Diet- or warfarin-induced vitamin K insufficiency elevates circulating undercarboxylated osteocalcin without altering skeletal status in growing female rats

To further characterize the skeletal role of vitamin K (K), markers of bone turnover, density, and strength were evaluated in rats with diet- or warfa rin (W)-induced K insufficiency. One hundred two, 7-week-old, female rats w ere randomly assigned to low K (phylloquinone [K1], 20 mu g/kg diet), contr ol K (K1, 1300 mu g/kg diet), low-dose W (W, 1.5 mg/kg control diet), or hi gh-dose W plus K (W/K1, 10/100 mg/kg diet). Femur bone mineral content (BMC ) and bone mineral density (BMD), plasma prothrombin time (PT) and prothrom bin concentration (PC), and serum total alkaline phosphatase (ALP) and skel etal alkaline phosphatase (sALP) were measured at baseline and days 20, 40, 60, and 80. Serum total osteocalcin (OC) and undercarboxylated osteocalcin (ucOC) and femur length (FL) were measured at baseline and day 80. Left fe mur OC was measured and biomechanical testing of the right femur and third lumbar vertebral body was performed at day 80. Low dietary K elevated circu lating ucOC (17% higher than control; p < 0.0001) at day 80. Furthermore, i n both W groups, essentially all circulating OC was undercarboxylated and f emur OC was lower than control (p < 0.0001). However, there was no change i n femur percent ucOC, suggesting deposition of less newly synthesized OC. N o between group differences were observed in PT, ALP, sALP, FL, BMC, BMD, o r bone strength. In conclusion, skeletal K insufficiency can be induced by W or diet manipulation. This does not hinder peak bone mass attainment in f emale rats; however, W causes less newly synthesized OC to be deposited in bone.