Alendronate therapy may be effective in the prevention of bone loss around titanium implants inserted in estrogen-deficient rats

BACKGROUND: This study evaluated whether alendronate (ALD) influences bone healing around titanium implants inserted in ovariectomized rats and whether it provides a residual effect after its withdrawal. METHODS: Bilateral ovariectomies were performed in 87 Wistar rats and one screw-shaped titanium implant was placed in the tibiae. The animals were divided into the following groups: group SHAM (N = 15): sham surgeries; group OVX (N = 15): ovariectomy; group AT (N = 15): OVX plus alendronate administration for 80 days; group AW (N = 14): OVX plus alendronate administration for 40 days; group ET (N = 14): OVX plus 17beta estradiol administration for 80 days; or group EW (N = 14): OVX plus 17beta estradiol administration for 40 days. Bone-to-implant contact (BIC), bone area (BA) within the limits of implant threads, and bone density in a 500 microm-wide zone lateral to the implant (BD) were obtained and measured for the cortical (zone A) and cancellous (zone B) regions. RESULTS: In zone A, data analysis showed no significant differences among the groups regarding BIC and BD (P >0.05), and a slight beneficial effect of estradiol on BA when compared with the OVX, EW, and AW groups (P <0.05). In zone B, OVX negatively impacted bone healing around the implants, resulting in reduced BA and BD (P<0.05). ALD (continuous/interrupted) and estradiol (only continuous) positively affected BIC, BA, and BD, resulting in values at the same level as the control group (SHAM). CONCLUSIONS: ALD may prevent the negative influence of estrogen deficiency on bone healing around titanium implants inserted in OVX rats. This positive effect, in contrast to estradiol, is sustained following its withdrawal.     

Smoking cessation may present a positive impact on mandibular bone quality and periodontitis-related bone loss: a study in rats

BACKGROUND: It has been previously shown that cigarette smoke inhalation (CSI) enhances bone loss in ligature-induced periodontitis. In this study, the hypothesis that the interruption of smoke exposure would reverse the impact of CSI on mandibular bone quality and periodontitis-related bone loss was tested. METHODS: Fifty-three Wistar rats were randomly assigned to one of the following groups: group 1: control, N = 16; group 2: 83 days of CSI prior to ligature placement, N = 17; or group 3: 90 days of CSI before and 60 days after ligature placement, N = 20. Animals were sacrificed 60 days after ligature placement, the jaws removed and immediately radiographed for photodensitometry analysis. Bone loss was histometrically evaluated. RESULTS: CSI did not affect unligated sites in either condition (P >0.05); however, smoke inhalation during the whole experimental period significantly enhanced bone loss in ligated teeth (P < 0.05). Moreover, similar levels of bone loss were observed for ligated teeth between the control and cessation groups (0.90 +/- 0.33 mm(2); 0.96 +/- 0.32 mm(2); 1.64 +/- 0.65 mm(2); groups 1, 2 and 3, respectively). Radiographically, continuous exposure to cigarette smoke promoted a significantly reduced bone density (1.74 +/- 0.38 aluminum equivalence [Al eq]; 1.74 +/- 0.14 Al eq; and 0.68 +/- 0.10 Al eq for groups 1, 2, and 3, respectively). CONCLUSIONS: Within the limits of the present investigation, it can be assumed that CSI may enhance bone loss in ligature-induced periodontitis, and negatively impact mandibular bone quality. Additionally, smoke exposure cessation seems to reverse its impact on mandibular bone, and, therefore, may be of clinical relevance.     

Lithium chloride assuages bone loss in experimental periodontitis in estrogen-deficient rats

Clinical Oral Investigations - Evidence shows that lithium, a medication commonly used for bipolar disorder treatment, presents bone anabolic activity. This study evaluated the effects of lithium...     

Alendronate therapy in cyclosporine-induced alveolar bone loss in rats

BACKGROUND AND OBJECTIVE: Cyclosporine A is an immunosuppressive drug that is widely used in organ transplant patients as well as to treat a number of autoimmune conditions. Bone loss is reported as a significant side-effect of cyclosporine A use because this can result in serious morbidity of the patients. As we have shown that cyclosporine A-associated bone loss can also affect the alveolar bone, the purpose of this study was to evaluate the effect of the concomitant administration of alendronate on alveolar bone loss in a rat model. MATERIAL AND METHODS: Forty Wistar rats (10 per group) were given cyclosporine A (10 mg/kg, daily), alendronate (0.3 mg/kg, weekly), or both cyclosporine A and alendronate, for 60 d. The control group received daily injections of sterile saline. The expression of proteins associated with bone turnover, including osteocalcin, alkaline phosphatase and tartrate-resistant acid phosphatase (TRAP), and also the calcium levels, were evaluated in the serum. Analysis of the bone volume, alveolar bone surface, the number of osteoblasts per bone surface and the number of osteoclasts per bone surface around the lower first molars was also performed. RESULTS: The results indicate that cyclosporine A treatment was associated with bone resorption, represented by a decrease in the bone volume, alveolar bone surface and the number of osteoblasts per bone surface and by an increase in the number of osteoclasts per bone surface and TRAP-5b. These effects were effectively counteracted by concomitant alendronate administration. CONCLUSION: It is concluded that concomitant administration of alendronate can prevent cyclosporine A-associated alveolar bone loss.     

雌激素缺乏对大鼠牙槽骨吸收影响的实验研究

目的观察雌激素缺乏对大鼠牙槽骨吸收的影响。方法34只雌性SD大鼠随机分为4组。第1组假手术(n=8),第2组卵巢切除(n=9),第3组卵巢切除加牙周结扎(n=9),第4组卵巢切除、牙周结扎加雌激素治疗(n=8)。适应性喂养7天后行假手术或双侧卵巢切除术。第4组于术后第二天起皮下注射苯甲酸雌二醇．20μg／kg体重／次,三天一次。第3、4两组于卵巢切除术后28天,结扎丝结扎上颌第一磨牙诱导牙周炎。第63天处死全部大鼠。常规取材。观察牙用组织组织学改变。测量牙用骨丧失值(PBL)。比较牙用骨支持率(PBS)。检测血清碱性磷酸酶(ALP)。结果采用成组f检验,第1、2两组的PBL分别为0．398±O．147mm,0．663±0．132哪。PBS分别为O．588±O．058。0．440±0．197,组间差异均有统计学意义(P<0．05);第2、3两组的PBL、PBS组间差异均有统计学意义(P<0．05)。第3组的PBL为0．875±0．197mm,PBS为0．336±O．087;第3、4两组的PBL、PBS组间差别没有统计学意义(P>0．05),第4组的PBL为O．823±0．119mm,PBS为0．360±0．950。结论雌激素缺乏促进牙槽骨吸收,茵斑刺激加剧骨质疏松大鼠牙槽骨的吸收,雌激素替代治疗不能预防骨质疏松大鼠因茵斑刺激引发的牙槽骨吸收。     

The influence of thyroid hormones on periodontitis-related bone loss and tooth-supporting alveolar bone: a histological study in rats

Background and Objective: Recent studies have pointed to potentially periodontal risk indicators, however no information is available on the impact of changes in thyroid hormone levels on the progression of periodontitis and on the quality of alveolar bone. Thus, the aim of the present study was to evaluate histologically, in rats, the influence of thyroid hormones on the rate of periodontal bone loss resulting from ligature placement and on the quality of tooth‐supporting alveolar bone. Material and Methods: Thirty‐six male Wistar rats were randomly assigned to the following groups: healthy (control, n = 12), hypothyroidism (n = 12) and hyperthyroidism (n = 12). Once alterations were confirmed by total serum levels of triiodothyronine and thyroxine, ligatures were randomly placed around one of the first mandibular molars. Thirty days later, the animals were killed and specimens routinely processed for serial decalcified sections. The parameters assessed were periodontitis‐related bone loss, quality of tooth‐supporting alveolar bone and the number of cells positive for tartrate‐resistant acid phosphatase (TRAP), a marker of bone resorption. Results: At the ligated sites, intergroup analysis revealed that hypothyroidism significantly increased the bone loss resulting from ligature‐induced periodontitis (p = 0.02) and the number of TRAP‐positive cells on the linear surface of bone crest (p = 0.01). In addition, no significant differences were detected regarding the quality of the bone (p = 0.24) or the number of TRAP‐positive cells in the area of the interradicular bone for ligated teeth among the groups (p = 0.17). Conclusion: It may be concluded that decreased serum levels of thyroid hormones may enhance periodontitis‐related bone loss, as a function of an increased number of resorbing cells, whereas the tooth‐supporting alveolar bone seems to be less sensitive to alterations in hormone levels.     

Effect of an estrogen-deficient state and its therapy on bone loss resulting from an experimental periodontitis in rats

OBJECTIVE: The aim of this study was to evaluate the impact of an estrogen-deficient state and its therapies (estrogen and calcitonin administration) upon bone loss resulting from an experimental periodontitis. METHODS: Fifty-eight Wistar rats were divided into four groups: group 1 (n = 15): sham operated; group 2 (n = 15): ovariectomized; group 3 (n = 14): ovariectomized plus calcitonin administration; group 4 (n = 14): ovariectomized plus estrogen administration. Twenty-one days after ovariectomy or sham surgeries, the ligature was randomly placed. Sixty days later, the animals were killed and the specimens routinely processed. In addition, serum levels of alkaline phosphatase and calcium were assessed. RESULTS: Intergroup analysis revealed that an estrogen-deficient state significantly increased bone loss resulting from periodontitis and that such an effect could not be prevented either by estrogen or calcitonin administration (0.34 +/- 0.13, 0.65 +/- 0.06, 0.63 +/- 0.19, 0.67 +/- 0.28 for groups 1, 2, 3 and 4, respectively). Furthermore, an estrogen-deficient state presented a direct effect on the alveolar bone regardless of plaque accumulation and this effect may be significantly reduced by estrogen administration (p < 0.05). Serum analysis demonstrated a higher bone turnover for the animals with estrogen deficiency, and estrogen therapy restored bone metabolism. CONCLUSION: Estrogen administration may prevent the direct effect of an estrogen-deficient state on alveolar bone; however, neither estrogen nor calcitonin administration could prevent this effect when associated with a response to a plaque-related inflammatory process.     

Effect of an estrogen-deficient state and alendronate therapy on bone loss resulting from experimental periapical lesions in rats

The aim of the research was to evaluate the impact of an estrogen-deficient state and alendronate (ALD) therapy on bone loss resulting from experimental periapical lesions in rats. Periapical lesions were induced on ovariectomized (OVX) and sham-ovariectomized (Sham) rats. After sample preparation, histologic and radiographic examination for periapical bone loss area and an enzyme histochemical test for tartrate-resistant acid phosphatase (TRAP) were performed. The results showed that OVX significantly increased bone loss resulting from periradicular lesions. After daily subcutaneous injection of ALD, the bone loss area and the number of TRAP-positive cells (osteoclasts) were reduced. These findings suggested that alendronate may protect against increased bone loss from experimental periapical lesions in estrogen-deficient rats. Given recent recognition of adverse effects of bisphosphonates, including an increased risk for osteonecrosis, the findings from this study should not be interpreted as a new indication for ALD treatment. However, they may offer insight into understanding and predicting outcomes in female postmenopausal patients already on ALD therapy for medical indications.     

Matrix metalloproteinase-2 may be involved with increased bone loss associated with experimental periodontitis and smoking: a study in rats

BACKGROUND: Smoking has been associated with periodontitis severity and is considered a risk factor for its development. It has been reported that matrix metalloproteinase (MMP) produced by host cells plays a major role in periodontal tissue destruction. Thus, the present study tested, in rats, the hypothesis that local increased levels of MMP-2 would be associated with the enhanced periodontitis-related bone loss after intermittent cigarette smoke inhalation (CSI). METHODS: Twenty-seven adult male Wistar rats were used. A ligature was placed around one of the mandibular first molars of each animal and they were randomly assigned to the following control (N = 13) or CSI (N = 14) group. Sixty days later, the animals were sacrificed, the gingival tissues harvested, and the specimens processed for decalcified sections. Extracts from the gingival tissues were prepared and assayed for MMP-2 expression. RESULTS: Intergroup comparisons (unligated sites) showed that CSI might directly affect alveolar bone (0.16 +/- 0.03 mm2 versus 0.24 +/- 0.09 mm2 for non-smokers and smokers, respectively; P = 0.001). Moreover, CSI significantly enhanced bone loss resulting from experimental periodontitis (0.64 +/- 0.36 mm2 versus 1.50 +/- 0.50 mm2 for non-smokers and smokers, respectively; P<0.05). In addition, zymography demonstrated that CSI also enhanced both MMP-2 levels and activity in the gingival tissues around ligated teeth. CONCLUSION: Within the limits of the present investigation, it can be assumed that the effect of CSI on MMP-2 levels and activity may account for the increased periodontitis progression rate observed in smokers.     

Low concentration alcohol intake may inhibit spontaneous alveolar bone loss in Wistar rats

Objective

The aim of the present study was to evaluate the influence of ethanol in low concentration (5%) in ligature-induced alveolar bone loss in Wistar rats.

Material and Methods

Thirty rats were randomly assigned to test and control groups (n = 15). Test group received a liquid diet containing ethanol 5% (vol./vol.) and standard rat chow. Control group received only tap water as the liquid diet and the same rat chow. In both groups, diet was delivered ad libitum. Alveolar bone loss was induced prior to the beginning of the study by means of ligatures placed around the upper second molars. The contra-lateral tooth remained as intra-group control. At the end of the nine weeks, the animals were killed and morphometric analysis of alveolar bone loss was performed by a blinded and calibrated examiner. Intra-group comparisons were performed by paired sample T-test and inter-group differences were compared by independent sample T-test (α = .05).

Results

Animals that drank ethanol in low concentration systematically presented less alveolar bone loss than the control group, regardless of the presence of ligature. Test group showed less alveolar bone loss (p = 0.04) in unligated teeth when compared to control group (0.32 ± 0.07 and 0.37 ± 0.07 mm, respectively). However, no significant difference (p = 0.14) was observed between Test and Control groups (0.78 ± 0.14 and 0.84 ± 0.18 mm, respectively) in ligated teeth.

Conclusion

The results of this study lead to the conclusion that low concentration alcohol intake did not affect the alveolar bone loss in ligature induced periodontal breakdown.     

Parathyroid hormone protects against periodontitis-associated bone loss

Parathyroid hormone (PTH) functions as a major mediator of bone remodeling and as an essential regulator of calcium homeostasis. In addition to the well-established catabolic effects (activation of bone resorption) of PTH, it is now recognized that intermittent PTH administration has anabolic effects (promotion of bone formation). The aim of this study was to investigate whether intermittent administration of PTH in rodents would block the alveolar bone loss observed in rats when a ligature model of periodontitis is used. Morphometric analysis showed that intermittent PTH administration (40 microg/kg) was able to protect the tooth site from periodontitis-induced bone resorption. In addition, there was a significant reduction in the number of inflammatory cells at the marginal gingival area in sections obtained from animals receiving PTH compared with control animals. These findings demonstrated that intermittent PTH administration was able to protect against periodontitis-associated bone loss in a rodent model.     

Influence of submandibulectomy on alveolar bone loss in rats

BACKGROUND: The incidence of dry mouth and its public health impact are increasing as the result of a progressively larger, medicated older population and because chronic diseases, like periodontitis, are prevalent pathologies among elderly patients. Periodontitis and continuous remodeling and rebuilding alveolar processes greatly affect the margin of the alveolar bone, and there is evidence indicating the role of submandibular glands in the regulation of immune/inflammatory reactions. The purpose of this study was to assess the effect of submandibular-sublingual complex ablation (Sx) on alveolar bone loss in rats submitted or not to ligature-induced experimental periodontal disease (EP). METHODS: Wistar male rats were submitted to Sx or sham operations (day 0). Two weeks later, unilateral EP was induced on the right mandibular first molars for 7 days with the contralateral side serving as control. Bone loss at the level of the dental pieces was estimated by bone histomorphometry on mesio-distally oriented sections of the molars and by the determination on lingual and vestibular mandibular surfaces of the distances from the cemento-enamel junction to the alveolar crest. RESULTS: Sx and EP significantly increased lingual and vestibular alveolar bone loss. Molars with EP exhibited greater lingual loss in Sx animals compared to those with the sham operation. EP induced similar interradicular bone loss in sham and Sx rats. CONCLUSION: Sx has a deleterious effect on the periodontal tissues, particularly marginal alveolar bone, indicating the importance of the submandibular/sublingual glands in maintaining healthy periodontal conditions.