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 Lewis.

'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.'

Gaucher Cells

Dr Mankin said that there are several different types of cells in your bones: osteoblasts 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) so 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 (hardening 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.'

Osteoporosis

'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 of activity.'

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 replacement therapy.'

'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.'

Bisphosphonates

'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.'

Joint Replacements

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 following advice:

It is probably unnecessary to give drugs during or after the operation to prevent clotting of the blood.

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 blood pressure.
Patients should get up quickly after the operation.
Blood counts should be measured regularly.

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.'

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.'

Advice

'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 of hope.'