JOURNAL OF BONE AND MINERAL RESEARCH
Volume 16, Number 4, 2001
©
2001 American Society for Bone and Mineral Research
Letter to the Editor
The Use of Vitamin K May Be a Good Choice for
Microgravity-Induced Bone Disorder
To the Editor:
of osteocalcin during space flight is unknown, we propose a
possible involvement of insulin-like growth factor I (IGF-I).
We have shown previously that vitamin K plus vitamin D
treatment increased the cortical bone mass in children with
skeletal unloading.
ported to improve bone markers in an astronaut. However,
the mechanism of action of vitamin K and its effect on bone
remained unknown.
Recently, we found that vitamin K treatment increased
serum carboxylated osteocalcin level and lumbar bone
mass and decreased serum undercarboxylated osteocalcin
level in long-term glucocorticoid-treated children with
Both vitamin K and IGF-I were reported to modulate car-
(11)
boxylated osteocalcin synthesis.
It has been suggested
(
1,2)
Vitamin K treatment was also re-
(12)
that skeletal unloading induces resistance to IGF-I ; there-
fore, vitamin K treatment may improve carboxylated osteo-
calcin synthesis which is suppressed by the resistance to
IGF-I. Further studies are needed to elucidate the role of
carboxylation of osteocalcin in bone.
(3)
(
4)
vitamin D treatment. In addition, the change of lumbar
bone mass showed an inverse correlation with the change
REFERENCES
(
4)
1. Sugiyama T, Tanaka H, Kawai S 1999 Vitamin K plus vitamin
D treatment of bone problems in a child with skeletal unload-
ing. J Bone Miner Res 14:1466–1467.
of serum undercarboxylated osteocalcin level. These
results suggest that vitamin K increases bone mass
through carboxylation of osteocalcin. In contrast, vitamin
K does not induce such an increase in adult patients with
2
. Sugiyama T, Saito Y, Kaichi I, Sugi M, Tanaka H, Kawai S
2000 Menatetrenone plus alfacalcidol treatment for bone prob-
lems in eight children with skeletal unloading. J Bone Miner
Metab 18:41–44.
(
5)
osteoporosis. The different effects of vitamin K on the
bone mass of children and of adults remain to be clari-
fied.
3
. Vermeer C, Wolf J, Knapen MHJ 1997 Microgravity-induced
changes of bone markers: Effects of vitamin K supplementa-
tion. Bone 20(suppl):16S.
We also found that the ratio of serum carboxylated os-
teocalcin level to serum intact osteocalcin level was posi-
tively correlated with the Z score for the ultrasound velocity
of tibiae, a possible indicator of bone quality, in healthy
4
. Inoue T, Sugiyama T, Matsubara T, Kawai S, Furukawa S
2001 Inverse correlation between the changes of lumbar bone
mineral density and serum undercarboxylated osteocalcin after
(6)
vitamin K (menatetrenone) treatment in children treated with
children. On the other hand, there was no correlation
between the serum levels of intact, carboxylated and under-
carboxylated osteocalcin, and the Z score for the ultrasound
2
glucocorticoid and alfacalcidol. Endocrinol J (in press).
5
. Shiraki M, Shiraki Y, Aoki C, Miura M 2000 Vitamin K2
(menatetrenone) effectively prevents fractures and sustains
(6)
velocity. These observations suggest that carboxylation of
osteocalcin is related to bone quality. Indeed, vitamin K
treatment was recently reported to reduce vertebral and hip
fractures without increasing bone mass in adult patients
lumbar bone mineral density in osteoporosis. J Bone Miner
Res 15:515–521.
6. Sugiyama T, Kawai S 2001 Carboxylation of osteocalcin may
be related to bone quality: A possible mechanism of bone
fracture prevention by vitamin K. J Bone Miner Metab (in
press).
(
5,7)
with osteoporosis
and to improve bone strength through
modification of hydroxyapatite crystals in rats with diabe-
7
. Booth SL, Tucker KL, Chen H, Hannan MT, Gagnon DR,
Cupples LA, Wilson PWF, Ordovas J, Schaefer EJ, Dawson-
Hughes B, Kiel DP 2000 Dietary vitamin K intakes are asso-
ciated with hip fracture but not with bone mineral density in
elderly men and women. Am J Clin Nutr 71:1201–1208.
. Wada S, Suda S, Kitahama S, Akiyama Y, Tomiuga T, Ito M,
Iitaka M, Katayama S 2000 Treatment with menatetrenone
(8)
tes. Although the precise mechanism is unclear, this may
be associated with a finding that osteocalcin stimulates bone
(
9)
mineral maturation.
Thus, our recent findings suggest that carboxylation of
osteocalcin plays an important role in vitamin K treat-
8
(4,6)
ment.
Carboxylation of osteocalcin was recently re-
(
vitamin K ) improved bone strength through modification of
2
ported to decrease early and remain low during space
hydroxyapatite crystals in NIDDM rats. J Bone Miner Res
5:S1;S309.
(10)
flight,
indicating that the use of vitamin K is a good
1
choice in the treatment for microgravity-induced bone dis-
order. Although the mechanism of decreased carboxylation
9. Boskey AL, Gadaleta S, Gundberg C, Doty SB, Ducy P,
Karsenty G 1998 Fourier transform infrared microspectro-
7
94