In the present study, we examined the effects of AsA
deficiency on bone metabolism and mechanical properties
in ODS rats, which provided a useful experimental model
of osteopenia caused by AsA deficiency (3, 4). ODS rats
placed on drinking water without AsA for 4 or 5 weeks
showed a decrease in body weight, which is one of the
prominent features of AsA deficiency and has been postulated to be due to malnutrition. It has been demonstrated
that the physiological changes during the stage at which
animals begin to lose body weight by AsA deficiency are
almost identical to those during starvation (1).
To minimize the involvement of the starvation factor in the
action of A deficiency on bone, the effects on bone
metabolism and mechanical strength were investigated in
ODS rats placed on drinking water without A for 2 or
3 weeks, by which the body weight was not significantly
altered.Biochemical parameters in the plasma related to bone
metabolism such as calcium and phosphorus concentrations, ALP activity A marker of osteoblastic activity
and TRACP activity A marker of osteoclastic activity
(9) were not changed by A deficiency for 2 weeks.
However, plasma ALP activity in the -A group for 3
weeks was significantly less than that in the control group,
indicating the reduction of bone formation by A
deficiency.
In fact, marked bone loss and a reduction in
bone formation were observed by CMR of the proximal
tibiae and by the measurement of the appositional rate of
bone mineral in the femora, respectively. As shown in
Fig. 3, in the -AsA group at 2 weeks, two labeled lines
were observed on the fluorescent micrographs in the midshaft of the femora, although the distance between these
lines was slightly smaller than that in the control group.
The micrographical observation was confirmed by the
morphometrical analysis, showing that the appositional
rate of bone minerals was significantly less in the -AsA
group than in the control group.
蛍光顕微鏡観察は形態計測による解析で確認した。骨塩増加率はコントロール群に比べ、-AsA群で優位に低かった。
However, in the -AsA
group at 3 weeks, only a faint single line was observed
around the periosteal surface. So, the appositional rate
was not detected in the -AsA group at 3 weeks. These
results indicate that the inhibition of bone formation
became severe with AsA deficiency for 2 weeks.
In accordance with histological findings of bone loss in
the - AsA group, dry weight and ash weight of the tibiae
decreased significantly, whereas ash content per dry
weight and Ca/P ratio of the tibiae were not different
from those in the control group. These results suggest
that the mineral composition of the bone was not affected
by AsA deficiency.
In the present study, parameters of femoral mechanical
properties were significantly less in the -AsA group at 3
weeks than those in the control group.
These changes in
mechanical properties were greater than those in dry
weight or mineral content. The magnitude of the change
in the total bone mineral content induced by AsA deficiency for 3 weeks was only 12%, whereas the strength,
stiffness, toughness and ductility were reduced by 32,
22, 59 and 32%, respectively. Our results are consistent
with those of Currey (14) who demonstrated that a slight
difference of ash content could explain a great difference
in the elastic modulus used as an indicator of stiffness.
これらの機械的特性の変化は乾燥重量やミネラル含量の変化よりも大きかった。3週間のAsA欠乏による骨中総ミネラル含有量の変化の度合いは12%だけであったが、強度、剛性、靭性および柔軟性は、それぞれ32%、22.59%、32%低下していた。これは結果は、灰含有量がわずかな違いが剛性の指標として用いられる弾性率の大きな違いに結びつくと示したCurrry(14)の結果と一致した。
機能特性におけるこれらの変化は、乾燥重量またはミネラル含有量における変化よりも、大きくなった。3週間の間のAsA欠損によって生じた全骨塩量における変化の程度はわずか12%であるのに対し、強度、剛度、靱性、及び延性は、それぞれ32%、22%、59%、32%だけ減少した。我々の結果は、灰成分の僅かな減少によって剛度の指標として用いられる弾性率の大きな変化が説明し得ることを示したCurry (14) の結果と一致している。
Thus, the biomechanical changes induced by AsA deficiency were greater than the chemical changes in bone,
indicating the usefulness of measuring mechanical properties as a sensitive method for the evaluation of the
bone status.
Not only bone mineral content but also bone macroand microarchitecture are involved in the mechanical
strength (15, 16). Macroarchitectural changes are reflected by morphometric measurements of length, cortical and
medullary area, and second moment of the area.
Kiebzak et al. (11)
proposed that the development of cortical
porosities with age in rats may be an adjustment of its architecture in order to maintain bone strength.
骨塩の内容だけでなく、骨のミクローおよびマクロ構造も機械的強度には寄与している(15,16)。マクロ構造の変化は形態学的な測定、すなわち長さ、皮質領、髄質領、そしてその領域の二次モーメントといったものに反映される。
Kiebzak et al. (11)は、ラットにおいて加齢とともに皮質空隙率が大きくなるのは、骨強度を保つために構造を調節しているのではないかと提唱した。
骨ミネラルの含有量だけでなく、マクロおよびミクロ構造が、機械的強度に影響している (15, 16)。マクロ構造は、長さ、皮層および延髄の面積、そして、面積の2次モーメントに反映される。Kiebzak et al. (11) は、ラットが年とともに皮層の多孔性を形成していくことは、骨の強度を保つための構造の調整であるかもしれないと提案している。