trait or characteristic of an individual, or manifest as disease. This change can be transmitted to offspring.

Sclera —The tough, fibrous, white outer protective covering of the eyeball.

Scoliosis —An abnormal, side-to-side curvature of the spine.



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Children's Brittle Bone Foundation. 7701 95th St., Pleasant Prairie, WI 53158. Web site: http://www.cbbf.org.

Osteogenesis Imperfecta Foundation. 804 W. Diamond Ave., Suite 210, Gaithersburg, MD 20878. Web site: http://www.oif.org.


"Osteogenesis Imperfecta." National Institutes of Health Osteoporosis and Related Bone Diseases—National Resource Center , July 2004. Available online at http://www.osteo.org/oi.html (accessed January 16, 2005).

Jennifer F. Wilson, MS Stephanie Dionne Sherk

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