N‐acetylcysteine decreases alveolar bone loss on experimental periodontitis in streptozotocin‐induced diabetic rats

Toker H, Ozdemir H, Balc? H, Ozer H. N‐acetylcysteine decreases alveolar bone loss on experimental periodontitis in streptozotocin‐induced diabetic rats. J Periodont Res 2012; 47: 793–799. © 2012 John Wiley & Sons A/S Background and Objective: The purpose of this study was to evaluate the morphometric and histopathological changes associated with experimental periodontitis in diabetic rats in response to systemic administration of N‐acetylcysteine (NAC), a sulfhydryl‐containing thiol antioxidant. Material and methods: Sixty Wistar rats were divided into six experimental groups: nonligated (NL) group; ligature‐only (L) group; streptozotocin‐only (STZ) group; STZ and ligature (STZ + L) group; and systemic administration of NAC and ligature (70 and 100 mg/kg body weight per day, respectively) (NAC70 and NAC100 groups). Diabetes mellitus was induced by 60 mg/kg of streptozotocin. Silk ligatures were placed at the gingival margin of the lower first molars of the mandibular quadrant. The study duration was 30 d and the animals were killed at the end of this period. Changes in alveolar bone levels were clinically measured and tissues were histopathologically examined to assess the differences among the study groups. Results: At the end of the 30‐d study period, alveolar bone loss was significantly higher in the STZ + L group compared with the other groups (p < 0.05). Also, alveolar bone loss in all the NAC groups was significantly lower than in the STZ + L and L groups (p < 0.05). The osteoblastic activity in the NAC100 group was significantly higher than in the other groups (p < 0.05). Conclusion: Within the limits of this study, it can be suggested that NAC, when administered systemically, prevents alveolar bone loss in the diabetic rat model.     

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目的研究能够快速建立稳定、可靠、重复性好的大鼠实验性牙周炎模型的方法,摸索建模的最佳时间并对比研究结扎与非结扎区域的牙槽骨破坏情况。方法本研究于2010年7月至2011年1月在中国医科大学基础医学院微生物学实验室及口腔医学院中心实验室完成。将18只SD大鼠随机分为对照组和4周、8周实验组。采用牙颈部结扎合并口腔接种牙周致病菌的方法,建立大鼠实验性牙周炎模型。分别于4周、8周时进行牙周检查,并利用放射影像和体视显微镜检查对比大鼠的牙周骨组织破坏情况。结果4周和8周实验组大鼠结扎区都出现牙龈红肿,探诊出血,均可探及较深的牙周袋。对照组和4周、8周实验组大鼠上颌三颗磨牙平均骨丧失量分别为（357．63±284．96）μm、（929．56±366．43）μm和（941．80±354．87）μm。与对照组相比,4周和8周实验组大鼠上颌磨牙的骨丧失量均显著增加,差异有统计学意义（P〈0．05）,但4周与8周实验组之间差异无统计学意义（P〉0．05）。结论采用牙颈部结扎合并口腔接种牙周致病菌的方法,4周左右即可形成稳定可靠的大鼠牙周炎模型。大鼠的牙周骨破坏在4周之后速度减缓。     

Enhanced alveolar bone loss in a model of non-invasive periodontitis in rice rats

Oral Diseases (2012) 18 , 459–468 Objective: The rice rat (Oryzomys palustris) develops periodontitis‐like lesions when fed a diet rich in sucrose and casein (H‐SC). We aimed to establish whether this model can accurately mimic the development of human periodontitis. Materials and Methods: For this purpose, 28‐day‐old rice rats (15/group) were assigned to standard (STD) or H‐SC diets and sacrificed after 6, 12, and 18 weeks. Jaws were processed for morphometric, histometric, histologic, histomorphometric, and micro‐CT analyses. Results: We found a progressive increase in horizontal alveolar bone loss (ABL) with age in maxillae of rats fed the STD diet as determined by morphometry. The H‐SC diet exacerbated horizontal ABL at the palatal surface at 12 and 18 weeks. Furthermore, increased vertical ABL was detected in mandibles and maxillae of rats fed the H‐SC diet for 12 and/or 18 weeks by histometry and micro‐CT. Remarkably, the H‐SC diet significantly increased bone remodeling at the interproximal alveolar bone of mandibles from rats fed for 6 weeks, but not in those fed for longer periods. Conclusions: These findings indicate that the H‐SC diet induced a transient increase in alveolar bone remodeling, which is followed by ABL characteristic of moderate periodontitis.     

Simvastatin therapy in cyclosporine A-induced alveolar bone loss in rats

Background and Objective:  Cyclosporine A treatment is important in the therapy of a number of medical conditions; however, alveolar bone loss is an important negative side-effect of this drug. As such, we evaluated whether concomitant administration of simvastatin would minimize cyclosporine A-associated alveolar bone loss in rats subjected, or not, to experimental periodontal disease.
Material and Methods:  Groups of 10 rats each were treated with cyclosporine A (10 mg/kg/day), simvastatin (20 mg/kg/day), cyclosporine A and simvastatin concurrently (cyclosporine A/simvastatin) or vehicle for 30 days. Four other groups of 10 rats each received a cotton ligature around the lower first molar and were treated similarly with cyclosporine A, simvastatin, cyclosporine A/simvastatin or vehicle. Calcium (Ca²⁺), phosphorus and alkaline phosphatase levels were evaluated in serum. Expression levels of interleukin-1β, prostaglandin E₂ and inducible nitric oxide synthase were evaluated in the gingivomucosal tissues. Bone volume and numbers of osteoblasts and osteoclasts were also analyzed.
Results:  Treatment with cyclosporine A in rats, with or without ligature, was associated with bone loss, represented by a lower bone volume and an increase in the number of osteoclasts. Treatment with cyclosporine A was associated with bone resorption, whereas simvastatin treatment improved cyclosporine A-associated alveolar bone loss in all parameters studied. In addition, simvastatin, in the presence of inflammation, can act as an anti-inflammatory agent.
Conclusion:  This study shows that simvastatin therapy leads to a reversal of the cyclosporine A-induced bone loss, which may be mediated by downregulation of interleukin-1β and prostaglandin E₂ production.     

Validation of a dental image analyzer tool to measure alveolar bone loss in periodontitis patients

Background and Objective:  Radiographs are an essential adjunct to the clinical examination for periodontal diagnoses. Over the past few years, digital radiographs have become available for use in clinical practice. Therefore, the present study investigated whether measuring alveolar bone loss, using digital radiographs with a newly constructed dental image analyzer tool was comparable to the conventional method, using intra-oral radiographs on film, a light box and a Schei ruler.
Material and Methods:  Alveolar bone loss of the mesial and distal sites of 60 randomly selected teeth from 12 patients with periodontitis was measured using the conventional method, and then using the dental image analyzer tool, by five dentists. The conventional method scored bone loss in categories of 10% increments relative to the total root length, whereas the software dental image analyzer tool calculated bone loss in 0.1% increments relative to the total root length after crucial landmarks were identified.
Results:  Both methods showed a high interobserver reliability for bone loss measurements in nonmolar and molar sites (intraclass correlation coefficient ≥ 0.88). Also, a high reliability between both methods was demonstrated (intraclass correlation coefficient nonmolar sites, 0.98; intraclass correlation coefficient molar sites, 0.95). In addition, the new dental image analyzer tool showed a high sensitivity (1.00) and a high specificity (0.91) in selecting teeth with ≥ 50% or < 50% alveolar bone loss in comparison with the conventional method.
Conclusion:  This study provides evidence that, if digital radiographs are available, the dental image analyzer tool can reliably replace the conventional method for measuring alveolar bone loss in periodontitis patients.     

Topical and intermittent application of parathyroid hormone recovers alveolar bone loss in rat experimental periodontitis

Tokunaga K, Seto H, Ohba H, Mihara C, Hama H, Horibe M, Yoneda S, Nagata T. Topical and intermittent application of parathyroid hormone recovers alveolar bone loss in rat experimental periodontitis. J Periodont Res 2011; 46: 655–662. © 2011 John Wiley & Sons A/S Background and Objective: Periodontitis is characterized by periodontal tissue inflammation and alveolar bone loss. The intermittent administration of parathyroid hormone (PTH), a major regulator of bone remodeling, has been demonstrated to stimulate osteoblastic activity. Although the systemic administration of PTH has been reported to protect against periodontitis‐associated bone loss, the effect of the topical administration of PTH is unclear. In this study, the effect of intermittent administration of PTH on osteoblastic differentiation was examined in cultured calvaria cells and then the effect of topical and intermittent administration of PTH was determined by measuring the recovery of alveolar bone loss after inducing experimental periodontitis in rats. Material and Methods: Alkaline phosphatase activity and bone nodule formation were measured in fetal rat calvaria cells. Experimental periodontitis was induced by placing nylon ligature around rat maxillary molars for 20 d. After ligature removal (day 0), PTH was topically injected into buccal gingiva three times a week for 10 wk. Micro‐computed tomography analysis and histological examination were performed on days 35 and 70. Results: Intermittent exposure of PTH in calvaria cells increased alkaline phosphatase activity and bone nodule formation by 1.4‐ and 2.4‐fold, respectively. Ligature procedures induced marked alveolar bone loss around the molars on day 0 and greater bone recovery was observed in the PTH‐treated rats on day 70. An increase in osteoid formation on the surface of alveolar bone was detected in the PTH‐treated rats. Conclusion: Intermittent treatment with PTH stimulated osteoblastic differentiation in fetal rat calvaria cell cultures, and topical and intermittent administration of PTH recovered alveolar bone loss in rat experimental periodontitis.