Effects of Cyclosporin A on Dental Alveolar Bone: A Histomorphometric Study in Rats

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Abstract
We have previously reported cyclosporin A (CA)-induced osteopenia around the dental alveoli of the mandibular incisors of rats. The drug-induced tooth displacement and the regional anatomical complexity around the mandibular incisors might complicate the local effects of CA. Therefore, the purpose of this study was to evaluate the dental alveolar bone histomorphology around maxillary secondary molars in CA-treated rats and to further elucidate the effects of CA on the dental alveolus. Twenty Sprague-Dawley rats were assigned to a CA and a control group. Animals in the CA group received CA (15 mg/kg) daily and the control rats received only mineral oil. At the end of weeks 2 and 4, five animals in each group were sacrificed. Dental alveoli around the maxillary second molar region were frontally sectioned and stained with toluidine blue by undecalcified histological processing. Ten serial tissue sections, 80 microm apart, were selected for histometric evaluation. Bone volume, bone-specific surface, and osteoid formation were measured at buccal, apical, and palatal locations in dental alveolus. Overall bone mass in dental alveolus decreased more in the CA group than in the control group at both observation intervals. All histometric measurements, except the bone-specific surface, were significantly affected by the alveolar location (palatal, apical, and buccal) and CA therapy (P= 0.004 and <0.001, 0.001 and <0.001, 0.004 and <0.001 for drug therapy and location of the dental alveolus in bone volume, marrow volume, and the ratio of bone surface to volume, respectively). Decreased bone volume, but increased marrow volume, were noted in the CA group compared to the control group. Although the alveolar bone surface area did not differ between the CA group and the control group, greater alveolar surface-to-volume ratio was noted in the CA group. For osteoid, more decreased volume, seam width, and fractional formation surface were observed in the CA group compared to the control group (P <0.001, <0.001, and = 0.046 in osteoid volume, seam width volume, and formation surface, respectively). Because the bone mass and the osteoid formation in the dental alveolus around the maxillary molar region showed a decrease after CA exposure, we conclude that this drug has inhibitory effects on the dental alveoli.