title: Diet- or warfarin-induced vitamin K insufficiency elevates circulating undercarboxylated osteocalcin without altering skeletal status in growing female rats.
abstract: To further characterize the skeletal role of vitamin K (K), markers of bone turnover, density, and strength were evaluated in rats with diet- or warfarin (W)-induced K insufficiency. One hundred two, 7-week-old, female rats were randomly assigned to low K (phylloquinone [K1], 20 microg/kg diet), control K (K1, 1300 microg/kg diet), low-dose W (W, 1.5 mg/kg control diet), or high-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 prothrombin concentration (PC), and serum total alkaline phosphatase (ALP) and skeletal 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 femur OC was measured and biomechanical testing of the right femur and third lumbar vertebral body was performed at day 80. Low dietary K elevated circulating ucOC (17% higher than control; p < 0.0001) at day 80. Furthermore, in both W groups, essentially all circulating OC was undercarboxylated and femur OC was lower than control (p < 0.0001). However, there was no change in femur percent ucOC, suggesting deposition of less newly synthesized OC. No between group differences were observed in PT, ALP, sALP, FL, BMC, BMD, or bone strength. In conclusion, skeletal K insufficiency can be induced by W or diet manipulation. This does not hinder peak bone mass attainment in female rats; however, W causes less newly synthesized OC to be deposited in bone.
authors.affiliation: University of Wisconsin Institute on Aging, University of Wisconsin, Madison 53706, USA.
authors.forename: A
authors.initials: A
authors.lastname: Haffa
authors.forename: D
authors.initials: D
authors.lastname: Krueger
authors.forename: J
authors.initials: J
authors.lastname: Bruner
authors.forename: J
authors.initials: J
authors.lastname: Engelke
authors.forename: C
authors.initials: C
authors.lastname: Gundberg
authors.forename: M
authors.initials: M
authors.lastname: Akhter
authors.forename: N
authors.initials: N
authors.lastname: Binkley
mesh_terms: D015502:Absorptiometry, Photon; D000818:Animals; D000925:Anticoagulants / Q000009:adverse effects*; D015519:Bone Density; D001846:Bone Development; D001842:Bone and Bones / Q000502:physiology*; D002264:Carboxylic Acids / Q000097:blood; D004032:Diet; D005260:Female; D015675:Osteocalcin / Q000097:blood*; D051381:Rats; D014812:Vitamin K / Q000008:administration & dosage; D014813:Vitamin K Deficiency / Q000097:blood / Q000503:physiopathology*; D014859:Warfarin / Q000009:adverse effects*
chemical_list: D000925:Anticoagulants; D002264:Carboxylic Acids; D015675:Osteocalcin; D014812:Vitamin K; D014859:Warfarin