Brussels, 03 Jan 2006
Researchers from the University of Bonn in Germany, working closely with scientists in the UK, the US, Israel and France, have discovered a previously unknown mechanism in the development of bone loss, or osteoporosis, which affects large numbers of women throughout the world.
The researchers, working under the direction of Dr Meliha Karsak from the Bonn-based Life & Brain Centre, discovered that mice with a defective CB2 'cannabinoidreceptor' have lower bone density.
'We know of two types of cannabinoidreceptors, CB1 and CB2,' explains Dr Karsak, 'The CB1 receptor is formed by nerve cells in the brain and is responsible for, among other things, the mental effect of cannabis. The CB2 receptor, on the other hand, does not occur in nerve cells and was previously unknown.'
Collaborating with research groups from the UK and Israel, Dr. Karsak's team found that when the CB2 gene was switched-off, the mice lost their stabilising trabeculae (tissue scaffolding), and the number of osteoclasts - cells that break-down bone tissue - increased by almost 50 per cent.
The team discovered that both the both destructive osteoclasts and constructive osteoblasts carried the CB2 receptors, and that endocannabinoids are used to regulate bone growth. This view was supported by further research on female mice with 'mouse osteoporosis', brought about through the removal of ovaries. When the mice were given a substance that bonded to the CB2 receptor, 'We were able to diminish the bone loss caused by ovary removal,' said Dr Karsak.
The team consulted a comprehensive French study to see how far the mouse findings could be applied to humans. They found that women with a specific CB2 gene variant were more frequent amongst osteoporosis sufferers than a healthy control. Women carrying the CB2 variant were found to have a three-fold increased risk of osteoporosis.
'In many women with osteoporosis the CB2 receptor functions, so in their cases the disease has other causes. For them we could consider stimulating the receptor through medication [as in the mouse study] and in this way slow down their bone loss,' explained Dr. Karsak.
This research opens the door for new types of treatment and diagnosis, based on the newly-discovered CB2 receptor. It is easy to identify women carrying the relevant CB2 defect, and the mechanism will be the target of osteoporosis research and new medicines in the long-term.
Dr Kaslik's research has won the German Society for Endocrinology's Osteology Prize, worth 8,000 euro, and the findings will be published in the prestigious Proceedings of the National Academy of Sciences (PNAS).