Brittle bone disease - osteogenesis imperfecta
|What is osteogenesis imperfecta?|
|How common are fractures?|
|What other clinical problems can occur?|
|Is OI inherited?|
|How is OI diagnosed?|
|What treatment can be given?|
|What about older women with OI?|
|What about older men?|
|How common is hearing loss in OI?|
|What is temporary brittle bone disease?|
|Where can I obtain fuller information about OI?|
What is osteogenesis imperfecta?
Osteogenesis imperfecta (OI) is the most common 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 known as 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 part of bone which is what shows 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 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 fail to occur when expected from an injury. The reason for these variations is quite 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 gray, the teeth may be discoloured and fragile and 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 than in people without OI. Excessive sweating or intolerance of heat are common complaints; the cause of this is not known.
Is OI inherited?
OI in an individual is present from the time of conception. In some cases, mostly the milder ones, the disorder passes from one generation to another. In some mild cases and most severe cases, it arises without any family history. In most, but not all, of these the cause is a new genetic mutation. It is important to obtain advice from a 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 cases the diagnosis is made from the pattern of fractures and the finding of any of the associated clinical features such as blue or gray 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 severe cases x-rays may show characteristic abnormalities the result of previous fractures. In many mild or moderate cases 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 the cases of mild OI a useful sign is seen in 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 difficult cases of OI. They frequently give normal results in bones that have not previously been fractured.
In the USA two specialised tests may be used for the diagnosis of OI. One involves taking a small piece of skin, culturing the cells and examining the collagen produced chemically. The other uses a blood sample and searches for mutations of the genes coding for the collagen of bone. Both tests are labour-intensive and neither test is more than 85% 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. 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 very helpful, particularly in children with very frequent fractures or appreciable deformity.
Competent occupational therapy help may be invaluable in ensuring that parents are given good advice in 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.
There is no drug treatment of osteogenesis imperfecta itself. Trials of growth hormone have been disappointing. Trials of various bisphosphonate drugs are in progress and have given encouraging results in some patients with the more severe types of OI. The management of older women with OI is discussed next.
What about older women with OI?
We know that after the menopause women with osteogenesis imperfecta lose bone like anybody else. This bone loss can be prevented with HRT. Because people with osteogenesis imperfecta 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 is also helpful in preventing blood vessel problems such as heart attacks. On the negative side, there is a very small increase in the likelihood of breast cancer. Another disadvantage is the fact that with some preparations regular monthly bleeds continue. However, for most people, this can be avoided by modern forms of HRT (continuous combined HRT). For most people with osteogenesis imperfecta the advantages of HRT greatly outweigh the disadvantages; without it the likelihood of fractures increases quite quickly after the menopause.
Stopping smoking is vital; smoking diminishes the bone by up to five per cent - a loss which people with osteogenesis imperfecta can ill afford. Apart from this there is evidence that smoking diminishes the effectiveness of HRT. Some women cannot or should not take HRT. For some, other drugs may have a place depending on a detailed specialist review. These include the selective oestrogen receptor modulators, such as raloxifene, or the bisphosphonates, such as etidronate and risedronate.
What about older men?
Men do not appear to have a menopause and older men with osteogenesis imperfecta do not have a rise in the fracture rate in later life.
How common is hearing loss in OI?
About fifty per cent of people with osteogenesis imperfecta find that they have impaired hearing with an onset mainly in the teenage years or early adult life. Not everyone is affected and, of those who have no hearing loss at the age of fifty, relatively few become deaf thereafter. Hearing loss in osteogenesis imperfecta 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 are a smaller number of people with osteogenesis imperfecta whose hearing loss is caused by problems in the inner ear and some with mixed causes. It is important to investigate hearing loss properly to find out exactly what the cause is, 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 whether or not surgery is appropriate needs discussion with an expert ENT surgeon, preferably someone with a special interest in osteogenesis imperfecta.
What is temporary brittle bone disease?
A special type of OI has become recognised in the last twenty years. In this fractures, and often many 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 has a website (www.brittlebone.org) and can be contacted by mail, e-mail or telephone (a freephone helpline is available at
08000 282459). In the United States the corresponding society is the
Osteogenesis Imperfecta Foundation (www.oif.org).
Both societies issue fact-sheets 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 and in Canada, South Africa, Australia and
Ó NHS Tayside; 2006; version 1.0
Disclaimer; no liability whatsoever is accepted for information given and all such information, especially with regard to drug usage (UK version provided), must be checked with a persons health provider.