Effect of estrogen on the development of disuse bone atrophy induced by tail-suspension in ovariectomized rats

Abstract

This study evaluated how ovariectomy and estrogen administration affect the development of disuse atrophy of the hind limbs induced by tail-suspension. Five-week-old female Wistar rats were ovariectomized and divided into two groups. One group received an intramuscular injection of estradiol dipropionate once a week (OVX-E(sub 2) group), and the other received a vehicle injection (OVX group). After the third injection, the rats were subjected to tail suspension in metabolic cages for one, three, five or seven days. Age-matched control rats not subjected to suspension were also housed individually in metabolic cages. In the OVX group, the wet weight of femurs decreased significantly after day three of tail-suspension. However, in the OVX-E(sub 2) group it decreased significantly only after day seven. Calcium and phosphorus contents in the femur tended to be higher in the OVX-E(sub 2) group than those in the OVX group. Alkaline Phosphatase (ALP) activity, one of the markers for bone formation, did not change by tail suspension in either the OVX or OVX-E(sub 2) group. Tartrate-Resistant Acid Phosphatase (TRAP) activity, one of the markers for bone resorption, increased significantly in the femur by tail suspension in both the OVX and OVX-E(sub 2) groups. In the latter group, however, TRAP activity was constantly lower than that in the OVX group during the course of tail-suspension. Urinary excretion of Deoxypyridinoline (D-Pyr) in the OVX group showed a tendency to increase on day one after tail-suspension. In contrast, D-Pyr excretion did not change in the OVX-E(sub 2) group at all. It was also noted that in the OVX-E(sub 2) group, D-Pyr excretion was lower than that in the OVX group. It was thus suggested that estrogen administration to OVX rats prevents the development of disuse bone atrophy through the prevention of bone resorption induced by tail-suspension.

卵巣摘出とエストロゲン投与が尾部懸垂により誘発された後脚の廃用性萎縮の進展にどのように影響するかを評価した。生後5週の雌Wistar系ラットの卵巣を摘出し、2群に分けた。1群には週に1回エストラジオールジプロピオナートを筋肉内注射し(OVX-E(sub 2)群)、他は溶剤を注入した(OVX群)。3回目の注入後、ラットを代謝ケージ内で1、3、5または7日間尾部懸垂した。同齢の対照ラットは尾部懸垂せずに代謝ケージ内に個別に収容した。OVX群では、大腿骨の湿重量は3日間の尾部懸垂の後に著しく減少した。しかし、OVX-E(sub 2)群では減少は7日後に初めて認められた。大腿骨中のカルシウムとりんの含量はOVX群よりもOVX-E(sub 2)群で高い傾向を示した。骨形成のマーカの1つであるアルカリ性ホスファターゼ活性度はOVX群でもOVX-E(sub 2)群でも尾部懸垂で変化しなかった。骨吸収のマーカの1つである酒石酸耐性酸性ホスファターゼ(TRAP)活性度はOVX群でもOVX-E(sub 2)群でも尾部懸垂で顕著に増加した。しかし、OVX-E(sub 2)群ではTRAP活性度がOVX群より尾部懸垂中いつも低かった。OVX群におけるデオキシピリジノリン(D-Pyr)の尿中排泄は尾部懸垂の1日後に増加の傾向を示した。これに対して、OVX-E(sub 2)群ではD-Pyr排泄は全く変化しなかった。OVX-E(sub 2)群ではD-Pyr排泄はOVX群の場合よりも低いことも認められた。OVXラットへのエストロゲン投与は尾部懸垂により誘発される骨吸収の阻止によって廃用性骨萎縮の進展を防止することがわかった。