Spotlight on Research for 2004

December 2004 (historical)

Homocysteine Level Predictive of Fracture Risk in Older Persons

Elevated levels of the amino acid homocysteine have long been associated with an increased risk of cardiovascular disease, including heart attack and stroke. But a new research study funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) suggests that high homocysteine levels also may be linked to the development of osteoporosis and related fractures. The study, published in the New England Journal of Medicine, also asks whether increasing one's intake of folic acid and other B vitamins might reduce the fracture risk from homocysteine.

Elevated levels of homocysteine are found in people with homocystinuria, an inherited metabolic disorder. Since people with homocystinuria are at an increased risk for osteoporosis, Boston researchers hypothesized that other people with elevated blood levels of homocysteine might also be at risk.

Robert McLean, M.P.H., of the Hebrew Rehabilitation Center for Aged and his colleagues from various Boston medical institutions conducted a survey of nearly 2,000 Framingham Osteoporosis Study participants who ranged in age from 59 to 91 years. Investigators reviewed blood homocysteine levels and screened for hip fracture in participants for a 16- to 19-year period. An analysis revealed that men and women with the highest homocysteine levels were at greater risk for hip fracture as compared to those with the lowest levels. The risk was increased fourfold in men and twofold in women, and it was independent of other risk factors for fracture, such as age and weight.

Levels of homocysteine are elevated in people who don't get adequate amounts of folic acid and other B vitamins (B6 and B12), and getting enough of these vitamins can significantly lower homocysteine levels. The authors suggest that increasing one's intake of folic acid and other B vitamins may result in a reduced risk of fracture. This hypothesis remains to be tested, however.

It is not clear from the study whether homocysteine has a direct effect on bone and fracture or whether it serves as a marker for something else that does. In an editorial accompanying the study, bone researcher Lawrence G. Raisz, M.D., from the University of Connecticut Health Center, reminds readers that low levels of folic acid and vitamin B12 have been directly linked to bone loss in postmenopausal women. Perhaps homocysteine serves as a marker for low levels of these vitamins, which are, in fact, the true foe of bone. Either way, elevated homocysteine levels are emerging as an important risk factor for hip fractures in older persons.

The mission of the NIAMS, a part of the Department of Health and Human Services' National Institutes of Health, is to support research into the causes, treatment and prevention of arthritis and musculoskeletal and skin diseases, the training of basic and clinical scientists to carry out this research, and the dissemination of information on research progress in these diseases. For more information about bone health, call the NIH Osteoporosis and Related Bone Diseases~National Resource Center at (202) 223-0344 or (800) 624-2663 or visit the NIAMS Web site at

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McLean R, et al. Homocysteine as a predictive factor for hip fracture in older persons. New England Journal of Medicine 2004;350:2042-9.