Elevated Homocysteine Levels Linked to Osteoporosis

ROTTERDAM, The Netherlands--A study published in the May 13 issue of The New England Journal of Medicine (350, 20:2033-2041, 2004) (http://content.nejm.org/cgi/content/short/350/20/2033) found increased homocysteine levels may be a considerable, independent risk factor for osteoporotic fractures in older men and women. High homocysteine levels in blood plasma are characteristic of homocystinuria, a rare autosomal recessive disease linked to early onset of generalized osteoporosis.

The authors of the study examined the relationship between circulating homocysteine levels and the incidence of osteoporotic fractures in 2,406 subjects 55 years of age or older who participated in two different prospective, population-based studies. One of the two studies consisted of two independent groups: 562 subjects in the first group, with a mean follow-up period of 8.1 years; and 553 subjects in the second group, with a mean follow-up period of 5.7 years. The other study consisted of a single group of 1,291 subjects, with a mean follow-up period of 2.7 years. Risk of fracture was assessed after adjustment for age, sex, body-mass index, and other characteristics that may be associated with the risk of fracture or with increased homocysteine levels.

Throughout the follow-up period, 191 subjects sustained osteoporotic fractures. The overall multivariable-adjusted relative risk of fracture was 1.4 for each increase of one standard deviation in the natural-log-transformed homocysteine level. The researchers found the risk similar in all three groups studied, as well as in men and women. The relationship between homocysteine levels and the risk of fracture appeared to be independent of other potential risk factors for fracture, such as bone mineral density.

The researchers concluded an elevated homocysteine level appears to be a significant, isolated risk factor for osteoporotic fractures in elderly men and women.

It has been suggested folic acid supplementation can be used to lower homocysteine levels in the April 9, 1998 issue of The New England Journal of Medicine (338, 15: 1009-1015, 1998) and in the Dec. 18, 1996 issue of the Journal of the American Medical Association (276, 23:1879-1885, 1996).