Vitamin K Treatment Reduces Undercarboxylated Osteocalcin but Does Not Alter Bone Turnover, Density, or Geometry in Healthy Postmenopausal North American Women

Binkley, Neil; Harke, Judith M.; Krueger, Diane; Engelke, Jean A.; Vallarta-Ast, Nellie; Gemar, Dessa; Checovich, Mary; Chappell, Richard J.; Suttie, John W.

doi:10.1359/jbmr.081254

Cited by 145 publications

(95 citation statements)

References 48 publications

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“…Several protein targets of vitamin K are osteoblastic proteins and components of the bone matrix including osteocalcin, matrix Gla protein, protein S, and Gas 6 (27,28). Under-carboxylated osteocalcin has been reported to correlate with BMD and hip fracture risk in elderly women (29,30), while vitamin K treatment effectively reduces under-carboxylated osteocalcin (31). The association between vitamin K levels and the osteocalcin carboxylation state has led to the suggestion that the primary mechanism underlying the protective influence of vitamin K on bone may involve carboxylation of osteocalcin (26).…”

Section: Introductionmentioning

confidence: 99%

“…The association between vitamin K levels and the osteocalcin carboxylation state has led to the suggestion that the primary mechanism underlying the protective influence of vitamin K on bone may involve carboxylation of osteocalcin (26). However, recent clinical data contrast with this notion and suggest that vitamin K treatment at doses capable of correcting under-carboxylated osteocalcin in healthy postmenopausal women do not correlate with altered bone turnover, density, or geometry (31). Consequently, a direct cause-effect relationship between osteocalcin Á-carboxylation and effects of vitamin K on bone mass remains unclear.…”

Section: Introductionmentioning

confidence: 99%

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Vitamin K2 stimulates osteoblastogenesis and suppresses osteoclastogenesis by suppressing NF-κB activation

2010

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Abstract. Several bone protective factors are reported to exhibit stimulatory activities on bone formation coupled with inhibitory effects on bone resorption; one such factor is vitamin K2. Vitamin K species [K1 (phylloquinone) and K2 (menaquinone)] have long been associated with bone protective activities and are receiving intense interest as nutritional supplements for the prevention or amelioration of bone disease in humans. However, the mechanisms of vitamin K action on the skeleton are poorly defined. Activation of the nuclear factor κB (NF-κB) signal transduction pathway is essential for osteoclast formation and resorption. By contrast, NF-κB signaling potently antagonizes osteoblast differentiation and function, prompting us to speculate that NF-κB antagonists may represent a novel class of dual anticatabolic and pro-anabolic agents. We now show that vitamin K2 action on osteoblast and osteoclast formation and activity is accomplished by down-regulating basal and cytokineinduced NF-κB activation, by increasing IκB mRNA, in a Á-carboxylation-independent manner. Furthermore, vitamin K2 prevented repression by tumor necrosis factor · (TNF·) of SMAD signaling induced by either transforming growth factor ß (TGFß) or bone morphogenetic protein-2 (BMP-2). Vitamin K2 further antagonized receptor activator of NF-κB (RANK) ligand (RANKL)-induced NF-κB activation in osteoclast precursors. Our data provide a novel mechanism to explain the dual pro-anabolic and anti-catabolic activities of vitamin K2, and may further support the concept that pharmacological modulation of NF-κB signal transduction may constitute an effective mechanism for ameliorating pathological bone loss and for promoting bone health.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Vitamin K2 stimulates osteoblastogenesis and suppresses osteoclastogenesis by suppressing NF-κB activation

2010

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“…Phylloquinone can also increase cOC in older adults 77 and lower ucOC/OC 78 but results for younger adults are inconclusive 77,79 . Furthermore, 45mg/d MK4 significantly decreased ucOC in postmenopausal women 71,72,76,80,81 , increased cOC and generally increased total OC 80,81 , although 1.5mg/d may be sufficient to decrease serum ucOC and ucOC/OC while increasing cOC 82 ; a dose of 1.5mg/d accords with the amount of MK4 obtainable from diet, whereas 45mg/d is pharmacological 83 .…”

Section: Bonementioning

confidence: 95%

“…In addition, a 2009 review and subsequent study showed that phylloquinone can dose-dependently reduce ucOC in postmenopausal women, with a consistently effective dose being 1mg/d, although there were inconsistent results for total OC 69,76 . Phylloquinone can also increase cOC in older adults 77 and lower ucOC/OC 78 but results for younger adults are inconclusive 77,79 .…”

Section: Bonementioning

confidence: 99%

Cardiovascular Calcification and Bone: A Comparison of the Effects of Dietary and Serum Vitamin K and its Dependent Proteins

Nicoll¹,

Howard²,

Henein³

2015

ICFJ

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This review compares the effect of vitamin K on cardiovascular (CV) calcification and bone health and shows that, in principal, the γ-carboxylation of the vitamin K-dependent proteins matrix Gla protein (MGP) and its bone equivalent osteocalcin (OC), generally ensures that hydroxyapatite is kept out of the CV system and is deposited in bone. This is an important finding, since there is currently no reliable treatment for CV calcification.Vitamin K2 (menaquinone) may be more effective in the arteries, while vitamin K1 (phylloquinone) is more active in bone. Nevertheless, there remains considerable uncertainty over the precise scope of the functions of MGP and OC, and their carboxylated and under-carboxylated forms, as well as the newly discovered vitamin K-dependent proteins. Although a diet high in vegetables could deliver adequate phylloquinone, supplementation of menaquinone may be necessary for those at risk of CV calcification. Several animal studies and one human study have demonstrated that arterial calcification could be reduced with vitamin K supplementation and there are further trials in progress. Patients on warfarin are particularly prone to CV calcification but there has been concern that supplementation would either counter warfarin treatment or destabilise INR. In fact, studies suggest that low dose phylloquinone did not increase coagulation and may improve the stability of anticoagulant therapy. Furthermore, use of oral anticoagulants which do not affect vitamin K metabolism, such as ximelagatran, could be used when there is a need for vitamin K supplementation for artery or bone health.

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“…Published commentary have also questioned the findings. (1,19,(26)(27)(28) Results of several placebo-controlled clinical trials of vitamin K 1 are now being reported. One (29) showed a modest positive effect of 200 mg/d of K 1 for 2 yr on BMD at the distal radius but not at any other skeletal site.…”

mentioning

confidence: 99%

Vitamin K and Bone: Past, Present, and Future

Gundberg

2009

Journal of Bone and Mineral Research

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Vitamin K Treatment Reduces Undercarboxylated Osteocalcin but Does Not Alter Bone Turnover, Density, or Geometry in Healthy Postmenopausal North American Women

Cited by 145 publications

References 48 publications

Vitamin K2 stimulates osteoblastogenesis and suppresses osteoclastogenesis by suppressing NF-κB activation

Vitamin K2 stimulates osteoblastogenesis and suppresses osteoclastogenesis by suppressing NF-κB activation

Cardiovascular Calcification and Bone: A Comparison of the Effects of Dietary and Serum Vitamin K and its Dependent Proteins

Vitamin K and Bone: Past, Present, and Future

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