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Preliminary Communication
March 2, 2005

Effect of Folate and Mecobalamin on Hip Fractures in Patients With Stroke: A Randomized Controlled Trial

Author Affiliations

Author Affiliations: Department of Neurology, Mitate Hospital, Tagawa (Drs Sato and Honda); Department of Sports Medicine, Keio University School of Medicine, Tokyo (Dr Iwamoto); and Departments of Rehabilitation Medicine (Dr Kanoko) and Vascular Biology (Dr Satoh), Institute of Brain Science, Hirosaki University School of Medicine, Hirosaki, Japan.

JAMA. 2005;293(9):1082-1088. doi:10.1001/jama.293.9.1082

Context  Stroke increases the risk of subsequent hip fracture by 2 to 4 times. Hyperhomocysteinemia is a risk factor for both ischemic stroke and osteoporotic fractures in elderly men and women. Treatment with folate and mecobalamin (vitamin B12) may improve hyperhomocysteinemia.

Objective  To investigate whether treatment with folate and vitamin B12 reduces the incidence of hip fractures in patients with hemiplegia following stroke.

Design, Setting, and Patients  A double-blind, randomized controlled study of 628 consecutive patients aged 65 years or older with residual hemiplegia at least 1 year following first ischemic stroke, who were recruited from a single Japanese hospital from April 1, 2000, to May 31, 2001. Patients were assigned to daily oral treatment with 5 mg of folate and 1500 μg of mecobalamin, or double placebo; 559 completed the 2-year follow-up.

Main Outcome Measure  Incidence of hip fractures in the 2 patient groups during the 2-year follow-up.

Results  At baseline, patients in both groups had high levels of plasma homocysteine and low levels of serum cobalamin and serum folate. After 2 years, plasma homocysteine levels decreased by 38% in the treatment group and increased by 31% in the placebo group (P < .001). The number of hip fractures per 1000 patient-years was 10 and 43 for the treatment and placebo groups, respectively (P < .001). The adjusted relative risk, absolute risk reduction, and the number needed to treat for hip fractures in the treatment vs placebo groups were 0.20 (95% confidence interval [CI], 0.08-0.50), 7.1% (95% CI, 3.6%-10.8%), and 14 (95% CI, 9-28), respectively. No significant adverse effects were reported.

Conclusion  In this Japanese population with a high baseline fracture risk, combined treatment with folate and vitamin B12 is safe and effective in reducing the risk of a hip fracture in elderly patients following stroke.