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An Association Between Homocysteine and Fractures

Several theories might account for the observed association between high homocysteine levels and increased risk for fractures.

Hyperhomocysteinemia is a risk factor for vascular disease; less well known is a possible association between plasma homocysteine levels and fractures. In two studies, investigators examined this link.

In the first study, researchers in the Netherlands analyzed data from three cohort studies that involved 2400 people (mean age, 74). During an average follow-up of nearly 5 years, those in the highest quartile of plasma homocysteine levels had a 2-fold increased risk for fractures, compared with those in the lower 3 quartiles. Adjustment for other risk factors, including bone-mineral density and dietary constituents, did not change this finding.

In the second report, Framingham Study researchers examined the association between plasma homocysteine levels and hip fractures in a cohort of 2000 people (mean age, 70). During an average follow-up of 14 years, men in the highest quartile of homocysteine levels had a 4-fold increased risk for hip fracture, compared with men in the lowest quartile; for women, the increased risk for hip fracture was 2-fold. These analyses also were adjusted for potential confounders, including cardiovascular disease, cognition, and physical function.

Comment: These findings suggest an association between homocysteine levels and fractures in elders, but whether this association is causal is unclear. One causal theory holds that homocysteine interferes with collagen cross-linking and thereby weakens bone. Alternatively, homocysteine might be an innocent bystander: That is, dietary or metabolic abnormalities that result in elevated plasma homocysteine levels also might predispose to fractures. The practical question, which hasn't been studied, is whether homocysteine-lowering therapies (e.g., folic acid supplementation) lower fracture risk.

— Allan S. Brett, MD

Published in Journal Watch General Medicine June 1, 2004

Citation(s):

van Meurs JBJ et al. Homocysteine levels and the risk of osteoporotic fracture. N Engl J Med 2004 May 13; 350:2033-41.

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McLean RR et al. Homocysteine as a predictive factor for hip fracture in older persons. N Engl J Med 2004 May 13; 350:2042-9.

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Raisz LG. Homocysteine and osteoporotic fractures -- Culprit or bystander? N Engl J Med 2004 May 13; 350:2089-90.

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• Medline abstract (Free)