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Variants Increase Risk of Bone Fracture

By R&D Editors | May 3, 2012

Findings from the largest international genetic study in osteoporosis revealed variants in 56 regions of the genome that influence individual’s bone mineral density, including 14 variants found to increase the risk of bone fracture, according to a study published this month in the leading genetic journal Nature Genetics.

Indiana University School of Medicine researchers contributed data from 1,500 patients to the collaboration with an international consortium of investigators from more than 50 centers across Europe, North America, Asia and Australia.

“The big news is we found 56 different regions of the genome which affect bone mass,” said Michael J. Econs, M.D., Glenn W. Irwin Jr. Professor of Endocrinology and Metabolism and director of the Division of Endocrinology and Metabolism at the IU School of Medicine.

“While the investigators uncovered several genes that were already known to play a role in bone metabolism, the researchers found many genes that were previously unknown to play an important role in bone biology,” said Dr. Econs, who also is a professor of medicine and of medical and molecular genetics.

“This new information not only provides insight into basic bone biology but may lead to genetic tests that could predict osteoporosis risk and allow early institution of preventive measures as well as provide molecular ‘targets’ for therapeutic agents to influence bone mineral density,” he said.

Osteoporosis predisposes individuals to fractures, particularly fractures of the wrist, spine and hip.  Like high blood pressure, osteoporosis is a “silent” disease, and many people don’t know they have it until they have a fracture. Hip fractures, the most devastating complication of the disease, frequently result in nursing home placement and increase mortality markedly over the year following the fracture.

Bone mineral density measured by Dual Energy X-Ray absorptiometry (DXA) is the most widely used measurement to diagnose osteoporosis and to assess the risk of fracture. At any given age, lower BMD results in higher risk of fracture.

Researchers studied more than 80,000 individuals with DXA scans and examined the relation with fracture in approximately 30,000 cases and 100,000 controls. While the investigators uncovered several genes that were already known to play a role in bone metabolism, the researchers found many genes that were previously unknown to play an important role in bone biology.  This new information not only provides insight into basic bone biology, but may lead to genetic tests that could predict osteoporosis risk and allow early institution of preventive measures as well as provide molecular “targets” for therapeutic agents to influence bone mineral density.

Dr. Econs said his lab has turned its attention to understanding how some of these genes influence bone density and whether increasing or decreasing the amount of protein these genes make will change bone strength. Much of his research and that of the other participating centers in the United States are funded by National Institutes of Health grants.

Other IU researchers involved in the study include Munro Peacock, M.D., professor of medicine; Tatiana Foroud, PhD, the P. Michael Conneally Professor of Medical and Molecular Genetics and Chancellor’s Professor at Indiana University-Purdue University Indianapolis; Daniel L. Koller, PhD, assistant research professor of medical and molecular genetics; and Siu Hui, PhD, professor of biostatistics.

Date: April 27, 2012
Source: Indiana University School of Medicine

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