Vitamin K supplementation does not prevent bone loss in ovariectomized Norway rats

Rats (n = 96) were randomized to 6 dosing groups [n = 16/group; Sham; OVX; OVX + BP (100 μg/kg/100 μg/mL saline sc); OVX + PK; OVX + MK-4; and OVX + MK-7] for 6 wk. Equimolar daily doses of 107 mg PK/kg, 147 mg MK-4/kg, and 201 mg MK-7/kg diet were provided.BP significantly increased bone strength and bone mineral density (BMD) vs. OVX (P < 0.05). However, PK, MK-4 or MK-7 did not change bone strength or BMD compared to the OVX group. Whereas supplementation of PK, MK-4 and MK-7 increased serum and tibia concentrations of each respective form, PK concentrations were consistently higher despite equimolar intakes.PK, MK-4, and MK-7 do not appear to prevent bone loss in OVX rats when administered concurrent with adequate intake of other nutrients.There has been considerable recent interest in the role of vitamin K in bone metabolism [1-3]. Vitamin K is essential for the γ-carboxylation of specific glutamate residues in bone-specific proteins, including osteocalcin (OC). Without this modification, OC lacks the ability to bind to the mineral hydroxyapatite [4]. In vitro studies indicate that vitamin K can enhance bone mineralization and decrease bone resorption, either in its role as an enzyme cofactor or by mechanisms independent of γ-carboxylation [5,6]. For example, recent evidence suggests that vitamin K promotes the expression of osteoblastic markers through steroid and xenobiotic receptors (SXR)/pregnane X receptor (PXR)-modulated gene transcription [2,6].Vitamin K exists in two primary forms in the diet: phylloquinone (PK) and menaquinones (MKn). PK, menaquinone-4 (MK-4) and menaquinone-7 (MK-7) have been collectively identified by various investigators as forms of vitamin K that have a potential role in preventing bone loss [7-10]. PK is the main dietary form of vitamin K, and is found in green leafy vegetables and vegetable oils [11]. MKn are primarily synthesized by bacteria in the gut, and differ from PK in the length of the side chain, which may contain 2-14