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Review
June 26, 2006

Vitamin K and the Prevention of Fractures: Systematic Review and Meta-analysis of Randomized Controlled Trials

Author Affiliations

Author Affiliations: York Trials Unit, Department of Health Sciences, University of York, York, England (Ms Cockayne and Drs Adamson, Lanham-New, Gilbody, and Torgerson); Centre for Nutrition and Food Safety, School of Biomedical and Molecular Sciences, University of Surrey, Guildford, England (Dr Lanham-New); and Vitamin K Laboratory, The Centre for Haemostasis and Thrombosis (The Haemophilia Reference Centre), St Thomas' Hospital, London, England (Dr Shearer).

Arch Intern Med. 2006;166(12):1256-1261. doi:10.1001/archinte.166.12.1256
Abstract

Background  Observational and some experimental data suggest that low intake of vitamin K may be associated with an increased risk of fracture.

Objective  To assess whether oral vitamin K (phytonadione and menaquinone) supplementation can reduce bone loss and prevent fractures.

Data Sources  The search included the following electronic databases: MEDLINE (1966 to June 2005), EMBASE (1980 to June 2005), the Cochrane Library (issue 2, 2005), the ISI Web of Science (1945 to June 2005), the National Research Register (inception to the present), Current Controlled Trials, and the Medical Research Council Research Register.

Study Selection  Randomized controlled trials that gave adult participants oral phytonadione and menaquinone supplements for longer than 6 months were included in this review.

Data Extraction  Four authors extracted data on changes in bone density and type of fracture. All articles were double screened and double data extracted.

Data Synthesis  Thirteen trials were identified with data on bone loss, and 7 reported fracture data. All studies but 1 showed an advantage of phytonadione and menaquinone in reducing bone loss. All 7 trials that reported fracture effects were Japanese and used menaquinone. Pooling the 7 trials with fracture data in a meta-analysis, we found an odds ratio (OR) favoring menaquinone of 0.40 (95% confidence interval [CI], 0.25-0.65) for vertebral fractures, an OR of 0.23 (95% CI, 0.12-0.47) for hip fractures, and an OR of 0.19 (95% CI, 0.11-0.35) for all nonvertebral fractures. Because 1 of the centers provided most of the data for hip fractures and this center had included populations with a very high fracture risk, 33-35 we undertook a sensitivity analysis excluding data from this center. The OR for hip fractures for the remaining 2 studies when combined was 0.30 (still a large effect); however, this finding was no longer statistically significant (95% CI, 0.05-1.74; P=18).

Conclusions  This systematic review suggests that supplementation with phytonadione and menaquinone-4 reduces bone loss. In the case of the latter, there is a strong effect on incident fractures among Japanese patients.

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