Level 2: Mid-level evidence

All women who are at risk for osteoporosis should receive counseling regarding universal preventive measures related to fracture risk, including calcium and vitamin D intake, weight-bearing exercise, smoking cessation, and avoidance of excess alcohol intake. Additional options for preventing osteoporosis continue to be an important research topic, including treatment with estrogen, bisphosphonates (alendronate, risedronate), raloxifene, calcitonin, and vitamin K. Caution is advised with vitamin K supplementation, as it will negate the anticoagulant effects of warfarin or other vitamin K antagonists.

The efficacy of oral phytonadione or menaquinone-4 (forms of vitamin K) for preventing osteoporosis or reducing fracture risk in adults was evaluated in a systematic review of 13 randomized trials (Arch Intern Med. 2006;166:1256-1261). All the included trials had outcome data on bone loss; seven trials had outcome data on fractures. Most of the studies were conducted in postmenopausal women in Japan. Eleven used menaquinone-4 (including all seven trials with fracture data), and two used phytonadione; the most common dose studied was menaquinone-4 45 mg p.o. daily. Only two trials had dropout rates >20%. In addition, only two trials involved allocation concealment, but neither of these reported fracture data.

Vitamin K was associated with reduced bone loss in 12 of the 13 trials. The only trial that reported negative results was a German study that evaluated phytonadione in premenopausal athletic women. Vitamin K was associated with reduced fracture rate in all seven trials that evaluated this outcome. The absolute risk reduction in hip fractures was 6% (NNT 17) in a meta-analysis of five trials. There was a 13% absolute risk reduction in vertebral fractures (NNT 8) in a meta-analysis of four trials. The absolute risk reduction in all nonvertebral fractures was 9% (NNT 11) in a meta-analysis of five trials.


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The review authors recommend a diet rich in vitamin K (green leafy vegetables and some vegetable oils) instead of supplements until these results are confirmed in large randomized trials.