32 genetic variations could play a role in osteoporosis risk

By Dr. Ananya Mandal, MDApr 16 2012

A team of international researchers have found 32 new genetic regions linked to fractures and osteoporosis. According to the new study published in the April 15 online edition of Nature Genetics, changes in these regions could offer protection from, or greater risk for, bone-weakening disease.

“We're learning that the genetic architecture of disease is very complex,” one of the study's authors and the methodological leader of the consortium, Dr. John Ioannidis, chief of the Stanford Prevention Research Center, said in a university news release.

The research, which involved 17 studies that compared common genetic variants in more than 100,000 people, pinpointed six regions linked to risk of fractures of the femur (thigh bone) or lower back.

Authors warn however that it would still be difficult to predict who is at greater risk for bone disease. People with the highest number of variants associated with decreased bone mineral density were only about one and a half times more likely than people with an average number of variants to have osteoporosis. The risk for fractures was only slightly higher. Meanwhile, compared to those with the fewest variants, people with the most variants were still just three to four times more likely to have had fractures and lower bone mineral density, the study revealed.

“As a result, the next step of incorporating this information into basic patient care is not clear,” Ioannidis concluded. “Each variant conveys a small quantum of risk or benefit. We can't predict exactly who will or won't get a fracture,” he explained.

The authors noted, their research could lead to the development of new anti-osteoporosis drugs. But even larger studies are needed to identify all of the genes critical to fighting bone disease, they added.

“We saw many of these regions and genes clustering within specific types of pathways, which suggests certain disease mechanisms. It certainly wouldn't be unexpected to eventually identify many more genetic regions involved in the regulation of osteoporosis and fracture risk,” Ioannidis said. “In reality, there may be 500 or more gene variants regulating osteoporosis. To find all of them, we'll need to study millions of patients. Is this unrealistic? I don't think so. Sooner or later this will be feasible,” he added.