Genes Determine Severity of Osteoporosis

Mutations leave some less prone to fractures, study finds

TUESDAY, Nov. 2, 2004 (HealthDayNews) -- Researchers have identified certain gene mutations that make people with osteoporosis less susceptible to fractures.

Interestingly, though, the mutations work through mechanisms other than bone mineral density (BMD), which is often the reason why bones break in people with this disease.

"These people had 20 percent fewer fractures but the same BMD, so the mutations may be a proxy for some bone quality issues," said Dr. Stephen Honig, director of the Osteoporosis Center at the Hospital for Joint Diseases in New York City. "The bone quality may be better." Honig was not involved in the study.

According to the study, which appears in the Nov. 3 issue of the Journal of the American Medical Association, osteoporosis affects up to 30 percent of women and 12 percent of men, most of them elderly. With the worldwide aging of the population, the condition is only going to become more widespread. The disease is characterized by reduced bone mass and a subsequent greater risk of fracture.

This study tried to determine genetic factors that might be contributing to susceptibility. To this end, the researchers looked at three polymorphisms, or mutations, in the area of the gene that codes for the estrogen receptor in 18,917 individuals at eight European centers.

None of the three polymorphisms had any effect on bone mineral density. On the other hand, they were associated with a 20 percent to 40 percent reduction in the risk of fracture.

This bolsters the idea that there are factors other than BMD involved in fracture occurrence and fracture protection, Honig said. It has already been shown that patients who take one of a family of drugs called bisphosphonates -- Actonel and Fosamax are examples of drugs in this class -- have about a 50 percent reduced risk of fracture. "That is far more than the fairly modest changes one sees in BMD," Honig said. "The theory is that down at the level of microarchitecture level, somehow the bisphosphonates afford some level of protection." Exactly how they do that is unclear.

Nor is it clear how these genetic mechanisms may work.

"The theory behind the paper is that may be some genetic factors resulting in the secretion of some protein that improves bone quality and reduces fractures, although we have no clue as to what this might be," Honig said.

To complicate matters further, however, the regions of the gene described in this paper are not those that would normally be producing these proteins. There must be another linkage that accounts for that.

"There may be a protein or proteins that may be secreted as a result of genetic messages coming out of this association that somehow confers some level of fracture protection even though it does not seem to influence the BMD," Honig said.

It's not entirely clearly what these findings mean for the treatment and diagnosis of osteoporosis.

More information

Visit the National Osteoporosis Foundation for more on bone mineral density and other aspects of osteoporosis.

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