Osteogenesis imperfecta (OI) is a genetic disorder in which bones break easily. Sometimes the bones break for no known reason. OI can also cause weak muscles, brittle teeth, a curved spine, and hearing loss. OI is caused by one of several genes that aren't working properly. When these genes don't work, it affects how you make collagen, a protein that helps make bones strong.

OI can range from mild to severe, and symptoms vary from person to person. A person may have just a few or as many as several hundred fractures in a lifetime.

No single test can identify OI. Your doctor uses your medical and family history, physical exam, and imaging and lab tests to diagnose it. Your doctor may also test your collagen (from skin) or genes (from blood). There is no cure, but you can manage symptoms. Treatments include exercise, pain medicine, physical therapy, wheelchairs, braces, and surgery.

OI, or “brittle bone disease,” is a condition causing fragile bones that break easily, sometimes for no obvious reason. Some people with OI have only a few fractures in their lifetimes. Others have hundreds. People who have severe forms of OI have fragile bones that are also deformed. Most people with OI experience physical disability. OI also can cause weak muscles, brittle teeth, a curved spine, and hearing loss. Most forms of OI are caused by abnormal genes that are passed down from one or both parents to their children.

There are currently 11 types of OI. Types I through IV are the most common. They are autosomal dominant forms of the disease. Autosomal dominance is a pattern of inheritance common to some genetic diseases. “Autosomal” means that the abnormal gene is located on one of the numbered, or non-sex, chromosomes. “Dominant” means that a single copy of the abnormal gene is enough to cause the disease; in other words, a person only needs to get the abnormal gene from one parent in order to inherit the disease, even though the matching gene from the other parent is normal. This is in contrast to an autosomal recessive disorder, where two copies of the mutation are needed to cause the disease; in other words, a person must inherit the abnormal gene from both parents in order to inherit the disease. Types VI through XI are autosomal recessive.

Osteogenesis imperfecta is a genetic disorder that causes a person's bones to break easily, often from little or no apparent trauma.

What is Osteogenesis imperfecta?

Osteogenesis imperfecta (OI) is a genetic disorder that causes a person's bones to break easily, often from little or no apparent trauma. OI is also called "brittle bone disease." OI varies in severity from person to person, ranging from a mild type to a severe type that causes death before or shortly after birth. In addition to having fractures, people with OI also have teeth problems (dentinogenesis imperfecta), and hearing loss when they are adults. People who have OI may also have muscle weakness, loose joints (joint laxity) and skeletal malformations.

OI occurs in approximately 1 in 20,000 individuals, including people diagnosed after birth. OI occurs with equal frequency among males and females and among racial and ethnic groups. Life expectancy varies depending on how severe the OI is, ranging from very brief (lethal form, OI type II) to average.

There are four well-known types of OI. These types are distinguished mostly by fracture frequency and severity and by characteristic features. Three additional types of OI (type V, VI and VII) have also been identified.

The vast majority (90 percent) of OI is caused by a single dominant mutation in one of two type I collagen genes: COL1A1 or COL1A2.The COL1A1 and COL1A2 genes provide instructions for making proteins that are used to create a larger molecule called type I collagen. This type of collagen is the most common protein in bone, skin and other tissues that provide structure and strength to the body (connective tissues). OI type VII is caused by recessive mutations in the CRTAP gene.

What are the symptoms of Osteogenesis imperfecta?

Osteogenesis imperfecta (OI) causes bones to be fragile and easily broken and is also responsible for other health problems.

Type I OI is the mildest form of the condition. People who have type I OI have bone fractures during childhood and adolescence often due to minor trauma When these individuals reach adulthood they have fewer fractures.

Type II OI is the most severe form of OI. Infants with type II have bones that appear bent or crumpled and fractured before birth. Their chest is narrow and they have fractured and misshapen ribs and underdeveloped lungs. These infants have short, bowed arms and legs; hips that turn outward; and unusually soft skull bones. Most infants with type II OI are stillborn or die shortly after birth, usually from breathing failure.

Type III OI also has relatively severe signs and symptoms. Infants with OI type III have very soft and fragile bones that may begin to fracture before birth or in early infancy. Some infants have rib fractures that can cause life-threatening problems with breathing. Bone abnormalities tend to get worse over time and often interfere with the ability to walk.

Type IV OI is the most variable form OI. Symptoms of OI type IV can range from mild to severe. About 25 percent of infants with OI type IV are born with bone fractures. Others may not have broken bones until later in childhood or adulthood. Infants with OI type IV have leg bones that are bowed at birth, but bowing usually lessens as they get older.

Some types of OI are also associated with progressive hearing loss, a blue or grey tint to the part of the eye that is usually white (the sclera), teeth problems (dentinogenesis imperfecta), abnormal curvature of the spine (scoliosis) and loose joints. People with this condition may have other bone abnormalities and are often shorter in stature than average.

How is Osteogenesis imperfecta diagnosed?

OI is often inherited from an affected parent. The diagnosis of OI is made on the basis of family history and/or clinical presentation. Frequent fractures, short stature, a blue hue to the white part of the eye (blue sclera), teeth problems (dentinogenesis imperfecta) and hearing loss that progresses after puberty may be present.

X-rays are also used to diagnose OI. X-ray findings include fractures that are at different stages of healing; an unexpected skull bone pattern called Wormian bones; and bones in the spine called "codfish vertebrae."

Laboratory testing for OI may include either biochemical testing or DNA-based sequencing of COL1A1 and COL1A2. Biochemical testing involves studying collagens taken from a small skin biopsy. Changes in type I collagen are an indication of OI.

DNA sequencing of COL1A1 and COL1A2 is used to identify the type I collagen gene mutation responsible for the altered collagen protein. DNA testing requires a blood sample for DNA extraction. Both tests are relatively sensitive, detecting approximately 90 percent and 95 percent, respectively, of individuals with the clinical diagnosis of OI. Normal biochemical and molecular testing in a child with OI warrants additional testing of less common collagen genes (CRTAP and P3H (LEPRE1)) responsible for some of the rare recessive forms of OI.

What is the treatment for Osteogenesis imperfecta?

There is currently no cure for OI. Treatment involves supportive therapy to decrease the number of fractures and disabilities, help with independent living and maintain overall health. OI is best managed by a medical team including the child's own doctor, and genetic, orthopedic and rehabilitation medicine. Supportive therapy is unique to each individual depending on the severity of their condition and their age.

Physical and occupational therapies to help improve their ability to move, to prevent fractures and to increase muscle strength are often useful.

Fractures are treated as they would be in children and adults who do not have OI. An orthopedic treatment called intramedullary rodding (placing rods in the bones) is used to help with positioning of legs that helps with more normal functioning when necessary.

A newer treatment with medication called biophosphonates is being used to help with bone formation and to decrease the need for surgery.

Is Osteogenesis imperfecta inherited?

Most types of OI are inherited in an autosomal dominant pattern. Almost all infants with the severe type II OI are born into families without a family history of the condition. Usually, the cause in these families is a new mutation in the egg or sperm or very early embryo in the COL1A1 or COL1A2 gene. In the milder forms of OI, 25-30 percent of cases occur as a result of new mutations. The other cases are inherited from a parent who has the condition. Whether a person has OI due to a new mutation or an inherited genetic change, an adult with the disorder can pass the condition down to future generations.

In autosomal dominant inherited OI, a parent who has OI has one copy of a gene mutation that causes OI. With each of his/her pregnancies, there is a 1 in 2 (50 percent) chance to pass on the OI gene mutation to a child who would have OI, and a 1 in 2 (50 percent) chance to pass on the normal version of the gene to a child who would not have OI.

Rarely, OI can be inherited in an autosomal recessive pattern. Most often, the parents of a child with an autosomal recessive disorder are not affected but are carriers of one copy of the altered gene. Autosomal recessive inheritance means two copies of the gene must be altered for a person to be affected by the disorder. The autosomal recessive form of type III OI usually results from mutations in genes other than COL1A1 and COL1A2.

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 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.

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.

Type II

• Frequently 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.)
• 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.
• 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 to moderate 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.
• “Mesh-like” appearance to bone when viewed under the microscope.
• Changes in the minerals in the bone.

Type VI

• Resembles Type IV OI in appearance and symptoms.
• Not always diagnosed at birth, and symptoms progress over time.
• “Fish-scale” appearance to bone when viewed under the microscope.
• Curved spine.
• Diagnosed by bone biopsy or genetic studies.
• Changes in the minerals in the 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.
• Hearing loss.
• Breathing problems.
• A deformed hip joint in which the neck of the femur is bent downward, a condition called coxa vara.

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.

People with OI have a gene that carries incorrect instructions 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. 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 inherit one normal copy and one copy of the gene that causes OI. The abnormal copy of the gene is stronger or “dominant” 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. 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, making them carriers of the disease. If one parent has OI because of a recessive mutation, all of their children will carry an abnormal gene that causes OI but will not necessarily have OI.

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 changed 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.

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’s 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’s 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 “telescoping” 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’s life. It’s 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.
• 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.
• 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’t 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 find genes that cause 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.

Infants who have recognizable OI at birth make up about 1 in every 16,000 to 20,000 births. The incidence rate is similar in people with milder forms of OI that become apparent later in life.

OI affects all genders, races and ethnic groups equally.

OI is caused by defects in or related to a protein called type 1 collagen (pronounced KOL-uh-juhn). Collagen is an essential building block of the body. The body uses type 1 collagen to make bones strong and to build tendons, ligaments, teeth, and the whites of the eyes.

Certain gene changes, or mutations, cause the collagen defects. Mutations in several genes can lead to OI. About 80%–90% of OI cases are caused by autosomal dominant mutations in the type 1 collagen genes, COL1A1 and COL1A2. Mutations in one or the other of these genes cause the body to make either abnormally formed collagen or too little collagen. Mutations in these genes cause OI Types I through IV.

The remaining cases of OI (types VI–XI) are caused by autosomal recessive mutations in any of six genes (SERPINF1, CRTAP, LEPRE1, PPIB, SERPINH1, and FKBP10) that code for proteins that help make collagen. These mutations also cause the body to make too little collagen or abnormally formed collagen.

These gene changes are inherited, or passed down from parents to their children; people who have OI are born with it. However, in some cases, the gene mutation is not inherited and occurs after conception.

All types of OI have some degree of bone fragility and fracturing, and many have some degree of bone deformity.

The symptoms of OI vary by type:

• Type I
  • Most common and mildest form of OI. It can be so mild that health care providers do not diagnose it in some people until they are adults.
  • Bone fractures occur mostly in years before puberty and decrease in frequency after puberty.
  • Normal height; a few inches shorter than same gender relatives
  • Little or no bone deformity
  • Brittle teeth in rare cases
  • Hearing loss in some cases
  • Blue sclera (whites of the eyes)
  • Easy bruising
  • Mild delay in motor skills
• Type II
  • Severe; usually results in stillborn birth or death in the first months of life
  • Severe bone deformity
• Type III
  • Most severe, nonlethal form
  • Hundreds of fractures starting very early in life
  • Severe bone deformities and physical disability that worsen over time
  • Sclera may be blue or grey
  • Triangular face and prominent forehead
  • Scoliosis (abnormal curving of the spine)
  • Sunken or protruding chest wall
  • Brittle teeth
  • Hearing loss
  • Very short height
  • Motor skill delays
  • Usually need wheelchairs
• Type IV
  • Similar to type I but with mild to moderate bone deformity
  • Dozens of fractures on average, most of which occur before puberty or after middle age
  • Motor skill delays
  • People with type IV often need braces or crutches to walk
  • Short height
  • Brittle teeth
  • Hearing loss in some cases
  • White or blue sclera
  • Scoliosis
  • Large head
  • Easy bruising
• Type V
  • Identical symptoms to Type IV except:
    • Normal sclera
    • Normal teeth
    • Severely limited ability to twist forearms clockwise or counterclockwise
  • Distinguished from Type IV by differing bone features at microscopic level
• Type VI
  • Identical symptoms to Type IV except:
    • Normal teeth
    • Greater frequency of fractures
  • Distinguished from Type IV by differing bone features at microscopic level
• Type VII and VIII
  • Similar to Types II and III
  • Severe or lethal bone deformity
  • Type VII can also involve small head, blue sclera, bulging eyes
  • Some people with Type VIII have lived into their second or third decade
• Type IX
  • Moderate to severe bone deformity and similar to Types III and IV
  • White sclera
  • Short height
• Type X
  • Severe and often leads to death.
• Type XI
  • Bone deformities worsen over time

The bone deformities and collagen defects common to OI can affect various internal organs, leading to secondary problems. These include:

Lung Problems

People with OI are more vulnerable to lung problems, including asthma and pneumonia. Viral and bacterial infections can become severe. In fact, respiratory failure is the most common cause of death in people with OI.

Lung problems result from a combination of factors. If the ribs and spine do not develop normally, there may be less space for the lungs to expand. Collagen also is an important building block of connective tissue in the lungs. If the body does not make enough collagen, or makes abnormal collagen, the lungs do not work properly. This makes it difficult for people with OI to get enough oxygen through their bodies. In addition, they may have problems coughing effectively to clear away mucus.

Heart Problems

Heart problems, such as incorrectly working valves and arteries, sometimes occur in people with OI.

Neurological Problems

People with OI often have enlarged heads, called macrocephaly (pronounced mak-roh-SEF-uh-lee). They can also have a condition called hydrocephalus (pronounced hahy-druh-SEF-uh-luhs), in which fluid builds up inside the skull, causing the brain to swell.

People with severe OI often have basilar (BAS-uh-ler) invagination (pronounced in-vaj-uh-NEY-shuhn), a malformation of the spinal column that puts pressure on the spinal cord and brain stem. It worsens over time and can cause severe headaches, changes in facial sensation, lack of control over muscle movements, and difficulty swallowing. If untreated, basilar invagination can lead to rapid neurological decline and inability to breathe.

If OI is moderate or severe, health care providers usually diagnose it during prenatal ultrasound at 18 to 24 weeks of pregnancy.

If a parent or sibling has OI, a health care provider can test the DNA of the fetus for the presence of an OI mutation. In this case, a health care provider obtains a sample of fetal cells by chorionic villus (pronounced KOHR-ee-on-ik VILL-uhs) sampling (CVS) or amniocentesis (pronounced am-nee-oh-sen-TEE-sis). The fetal cells can also be tested for the presence of abnormal collagen.

For amniocentesis, a health care provider takes a small amount of fluid from the sac surrounding the fetus for testing. He or she takes the sample by inserting a thin needle into the uterus through the abdomen. For CVS, a health care provider uses a similar procedure to take a sample of tissue from the placenta for testing.

If OI is not detected prenatally, parents or a health care provider may notice symptoms in an infant or child. The health care provider may perform the following:

• Physical exam, which includes:
  • Measuring the length of limbs
  • Measuring the head circumference
  • Examining the eyes and teeth
  • Examining the spine and rib cage
• Personal and family medical history, which include questions about:
  • Broken bones
  • Hearing loss
  • Brittle teeth
  • Adult height
  • Racial background
  • Whether close relatives have had children together
• X-ray
• Bone density test
• Bone biopsy, in some cases

Health care providers may send blood or skin samples to a lab for collagen or genetic testing. These tests usually confirm whether a person has OI.

OI treatments are designed to prevent or control symptoms and vary from person to person. Early intervention is important to ensure optimal quality of life and outcomes. Treatment for OI and its related symptoms may include:

• Fracture care
• Physical therapy
• Bracing
• Surgical procedures
• Medication
• Treatments for Related Conditions

Fracture Care

Casting, splinting, and bracing fractured bones can help them heal properly. However, bones may weaken if they are held in one place for long periods. Health care providers try to strike a balance between healing fractures and maintaining bone strength.

Physical Therapy

Physical therapy aims to maintain functioning in as many aspects of life as possible. A usual program combines muscle strengthening with aerobic conditioning. Many children with OI have delayed motor skills because their muscles are weak. A physical rehabilitation program can include strengthening of deltoids, biceps, and important lower muscles, such as the gluteus maximus, gluteus medius, and trunk extensors. When these muscles are strong, children can lift their arms and legs against the pull of gravity and get around independently.

Bracing

For some people with OI, wearing braces on the legs can provide support for weak muscles, decrease pain, and keep joints properly aligned. Braces can allow people to get around and function more easily.

Surgical Procedures

Some people with OI undergo surgery to correct bone deformities, including scoliosis and basilar invagination. A common surgical procedure for OI patients, “rodding,” is the placement of metal rods in the long bones of the legs. This strengthens them and helps prevent fractures. Some rods get longer as the legs grow. But they also can work their way out of the bone. Surgery can also be performed to improve hearing loss.

Medication

Bisphosphonates (pronounced bis-FOS-foh-neyts) are drugs used to treat osteoporosis. They also are useful for OI, especially in children. These drugs do not build new bone, but they slow the loss of existing bone. They have been shown to reduce vertebral compressions and some long bone fractures. However, controlled trials show no improvement in motor skill or decrease in bone pain.

Treatments for Related Conditions

Although these treatments are not specifically for OI, individuals with OI might rely on the following to address conditions related to OI:

• Hearing aids for hearing loss
• Crowns and similar dental devices for brittle teeth
• Oxygen administration for people with lung problems

People with osteogenesis imperfecta (OI) usually require the services of a health care team that includes several specialists, along with a primary care physician. The orthopaedist (a doctor who specializes in bone and joint disorders) treats fractures and recommends surgical interventions such as rodding surgery. The orthopaedist plays an important role in the lives of children and adults who have OI. Some orthopaedists are members of a team of specialists at an OI clinic that may also include a geneticist, an endocrinologist, a nephrologist, a neurologist, a physical therapist, an occupational therapist, and a nutritionist. In some private offices and OI clinics, a nurse or nurse practitioner is available to answer questions about cast care and orthopaedic surgery.

General principles for good communication

• Keep detailed medical records. Include lists of fractures, how they occurred, and how they were treated as well as information on all surgeries.
• Keep a brief summary of key points in the medical history. Include surgeries, complications, allergies, and a list of any rods, pins, or other implanted devices. Include both your OI and non-OI health information in your medical history.
• Find a surgeon who is knowledgeable about OI and has experience doing procedures for OI patients, or who is willing to consult with surgeons who have OI experience before doing a procedure.
• Find and meet with a new orthopaedist before having a fracture or other emergency to establish a relationship and ask some general questions.
• Find a doctor who treats you with respect, listens to you, and is interested in the information on OI that you provide.
• Plan ahead for emergencies. Learn how to contact the doctor, where to go for x-rays, what to do on a weekend or holiday, and which hospital to go to. If the doctor is part of a group, find out if other members are experienced in OI as well.
• When you answer your doctor’s questions, do not exaggerate, deny, or deliberately omit information.
• Be an attentive listener. Whenever possible, bring a trusted person to your appointments.

Prepare for the appointment

• Make a list of symptoms and the events leading up to the injury.
• Be specific about the date, time, and location of the injury and the type of pain.
• Prepare a list of questions. Be ready to ask the most important question first.
• Bring paper and pencil to write down the doctor’s answers.
• When possible, bring copies of previous x-rays that show the baseline status of the bone(s) in question.
• Bring a list of all drugs, vitamins, minerals, other nutritional supplements, over-the-counter medicines, and alternative treatments you are taking. Include information about dose, reason for taking, and how long you have been on the medication.

The following list of questions is not a script. It is a list of ideas to help you have a productive conversation with your doctor. Review this list before your appointment, and select the questions that are important to you. Be sure to listen carefully during your appointment. Your doctor may answer many of these questions before you ask them.

General questions:

• What should I do if I suspect a fracture during office hours? What about on a weekend or holiday?
• What does it mean if no fracture shows up on the x-ray? Is the resolution high enough to show microfractures?
• Do any of my medications interfere with fracture healing?
• Will any of the medicines I am taking interfere with fracture healing?
• What are my treatment options?

When tests, medications, or other treatments are prescribed:

• What is the exact name of the test, drug, or treatment?
• Will my size influence the drug dose you prescribe?
• What are the costs, risks, and benefits?
• Are there any alternatives?
• What will happen to me if I don’t have the treatment?
• Will this treatment affect my bone mineral density?

When surgery is recommended:

• What are the success rates for this surgery?
• What complications are possible? How often do they happen?
• How many times have you performed this operation?
• Am I a good candidate for surgery?
• Should I stop taking any of my medications before surgery? How long before?
• Is the procedure done on an inpatient or outpatient basis?
• Exactly what will occur during the surgery?
• How long will the operation take?
• Is the anesthesiologist familiar with OI?
• How long will I have to stay in the hospital after the operation?
• Will the nursing staff know how to treat me? Have they ever cared for a person with OI before?
• What kind of special nursing care will I need at home?
• What will I need to take care of myself at home?
• How long will I be out of work or out of school?
• Will I need a wheelchair or other equipment while I recover?
• Will follow-up care with a physical or occupational therapist be needed?

When rodding surgery is recommended:

• What types of rods are available?
• Which rod do you recommend, and why?
• What complications are possible?
• If I have been taking bisphosphonates, how long before and after surgery should I discontinue them?

When spine surgery is recommended:

• What can I do to prepare for this operation?
• Will this affect growth (if the patient is a growing child)?
• How will a fused spine affect my activities of daily living?
• Will this require a bone graft?
• Is there a chance my bone is too soft to use instruments? What will be done then?
• How much of the curve in my spine will the surgery be able to correct?
• Will I continue to be at risk for new compression fractures of the spine after the surgery?
• What risks are involved with this surgery? Is there a risk of paralysis?
• How long will the surgery take?
• How long will I be hospitalized after the surgery?
• How long will I need bed rest after the surgery?
• Will I need to wear a brace after surgery? For how long?
• When will I be able to return to sitting up? To walking?
• When will physical therapy start?
• Is there a risk that the rods or other instruments might break?
• How long will it take for the fusion to heal fully?
• Will I need to avoid bending, twisting, or exercising immediately after surgery? If so, for how long?
• Will I need modifications to any equipment, such as my wheelchair or bed?

When a cast, splint, or bandage is applied:

• Can this get wet? Can I swim with it on?
• Will my knee, ankle, elbow, or another joint be immobilized?
• How long will the cast, splint, or Ace bandage stay on?
• What do I need to look out for while I am in the cast (e.g., changes in skin color, odors, skin sores, temperature of fingers or toes)?
• What will I need to take care of myself at home? Do I need to rent any equipment?
• How much activity can I do? When can I resume weight-bearing activity?

Other situations:

• What options are available to treat a nonunion fracture (a broken bone that has failed to heal)?
• Will the type of orthopaedic rods, pins, or other implants in my body exclude me from having an MRI?

Pain management:

• Which type of medication will I need? What are their complications or side effects?
• Will any pain medications interfere with healing?

Physical therapy and exercise:

• When can I resume weight-bearing and start my normal activities?
• What type of physical therapy do I need to do to regain strength and function? How many times a week, how long a session, and how many sessions in total are needed?
• Do you keep in contact with the physical therapist?
• Does the therapist have experience working with a person with OI?
• If my insurance company won’t cover physical therapy in a medical setting, can I go to a gym?
• What precautions should I take to prevent a second fracture?

Closing:

• How can I reach you if I have questions later?
• When should I return for my next appointment?

Introduction

Constipation is a problem for some people with osteogenesis imperfecta (OI). Constipation, in medical terms, is a decrease in frequency of stools or bowel movements with hardening of the stool. As a consequence, people with constipation may feel bloated and have gas but find it difficult to pass stools. Because the stool becomes quite hard, passing it may be uncomfortable and lead to further unwillingness to try, especially in infants and young children. Fecal impaction, or clogging of the bowel with hardened stool, can be a serious complication. Treatment of constipation in people with OI is often challenging.

• Causes of constipation
• Managing constipation
• Diet and fluids
• Exercise and activity
• Home remedies
• Medications
• For your information

Causes of constipation

Constipation can be caused by inadequate dietary fiber, lack of exercise, and dehydration. Colon obstruction and illness are additional causes. Some medications, especially painkillers, can cause constipation because they decrease the normal motion and movement of the bowel. Adults with OI and parents of children with OI are encouraged to check with their doctor or pharmacist about side effects and possible drug interactions from their medicines and dietary supplements.

OI may contribute to constipation, especially in people with the short stature and pelvic malformation. The colon and bowel may be prevented from functioning normally if the hips and pelvis are narrow or malformed. A specific pelvic malformation, known as acetabular protrusion, can affect some people with OI Type III and cause a predisposition to constipation. Diminished mobility and low levels of physical activity also contribute to constipation.

Managing constipation

Managing constipation usually involves a combination of approaches. It is essential to determine the extent of the problem and develop a plan to correct it. Doctors advise:

• Keep a record of bowel movements, diet, and fluid intake. Even when a child appears to be "regular," keeping records about diet, illnesses, exercise, and bowel movements will help caregivers figure out if something in particular triggers the problem.
• Be consistent about diet, exercise and activity, and fluid intake.

Children and adults with OI who become constipated often respond well to diet changes, a change in activity level, and mild home remedies. The primary care doctor should be consulted about the appropriateness of home remedies. A nutritionist or registered dietitian may offer useful suggestions for modifying the diet. If the problem persists, a gastroenterologist may be needed.

Treatment choices for constipation include:

• Diet and fluids.
• Exercise and activity.
• Certain home remedies.
• Medications.

Diet and fluids

These changes to the diet can help people with constipation:

• Gradually add fiber to the diet, including whole grain breads, whole grain cereals, bran cereals or muffins, and popcorn.
• Increase the amount of fruits, fruit juice, and vegetables.
• Reduce the amount of processed foods and refined sugars.
• Avoid "junk" foods that are high in fat and low in fiber.
• Include foods, such as yogurt with active cultures, which contain the bacteria Lactobacillus acidophilus.
• Drink water throughout the day.

Strive for a diet that keeps the stool soft. Too much fiber has the secondary effect of creating too much bulk for someone with a connective tissue disorder. This can put pressure on the rectum. This pressure, along with inactivity, too much prolonged sitting, the lax or elastic muscles that a person with OI tends to have in the pelvic floor, and chronic constipation can lead to a more serious problem called rectal prolapse.

Exercise and activity

Adding exercise and physical activity can help prevent and relieve constipation. Exercise helps move digested food through the intestines. Infants, children, and adults who sit, recline, or use a wheelchair require regular position changes. People should consult with their primary care doctor and physical therapist about beneficial exercises that suit their particular needs and abilities. For example, infants benefit from water play that encourages them to kick. Children and adults can benefit from swimming, walking, or bicycling.

Home remedies

Home remedies may include:

• Allowing enough time on the toilet. Some doctors suggest 10 to 15 minutes at least twice a day.
• Enemas, but only when recommended by a doctor.

Medications

For some children, regular medication or even a prescription laxative may be necessary. Use of medication, whether prescription or over-the-counter, must be discussed with your doctor.

Children on medication need to be carefully monitored. Taking a medication too often can reduce its effectiveness or aggravate negative side effects.

Medications for constipation can include:

• Suppositories.
• Mineral oil.
• Stool softeners.
• Laxatives, such as Senokot.
• Prescription laxatives, such as MiraLAX.

Talk with the doctor about all treatment options, including home remedies. Persistent, painful constipation should not be ignored, and a referral to a gastroenterologist may be required.

Staying well hydrated, eating a healthy diet, and increasing exercise can reduce the frequency of constipation in children and adults who have OI.

OI does not affect fertility. However, about one-half of women with OI give birth by cesarean section. This is because they often have pelvic bone abnormalities that prevent vaginal birth. Women with OI also are more likely to have infants who present in the breech position (feet first).

Women who have OI, have partners with OI, or have already had a child with OI should consider genetic counseling. A genetic counselor is a health care professional who understands the risks of having an infant with OI and can explain prenatal tests that can identify this disorder so that the family can provide care.

What is osteogenesis imperfecta?

Osteogenesis imperfecta (OI) is a genetic disorder characterized by bones that break easily, often from little or no apparent trauma. OI is highly variable, and signs and symptoms range from mild to severe. In addition to broken bones, people with OI sometimes have muscle weakness or joint laxity (loose joints), and they often have skeletal malformations including short stature, scoliosis (curvature of the spine), and bowing of long bones. A classification system featuring different types of OI is commonly used to help describe how severely a person with OI is affected. OI occurs with equal frequency in males and females and among all ethnic and racial groups.

OI is caused by genetic defects that affect the body’s production of type I 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 dominant (classical) OI, a person has too little type I collagen or a poor quality of type I collagen due to a mutation in one of the type I collagen genes. In recessive OI, mutations in other genes interfere with collagen production. The result in all cases is weak bones that break easily.

What is osteoporosis?

Osteoporosis is a condition in which the bones become less dense and more likely to break. Fractures (broken bones) from osteoporosis can result in significant pain and disability. In the United States, more than 53 million people either already have osteoporosis or are at high risk due to low bone mass.

Risk factors for developing osteoporosis include:

• Thinness or small frame.
• Family history of the disease.
• Being postmenopausal and particularly having had early menopause.
• Abnormal absence of menstrual periods (amenorrhea).
• Prolonged use of certain medications, such as those used to treat lupus, asthma, thyroid deficiencies, and seizures.
• Low calcium intake.
• Lack of physical activity.
• Smoking.
• Excessive alcohol intake.

Osteoporosis is a silent disease until a fracture occurs. Osteoporosis can often be prevented. However, if undetected, it can worsen over many years without symptoms. It has been called “a childhood disease with old age consequences,” because building healthy bones in a person's youth is important to help prevent osteoporosis and broken bones later in life.

The link between OI and osteoporosis

The term osteoporosis describes bone loss that is extensive enough to increase the risk of fracture. The term is a general one, not related to any specific cause for the bone loss. In fact, there are many causes of osteoporosis. Nearly all people with OI have osteoporosis, because they do not develop appropriate bone mass at any age. Women and men with OI can experience additional bone loss, such as age-related bone loss, superimposed on a background of OI. Symptoms of additional bone loss may appear at a younger age than commonly seen in people who do not have OI. When women and men with OI reach middle-age, their risk of breaking bones more easily increases even further. Factors such as a diet low in calcium and vitamin D, smoking, decreased activity, and decreased levels of protective sex hormones (e.g., testosterone, estrogen) can compromise bone density and lead to a return to the fracture cycles they experienced as children.

Osteoporosis management strategies

Strategies for prevention and treatment of osteoporosis in people with osteogenesis imperfecta are generally the same as those for people who do not have OI.

Nutrition. For healthy bones, it is important to have a diet with levels of calcium and vitamin D that are appropriate for the person’s size. Good sources of calcium include reduced-fat dairy products and calcium-fortified foods and beverages. When a person has a significant calcium deficiency, supplements can help ensure that the daily calcium requirement is met, assuming that urine calcium levels are not elevated.

Vitamin D plays an important role in calcium absorption and bone health. It is made in the skin through exposure to sunlight. Vitamin D supplements may be needed if foods fortified with vitamin D are not part of the diet.

Exercise. Like muscle, bone is living tissue that responds to exercise by becoming stronger. Weight-bearing and resistance exercises are best for preventing bone loss. Weight-bearing exercises force you to work against gravity. They include walking, standing, and dancing. Resistance exercises – such as lifting weights – can also strengthen bones. Swimming can also be a beneficial form of exercise. Because water activities do little to increase or maintain bone density, however, people with OI also should try to add walking or other weight-bearing exercise to their physical activity program, if possible.

Exercise can be challenging for people with OI, who must cope with muscle weakness, bone fragility and malformations, joint instability, and pain. However, regular exercise in moderation, such as walking, can help prevent bone loss and provide other health benefits. All adults, including those who spend most of their time in wheelchairs, need to consult with their doctor and a physical therapist about developing an appropriate exercise program.

Healthy lifestyle. Smoking has a negative effect on all body systems, including bones. Excess alcohol consumption also can have negative effects on bone health and predispose a person to falls and fractures.

Bone density test. Bone mineral density (BMD) tests measure bone density in various sites of the body. BMD measurements are often reported in terms of peak bone mass in young adults. However, people with OI, because of short stature, curvature of the spine, past vertebral fractures, or the presence of metal rodding, may not be able to get an accurate reading. Nearly all adults who have OI have low BMD.

Medication. There is no cure for osteoporosis. However, medications are available to prevent bone loss, increase bone mass, and treat the disease. Women and men who have OI seem to be using these medications successfully. Consult with your doctor to determine which medication is right for you. Many of these medications require long-term use.