Effect of combined administration of vitamin D3 and vitamin K2 on bone mineral density of the lumbar spine in postmenopausal women with osteoporosis

doi:10.1007/s007760070003

Journal of Orthopaedic Science

Volume 5, Issue 6, November 2000, Pages 546-551

https://doi.org/10.1007/s007760070003 Get rights and content

Abstract

The effect of the combined administration of vitamin D₃ and vitamin K₂ on bone mineral density (BMD) of the lumbar spine was examined in postmenopausal women with osteoporosis. Ninety-two osteoporotic women who were more than 5 years after menopause, aged 55–81 years, were randomly divided into four administration groups: vitamin D₃ (1α hydroxyvitamin D₃, 0.75µg/day) (D group; n 5 29), vitamin K₂ (menatetrenone, 45mg/day) (K group; n 5 22), vitamin D₃ plus vitamin K₂ (DK group, n 5 21), and calcium (calcium lactate, 2g/day) (C group; n 5 20). BMD of the lumbar spine (L2–L4) was measured by dual energy X-ray absorptiometry at 0, 1, and 2 years after the treatment started. There were no significant differences in age, body mass index, years since menopause, and initial BMD among the four groups. One-way analysis of variance (ANOVA) with repeated measurements showed a significant decrease in BMD in the C group (P, 0.001). Two-way ANOVA with repeated measurements showed a significant increase in BMD in the D and K groups compared with that in the C group (P, 0.05 and P, 0.001, respectively), and a significant increase in BMD in the DK group compared with that in the C, D, and K groups (P, 0.0001, P, 0.05 and P, 0.01, respectively). These findings indicate that combined administration of vitamin D₃ and vitamin K₂, compared with calcium administration, appears to be useful in increasing the BMD of the lumbar spine in postmenopausal women with osteoporosis.

References (28)

BeresfordJ.N. et al.
Production of osteocalcin by human bone cells in vitro. Effects of 1,25(OH)₂D₃, 24,25(OH)₂D₃, parathyroid hormone, and glucocorticoids
Met Bone Dis Rel Res
(1984)
Dawson-HughesB.
Calcium supplementation and bone loss: a review of controlled clinical trials
Am J Clin Nutr
(1991)
AloiaJ.F. et al.
Calcitriol in the treatment of postmenopausal osteoporosis
Am J Med
(1989)
ChristiansenC. et al.
Effect of 1,25-dihydroxy-vitamin D₃ in itself or combined with hormone treatment in preventing postmenopausal osteoporosis
Eur J Clin Invest
(1981)
CummingR.G.
Calcium intake and bone mass: a quantitative review of the evidence
Calcif Tissue Int
(1990)
DalskyG.P. et al.
Weight-bearing exercise training and lumbar bone mineral content in postmenopausal women
Ann Intern Med
(1988)
EttingerB. et al.
Postmenopausal bone loss is prevented by treatment with low-dosage estrogen with calcium
Ann Intern Med
(1987)
FalchJ.A. et al.
Postmenopausal osteoporosis: no effect of 3 years treatment with 1,25-dihydroxycholecalciferol
Acta Med Scand
(1987)
GallagherJ.C. et al.
The effect of calcitriol on patients with postmenopausal osteoporosis with special reference to fracture frequency
Proc Soc Exp Biol Med
(1989)
GallagherJ.C. et al.
Treatment of postmenopausal osteoporosis with high dose of synthetic calcitriol
Ann Intern Med
(1990)

HaraK. et al.

Menatetrenone inhibits bone resorption partly through inhibition of PG E2 synthesis in vitro

J Bone Miner Res

(1993)

HaraK. et al.

Influence of vitamin D₃ on inhibitory effect of vitamin K₂ on bone loss in ovariectomized rats

Folia Pharmacol Jpn

(1994)

HauschkaP.V. et al.

Direct identification of the calcium-binding amino acid, γ-carboxyglutamate, in mineralized tissue

Proc Natl Acad Sci USA

(1975)

HaushkaP.V. et al.

Calcium-dependent γ-helical structure in osteocalcin

Biochemistry

(1982)

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Effect of combined administration of vitamin D3 and vitamin K2 on bone mineral density of the lumbar spine in postmenopausal women with osteoporosis

Abstract

Met Bone Dis Rel Res

Am J Clin Nutr

Calcitriol in the treatment of postmenopausal osteoporosis

Am J Med

Effect of 1,25-dihydroxy-vitamin D3 in itself or combined with hormone treatment in preventing postmenopausal osteoporosis

Eur J Clin Invest

Calcium intake and bone mass: a quantitative review of the evidence

Calcif Tissue Int

Weight-bearing exercise training and lumbar bone mineral content in postmenopausal women

Ann Intern Med

Postmenopausal bone loss is prevented by treatment with low-dosage estrogen with calcium

Ann Intern Med

Postmenopausal osteoporosis: no effect of 3 years treatment with 1,25-dihydroxycholecalciferol

Acta Med Scand

The effect of calcitriol on patients with postmenopausal osteoporosis with special reference to fracture frequency

Proc Soc Exp Biol Med

Treatment of postmenopausal osteoporosis with high dose of synthetic calcitriol

Ann Intern Med

Menatetrenone inhibits bone resorption partly through inhibition of PG E2 synthesis in vitro

J Bone Miner Res

Influence of vitamin D3 on inhibitory effect of vitamin K2 on bone loss in ovariectomized rats

Folia Pharmacol Jpn

Direct identification of the calcium-binding amino acid, γ-carboxyglutamate, in mineralized tissue

Proc Natl Acad Sci USA

Calcium-dependent γ-helical structure in osteocalcin

Biochemistry

Effect of combined administration of vitamin D₃ and vitamin K₂ on bone mineral density of the lumbar spine in postmenopausal women with osteoporosis

Effect of 1,25-dihydroxy-vitamin D₃ in itself or combined with hormone treatment in preventing postmenopausal osteoporosis

Influence of vitamin D₃ on inhibitory effect of vitamin K₂ on bone loss in ovariectomized rats