Vitamin K in the Treatment and Prevention of Osteoporosis and Arterial Calcification

Jamie Adams; Joseph Pepping

Am J Health Syst Pharm. 2005;62(15):1574-1581.

Vitamin K for Osteoporosis: Rationale

A number of human-cell studies have helped define the role of vitamin K and osteocalcin in bone health. Both phylloquinone and menaquinone promote bone mineralization; however, menaquinone has been shown to be more potent,^[34] likely because of the enhanced carboxylation of osteocalcin by menaquinone. Menaquinone has been shown to increase osteocalcin accumulation on the cell layer.^[34] In vitro, phylloquinone and menaquinone (MK-4) inhibit osteoclast formation and induce the differentiation of osteoprogenerator cells into osteoblasts.^[35]

The results of recent human and animal studies have suggested that concurrent use of menaquinone and vitamin D may substantially reduce bone loss.^[9,36,37] In rats with ovariectomy-induced bone loss, menaquinone and vitamin D₃ had a synergistic effect on bone-loss reduction.^[9] Hirano and Ishii^[37] found that the coadministration of calcium, menaquinone, and vitamin D in rats increased the peak bone mass and reduced the loss of bone mineral density (BMD).

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Abstract and Introduction
Vitamin K
Vitamin K for Osteoporosis: Rationale
Vitamin K for Osteoporosis: Clinical Studies
Arterial Calcification
Adverse Effects and Dosage of Vitamin K
Discussion
References

Table 1. Epidemiologic Studies of Vitamin K and Bone Health ^a
Ref.	Subjects	Variables Studied	Outcome
8	113 postmenopausal women	UcOC, BMD	UcOC and BMD inversely related
38	72,327 women	Vitamin K intake, hip fracture rate, BMD	Vitamin K intake of >109 µg/day reduced risk of hip fracture by 30%; no correlation between vitamin K and BMD
39	888 men and women	Vitamin K intake, hip fracture rate, BMD	65% reduced risk of fractures in highest quartile of vitamin K intake compared with lowest quartile
40	104 elderly women with hip fractures; 255 controls	UcOC, hip fracture rate, BMD	UcOC (not total OC) predicted fracture risk independently of femoral BMD
41	195 elderly women^b	UcOC, hip fracture rate	Fracture risk 5.9 times higher in women with elevated UcOC at start of study
42	183 elderly women^c	UcOC, hip fracture rate	Fracture risk 3.1 times higher in women with elevated UcOC at start of study
43	212 women	UcOC, BMD	UcOC was independent marker for BMD in women 1-10 yr postmenopause

^aUcOC = undercarboxylated osteocalcin level, BMD = bone mineral density, OC = osteocalcin level.
^b18-month prospective study.
^cThree-year follow-up study.

Table 2. Intervention Studies of Vitamin K's Effect on Bone Variables ^a
Ref.	Subjects	Treatment	Outcome
12	92 postmenopausal women with osteoporosis	Group D: Vitamin D₃ 0.75 µg/day Group K: Menaquinone 45 mg/day Group DK: D and K treatment Group C: Calcium 2 g/day All treatments for 2 yr	BMD improved more in group DK than in group D or group K; increase in lumbar spine BMD significantly greater in group DK than group C
29	219 healthy men and women	Phytonadione 1 mg/day for 2 wk	In all treated groups, mean UcOC decreased from 7.6% to 3.4%; age and sex did not affect the decrease
32	100 healthy adults	Phytonadione 250, 375, 500, or 1000 µg/day or placebo for 2 wk	Phytonadione 1000 µg/day produced greatest carboxylation of OC
33	21 healthy older women	Phytonadione 18 µg/day for 4 wk, then 86, 200, and 450 µg/day, each for 2 wk	Carboxylation of OC not restored by phytonadione 450 µg/day
44	23 postmenopausal women	Phytonadione 80 µg/day, vitamin D₃ 350-400 units/day, both, or placebo for 1 yr	Phytonadione at study dosage needed to attain premenopausal %carbOC
46	46 women with osteoporosis	Menaquinone 45 mg/day for 2 yr	Treated group had fewer new vertebral fractures (13) than placebo group (30)
47	20 elderly women with osteoporosis	Calcium 200 mg/day for 2 wk with or without menaquinone 45 mg/day	Menaquinone group had reduction in UcOC without change in OC
48	20 postmenopausal women	Phytonadione 1 mg/day for 2 wk with or without vitamin D₂ 400 units/day	Carboxylation of OC improved in both groups; vitamin D₂ had no effect
49	113 women with fractures and 91 women without fractures	Menaquinone 45 mg/day, vitamin D₃ 1 µg/day, or both for 4 wk	UcOC decreased in menaquinone groups but not group receiving vitamin D₃ only
54	94 postmenopausal women with osteoporosis (84 controls, 10 treated)	Menaquinone 45 mg/day witheither conjugated estrogens 0.625 mg/day or medroxyprogesterone acetate 2.5 mg/day for 1 yr	Menaquinone-hormonal treatment improved BMD that had been decreasing during hormonal treatment alone

^aBMD = bone mineral density, UcOC = undercarboxylated osteocalcin level, OC = osteocalcin level, %carbOC = percentage of total osteocalcin that is carboxylated.

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Vitamin K in the Treatment and Prevention of Osteoporosis and Arterial Calcification

Vitamin K for Osteoporosis: Rationale

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