Bisphosphonate가 흰쥐 치아 및 이틀뼈 성장에 미치는 영향
Effects of Bisphosphonate on the Tooth and Alveolar Bone Growth in Rats
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Bisphosphonate는 뼈 조직 흡수를 억제하는 작용을 가지고 있으며, 교정적 치아 이동과 뼈조직 재생을 위한 여러 임상적 적용이 시도되고 있다. 본 연구는 bisphosphonate가 성장기 뼈 조직과 치아에 영향을 미친다는 전제 하에, 치아 맹출에 미치는 영향과 맹출 기전을 구명하고자 시도되었다. 출생 22일 흰쥐에서 대조군의 위, 아래 앞니 및 어금니는 모두 맹출되어 있었으나, bisphosphonate를 저농도 (0.5 mg/kg) 및 고농도 (2.5 mg/kg)로 10일간 투여후, 두 군 모두에서 모든 치아가 맹출되어 있지 않았다. Bisphosphonate 투여 대조군에서 첫째 및 둘째큰어금니의 법랑질모세포는 교두부를 포함하여 대부분 원주형의 분비기 형태를 보였으며, bisphosphonate에 의한 뚜렷한 변화 소견은 관찰되지 않았다. Bisphosphonate 투여군에서 법랑질 및 상아질 형성 과정에서 뚜렷한 변화는 관찰되지 않았으나 치아 상방 이틀뼈는 대조군에 비하여 굵은 해면뼈 소견을 보였다. 대조군에서 아래턱 첫째큰어금니 상방 이틀뼈에 출현한 뼈파괴세포 수는 출생 3, 7, 10일 후에 각각 16.2±3.9, 30.5±7.7, 40.3±2.1개로 뼈파괴세포 수는 10일에서 최대 증가하였다 (p⁄0.05). 저농도와 고농도의 bisphosphonate를 3일간 투여한 군에서 뼈파괴세포 수는 각각 21.5±3.1, 25.7±2.3개로 고농도 투여군에서 유의하게 증가하였으며(p⁄0.01), 7일간 투여군에서도 41.5±2.4, 48.3±7.0개로 유의한 증가를 보였다(p⁄0.01). 그러나 10일간 투여 군에서는 저농도 및 고농도 투여군에서 각각 28.3±5.1, 9.7±9.6개로 bisphosphonate 투여군에서 모두 현저하게 감소하였다(p⁄0.01). Bisphosphonate 투여 후 각 군에서 출현한 뼈파괴세포 크기는 대조군에서 1081.6±299.8 µm2, 저농도군에서 1017.3±514.9 µm2, 고농도군에서 1282.2±123.8 µm2로 각 군 간에 유의한 차이가 없었다(p¤0.05).이상의 결과는 bisphosphonate는 뼈파괴세포의 형성을 억제함으로써 치아 맹출을 억제하며, 치아 맹출에 뼈파괴 세포의 작용이 필수적임을 시사하였다.
Abstract
Eruptive movement of the tooth germ accompanies the resorption and formation of the surrounding alveolar bone. Bisphosphonate has effects on osteoclasts to inhibit bone resorption, being currently used for the treatment of bone disease such as osteoporosis. This study was conducted to elucidate effects of bisphosphonate on tooth eruption in growing rats. Alendronate, a derivative of bisphosphonate, was injected into newborn rats at the concentration of 0.5 mg/kg and 2.5 mg/kg for 3, 7 and 10 days. The incisor and molar teeth normally erupted at postnatal 22 days in the saline-treated control group, whereas no teeth could not be seen in both groups of the alendronate treatment. No conspicuous histological changes could not be found in the teeth germs in the alendronate treated rats. The number of osteoclasts in both the first and the second molars was maximum on the postnatal day 10. The number of osteoclasts significantly increased by both 3 and 7 days of alendronate treatment (p⁄0.01). But the number significantly decreased by 10 days of alendronate treatment in both concentrations (p⁄0.01). The size of osteoclasts was not different between the control and alendronate groups. Thus, these results suggest that bisphosphonate acts on osteoclast formation to inhibit bone resorption and subsequent tooth eruption.
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