Type I Osteogenesis Imperfecta

Osteogenesis imperfecta (OI) is a genetic disorder of collagen that causes brittle bones and other symptoms. OI is classified into types, numbered with Roman numerals. Type I osteogenesis imperfecta is the mildest form of OI. It is also the most common form of OI. Historically, Type I OI has also been referred to as "OI Tarda."

What is Type I OI?

Nearly all cases of OI, mild or severe, are caused by a dominant genetic mutation that affects the body's production of type 1 collagen. Type 1 collagen is the main protein building block in bone, and is important in other connective tissues. When there is a problem with the body's production of type 1 collagen, the bones are brittle and break more easily than normal.

Type I OI is different from all other types of OI in an important way. A person with Type I OI has approximately half the normal amount of type 1 collagen in his or her body. The collagen that is present, however, is normal in structure. A person with Type II, Type III, or Type IV OI (the moderate to severe types of OI) has not only a reduced amount of type 1 collagen, but also collagen that is abnormal in structure. In other words, Type I OI is caused by deficient type 1 collagen. The other types of OI are caused by low levels of defective type 1 collagen.

Signs and Symptoms of Type I OI

OI affects people in several different ways. Even among people with Type I OI, there is variability. The following is a list of signs and symptoms common among people with Type I OI. Many people with Type I OI have only some--not all--of these signs and symptoms:

Ø Bones predisposed to fracture. Most fractures occur before and during puberty.

Ø Somewhat predisposed to other connective tissue injuries, such as dislocations.

Ø Skin bruises easily.

Ø Normal or near-normal stature, as compared with unaffected family members.

Ø Loose joints, low muscle tone, and lax ligaments.

Ø Sclera (whites of the eyes) usually have a distinctly blue, purple, or gray tint.

Ø Somewhat triangular face.

Ø Tendency toward spinal curvature (scoliosis).

Ø Bone deformity absent or minimal.

Ø Brittle teeth possible.

Ø Hearing loss possible, often beginning when the person is a teen or young adult, but which may occur sooner.

Some people with Type I OI are very mildly affected. They may have only a few fractures, be of average or even above-average height, be able to walk and run, and have barely noticeable signs of OI, such as blue sclera or loose joints. In fact, some people are so mildly affected that they are not diagnosed until their teen or adult years, and in some cases only after they have a child diagnosed with Type I OI.

Other people with Type I OI have more distinct signs and symptoms. They may have several dozen or more fractures; sometimes use a wheelchair, walker, braces, or crutches for mobility; be somewhat smaller than the rest of their family; and/or require treatments such as rodding surgery (see below).

In most cases, people with Type I OI experience fewer fractures after puberty, when the bones are no longer growing as quickly. Though it may seem that some people with mild OI "grow out of it" after puberty, the genetic defect still exists, and adults with Type I OI need to be aware of how the disorder may affect them throughout their life, especially women when they go through menopause.

Diagnosis of Type I OI

Babies with Type I OI may or may not be born with fractures. A baby may have other outward signs of OI, such as blue sclera or loose joints, but these signs may go unnoticed in a family with no history or knowledge of OI. Furthermore, blue sclera can occur even in healthy infants until about 18 months of age. A child with Type I OI may sustain his or her first fracture during some ordinary activity, such as when a caregiver pulls on the ankles when changing a diaper, a doctor does a physical exam, or a toddler falls while learning to walk. Other children with OI may not experience fractures until the school years, when they begin participating in physical education, sports, and recreational activities.

The occurrence of fractures after little or no trauma is often the first clue that a child may have OI. To diagnose the disorder, a physician can look for other clinical features of OI, and obtain a family history to determine if other family members have a history of fractures or other OI symptoms. Collagen testing of a skin biopsy and/or DNA testing of a blood sample can help confirm a diagnosis of OI in some situations. However, approximately 10 to 15 percent of individuals with mild OI who have collagen testing, and approximately 5 percent of those who have DNA testing, test negative for OI despite having the disorder.

Families in which one parent has OI may be able to arrange for prenatal testing through chorionic villus sampling or amniocentesis. In most cases of Type I OI, this type of prenatal diagnosis requires knowledge of the affected parent's genetic mutation, which may be hard to determine. Ultrasound may not detect Type I OI in a fetus, because the child is unlikely to have fractures or bone deformity before birth. When prenatal diagnosis is not possible, or not desired, a sample of the child's umbilical cord can be taken at birth and sent for collagen testing. When a parent has OI, it is recommended that the newborn be tested and examined by a knowledgeable clinician as soon as possible. The information will help parents make decisions about their baby's care, and help protect the family from unwarranted child abuse accusations.

Managing and Treating Type I OI in Children

The cornerstones of treatment for a child with Type I OI are fracture management, therapy to regain strength and mobility after fractures, and an ongoing program of safe exercise and activity to develop muscle control and build strength. Recognizing that prolonged immobilization can weaken muscles and bones, many orthopedists prefer short-term casting of fractures, followed as soon as possible by a splint or brace that can be removed for appropriate exercise.

Rodding surgery (in which metal rods are inserted into the long bones) is a standard treatment for children with OI in two situations: 1) to set a particularly bad fracture, or 2) to straighten and strengthen a bone that is bowed (curved) to the extent that it is breaking repeatedly. A rod may also provide strength. Many children with Type I OI have minimal bone deformity, and do not require rodding surgery unless they have a particularly bad fracture. Some children with Type I OI, however, do have problems with repeated fractures and increasing deformity of a long bone, and in such cases rodding surgery may be appropriate.

Some infants with mild OI have delays in gross motor skills, such as pulling to a stand, crawling, or walking. These delays may be due to fractures, low muscle tone, loose joints, and/or a child's fear of movement due to previous fractures. Physical and occupational therapy are recommended as soon as such delays are noticed. Therapists can instruct parents in the best ways to hold, position, and encourage their child to learn new skills. Most infants with OI will qualify for their state's Early Intervention Program, which provides therapy and other services free of charge.

Older children with Type I OI may also benefit from physical and occupational therapy to maximize strength and function. Outside of therapy, regular exercise geared toward the child's interests helps children socialize with peers, as well as develop bone and muscle strength. Water therapy and swimming are particularly good exercises for children with OI, as the gravity-free environment reduces fracture risk. Many children with Type I OI swim, dance, ride regular or adapted bikes, and participate in other recreational and competitive activities. A child's physician and/or therapist can advise the family on safe exercise for a particular child.

The bisphosphonate medications (such as pamidronate and alendronate) show promise for strengthening bone and improving function in children with OI. These medications are currently being studied for OI in clinical trials. Most clinical trials initially accepted only severely affected children, but some trials have since expanded to include some children with Type I OI. Because the long-term effects of these medications on children are still being studied, they are generally given to children for whom frequent fractures are a problem. Parents of children with Type I OI should talk to their child's health care team about whether the medications are appropriate for their child.

Children with Type I OI should be monitored regularly for OI-related problems such as hearing loss and scoliosis (spinal curvature). Regular hearing tests by an audiologist in a soundproof room should begin after a child's first birthday. An orthopedist should examine a child for scoliosis annually, including x-rays if needed, starting around age six.

Managing and Treating Type I OI in Adults

Osteoporosis (low bone density) is an almost universal consequence of having OI. It is therefore vital for teens and adults with OI (both male and female) to build bone density and prevent bone loss through safe exercise, diet, and in some cases, medication. It is recommended that adults with OI have a bone density test to establish a baseline, which will allow their physician to monitor whether their bone density is changing over time.

In addition to its importance for bone density, exercise is also important for maintaining strength, function, and general health. Swimming and water exercise provide excellent, safe exercise for people with OI. Walking (with or without aids), weight training, and non-contact recreational sports can also be appropriate for some people with Type I OI. Adults with OI are encouraged to consult their orthopedist, physical therapist, or other professional knowledgeable about OI to determine the most appropriate fitness program.

Bone density can also be maintained by eating calcium-rich food. Dairy products are the richest source of calcium, but some vegetables, some nuts, tofu, and calcium-fortified products such as orange juice and cereal are also sources. Adults with OI have the same needs for calcium as other adults; excessive consumption of calcium or use of supplements is neither necessary nor recommended, as it can lead to other health problems. Caffeine and alcohol should be consumed in moderation, as excessive intake can lead to bone loss if adequate calcium is not present. Some medications, such as steroids (for example, prednisone) and corticosteroids, also contribute significantly to bone loss, as does smoking.

Many adults with OI take bisphosphonate medications (such as alendronate). These medications are FDA-approved for preventing and treating osteoporosis in adults. Several researchers are conducting clinical trials of bisphosphonates specifically for treating OI in adults.

Many women with Type I OI are concerned about menopause and the possibility of more frequent fractures, as additional osteoporosis can develop. The experience of postmenopausal women with OI varies greatly; some do experience an increase in fractures, while others do not. The strategies mentioned above to maintain bone density and general health will help each woman maximize her chances to stay active and healthy as she ages. Bone density measurements and medicines or hormones to prevent bone loss should be discussed with the physician.

Adults with Type I OI seem to have the same risks as the general population for common health problems such as diabetes, heart disease, and cancer. Maintaining a healthy weight, exercising regularly, eating a nutritious diet, and avoiding risky behaviors such as smoking and excessive alcohol consumption are vital not only for bone health, but also for general health and well-being.

Approximately 50 percent of people with Type I OI experience hearing loss starting in their teens or young adulthood. Regular hearing tests by an audiologist are highly recommended. Hearing loss, depending on what type it is, can frequently be treated with hearing aids, surgery, or a combination.

Social, Emotional, and Family Issues

Many people with OI Type I do not appear disabled, so there is potential for others to misunderstand or underestimate the disorder. Parents may provide information about preventing fractures to teachers, babysitters, or other caregivers, only to have the caregivers dismiss them as being "overprotective." Providing written information--such as materials from the OI Foundation and a letter from the child's doctor briefly explaining the OI diagnosis and the recommended precautions--can help reinforce the information provided by parents.

Likewise, it is important for a child's siblings and peers to receive age-appropriate information about OI. It is common for peers to wonder why their classmate does adapted activities during physical education, or can't participate in contact sports. Some children with mild OI are accused of being "clumsy," "lazy," or "faking it" when they have yet another injury. In most cases, such teasing comes out of ignorance, not malice. Many children with OI or their parents give a brief presentation to the class at the beginning of each school year to explain OI. Visual aids and props (such as the child's braces, or a cast or splint) are particularly well-received by young children.

Some families with mildly affected children have been accused of child abuse when their child goes to the emergency room with unexplained fractures. Once an OI diagnosis is made, families should ask for a letter on medical letterhead confirming the diagnosis, and explaining what it means. Copies of the letter should be kept in the diaper bag, the car, with the child's medical and school records, and anywhere else it might be useful, particularly when the family is traveling or visiting the emergency room.

Adults with Type I OI will typically know about their diagnosis when deciding whether to have children. There is a 50 percent chance that a person with Type I OI will pass the disorder on to a child. The risk remains the same for each child. A child will usually inherit the same type of OI as his or her parent; however, it is possible that the child's signs and symptoms will be somewhat milder or more severe than the parent's. Adults with Type I OI who are considering having children may wish to consult a genetic counselor, and have a skin biopsy to confirm their own OI diagnosis, before conceiving a child. Having this information on file makes it easier to test a newborn for OI, if the parents desire. Type I OI does not appear to affect fertility or predispose women to particular pregnancy complications. Research suggests that pregnancy and breastfeeding may affect a woman's bone density, and may increase the risk of fracture. It is therefore particularly important that women with OI eat a calcium-rich diet and exercise appropriately while pregnant and breastfeeding.

For More Information

The OI Foundation publishes numerous resources providing more information on topics mentioned in this fact sheet, including diagnosis, treatment, social/emotional concerns, pregnancy, nutrition, scoliosis, hearing loss, osteoporosis, and helping children explain OI to their peers.

This information is brought to you by the
NIH Osteoporosis and Related Bone Diseases~National Resource Center (ORBD~NRC)
and the Osteogenesis Imperfecta Foundation

National Institutes of Health
Osteoporosis and Related Bone Diseases
National Resource Center
1232 22nd St., NW
Washington, DC 20037-1292
Tel: 800/624-BONE or 202/223-0344
Fax: 202/293-2356, TYY: 202/466-4315
http://www.osteo.org
E-mail: orbdnrc@nof.org

The 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 Environmental Health Sciences, NIH Office of Research on Women's Health, Office of Women's Health, PHS, and the National Institute on Aging. The Resource Center is operated by the National Osteoporosis Foundation, in collaboration with the Paget Foundation and the Osteogenesis Imperfecta Foundation.