Article - EDS and Osteoporosis

February 26, 2004

I have a more current article then this for anyone who wants it....but this

is still useful. If you want the more current one, shout!

EHLERS-DANLOS SYNDROME AND OSTEOPOROSIS

Dr. Atul A Deodhar. MD. MRCP

Division of Arthritis and Rheumatic Diseases (L329A)

The Oregon Health Sciences University

Ehlers-Danlos syndrome (EDS) is an inherited disorder of connective tissue

that shows extreme variations in its clinical presentations. The most common

symptoms are loose skin and hypermobility of the joints. The serious

manifestation of dilatation of the blood vessels is fortunately rare. Bone

is an important member of the connective tissue group, but very little is

known about bone involvement in EDS. Osteoporosis is the most common disease

that affects bones. This article argues that people with EDS are likely to

be genetically susceptible to osteoporosis and hence need to learn more

about this very important health issue. It also suggests preventive

strategies by modifying the important environmental factors that are known

to accelerate bone loss and development of osteoporosis.

Osteoporosis can be defined as a reduction in bone mass that leads to

increased risk of fractures. It is an enormous public health problem for

most societies in terms of disability, pain and socioeconomic costs. With

the aging of these communities these costs can only increase. We have only

recently become aware of the magnitude of the problem. In the United States

for a white woman above the age of 50, the lifetime risk of any hip,

vertebral or distal forearm fracture is 40 percent and for a man it is13

percent. In England and Wales, approximately 50,000 hip fractures occur

every year. As a result, half of these patients cannot walk independently

and 30 percent of them become totally dependent. A fifth of 70 year old

women have a vertebral fracture causing considerable disability, pain and

loss of quality of life. The problem of forearm fractures is underestimated

even though it results in prolonged pain and impaired function. The overall

hospital cost of osteoporotic fractures to the National Health Service in UK

is estimated to be £615 million per year and is rising.

Bone is a living tissue, continually remodeling and renewing itself

throughout life, to respond to physical stresses. Bone grows from birth

through puberty to reach its maximum around the age of thirty-five. This

phase in life when we have the best possible bone strength is termed the

peak bone mass. Bone mass then begins to decline due to the imbalance of

formation and resorption. This loss is particularly rapid in women in the

first 10 years after menopause because of the lack of female sex hormone,

estrogen. Osteoporosis therefore is the end result of an inadequate

attainment of peak bone mass, or a subsequent rapid loss, or a combination

of both. Evidence suggests that there is a strong genetic influence on peak

bone mass. The level of peak bone mass is also modified by environmental

factors like hormones, nutrition and exercise.

The environmental influences on bone are well known. For instance, a life

long high intake of calcium is associated with greater bone mass; there is a

positive effect of physical activity on bone observed in athletic

individuals and there is a loss of bone mass following prolonged immobility.

The use of certain medications like heparin and corticosteroids are also

known to cause rapid bone loss. The other very important factors are the sex

hormones; estrogen and testosterone. Lack of these sex hormones for instance

in delayed puberty, prolonged absence of menstrual periods or early

menopause can influence bone mass adversely.

Let us now consider the genetic influence on bone strength. A number of

family and twin studies have demonstrated that genetic factors play a very

important role in the development of osteoporosis by influencing peak bone

mass. Identical twins, who share 100% of their genes, have remarkably

similar bone density. In family studies, daughters of women with prior

vertebral fractures have been shown to have low bone density. Collagen is

the main protein constituent of bone. Genetic defects in the formation of

collagen can cause osteoporosis. Osteogenesis imperfecta is a good example

of this.

Osteogenesis imperfecta (01) is a genetic connective tissue disease,

characterized by increased fragility of bones. Affected persons may have

multiple fractures with minimal trauma. Some patients with Ol have a very

severe form of osteoporosis while mild cases with Ol can present late in

life, and can be mistaken for 'post-menopausal osteoporosis'. Ol has been

associated with defects in the structure or synthesis of type I collagen.

Type I collagen not only plays a crucial scaffolding role in bone, it is

also an important protein in the skin. In some types of EDS, the defects at

the molecular level have been identified and include similar abnormalities

in the synthesis and processing of types I and 3 collagens. EDS and Ol are

therefore closely related and are known to co-exist. Theoretically we can

postulate that some forms of EDS with type 1 collagen defects could have

osteoporosis.

Clinical evidence to suggest that patients with EDS also have osteoporosis

is limited. The scientific literature contains only two small bone density

studies in patients with EDS. Coelho and colleagues from Portugal assessed

bone density in 4 patients with type I EDS. They were 3 males and 1 female

with ages ranging from 16 to 25 years. None of these patients had any other

significant risk factors for low bone mass and none had a clinical or

radiological evidence of fractures. All patients had low bone density in the

lumbar spine but not in the hip. We measured bone density in five female and

two male patients with EDS in Cornwall. Six had type 2 and one patient had

type 3 EDS. They were between the ages of 16 to 70 and were referred by

their family physicians for assessment of bone density. They did not have

any predisposing factor for osteoporosis. We found that four out of seven

patients had significantly reduced bone mass both in the hip and in the

lumbar spine, two had significantly reduced bone mass n the hip only and the

16 year old had moderately reduced bone density in the spine. They were thus

at increased risk of developing fractures. We hypothesize that the

abnormality of the collagen framework in EDS may lead to faulty deposition

of calcium in the bones', with resultant reduced bone mass.

The presence of osteoporosis can be suggested by history and physical

examination but the only way to diagnose osteoporosis with certainty is by a

bone density measurement. This test usually takes 10 to 15 minutes to

perform, is painless and uses very small quantities of x-rays. Generally a

repeat measurement is carried out a year or so later to check for the rate

of loss of bone mass. If you are worried about the possibility of

osteoporosis, speak to your family physician and ask for a bone density

measurement test. If you are found to be osteoporotic. What can be done?

As we can not change our genetic background, management of osteoporosis in

the setting of Ehlers-Danlos syndrome will depend on awareness of the

problem and modifying the environmental factors. As a general measure, every

person with EDS should have adequate calcium intake (I to 1.5 grams per day)

in their diet. A pint of skimmed milk or equivalent amount of dairy products

per day will provide one gram of calcium. If for some reason, the person is

unable to tolerate dairy products the diet should be supplemented with

tablets of calcium. For those above the age of 65, it may be worth

considering vitamin D supplements (800 international units per day) too.

Increased physical activity in the form of regular weight bearing exercises

like brisk walking, have beneficial effects on bone mass. The majority of

osteoporotic fractures are associated with falls. The risk factors for

falling are numerous, but are mainly related to advanced age or ill health.

A general improvement in fitness has the greatest effect in reducing the

risk of falling.

There are no studies in patients with EDS looking at the benefits of

different medication in treatment of osteoporosis. However, till such

studies become available, there is no reason to deny patients with EDS and

osteoporosis the benefits of currently available therapies. Women with EDS

at menopause should consider the use of hormone replacement therapy (H RT)

for at least ten years unless there is an absolute contraindication. HRT

has been shown to prevent loss of bone and halve the risk of myocardial

infarction and stroke. For these reasons, it may be worth considering HRT in

every woman with EDS at menopause. In the last few years, many other

treatments have become available to treat pre-existing osteoporosis.

Intra-nasal calcitonin, oral slow release fluoride and newer bisphosphonates

such as alendronate have been shown to be effective in halting the bone loss

and in some cases reducing fracture risks. These treatments can be very

potent and need to be used under careful monitoring by a specialist. Wit the

present resurgence of interest in osteoporosis; new hormonal and

non-hormonal agents are undergoing clinical trials. The next decade promises

to be very exciting in the development of novel therapies to treat

osteoporosis.

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