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| Brittle bone disease (osteogenesis imperfecta) |
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Written by Dr Colin R Paterson, consultant physician
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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 called collagen; which 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 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 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.
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The joints may be lax.
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The whites of the eyes may be blue or grey.
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The teeth may be discoloured and fragile.
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There may be an increased liability to bruising (thought to be
due to the defective collagen in small blood vessels).
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Deafness may occur (see below).
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Hernias are more common in people with OI.
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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 people, mostly those with milder OI, the disorder passes
from one generation to another. In some of these people, and in most with
severe OI, it arises without any family history. In most, but not all, of these
the cause is a 'new genetic mutation' - in other words the
responsible change in the person's genes arises anew, and not because it
has 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 only 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 people with 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 OI. They
frequently give normal results in bones that have not previously been
fractured.
In the USA 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 the collagen of bone. 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.
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.
Help in the form of competent occupational therapy 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 for OI 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.
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 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 OI 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
5 per cent - a loss which people with OI 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 (Evista), or the
bisphosphonates, such as
etidronate (Didronel)
and
risedronate (Actonel).
What about older men?
Men do not appear to have a 'menopause' and older men
with OI do not have a rise in the 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 and, of those who have no hearing loss at the age of
50, relatively 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 are 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 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 (ear, nose and throat) surgeon, preferably someone with a special
interest in OI.
What is temporary brittle bone disease?
A special type of OI has become recognised in the last 20
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 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 and in
Canada, South Africa, Australia and New Zealand.
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Last updated 04.10.2005
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