Identifying genes that lead to osteoporosis is an important first step in helping to treat this serious condition, which affects over 2 million Australians.*
Out of 100 ‘knockout mice’, the first generated on a ‘pipeline’ set up by the UK’s Wellcome Trust Sanger Institute (as part of a global effort to knockout every gene in the genome one by one) the scientists identified 9 genes that appear to weaken or strengthen bone.
Professor Peter Croucher from Sydney’s Garvan Institute of Medical Research, in collaboration with Dr Duncan Bassett and Professor Graham Williams from Imperial College London and colleagues at the Sanger Institute, used micro-CT and digital x-ray microradiography in combination with statistics and load bearing experiments to measure whether or not each of the first 100 genes impacted upon bone. Their results are published in PLoS Genetics, now online.
“We wanted to see what screening the first 100 knockout mice off the pipeline would tell us about the impact of these genes on bone, and whether or not our approach was an effective one,” said Professor Peter Croucher.
“The approach was successful in that we identified 9 genes that had not previously been described – each of which appeared to be important in regulating our skeleton. This suggests that roughly 8-10% of all genes may be involved in some way.”
“We believe a systematic screening of knockout mice in this way will give us the scale of data we need to define the structural and functional variations in genes that determine bone strength.”
“CT scans and microradiography give us the structural information we need, and fracturing the bones afterwards tells us whether or not there is an increase or a decrease in the propensity to fracture. That’s the functional endpoint.”
“This has allowed us to describe four functional classifications of bone. Normal bone is strong and flexible, whereas abnormal bone can be strong but brittle, or weak and brittle, or weak but flexible.”
“At the moment, we’re trying to understand the potential role of the 9 genes we’ve just identified. Our results suggest that if you were to block some of them, it would result in higher bone mass and stronger bones. We’ll be making antibodies to those genes to test our results.”
“We believe that many genes will be individual players in complex pathways – so they will act as pointers to those pathways, and obviously some pathways will be much more important than others. It’s our aim to pinpoint the critical pathways.”
The study participants will be applying to The Wellcome Trust to fund the screening of the next 800-1000 genes off the Sanger Institute pipeline, over a period of 5 years.
Notes to Editors*
In Australia, someone is admitted to hospital with an osteoporotic fracture every 5-6 minutes, averaging 262 hospitalisations each day. It has already been shown by Garvan and others that osteoporotic fractures increase a person’s risk of dying, even after relatively minor fractures if that person is elderly. Osteoporosis is truly a silent killer.
Only about 30% of women and 10% of men with osteoporosis receive treatment for the condition, an unacceptable fact when there is good evidence that treating osteoporosis reduces fractures and reduces mortality.
From the age of 60, 40% women and 25% men will sustain a fracture due to osteoporosis, with the risk being higher in people with a family history of fracture.
Economic consultancy Access Economics estimates the total cost to Australia, which includes factors such as carers and lost income, to be $7 billion per year i.e. almost $20 million every day.
There are 20,000 genes in the human genome, and until now, only a handful have been unequivocally linked to osteoporosis and fragility fractures.
The Garvan Institute of Medical Research was founded in 1963. Initially a research department of St Vincent’s Hospital in Sydney, it is now one of Australia’s largest medical research institutions with over 600 scientists, students and support staff. Garvan’s main research programs are: Cancer, Diabetes & Obesity, Immunology and Inflammation, Osteoporosis and Bone Biology and Neuroscience. Garvan’s mission is to make significant contributions to medical science that will change the directions of science and medicine and have major impacts on human health. The outcome of Garvan’s discoveries is the development of better methods of diagnosis, treatment, and ultimately, prevention of disease.
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