Amino Acid Linked to Bone Fractures

Monitoring homocysteine levels may offer protection against osteoporosis

WEDNESDAY, May 12, 2004 (HealthDayNews) -- High levels of homocysteine, an amino acid found in the blood, appears to be a risk factor for hip fractures in older people.

Experts aren't yet sure, however, if homocysteine is the actual cause of the fractures or if it is associated in a more "innocent" way.

If it were a cause, this finding could have a major public health impact because homocysteine levels can be manipulated through dietary changes.

"Homocysteine can be easily lowered and that would potentially reduce the risk," said Dr. Douglas P. Kiel, senior author of one of two articles on the subject appearing in the May 13 issue of the New England Journal of Medicine. He is also director of medical research at the Hebrew Rehabilitation Center in Boston.

At present, however, "we aren't sure how important it is," said Dr. Lawrence G. Raisz, author of an accompanying editorial in the journal and a professor of medicine at the University of Connecticut Health Center in Farmington.

Elevated homocysteine levels are already recognized as a risk factor for cardiovascular disease as well as cognitive impairment. It's also known that people with homocystinuria, a genetic disease marked by high levels of homocysteine, have an increased prevalence of osteoporosis.

In the first study, Kiel and his colleagues decided to delve further into the subject by examining the association between homocysteine levels and the risk of hip fractures in a group of 825 men and 1,174 women ranging in age from 59 to 91.

The participants were divided into four groups, depending on their homocysteine levels. Men in the highest quartile had almost four times the risk of hip fracture as men in the lowest quartile, while women in the top group had 1.9 times the risk.

The second study, this one done by researchers in the Netherlands, also found increased homocysteine levels seemed to be an independent risk factor for osteoporotic fractures in a group of 2,406 men and women over the age of 55. People in the highest quartile had about double the risk of fracture as people in the other three quartiles.

"The question still remains, is it the homocysteine itself or is the homocysteine a marker for some other risk factor that has the direct adverse effect on the skeleton," Kiel said.

The arguments in favor of homocysteine as a causal factor include the fact that, in individuals with homocystinuria, high homocysteine levels weaken the collagen of the bones, Kiel noted.

"The Dutch study didn't see a difference in bone density to go with an increase in fractures so the total amount of bone wasn't different," Raisz pointed out. "It may be the quality of the bone. One possibility is that high homocysteine levels cause bone of poorer quality to be made."

It's also possible that other, associated phenomena may be responsible, such as nutrition, low estrogen levels or some as yet unknown factor, Raisz added.

For the moment, more studies are needed to try to get at the underlying mechanisms at work.

If it does turn out that homocysteine levels are responsible for an increased risk of fractures, the solution could be as simple as increasing intake of folic acid and vitamins B 6 and B 12, Kiel said.

More information

The American Heart Association has more on homocysteine and heart disease. The National Osteoporosis Foundation has more on osteoporosis.

SOURCES: Douglas P. Kiel, M.D., director, medical research, Hebrew Rehabilitation Center, and associate professor, medicine, Harvard Medical School, both in Boston; Lawrence G. Raisz, M.D., professor, medicine, University of Connecticut Health Center, and head, University of Connecticut Center for Osteoporosis, both in Farmington; May 13, 2004, New England Journal of Medicine
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