Abstract
This study was performed to examine the effect of bisphosphonate, an inhibitor of bone resorption, on the formation of osteoclast and bone resorption during experimental tooth movement. Whether bisphosphonate has a cytotoxicity in high dose was also examined. Eighty-seven male Sprague-Dawley rats, weighing 260-350g, were classified into normal (no appliance + $0.9\%$ NaCl), control (appliance + $0.9\%$ NaCl) and four bisphosphonate-treated (appliance + 0.8, 4, 20 or 100mg/kg) groups. The maxillary left first molar was moved mesially with the tipping movement using 50-70g of force. Bisphosphonate(etidronate disodium) was injected intraperitoneally with a dose of 0.8, 4, 20, or 100 mg/kg simultaneously with the application or the orthodontic force. They were killed at day 1, 3, or 7 after the application or the orthodontic force. The activities of serum acid phosphatase and lactate dehydrogenase (LDH) were assayed, and osteoclasts and the degree of bone resorption were examined histologically. The results obtained were as follows: 1. Acid phosphatase activities were significantly higher in the appliance groups, both control and bisphosphonate-treated (4, 20, and 100 mg/kg) groups, at days 1 and 3 than these in normal. At day 1, bisphosphonate-treated(4, 20mg/kg) groups showed even higher acid phosphatase than control. However, at day 7, no significant difference was noted between the control and bisphosphonate-treated groups. 2. LDH activities in the 4, 20mg/kg bisphosphonate-treated groups were increased during the experimental Periods examined, but there were no significant differences in the 0.8, 100mg/kg bisphosphonate-treated groups. 3. There was no bone resolution at day 1, but severe bone resorption was observed at days 3 and 7 in the control. Bone resorption was reduced by bisphosphonate-treatment at day 3. Bone resolution observed at day 7 was similar between the control and bisphosphonate-treated groups. 4. Few osteoclasts were observed at the alveolar bone in the control and bisphosphonate-treated groups at day 1. At day 3, numerous osteoclasts were shown in the control, the degree of which was reduced in bisphosphonate-treated groups. These results suggest that the inhibition of the osteoclast formation was not the mechanism of bone resorption by the bisphosphonate-treatment during experimenal tooth movement. There was no distinct cytotoxicity with a high dose of bisphosphonate. And the drug should be administrated repeatedly to maintain the inhibitory effect of bone resolution.
백서에서 실험적 치아 이동시 bisphosphonate가 파골세포의 형성에 미치는 영향과 골 흡수 억제기전을 규명하고 독성유무를 알아보고자 하였다. 체중 260-350g의 웅성 백서 87마리를 정상군(장치비장착 + $0.9\%$ NaCl), 대조군(장치장착 + $0.9\%$ NaCl) 및 장치장착후 bisphosphonate 투여군(0.8 mg, 4 mg, 20 mg, 및 100 mg/kg) 으로 분류하였다. 상악 좌측 제1대구치를 근심으로 치아이동이 일어나도록 50-70g의 교정력을 가하고, 교정장치 장착후 1일, 3일 및 7일째에 혈청 acid phosphatase와 lactate dehydrogenase (LDH)의 활성도를 측정하고, 또한 제1 대구치를 포함한 상악골 일부에서 파골세포수 및 골흡수 정도를 조직학적으로 관찰하여 다음과 같은 성적을 얻었다. 1. Acid phosphatase 활성도는 장치후 1일째와 3일째에 대조군과 bisphosphonate 투여군에서 모두 정상군에 비해 2-3배 높았으나, 7일째에는 정상군과 유의한 차이를 보이지 않았다. 2. LDH활성도는 bisphosphonate 4 mg과 20 mg/kg 투여군에서 전 실험기간에 걸쳐 증가된 양상을 보였으나 0.8 mg과 100 mg/kg 투여군에서는 유의한 차이를 나타내지 않았다. 3. 골흡수는 장치후 1일째에 대조군과 bisphosphonate투여군에서 모두 관찰되지 않았으나, 3일 이후에 나타나 7일째까지 지속되었다. Bisphosphonate 4, 20 및 100 mg/kg군에서의 골흡수정도는 3일째에는 대조군에 비해 미약하였으나 7일째에는 대조군과 유사하게 나타났다. 4. 파골세포는 1일째에 대조군이나 bisphosphonate투여군 모두에서 거의 관찰할 수 없었다. 3일째에 대조군에서는 파골세포가 다량 출현하였으나 bisphosphonate 투여군에서는 약물의 용량이 증가함에 따라 감소하여 나타났다. 이상의 결과로 실험적 치아이동시 파골세포의 형성억제가 bisphosphonate에 의한 골흡수 억제기전이 아님을 알 수 있었고, bisphosphonate는 투여량이 증가에 따른 뚜렷한 세포독성은 관찰되지 않았으며, 골흡수 억제효과를 지속시키기 위해서는 약물이 반복적으로 투여되어야 할 필요가 있음이 시사되었다.