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Gene Hikes Risk of Osteoporosis

8 April 1998 6:00 pm
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Women who have certain versions of a gene that helps make the protein collagen are likely to have weaker than normal bones--and a higher risk of fractures--after they reach menopause. The finding, published in tomorrow's New England Journal of Medicine, raises the possibility that genetic tests might be used to identify and help women who may develop fragile bones (osteoporosis).

There have been several hints before now that genes are important in osteoporosis. Twin studies, for example, have shown that genetic factors determine about 80% of the variation in how bones fare with age. In 1996, researchers discovered that low density bones and fractured vertebra seem to accompany a different form, or allele, of a gene called COLIA1. This gene helps makes collagen, the protein that forms bone matrix and is essential for bone growth.

To see if these variations could predict the risk of weak bones and fractures, British and Dutch researchers studied a group of 1778 postmenopausal women enrolled in a long-term investigation called the Rotterdam Study. The team looked for patterns associated with two COLIA1 alleles, called S and s. Women who had one copy of the s allele had bone density in the thighbone and lower spine that was 2% less than that of women with no s alleles. During almost 4 years of observations, the researchers found that women with one copy of s had a 40% higher risk of wrist, hip, and other bone fractures. Women with two copies of s fared even worse: They had bones that were 4% less dense--and faced a 280% higher risk of fracture--than did women without any s alleles, says team member Andre Uitterlinden, a molecular geneticist at Erasmus University in Rotterdam, the Netherlands.

This finding reinforces the need for healthy women with osteoporotic relatives to consider diet, exercise, and possibly drug regimens, says Darwin Prockop, a geneticist at Allegheny University in Philadelphia. He also cautions that a complete understanding of the genetics of osteoporosis is far off.

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