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Folic acid and vitamin B12 decrease risk of hip fracture in stroke patients

The JAMA Network Journals

Patients who took folic acid and vitamin B12 after their stroke had a reduced risk of hip fracture compared to patients who took placebo, according to an article in the March 2 issue of JAMA.

According to background information in the article, stroke patients have a two to four times greater risk of hip fracture than their healthy peers. Researchers believe this may be due to higher levels of plasma homocysteine (an amino acid) in stroke patients, which may be associated with osteoporosis and the risk of a hip fracture. Homocysteine levels may be decreased by treatment with folic acid and vitamin B12.

Yoshihiro Sato, M.D., from the Mitate Hospital, Tagawa, Japan, and colleagues investigated the occurrence of hip fractures in stroke patients who were given folic acid and vitamin B12, and those who received placebo. Of patients studied, 314 received 5 mg of folate and 1500 micrograms of B12, while 314 patients received placebo. Participants were instructed to keep track of falls on a daily calendar. Five hundred fifty-nine patients completed this two-year follow-up.

The researchers recorded six hip fractures in patients who received folic acid and B12, and 27 hip fractures in the placebo group. The difference in total number of fractures over the two-year follow up was significant, with eight fractures in the treatment group and 32 in the placebo group. Patients receiving folic acid and B12 experienced a 38 percent decrease in their plasma homocysteine levels, while levels increased by 31 percent in the placebo group.

"Treatment with folate and mecobalamin [vitamin B12] was effective in reducing the risk of the serious poststroke complication of fractures. The high incidence of hip fractures in elderly patients with stroke may be attributed to frequent falls, as well as osteoporosis..." the authors write. "In our study, the number of falls was similar in both groups during the follow-up period and the combined therapy with folate and [vitamin B12] prevented hip fractures in patients with stroke despite frequent falls."


(JAMA. 2005; 293: 1082 - 1088. Available post-embargo at

Editorial: Homocysteine and Fracture Prevention

In an accompanying editorial, Joyce B.J. van Meurs, Ph.D., and André G. Uitterlinden, Ph.D., from the Erasmus Medical Center, Rotterdam, the Netherlands, discuss factors involved in the association between homocysteine levels and fracture risk.

"In this issue of JAMA, Sato and colleagues present the first evidence that an elevated homocysteine level might indeed cause more brittle bones," the editorialists write. "In, Japanese patients following stroke who were treated with folate and vitamin B12 had a five times lower risk for hip fracture over a follow-up period of two years compared with the placebo group. This is a very large risk reduction, but care should be taken in interpreting these results."

"Despite the potential limitations of the study by Sato et al, the results show that -- at least in patients following stroke -- folate and vitamin B12 supplementation is effective in preventing hip fracture. Whether a similar effect can also be obtained in other (high fracture risk) patients can only be answered by other intervention studies. After the initial observation of association between circulating homocysteine levels and fracture risk less than one year ago, these results now support a causal link."

(JAMA. 2005; 293: 1121 - 1122. Available post-embargo at

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