Understanding Gaucher Bones
Dr Henry Mankin spoke about the bone complications of Gaucher
Disease at two talks recently: one at the Royal Free Hospital, London on
9 November 1999 and the other at the US Gaucher Conference in Arlington,
Virginia on 3 October 1999. Dr Mankin is Chief of the Gaucher Disease and
Bone Cancer Program at Massachusetts General Hospital in Boston, USA and
has served as Chief of Orthopedic Surgery and Professor of Orthopedics
in Harvard Medical School. This is a summary of both talks by Susan
'Bone is a living tissue,' explained Dr Mankin. 'It reflects everything
that goes on in your body and everything in your body contributes to your
bones. Bone is not a permanent fixture. It is alive, made up of crystals
and normally recycles regularly.'
Mankin said that there are several different types of cells in your bones:
which build bone, osteocytes which care for the bone and osteoclasts
which destroy the bone. Another set of cells in the bones are guest
cells: bone marrow cells which make blood including the red and white cells.
Gaucher cells accumulate in the bone marrow and grow bigger and bigger.
'The bone marrow fills up with them. The Gaucher cells throw out the healthy
guest cells and there is less bone marrow. The balance between osteoblasts
and osteoclasts are closely tied. If less bone is made, then less bone
is destroyed; and if less bone is destroyed, then less bone is made. I
believe that in patients with Gaucher Disease the osteoclasts are in very
small number as compared with other people and this stops the osteoblasts
building up more bone. These Gaucher cells live forever.'
This causes a number of things to happen. The bones fail to remodel
(grow properly) and there is a decrease in bone substance (diffuse osteopenia)
the patients have lower bone density. Lytic lesions (holes) appear
in the bone and the cortex (hard rim of the bone) thins. The bone
becomes weak and patients experience fractures in the hips, shoulders and
spine, Osteonecrosis (death of the bone) leads to sclerotic lesions
of the bone).
'Bone crises are another feature of Gaucher Disease. When a patient
has a bone crisis, there is a loss of blood supply throughout a whole segment
of bone. The patient's temperature rises and he or she is often in immense
pain. I believe this kills the Gaucher cells and releases fatty acids.
These acids combine with calcium to make the bones more dense but this
does not mean the bones become stronger - they actually weaken.'
'Everyone's bones, whether they have Gaucher disease or not, grow until
the age of 30 years after which their bones diminish at 0.3% a year. So
between the age of 30-40, you lose 3%. Each decade after that, another
3% is lost.'
'However in most women after menopause, this number increases by 10
fold. Therefore for women between the age of say 45 and 55, they lose 30%
of their bone strength during their first ten years of menopause. This
is called post menopausal osteoporosis. After ten years they go
back to losing 0.3% a year. However in women with Gaucher disease, their
bones may suffer additional loss. Although as there is not much osteoclastic
activity in patients with Gaucher disease anyway, there may be less loss
Enzyme Replacement Therapy
'The bone marrow of patients has been shown to improve after enzyme replacement
therapy but the bones don't respond as rapidly as the spleen and liver.
Despite this, I have found that bone fractures heal more easily on enzyme
'In my opinion, enzyme replacement therapy takes three years to change
the picture. However I believe, on the basis of our experimental studies,
that if the dose is low, the bones don't do so well. I recommend 60 units
per kilogram of bodyweight (u/kg/bw) every two weeks. I have found that
patients with 30 u/kg/bw every two weeks hold their own and patients with
15 u/kg/bw seem to deteriorate where their bones are concerned.'
'I prefer infusions of pamidronate (Aredia) once a month to alendronate
(Fosamax) which I do not think is as effective in treating the bones of
Gaucher patients. I believe bisphosphonates inhibit the osteoclast population
and therefore may prove less useful in helping non-enzyme treated patients.
Our view is that the enzyme replacement therapy and pamidronate should
be given together.'
Dr Mankin said there are several reasons why patients should contemplate
a total joint replacement, whether it be of the hip, shoulder or knee.
The joints may be painful, hard to live with and limiting. He gave the
It is probably unnecessary to give drugs during or after the operation
to prevent clotting of the blood.
Dr Mankin was asked how long hip replacements last. He replied: 'Devices
now last between 10-12 years but I recently saw a patient who needed a
revision (new replacement ) after 22 years. How do you tell if you need
a revision? When you get pain.'
Delay the operation as long as possible.
It is important to have a scrupulously clean environment during the operation.
When the cement goes in, caution should be taken to maintain the patient's
Patients should get up quickly after the operation.
Blood counts should be measured regularly.
He also spoke about the risks of surgery. 'There is no disease that
cannot be made worse with an operative procedure.'
Bone Crises and Pain
'The number of bone crises have decreased after patients have started enzyme
replacement therapy. If a patient does suffer from a bone crisis, hyperbaric
oxygen therapy in hyperbaric chambers appears successful in treating bone
crises. These chambers are available in some hospitals and naval establishments
where they were originally used for deep sea divers who rose to the surface
too quickly and suffered 'the bends.' This procedure can reduce pain, sediment
rate and temperature. Patients should receive four hours of treatment a
day for four days. Oxygen can also give relief.'
'Exercise is crucial. Riding a bike and walking are load bearing: walk
every day. Swimming is also good. I recommend physical therapy as well.'
Dr Mankin also commented on the value of measuring calcium and vitamin
D levels in those with Gaucher Disease so that appropriate treatment could
be given if necessary.
'Act your age and don't overdo things,' concluded Dr Mankin. 'Get enough
sleep. Altitude changes may be difficult for some people with Gaucher disease.
And most of all, enjoy your life. The only real tragedy of life is a loss
Source: Gaucher's News February 2000. © Copyright Gauchers