US researchers have identified a key mouse gene involved in bone density, which they say could lead to new treatments for the bone-weakening disease osteoporosis. A team lead by scientists at Oregon Health and Science University found that mice lacking the Alox15 gene have stronger, more dense bones than normal mice. They also found that drugs that cancelled out the gene's effects improved the bone density of mice with osteoporosis symptoms. 'It points the way toward potent, useful human therapies', said team leader Eric Orwoll of the study, which was published in the journal Science.
Osteoporosis affects one in three women, and one in 12 men in the UK. It is a disease of old age, in which the bones gradually become more porous (less dense), and weaker. The disease often remains undetected until a patient falls and fractures their wrist, hip or spine. People with low 'bone mineral density' (BMD) are more likely to develop the disease than those with a higher BMD. While diet, lifestyle and smoking are all known to affect BMD, genetic factors are also thought to play an important role. In November 2003, Icelandic firm deCODE found that certain versions of a gene called BMP2 increased the risk of osteoporosis.
To identify other genes that affect bone density, the US researchers carried out genetic studies in laboratory mice. They identified the Alox15 gene by studying mice with a form of osteoporosis, and then bred 'knockout' mice that completely lacked this gene. Alox15 makes a protein called 12/15 lipoxygenase, which can trigger certain body cells to turn into fat-storing cells. In the case of bone marrow stem cells, increased amounts of this protein makes them grow into fat cells, rather than bone-producing cells. But drugs that block the effects of the lipoxygenase appear to reverse this process, the researchers say.
Co-author Gary Peltz, of pharmaceutical firm Roche, said: 'The study demonstrates that mouse genetic discoveries can lead to new opportunities for human therapeutics'. The team hope that their findings will help identify the human counterpart of Alox15, and shed light on osteoporosis in humans. They also say that their methods 'should be applicable to finding genes for other complex disorders'.