Abstract
Previous research suggests vitamin K may increase bone mass, prevent loss of bone mineral density (BMD), and possibly reduce fracture incidence. The purpose of this study was to update the systematic review and meta-analysis of the effect of both vitamin K1 and vitamin K2 (menaquinone-4 and menaquinone-7) on bone turnover, BMD and fracture risk that we published in 2007 in the light of key vitamin K supplementation studies completed in the last 30 months. The Cochrane Library (1994-2009) and EMBASE (1980-2009) databases were searched for relevant cross sectional, longitudinal and intervention studies. Thirty three studies were included in the systematic review and seven in the meta-analysis. Results from the systematic review for vitamin K1 suggested a significant negative correlation with undercarboxylated osteocalcin (ucOC), but mixed results for total OC, bone resorption markers and fracture, and no association with BMD. The meta analysis supported these results, showing a significant effect of vitamin K1 supplementation on reducing ucOC (p,0.00001, Z=15.59, weighted mean difference=-21.23 95% CI (-23.90 to-18.57)), but no significant effect on BMD at any site (P=0.78, Z=0.28, weighted mean difference=0.00, 95%CI (0.00 to 0.01)). There was insufficient data to analyse fracture incidence, bone resorption or OC in the K1 metaanalysis. Results from the systematic review of K2 studies showed a significant negative association of K2 on ucOC in intervention studies. The intervention studies, but not cross-sectional studies, independently associated vitamin K2 with fracture risk. No effect of vitamin K2 supplementation on bone resorption was found for any study type, but the intervention studies were associated with increased BMD. This was supported by results from the vitamin K2 meta-analysis for a reduction in ucOC (p,0.00001, Z=8.75, weighted mean difference=95% CI (-68.54 to-43.45)) and increased BMD from combined sites (p=0.004, Z=3.86, weighted mean difference= 95% CI (1.24-6.48)). These findings suggest vitamin K; especially K2, may be beneficial for bone health, as ucOC is an independent risk factor for osteoporotic fracture. In this analysis, K2, but not K1 supplementation, was associated with increased BMD. However, overall the results from the studies were too conflicting to recommend routine supplementation. Further, higher quality and more homogenous studies are needed before any clear conclusions can be made about vitamin K and bone health.