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

PURPOSE: 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). METHODS: 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). RESULTS: 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%. CONCLUSIONS: 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.

The relationship of joint hypermobility, bone mineral density, and osteoarthritis in the general population: the Chingford Study.

OBJECTIVE: The prevalence of hypermobility and its consequence in an aging female population is unknown. Case studies of patients with the benign joint hypermobility syndrome suggest both a tendency toward osteopenia and an association with premature osteoarthritis (OA). We assessed hypermobility and its relationship to bone mineral density (BMD) and OA in a postmenopausal female community population. METHODS: Joint hypermobility was assessed by the Beighton and the (more quantitative) Contompasis scores in 716 female subjects under followup in the Chingford Study (age range 53-72, mean 61 yrs, SD 5.8). RESULTS: We found 79 of 716 subjects (11%) had a hypermobility score > 1/9 on the Beighton scale (spine in 75/79); 82/716 had a Contompasis score > 22 (normal < 18). Only one had a 4/9 Beighton score indicative of generalized joint hypermobility. Subjects with Contompasis > 22 were more physically active and less likely to smoke. They had a reduced risk of knee OA (joint space narrowing) (OR 0.48, 95% CI 0.27-0.83, after adjusting for age, height, weight, and activity), but no change in risk of OA in spine or hands. Hip BMD was increased by 3% in this more hypermobile subgroup (p < 0.05). A similar effect was seen for knee OA, but not BMD in those with a Beighton score > 1. CONCLUSION: Our data suggest that in this postmenopausal population the tendency to joint hypermobility may be a marker for fitness, manifested by reduced knee OA and increased hip BMD. The incidence of generalized hypermobility (Beighton > 4/9) was very low (0.14%) compared with the localized form (seen in 11%) and other studies. Those with mild degrees of hypermobility showed no evidence of premature OA or reduced BMD, as reported in some of the rarer heritable disorders of connective tissue.