Brittle bone disease (osteogenesis imperfecta)

What is brittle bone disease (osteogenesis imperfecta) and how common are fractures?

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What is osteogenesis imperfecta?

Osteogenesis imperfecta (OI) is an inborn disease causing fractures in childhood. It also causes fractures in adults.

OI is a genetic disorder usually resulting from abnormalities of the genes that control the production of a protein called collagen. This is the main protein in bone and essential for its strength.

The fragility of bone in OI is due to the collagen problems. It has nothing to do with the calcium component of bone, which is what shows up on X-rays.

How common are fractures?

Some OI children are born with fractures that have taken place in the womb. Others have their first fractures soon after birth or several years later. Some people with OI have so few fractures in childhood that the correct diagnosis is not made.

Fractures are difficult to predict, especially in childhood. Some occur with normal handling. Some occur spontaneously or with so little trauma that the usual signs of a fracture may not be seen and the fracture is not identified till some weeks or months later, when an X-ray is done for another reason.

The bones do not always behave in a brittle way: fractures may not occur when they might be expected from an injury. The reason for these variations is unknown.

In both sexes and in almost all types of OI the fracture rate diminishes during the teenage years and remains low in adult life. The reason for this is not known.

What other clinical problems can occur?

Besides fractures, there may be problems in other parts of the body. Most of these are, like the fractures, the result of the defects of collagen.

  • The joints may be lax.
  • The whites of the eyes may be blue or grey.
  • The teeth may be discoloured and fragile.
  • There may be an increased liability to bruising (thought to be due to the defective collagen in small blood vessels).
  • Deafness may occur (see below).
  • Hernias are more common in people with OI.
  • Excessive sweating or intolerance of heat are common complaints. The cause of this is not known.
  • Growth may be impaired.

    Is OI inherited?

    OI in an individual is present from the time of conception.

    In some people, mostly those with milder OI, the disorder passes from one generation to another. In others, including most of the patients with severe OI, it arises without any family history. In many of these the cause is a 'new mutation' – in other words the abnormality in the genes arises anew, and has not been passed on from a parent.

    It is important to obtain advice from a specialist in gene problems (clinical geneticist), who may be able to identify the pattern of inheritance and advise on the risk to further children or the risk of passing on the condition.

    How is OI diagnosed?

    In most people the diagnosis is made from the pattern of fractures and the finding of any of the associated clinical features, such as blue or grey whites of the eyes. However, it is important to recognise that none of these signs may be present and that the diagnosis may be very difficult.

    In severely affected people, X-rays may show characteristic abnormalities – the result of previous fractures. In many people with mild or moderate OI, the X-rays may appear normal at the time of the first few fractures.

    Later, in bones that have been the site of previous fractures, the bones may appear demineralised (less white on X-ray), and reduced radiation may be needed to obtain satisfactory films for the diagnosis of fractures.

    In about half of children with mild OI, a useful sign is seen in X-rays of the back of the skull where there may be additional small bones in the sutures known as wormian bones.

    Bone density measurements are usually unhelpful for the diagnosis of OI. They often give normal results in bones that have not previously been fractured.

    Two specialised tests are sometimes used for the diagnosis of OI. One involves taking a small piece of skin, culturing the cells and chemically examining the collagen produced. The other uses a blood sample and searches for mutations of the genes coding for collagen. Both tests are labour-intensive, and neither test is more than 85 per cent accurate in identifying cases of OI.

    What treatment can be given?

    The mainstay of treatment is competent orthopaedic care at the time of fractures, to ensure that each fracture heals in a good position.

    After a fracture, patients should be mobilised as early as possible to minimise the loss of bone due to immobilisation.

    In some circumstances 'rodding' operations, in which fixed or telescopic metal rods are inserted into the shafts of bones, are helpful – particularly in children with frequent fractures or appreciable deformity.

    Help in the form of competent occupational therapy may be invaluable in ensuring that parents are given good advice on the handling of a young child, in prescribing the most appropriate seating or wheelchairs, in advising on adaptations to the home and on practical ways of ensuring a good education.

    Exercise within the limits imposed by the need to reduce the danger of fractures is valuable in strengthening the bones; swimming is particularly helpful.

    There is no drug treatment for OI itself. Various bisphosphonate drugs have given encouraging results in some children with the more severe types of OI. There's no reliable evidence of their value in the milder types of OI or in adults.

    It is important not to smoke. Smoking diminishes the bone by up to 5 per cent – a loss that people with OI can ill afford.

    What about older women with OI?

    We know that after the menopause, women with OI lose bone like anybody else. This bone loss can be prevented with hormone replacement therapy (HRT).

    Because people with OI already have bones that are prone to fractures, women with OI should consider taking HRT from approximately the time of the menopause.

    Like any drug treatment, HRT has advantages and disadvantages. On the positive side, HRT preserves the bones and relieves menopausal symptoms. On the negative side, there is a small increase in the likelihood of breast cancer. This risk is reduced by the use of low dose preparations.

    For most people with OI the advantages of HRT outweigh the disadvantages – without it the likelihood of fractures increases quite quickly after the menopause.

    Some women cannot or should not take HRT. Other drugs may have a place depending on a detailed specialist review.

    What about older men?

    Men do not appear to have a 'menopause', and older men with OI do not usually have a rise in fracture rate in later life.

    How common is hearing loss in OI?

    About 50 per cent of people with OI find that they have impaired hearing with an onset mainly in the teenage years or early adult life.

    Not everyone is affected. Of those who have no hearing loss at the age of 50, few become deaf thereafter.

    Hearing loss in OI is most commonly due to problems in the small bones in the middle ear, which may be fractured or deformed so that sounds are not transmitted effectively to the inner ear.

    There is a smaller number of people with OI whose hearing loss is caused by problems in the inner ear and some with mixed causes. It is important to investigate hearing loss to find out the exact cause, because this influences treatment.

    For most people with both types of hearing loss, hearing aids are the first line of treatment at any age.

    The hearing loss that is caused by problems in the middle ear may, if severe or progressive, be helped by surgery. The decision about surgery needs discussion with an expert ENT (ear, nose and throat) surgeon.

    What is temporary brittle bone disease?

    A special type of OI has been recognised in the last 25 years. In this, fractures occur in the first year of life and largely in the first six months.

    The identification of this disorder is still controversial, in part because the cause is not yet known.

    The disorder is more common in infants born before term and in twins. In some cases there are minor features of collagen abnormality in parents or other relatives.

    Where can I obtain fuller information about OI?

    In the UK, the Brittle Bone Society can be contacted by mail, e-mail or telephone. In the United States the corresponding society is the Osteogenesis Imperfecta Foundation.

    Both societies issue factsheets on different aspects of OI and may be able to give advice on appropriate specialists, welfare provision and education.

    There are similar societies in many European countries, in Canada, in Australia and in some Latin American countries.

    Last updated

    Formerly reader in medicine at the University of Dundee
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