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Genes Linked to Osteoporosis Identified

Could be potential targets for new treatments, two studies suggest

TUESDAY, April 29 (HealthDay News) -- Two teams of researchers report finding a series of gene variants linked to bone density and the risk for fracture, which might also be linked to osteoporosis.

While not a predictor of individual risk for osteoporosis, this finding could lead to new therapies to combat the disease, they noted.

"When we look at a screening of genes for osteoporosis and low-impact fractures, we find five loci in the genome, and a couple of them fall into very well-known areas associated with the formation of bone," said researcher Dr. Kari Stefansson, founder and CEO of deCODE Genetics in Reykjavik, Iceland. His team's report was published Tuesday online as an early release from the New England Journal of Medicine.

Osteoporosis, however, involves many genes, not just the five areas identified in this study, Stefansson noted. "Osteoporosis is a very complex phenomenon," he said.

Stefansson was clear that these findings are not something that can be used in diagnosing osteoporosis. "It is a very exciting insight into the biology," he said. "We are beginning to understand osteoporosis."

One of the genes, the researchers identified it as the RANKL gene, is a target of new drugs in clinical trials being tested for osteoporosis, Stefansson said.

In the study, Stefansson and colleagues analyzed genes from 5,061 Icelanders. The researchers looked at those associated with bone mineral density.

Stefansson's team found a significant association with bone mineral at five gene regions. These regions are close to or included in genes that have previously been shown to be associated with bone and the development of osteoporosis.

In addition to RANKL, the other genes are the estrogen receptor 1 gene, the osteoporosis gene, and a gene region, including 40 genes called ZBTB40. In addition, the gene region identified as 6p21 is also involved in bone mineral density, the researchers reported.

Identifying these genes is not going to have an immediate impact on osteoporosis diagnosis or treatment, Stefansson said. However, in the near future, these genes may be drug targets for treating osteoporosis, he added.

"These genes do not have a diagnostic value, because their impact on individuals is rather small," Stefansson said. "Although these genes explain a very large part of the disease in our society, because just one loci we found explains 17 percent of all cases of osteoporosis in the population."

One expert thinks that these genes are only a small part of the story of osteoporosis.

"Taken together, these genes only account for 3 percent of variation in bone density," said Dr. J. Chris Gallagher, a professor of medicine and endocrinology at Creighton University School of Medicine in Omaha, Neb., and a board member of the North American Menopause Society.

Gallagher noted that a couple of these genes, including the osteoporosis gene and RANKL, are already being looked at as targets for drug therapy.

Moreover, these genes are not strong predictors of osteoporosis, Gallagher said. "It means there are many more things involved that contribute to the overall picture," he said.

In a second study, published in the April 29 early online edition of The Lancet, an international team of researchers reported identifying two genetic variants that, when present together, significantly increase the risk of osteoporosis and bone fractures.

These variants are found in 22 percent of the people studied, perhaps making them targets for screening, the researchers noted. Having both of these variants increases the risk for osteoporosis by 20 percent and the risk for osteoporosis-related fractures by 30 percent, the researchers reported.

The researchers concluded that these gene variants "could be used in the future, in addition to traditional risk factors, to better identify populations who are at high risk for osteoporotic fractures."

More information

For more about osteoporosis, visit the U.S. National Institute of Arthritis and Musculoskeletal and Skin Diseases.

SOURCES: Kari Stefansson, M.D., Ph.D., deCODE Genetics, Reykjavik, Iceland; J. Chris Gallagher, M.D., professor, medicine and endocrinology, Creighton University School of Medicine, Omaha, Neb., and board member, North American Menopause Society; April 29, 2008, New England Journal of Medicine, online; April 29, 2008, The Lancet, online

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