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Researchers discover 'thermostat' that regulates bone density

Researchers tracking the cause of a rare genetic disorder that causes brittle bones have discovered a genetic thermostat that appears to control the accumulation of bone mass during growth. The findings could substantially increase understanding of why many people fail to achieve sufficient bone mass during the first three decades of life, a significant risk factor for the development of osteoporosis.

Osteoporosis is the underlying cause of more than 1.7 million hip fractures annually worldwide. In the United States alone the cost of treating osteoporotic fractures approaches $15 billion annually.

In an article published in the November 16, 2001, issue of the journal Cell, an international consortium of 62 clinicians and scientists led by Howard Hughes Medical Institute investigator Matthew L. Warman reported the discovery of the cause of the inherited disorder, osteoporosis-pseudoglioma syndrome (OPPG). Studies of families with OPPG led the researchers to mutations in a completely unsuspected gene called LDL receptor-related protein 5 (LRP5), which codes for a protein whose precise cellular function remains unknown.

I became interested in this extremely rare disease in 1993 after meeting three affected patients, said Warman, who is at Case Western Reserve University and University Hospitals of Cleveland. Their sever symptoms of very brittle bones and progressive blindness convinced us that this was an important disease to solve. So, with the support of my mentor, professor Bjorn Olsen at Harvard Medical School, we formed an osteoporosis-pseudoglioma collaborative group to enlist affected families and their physicians in this effort.

Although the researchers were able to identify the region of the genome that apparently harbored the gene mutation responsible for OPPG, they did not zero in on the gene responsible until a good working draft of the human genome sequence became available. This led the research team to LRP5.

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Contact: Jim Keeley
keeleyj@hhmi.org
301-215-8858
Howard Hughes Medical Institute
15-Nov-2001


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