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Can Vitamin C Prevent Complex Regional Pain Syndrome in Patients with Wrist Fractures?: A Randomized, Controlled, Multicenter Dose-Response Study

Zollinger, P.E. MD; Tuinebreijer, W.E. MD, PhD, MSc, MA; Breederveld, R.S. MD, PhD; Kreis, R.W. MD, PhD

Journal of Bone & Joint Surgery - American Volume: July 2007 - Volume 89 - Issue 7 - p 1424–1431
doi: 10.2106/JBJS.F.01147
Scientific Articles

Background: Complex regional pain syndrome type I is treated symptomatically. A protective effect of vitamin C (ascorbic acid) has been reported previously. A dose-response study was designed to evaluate its effect in patients with wrist fractures.

Methods: In a double-blind, prospective, multicenter trial, 416 patients with 427 wrist fractures were randomly allocated to treatment with placebo or treatment with 200, 500, or 1500 mg of vitamin C daily for fifty days. The effect of gender, age, fracture type, and cast-related complaints on the occurrence of complex regional pain syndrome was analyzed.

Results: Three hundred and seventeen patients with 328 fractures were randomized to receive vitamin C, and ninety-nine patients with ninety-nine fractures were randomized to receive a placebo. The prevalence of complex regional pain syndrome was 2.4% (eight of 328) in the vitamin C group and 10.1% (ten of ninety-nine) in the placebo group (p = 0.002); all of the affected patients were elderly women. Analysis of the different doses of vitamin C showed that the prevalence of complex regional pain syndrome was 4.2% (four of ninety-six) in the 200-mg group (relative risk, 0.41; 95% confidence interval, 0.13 to 1.27), 1.8% (two of 114) in the 500-mg group (relative risk, 0.17; 95% confidence interval, 0.04 to 0.77), and 1.7% (two of 118) in the 1500-mg group (relative risk, 0.17; 95% confidence interval, 0.04 to 0.75). Early cast-related complaints predicted the development of complex regional pain syndrome (relative risk, 5.35; 95% confidence interval, 2.13 to 13.42).

Conclusions: Vitamin C reduces the prevalence of complex regional pain syndrome after wrist fractures. A daily dose of 500 mg for fifty days is recommended.

Level of Evidence: Therapeutic Level I. See Instructions to Authors for a complete description of levels of evidence.

1 Department of Orthopaedic Surgery, Ziekenhuis Rivierenland, President Kennedylaan 1, 4002 WP Tiel, The Netherlands. E-mail address:

2 Relweg 59, 1949 EC Wijk aan Zee, The Netherlands

3 Departments of Surgery (R.S.B., R.W.K.) and Burn Wounds (R.W.K.), Red Cross Hospital, Vondellaan 13, 1942 LE Beverwijk, The Netherlands

Copyright 2007 by The Journal of Bone and Joint Surgery, Incorporated
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