Technical Abstract: Few data exist on the association between vitamin K status and bone mineral density (BMD) in men and women of varying ages. We examined cross-sectional associations between biochemical measures of vitamin K status and BMD at the hip and spine in 741 men and 863 women (mean age: 59y; range: 32-86y) who participated in the Framingham Heart Study (1996-2000). Vitamin K status was assessed by plasma phylloquinone and percentage undercarboxylated osteocalcin (%ucOC). Among the men, low plasma phylloquinone concentrations adjusted for triglycerides, and elevated serum %ucOC levels were associated with low BMD at the femoral neck, (P=0.03 and 0.009, respectively). Among post-menopausal women not using estrogen replacements, there was an association between plasma phylloquinone and spine BMD (p=0.007), with a non-significant trend of an inverse association with %ucOC (p=0.08). In contrast, there were no significant associations between biochemical measures of vitamin K and BMD in either premenopausal women or postmenopausal women using estrogen replacements. Clinical trials are required to isolate any putative effects of vitamin K on rates of bone loss. The target population in these trials may be critical, as suggested by the findings of this study.