Serum vitamin K1 (phylloquinone) is associated with fracture risk and hip strength in post-menopausal osteoporosis: A cross-sectional study.

Abstract

Vitamin K may play a potential role in bone metabolism, although further evidence is needed. The mechanisms behind its skeletal effects and optimum intake for maintaining bone health remain poorly defined. To elucidate these two issues, we investigated the association between circulating vitamin K1 (phylloquinone) concentrations with fracture risk, bone mineral density (BMD), hip geometry and plasma dephospho-uncarboxylated-Matrix Gla Protein (dp-ucMGP), an extra-hepatic vitamin K dependent protein (VKDP), in post-menopausal osteoporosis (PMO). We studied 374 women aged (mean [SD]) 68.7[12.3] years with PMO. Information including demographics, lifestyle habits and previous fractures was captured through a questionnaire. Serum was analysed for vitamin K1. BMD at the lumbar spine (LS), total hip (TH) and femoral neck (FN) (n=277) and hip structural analysis (HSA) parameters (n=263) were derived from DXA scans. VKDPs including undercarboxylated prothrombin (PIVKA-II) and dp-ucMGP were measured in a sub-group (n=130). Serum vitamin K1 was significantly lower in the group with fractures (prevalent fractures: 0.53 [0.41], no fractures; 0.65 [0.66] μg/L, p=0.04) and independently associated with fracture risk. The adjusted odds ratio (95% CI) per μg/L increase in vitamin K1 was 0.550 (0.310-0.978, p=0.042). Among the HSA parameters, serum vitamin K1 was positively associated with cross-sectional area (CSA) (p=0.02), cross sectional moment of inertia (CSMI) (p=0.028) and section modulus (Z) (p=0.02) at the narrow neck (NN) of femur. Dp-ucMGP was detectable in 97 (75%) participants with serum vitamin K1 of 0.26 [0.15] μg/L, whilst PIVKA-II was above the clinical threshold in only 3.8%. Our data suggest that the positive effect of vitamin K on fracture risk may be related to its effects on bone strength. Higher concentrations of serum vitamin K1 may be required for vitamin K's skeletal effects compared to coagulation. Further prospective or interventional studies are needed for confirmation and should include measures of bone quality.