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A Randomized Controlled Trial

Yoshihiro Sato, MD; Yoshiaki Honda, MD; Jun Iwamoto, MD; Tomohiro Kanoko, PhD; Kei Satoh, MD

JAMA. 2005;293:1082-1088.

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.

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.

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