ARTICLE
The effect of vitamin K2 (MK-4) on reduced “bone quality” by
magnesium insufficiency
Norio Amizuka1, 2, Minqi Lil, 2,
2 Masatoshi Kobayashi3, Shoji Akahane4,
Kuniko Hara3, Kiichi Takeuchi1, Hidehiro
Ozawa4, Yasuhiro Akiyama3, Takeyasu
Maeda1, 2
Divisions of 1 Oral Anatomy, Niigata University
Graduate School of Medical and Dental Sciences,
2 Center for Transdisciplinary Research, Niigata
University Niigata Japan
3 Pharmacological Evaluation Section, Department of
Drug Research II, Eisai. Co. Ltd., Tokyo, Japan
4 Institute for Dental Science, Matsumoto Dental
University, Shiojiri, Japan
Mg-insufficient bone reveals fragility to mechanical loading
despite normal or higher levels of bone mineral content (Kobayashi
et al., Bone 2004: 35; 1136). The administration with
vitamin K2 (MK-4: menatetrenone), however, inhibited the reduced
maximum load and elastic modulus of the Mg-insufficient bone,
indicating that MK-4 increased the “bone quality”. Therefore, we
have examined bone remodeling and mineral of the tibiae and femora
of 4-week-old Wistar male rats fed normal (control group, 0.09%
Mg), Mg-insufficient (low Mg group, 0.006% Mg), or MK-4
supplemented Mg-insufficient diets (MK-4 group, 30 mg/kg MK-4,
0.006% Mg) for 4-, or 8-weeks. The termini of the shortened
metaphyseal trabeculae of low Mg groups localized many osteoclasts
with well-developed ruffled borders. In addition, the
Mg-insufficient cortical bones showed complicated meshwork of
cement lines, implying accelerated bone remodeling. In contrast,
the MK-4 groups showed osteoclasts with poorly-formed ruffled
borders on metaphyseal trabeculae, and fewer numbers of cement
lines in the cortical bone. Thus, MK-4 appeared to inhibit
osteoclastic bone resorption once stimulated by Mg-insufficiency,
thereby normalizing bone remodeling. An electron probe
microanalyzer (EPMA) demonstrated an increased and decreased
concentrations of Ca and Mg in the low Mg group, respectively.
X-ray diffraction provided various chemical formulae of mineralized
crystals including hydroxyapatites (HA) in the control group, but
an extremely-elevated purity of HA [Cai0(P04)6(OH)2] in the low Mg
group. Consistently, Mg-insufficient bone showed large mineralized
nodules and premature mineralization of collagen fîbrils in the
osteoid. Therefore, an increased concentration of Ca in the
Mg-insufficient bone may cause the high purity of HA, larger
mineralized nodules and premature collagenous mineralization. In
contrast, MK-4 did not affect the concentration of Mg and Ca, or
HA-purity, but prevented mineralization accelerated by
Mg-insuffîciency. Thus, MK-4 appears to recover the “bone quality”
lessened by Mg insufficiency by two mechanisms: controlling bone
turnover and mineralization.
Key words : magnesium, vitamin K2 (MK-4:
menatetrenone), bone, bone quality, histology
The relationships between
markers of either bone
resorption or bone formation and serum magnesium or calcium levels
Noboru Saito1, Yoshihisa Ando2, Naoto
Tabata2, Saburou Saito1, Shoji
Nishiyama3
1 Department of Internal Medicine and Center for
lifestyle-related Diseases
2 Department of Surgery and Center for Alimentary Tract
and Liver Diseases
3 Miyazaki Medical Center Hospital, Department of
Hygiene, Faculty of Medicine, Showa University
This study is aimed to clarify the relationships between bone
resorption or formation markers and serum magnesium (Mg) or calcium
(Ca) levels in elderly inpatients. In this study
107 inpatients (33 males, 74 females) were
recruited, who did not take furosemide, spironolactone,
alfacalcidol and magnesium oxide, and who showed below
30 mg/dL of BUN to exclude cases with renal failure. Fasting
blood samples and urinary samples were obtained early in the
morning. Markers of bone resorption such as urinary
deoxypyridinoline (DPd) and N-telopeptide (NTx) were measured by
ELISA, which were divided by urinary creatinine (Cr) and expressed
as DPd/cr and NTx/cr. As a bone formation marker serum osteocalcin
(OC) was measured by IRMA. Serum Mg was measured by xylizil blue
method, and Ca was measured by OCPC.
Urinary DPd/cr and NTx/cr tended to increase by aging, but not
significantly. In elderly inpatients aged 65 to 79 years old,
10 males over 60 nMBCE/mM/cr of NTx/cr showed a high
level of DPd/cr and lower levels of serum Mg, Ca, zinc (Zn), total
protein (TP) and albumin (Alb) compared to 8 males below it,
while 21 females over it did a high level of DPd/cr and a
lower level of serum Ca compared to 12 females below it.
Therefore, urinary NTx/cr and DPd/cr were inversely related to
serum Mg, Ca, Zn, TP and Alb in males, while these were inversely
related only to serum Ca in females.
Key words : deoxypyridinoline, N-telopeptide,
osteocalcin, serum magnesium, serum calcium
Magnesium and other
mineral levels in blood of
middle age Japanese men and women
R Takeda1, 3, T. Nakamura1, T.
Suyama2, Y. Minakuchi2, M.
Ishida3, M. Imanishi3, H.
Shigetomi3, A. Takeda3, R.
Kitamura2, T. Takeda3, M.
Kimura3
1 Graduate School of Medicine, Kyoto
University
2 Takeda Hospital Health Center
3 Takeda Research Institute of Life Science
<kimura@takedahp.or.jp>
To clarify mineral nutritional status, 424 men
(46.3 ± 8.2 years) and 274 women
(45.7 ± 8.7 years), total 698 inhabitants
living in Kyoto and Shiga prefectures in Japan were selected for
volunteers as healthy subjects (have no disease) with informed
consent. Magnesium (Mg), calcium (Ca), sulfur (S), iron (Fe),
phosphorus (P), zinc (Zn) and copper (Cu) concentrations in blood
after wet digestion by nitric acid were determined by inductively
coupled plasma-atomic emission spectrometry (OPTIMA4300DV:
Perkin-Elmer Co. Ltd., USA). Blood mineral levels were as follows
(average ± SD): Mg(μg/mL): 37.4 ± 3.2, Ca
(μg/mL): 57.9 ± 3.8, S(mg/mL):
1.56 ± 0.11, Fe(μg/mL): 520 ± 38, P(μg/mL):
393 ± 32, Zn(μg/mL): 6.67 ± 0.78, Cu(ng/mL):
779 ± 93 in men and Mg(μg/mL): 34.6 ± 3.2,
Ca(μg/mL): 62.5 ± 3.8, S(mg/mL): 1.47 ± 0.11,
Fe(μg/mL): 442 ± 46, P(μg/mL): 367 ± 31,
Zn(μg/mL): 5.84 ± 0.74, Cu(ng/mL):
837 ± 119 in women. Mg, S, Fe, P and Zn
concentrations in blood of men were significantly high compared to
that of women, and Ca and Cu concentrations in men were low
compared to that of women.
Key words : human, magnesium, calcium, phosphorus,
zinc
Stimulatory effect of
fructooligosaccharides on
intestinal magnesium absorption
Atsutane Ohta
Laboratory of Applied Nutrition, Faculty of Clinical
Pharmaceutical Science, Division of Pharmaceutical Science, Josai
International University
The Japanese Recommended Daily Allowance (Sixth revision) for
magnesium has been established at 300 mg/day. However, there
is little information about the dietary magnesium intake of
Japanese. Several reports showed that Japanese dietary magnesium
intake is about 200 to 250 mg/day. Thus, Japanese magnesium
intake seems to be insufficient. Therefore, it is important that
intestinal absorption of magnesium be increased in Japanese.
Generally, about 35 to 70% of dietary magnesium is absorbed in the
intestine. Intestinal magnesium absorption is believed to occur
primarily in the ileum. However, several reports have revealed that
magnesium absorption takes place not only via the small
intestine, but also via the large intestine. The
contribution of each intestinal segment to magnesium absorption
remains unclear.
It has been reported that several nutrients inhibit intestinal
magnesium absorption. Excess dietary calcium and phosphorus inhibit
magnesium absorption by forming insoluble compounds with magnesium
in the intestine. Many researchers confirmed that nondigestible
carbohydrates such as fructooligosaccharides and resistant starch
stimulate intestinal magnesium absorption in rats, and speculated
that these stimulatory effects of nondigestible carbohydrates take
place via the large intestine. Recently, several classical
balance studies and the stable isotope method confirmed that
nondigestible carbohydrates stimulate intestinal magnesium
absorption in humans. Nutritional function of magnesium is very
important, because magnesium is essential for over
300 enzymatic reactions in the human body. Future studies
should be conducted to clarify the health benefits of the
stimulatory effect of nondigestible carbohydrates on intestinal
magnesium absorption.
Key words : magnesium, fructooligosaccharides,
nondigestible carbohydrate, absorption, large intestine
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