Supraphysiologic Testosterone Administration Impairs Late Osseointegration in Male Rats.

PURPOSE: To evaluate the effect of supraphysiologic administration of testosterone in an early and late model of implant osseointegration in rat tibiae. MATERIALS AND METHODS: A total of 40 rats were randomly allocated into four groups (n = 10/ group), which were divided according to the type of experiment and time of osseointegration: (1) vehicle (14 days), (2) testosterone (14 days), (3) vehicle (42 days), and (4) testosterone (42 days). Testosterone cypionate (7.5 mg/kg) administration started 4 weeks before implant placement, and the injections were performed daily until euthanasia. Machined-surface titanium implants (2.2 mm in diameter and 4 mm high) were placed bilaterally in the tibia of animals 28 days after the first testosterone injection. At days 14 and 42 after implant placement, euthanasia was performed and the tibiae were harvested to perform biomechanical evaluation and histomorphometric analysis of bone-to-implant contact (BIC%) and bone between the threads (BBT%). RESULTS: There was no statistical difference in the removal torque of the implants between the groups treated with the vehicle (control group) or testosterone (P > .05). At 14 days of osseointegration, the BIC% and BBT% did not differ between vehicle or testosterone groups (P > .05), while at 42 days, both the BIC% and BBT% were significantly reduced by testosterone compared to the vehicle group (P < .05). CONCLUSIONS: Testosterone cypionate in supraphysiologic dose impaired late-phase osseointegration in rat tibiae.

Gingival bleeding as a predictor of handgrip strength-an observational study and a pilot randomized clinical trial.

OBJECTIVE: The aim of this study was to (i) assess the association between self-reported periodontal disease and gingival bleeding as predictors of handgrip strength (HGS) in the elderly and (ii) evaluate the impact of baseline periodontal clinical parameters on the improvement of HGS in trained or non-trained treated periodontitis patients. METHODS: For (i), cross-sectional data from the Brazilian Longitudinal Study of Aging were retrieved and association between HGS (dependent variable) and self-reported gingival bleeding, periodontal disease, and missing teeth was analyzed using multiple linear regressions. For (ii), a pilot study was conducted with 17 patients randomly allocated to two groups-physical training or non-training-and followed for 45 days after subgingival instrumentation. Clinical parameters and HGS were recorded before and after treatment. RESULTS: The observational study showed a significant association between HGS and tooth loss, edentulism and gingival bleeding. The clinical trial showed that baseline bleeding on probing, but not other parameters, was associated with delta HGS. CONCLUSION: Taken together, our findings suggest that gingival bleeding could act as a predictor of handgrip strength and its improvement after non-surgical periodontal therapy. CLINICAL RELEVANCE: Gingival bleeding, either as self-perceived or clinically detected, may impact handgrip strength, an important marker of muscle frailty and mortality.

Associations between physical activity domains and oral health: an analysis of a Brazilian population-based study.

Physical activity comprises four domains (leisure, transportation, domestic, and work activities) that may be differently associated with oral health. The aim of this study was to assess the association between each physical activity domain and oral health conditions in Brazilian adults. A total of 38,539 participants in the 2019 Brazilian Health Survey aged 30 years or older were analyzed. The outcomes were self-perceived oral health (dichotomous) and self-reported number of missing teeth (counts). The presence, frequency, and time of activity in each domain and their combination were analyzed as main exposures. Odds ratios (OR) and mean ratios (MR) were estimated by fitting multivariable models. Higher leisure time physical activity was the only domain associated with better self-perception of oral health (OR = 1.32; 95%CI 1.26-1.38) and lower tooth loss (MR=0.88; 95%CI 0.86-0.90). Higher levels of work, transportation, and household activities were significantly associated with worse self-perception of oral health, while higher levels of work- and transportation-related physical activities were also associated with greater tooth loss. When the total recommended weekly physical activity time was analyzed, no significant associations were found. Sensitivity analysis suggested that this pattern persists in potential periodontitis-related cases, such as when selecting older age or excluding individuals with no tooth loss. In conclusion, leisure physical activity was the only domain with the potential of reflecting the benefits of physical activity on oral health. The inclusion of other domains can confound this association.

Associations between physical activity domains and oral health: an analysis of a Brazilian population-based study

Abstract Physical activity comprises four domains (leisure, transportation, domestic, and work activities) that may be differently associated with oral health. The aim of this study was to assess the association between each physical activity domain and oral health conditions in Brazilian adults. A total of 38,539 participants in the 2019 Brazilian Health Survey aged 30 years or older were analyzed. The outcomes were self-perceived oral health (dichotomous) and self-reported number of missing teeth (counts). The presence, frequency, and time of activity in each domain and their combination were analyzed as main exposures. Odds ratios (OR) and mean ratios (MR) were estimated by fitting multivariable models. Higher leisure time physical activity was the only domain associated with better self-perception of oral health (OR = 1.32; 95%CI 1.26-1.38) and lower tooth loss (MR=0.88; 95%CI 0.86-0.90). Higher levels of work, transportation, and household activities were significantly associated with worse self-perception of oral health, while higher levels of work- and transportation-related physical activities were also associated with greater tooth loss. When the total recommended weekly physical activity time was analyzed, no significant associations were found. Sensitivity analysis suggested that this pattern persists in potential periodontitis-related cases, such as when selecting older age or excluding individuals with no tooth loss. In conclusion, leisure physical activity was the only domain with the potential of reflecting the benefits of physical activity on oral health. The inclusion of other domains can confound this association.

Supraphysiological testosterone supplementation improves granulation tissue maturation through angiogenesis in the early phase of a cutaneous wound healing model in rats.

OBJECTIVE: The aim of this study was to evaluate the effects of both testosterone depletion and supraphysiological testosterone supplementation in the early phase of an animal cutaneous wound healing model in comparison with the physiological hormonal condition. MATERIAL AND METHODS: Forty rats were distributed into the following four groups: Control, Orchiectomy (OCX), Durateston (Dura) and OCX+Dura. On day 1, the testicles were removed (OCX group) and the rats (Dura group) received a supraphysiological dose (250 mg/kg) of exogenous testosterone weekly. After 15 days a full-thickness excisional skin wound was created in all animals, which was healed by the second intention for 7 days. On day 22, the rats were euthanatized and the wounds were harvested for histopathological evaluation, immunohistochemistry analyses and multiplex immunoassay. One-way ANOVA and post-hoc Tukey tests were performed. RESULTS: It was found that the supraphysiological testosterone level increased extracellular matrix deposition, promoted higher blood vessel formation and reduced wound contraction (p < 0.05). Additionally, it also stimulated PCNA-positive fibroblasts and KGF-positive cells (p < 0.05), while orchiectomy reduced the expression of IL-6 and TNF-α and increased VEGF and PDGF (p < 0.05) . CONCLUSION: In conclusion, the results provide evidence that supraphysiological testosterone supplementation plays a positive role in the early phase of cutaneous wound healing, thus improving granulation tissue maturation through the enhancement of angiogenesis.

Association between tooth loss, chronic conditions, and common risk factors: Results from the 2019 Brazilian Health Survey.

BACKGROUND: The aim of this study was to evaluate the association between systemic non-communicable diseases (NCDs; including lung, kidney, mental and cardiovascular diseases, arthritis, cancer and spinal problems), common risk factors, and tooth loss (TL), as an endpoint of prevalent oral NCDs (periodontitis and caries). METHODS: A total of 60,271 noninstitutionalized adults (≥30 years) were evaluated, using data from the 2019 Brazilian National Health Survey. Negative binomial regressions were performed, adjusting for sex, age, ethnicity, educational attainment, oral hygiene, risk factors for periodontitis and caries (diabetes, smoking, and a cariogenic diet). The dependent variable was TL expressed as a numerical value. RESULTS: Diabetes, current smoking and a frequent cariogenic diet were significantly associated with TL-Incidence Rate Ratio (IRR [95% CI]): 1.11 (1.08 to 1.14), 1.28 (1.25 to 1.31), and 0.97 (0.94 to 0.99), respectively. Significant associations were observed for TL and all assessed NCDs, except kidney diseases, cancer and musculoskeletal diseases related to work, with IRR ranging from 1.06 for hypertension and asthma to 1.16 for rheumatoid arthritis. Regular consumption (4 to 7 d/wk) of vegetables, fruits and beef; alcohol up to 8 doses/wk; and physical exercise were associated with a lower IRR for TL (P < 0.05). Obesity, but not overweight, was associated with increased TL (1.05 [1.03 to 1.07]). Smoking, hypertension, arthritis, other mental diseases and spinal problems further increased the IRR for TL in individuals with diabetes (P < 0.05). CONCLUSION: We conclude that certain chronic systemic conditions are associated with TL in Brazilian adults. This is likely because of shared risk factors; however, causal associations cannot be examined in this cross-sectional dataset.

Mandibular-related bone metabolism in orchiectomized rats treated with sex hormones.

OBJECTIVE: This study aimed to compare the impact of testosterone and estrogen replacement therapy on mandibular bone density and bone-related markers. DESIGN: Forty male adult rats were randomly allocated to 4 experimental groups (n = 10/group): Sham (Control); Orchiectomy; Orchiectomy plus testosterone replacement; and orchiectomy plus estradiol replacement. Twenty-four days after orchiectomy, the hemi-mandibles were collected and processed for analysis of microhardness in cortical and trabecular bone, radiographic bone density and histomorphometric evaluation. Serum was collected for the analysis of calcium, phosphorus, alkaline phosphatase and magnesium. RESULTS: The orchiectomy group had the lowest mandibular bone density (p < 0.01) and also their serum levels of alkaline phosphatase were higher than all other experimental groups (p < 0.001). Estradiol replacement significantly reduced microhardness when compared to orchiectomy in cortical bone (p < 0.05). Both testosterone and estrogen replacement reverted orchiectomy impact on this parameter (p < 0.01); and decreased alkaline phosphatase to levels comparable to the Sham-Control group. The effect of estrogen was more pronounced than testosterone, and a statistically significant difference was observed between Sham-Control and testosterone replacement (p < 0.05) but not between Sham-Control and estradiol replacement groups. CONCLUSION: Our findings demonstrated that both estradiol and testosterone replacement therapies play a role in mandibular bone metabolism, but suggest different pathways.

Periodontal clinical status, microbial profile, and expression of interleukin-1ß in men under androgenic anabolic steroids abuse.

OBJECTIVES: Androgenic anabolic steroids (AAS) abuse is a serious health problem associated to several systemic complications. Here, we evaluated the periodontal clinical status, microbial profile, and expression of total protein (TP) and interleukin (IL)-1ß in men using AAS. MATERIALS AND METHODS: Men using AAS were recruited (case group) and matched for age with men who had never used AAS (control group) but also performed physical activities. Plaque index (PI), marginal bleeding (MB), probing depth (PD), clinical attachment level (CAL), and bleeding on probing (BoP) were evaluated. Crevicular fluid and subgingival biofilm were collected from healthy and diseased sites (PD ≥ 4 mm with CAL ≥ 1 mm and BoP) and evaluated for TP, IL-1ß, and proportions of 40 bacterial species. RESULTS: Thirty patients were included (n = 15/group). AAS consumers had significantly higher mean PD and higher percentage of diseased sites; sites with PD ≥ 4 mm or with CAL ≥ 1 mm than non-consumers. Also, AAS users showed a more dysbiotic biofilm containing lower proportions of host-compatible species and higher proportions of pathogens. IL-1ß expression was statistically higher in diseased than in healthy sites only in the control group. A statistically positive correlation was detected between periodontal pathogens and IL-1ß expression. The number of AAS cycles was positively associated with higher percentages of periodontal pathogens, but not with IL-1ß or total protein concentrations. CONCLUSIONS: AAS intake can worsen clinical and immunological periodontal conditions and the biofilm composition in healthy sites. CLINICAL RELEVANCE: Dental care professionals should perform full mouth periodontal screening and schedule regular follow-up appointments for patients under AAS use.

Testosterone Increases Fibroblast Proliferation in vitro Through Androgen and Estrogen Receptor Activation.

BACKGROUND: Skin-related disorders and periodontitis are distinct diseases that have been associated with altered levels of testosterone. Understanding the mechanisms through which testosterone mediates gingival enlargement in animals and humans is crucial for preventing or treating this condition. In this study, we investigated the impact of different doses of androgens, the role of aromatase inhibition, and the effects of testosterone association with sex hormone receptor antagonists or aromatase inhibitors on human gingival fibroblast proliferation and migration in vitro. METHODS: Fibroblasts were cultivated in Dulbecco's Modified Eagle's Medium in a humidified atmosphere and treated with different doses of testosterone or dihydrotestosterone, and testosterone in association with: aromatase inhibitor - anastrozole; antagonist of androgen receptors - flutamide; and antagonist of estrogen receptors - fulvestrant. RESULTS: Low (1nM) and high (1µM) doses of testosterone significantly increased cell migration, but the higher dose did not alter cell proliferation. Those effects were related to both androgen and estrogen receptors activation, as evidenced by the dihydrotestosterone and drug interaction groups. CONCLUSIONS: Testosterone association with sex hormone receptor antagonists flutamide and fulvestrant suggests that not only androgen receptors, but also estrogen receptors, may take part in fibroblast cell proliferation and migration in vitro.

Role of testosterone and androgen receptor in periodontal disease progression in female rats.

BACKGROUND: Sex hormone therapy has strict recommendations in the treatment of postmenopausal symptoms, in which testosterone (TES) replacement may play a potential role. However, it remains unclear whether TES affects the course of chronic inflammation and alveolar bone loss in females. Herein, we investigated the role of androgen receptor and TES on the inflammatory response and alveolar bone resorption associated with ligature-induced periodontal disease in female rats. METHODS: Fifty female Holtzman rats were divided in five groups (n = 10/group): androgen receptor antagonist (flutamide); estrogen receptor antagonist (fulvestrant); TES supplementation; aromatase inhibitor (anastrozole); and TES plus anastrozole. Periodontitis was induced by ligatures around the lower first molars for 2 weeks. Twenty animals (n = 10/group) were used as untreated ligated or non-ligated controls. Bone loss and the number of osteoclasts were measured through radiographic and immunohistochemical analysis, respectively. Inflammatory cytokines, chemokines and bone markers were measured by multiplex immunoassay and ELISA in serum samples and periodontal tissues. RESULTS: The blockage of androgen receptor significantly increased radiographic bone loss and tissue levels of IL-1α (P <0.05), IL-1ß (P <0.001) and IL-10 (P <0.01) compared with the periodontitis group. Testosterone supplementation significantly increased EGF levels in tissue samples, whereas when combined with aromatase inhibitor anastrozole significantly increased both EGF and VEGF (P <0.05). None of the treatment conditions significantly impacted the number of osteoclasts compared with the periodontitis group. CONCLUSIONS: Androgen receptor activation is an important factor in the regulation of several inflammatory markers, and its blockage significantly increases bone loss.

Sex hormone replacement therapy in periodontology-A systematic review.

OBJECTIVE: To analyse whether sex hormone replacement therapy (HRT) improves periodontal parameters and dental implants osseointegration in humans. MATERIALS AND METHODS: Electronic databases and hand searches were performed from June to August 2018 in SciELO, LILACS and PubMed/MEDLINE. Human observational and interventional studies that evaluated the following parameters were included: clinical attachment loss (CAL), probing pocket depth (PPD), bleeding on probing (BOP), radiographic bone loss (RBL) or osseointegration. RESULTS: Initial search retrieved 1,282 non-duplicated articles. Fifteen studies were selected after inclusion criteria were applied. All studies were performed in postmenopausal women. Mean differences for PPD reduction ranged from 0.02 to 0.2 mm in HRT-positive patients; mean CAL gain -0.18 to 0.54 mm; mean RBL reduction -0.87 to 0.15 mm; and mean BOP reduction 9%-30.3%. Failure rate of dental implants increased -5.5% to 11.21% when HRT was used. CONCLUSIONS: Very low but consistent evidence suggests a reduction in BOP and no impact on RBL in postmenopausal women receiving HRT. There are inconsistent reports that suggest that HRT in postmenopausal women: (a) improves or does not impact PPD reduction and CAL gain; and (b) does not impact or increase implant loss. In summary, there is no evidence to support HRT prescription for either men or women for periodontal/implant placement purposes.

Long-term testosterone depletion attenuates inflammatory bone resorption in the ligature-induced periodontal disease model.

BACKGROUND: Testosterone is known to affect bone in physiological and pathological conditions. The purpose of this study is to evaluate the role of testosterone in experimental periodontal disease in rats. METHODS: In this study we used a ligature model of periodontal disease in rats submitted to orchiectomy (OCX, testosterone depletion) with and without testosterone replacement therapy (TR). Control animals were sham-operated and retained physiological testosterone levels. Sixty-two days after orchiectomy and sham operations, ligatures were placed around the lower first molars for 2 weeks to induce experimental periodontal disease. Negative control animals received no ligatures. The outcomes assessed in the periodontal tissues were: inflammatory cytokine expression by enzyme-linked immunosorbent assay (ELISA), stereometric analysis of the inflammatory process and quantitation of inflammatory bone resorption by microcomputed tomography (µ-CT). RESULTS: The OCX+TR group showed the greatest increase in fibroblastic cells and blood vessels with reduced inflammatory cell numbers in the gingival tissue with induction of periodontal disease. There were no significant differences between OCX and Sham-operated groups in all the stereometric parameters assessed. Ligature placement induced inflammatory bone resorption, which was significantly attenuated in OCX animals. Experimental periodontitis induced a significant increase in interleukin (IL)-1ß, but the lowest levels were observed in the periodontitis/OCX group. IL-6 levels were not affected by OCX, but were significantly reduced in OCX+TR animals. CONCLUSION: The findings of the present study suggest that testosterone depletion attenuates inflammatory bone resorption in ligature-induced periodontitis, which may be partly mediated via decreased production of IL-1ß.

The role of androgens on periodontal repair in female rats.

BACKGROUND: Testosterone replacement enhances cognitive function and musculoskeletal health in postmenopausal women. However, the biological role of testosterone on inflammation and bone metabolism in females is not well understood. Our objective was to measure the impact of androgens and their receptors on periodontal tissues during periodontal repair in female rats. METHODS: Seventy female Holtzman rats were divided into seven groups (n = 10/group): negative control; repair control; androgen receptor antagonist (flutamide, 50 mg/kg, every other day); estrogen receptor antagonist (fulvestrant, 1.5 mg/kg/day); testosterone supplementation (durateston, 250 mg/kg, weekly); aromatase inhibitor (anastrozole, 0.2 mg /kg/day); testosterone plus anastrozole. Cotton ligatures were kept for 13 days, when pharmacological treatment was initiated. On day 14, the ligatures were removed. The rats were euthanized on the 17th or the 28th day (n = 5/group/period) for the evaluation of markers related to inflammation and bone. The tissue and serum samples were evaluated using a multiplexed immunoassay for the inflammatory targets. Radiographic and histologic analyses were performed to assess changes in tissues. RESULTS: Blockage of androgen receptors had little effect on inflammatory cell count, although it tended to increase interleukin (IL)-4, vascular endothelial growth factor (VEGF), and epidermal growth factor (EGF) as well as decrease IL-1ß, tumor necrosis factor (TNF)-α, and IL-6. Flutamide also significantly impaired bone repair (P < 0.05) and had greater osteoclast count, although this last difference was not statistically significant. Testosterone supplementation significantly increased the inflammatory cell count, decreased the levels of IL-4, IL-10, IL-1ß, IL-6, and TNF-α; and increased VEGF and EGF. CONCLUSION: The blockage of androgen receptors significantly impair bone repair in females through mechanisms that are different from those related to estrogen receptors.

Avaliação contínua da aprendizagem por meio da aplicação de quiz semanal no ensino da Periodontia / Continuous learning evaluation through the application of weekly quiz in Periodontics

A avaliação contínua e rotineira mantém o estudante sob constante estudo, leitura e aprendizado, além de suavizar o impacto das avaliações teóricas formais sobre os critérios tradicionais de aprovação. O objetivo deste estudo foi avaliar o impacto da aplicação de quiz semanal sobre a nota da avaliação teórica formal no componente curricular Periodontia I do Curso de Odontologia da Universidade Federal do Paraná. Para este estudo observacional retrospectivo, avaliaram-se os campos "nota quiz" e "nota avaliação" dos diários de classe das turmas do primeiro e segundo semestres de 2016, respectivamente "sem quiz" (n=53) e "com a realização de quiz semanal" (n=55). As avaliações teóricas formais foram idênticas para as duas turmas. Os dados referentes ao número de quizzes realizados e média das notas de quiz foram tabulados. As análises estatísticas utilizadas foram teste t de Student e coeficiente de correlação de Spearman. A aplicação de quiz semanal deslocou a curva referente às notas de avaliação teórica à direita, sendo que as notas foram significativamente maiores neste grupo (p<0.01). Além disso, houve correlação significativa entre a nota da avaliação teórica e o número de quizzes realizados por cada estudante (r=0,39; p<0,01), bem como com a média da nota do quiz (r=0,47; p<0,01). Concluiu-se que a utilização de quiz semanal como instrumento de avaliação da aprendizagem influi positivamente no grau de conhecimento adquirido, provavelmente devido a um maior estímulo à leitura e estudo constante (AU).

Continuous and routine evaluation keeps the student studying, reading and learning permanently, as well as lightens the impact of formal theoretical exams on the traditional criteria for passing a course. The aim of this study was to evaluate the impact of weekly quiz application on the formal theoretical exam score in the course of Periodontics I ­ a theoreticalpractical course ­ at the School of Dentistry at Federal University of Paraná, Brazil. For this retrospective observational study, the fields "quiz score" and "exam score" of the register book from students of the first and second term of 2016, "no quiz" (n=53) and "weekly quiz application" (n=55), respectively, were analyzed. Formal theoretical exams were identical for both students groups. Data related to the number of quizzes taken by each student and quiz scores were tabulated. Student's t-test and Spearman correlation coefficient test were used for statistical analyses. Weekly quiz application moved the theoretical exam scores curve to the right and scores were significantly greater in this group (p<0.01). Besides, there was a significant correlation between theoretical exam score and the number of quizzes taken by each student (r=0.39; p<0.01), as well as with mean quiz score (r=0.47; p<0.01). We concluded that weekly application of quiz as an evaluation instrument in Periodontics positively influences acquired knowledge, probably due to stimulating permanent studying (AU).

Comparison Between Dexamethasone and Ibuprofen for Postoperative Pain Prevention and Control After Surgical Implant Placement: A Double-Masked, Parallel-Group, Placebo-Controlled Randomized Clinical Trial.

BACKGROUND: Postoperative pain is a potential adverse side effect of oral surgeries, and attempts should be made to prevent or minimize it. This study compares efficacy of preemptive ibuprofen and dexamethasone protocols for pain prevention or control after surgical implant placement. METHODS: This prospective, double-masked, parallel-group, placebo-controlled, randomized clinical trial included 117 patients with planned dental implant placement. Patients were assigned to receive one of three different protocols: 1) 600 mg ibuprofen 1 hour before surgery and another 600 mg 6 hours after the first dose; 2) 4 mg dexamethasone 1 hour before surgery and another 4 mg 6 hours after the first dose; or 3) placebo. Rescue medication (1,000 mg acetaminophen) was made available to each patient, and they were instructed to take it as necessary. Pain intensity was evaluated via a 101-point numeric rating scale and a visual analog scale, and discomfort was evaluated using a four-point verbal rating scale hourly for the first 8 hours after surgery and three times daily for the following 3 days. RESULTS: Ibuprofen and dexamethasone significantly reduced pain (Kruskal-Wallis; P <0.05) up to 3 days after surgery and discomfort (P <0.05) up to 2 days after surgery compared with placebo treatment. Both treatments reduced the number of painkillers taken and increased time before the first painkiller was taken (P <0.01). CONCLUSION: Steroidal dexamethasone is as effective as non-steroidal ibuprofen for preventing or controlling postoperative pain and discomfort after surgical implant placement.

Androgen receptors and experimental bone loss - an in vivo and in vitro study.

Testosterone is a sex hormone that exhibits many functions beyond reproduction; one such function is the regulation of bone metabolism. The role played by androgen receptors during testosterone-mediated biological processes associated with bone metabolism is largely unknown. This study aims to use a periodontal disease model in vivo in order to assess the involvement of androgen receptors on microbial-induced inflammation and alveolar bone resorption in experimental bone loss. The impact of hormone deprivation was tested through both orchiectomy and chemical blockage of androgen receptor using flutamide (FLU). Additionally, the direct effect of exogenous testosterone, and the role of the androgen receptor, on osteoclastogenesis were investigated. Thirty male adult rats (n=10/group) were subjected to: 1-orchiectomy (OCX); 2-OCX sham surgery; or 3-OCX sham surgery plus FLU, four weeks before the induction of experimental bone loss. Ten OCX sham-operated rats were not subjected to experimental bone loss and served as healthy controls. The rats were euthanized two weeks later, so as to assess bone resorption and the production of inflammatory cytokines in the gingival tissue and serum. In order to study the in vitro impact of testosterone, osteoclasts were differentiated from RAW264.7 cells and testosterone was added at increasing concentrations. Both OCX and FLU increased bone resorption, but OCX alone was observed to increase osteoclast count. IL-1ß production was increased only in the gingival tissue of OCX animals, whereas FLU-treated animals presented a decreased expression of IL-6. Testosterone reduced the osteoclast formation in a dose-dependent manner, and significantly impacted the production of TNF-α; FLU partially reversed these actions. When taken together, our results indicate that testosterone modulates experimental bone loss, and that this action is mediated, at least in part, via the androgen receptor.

Associations Between Sex Hormone Levels and Periodontitis in Men: Results From NHANES III.

BACKGROUND: Sex hormones are linked to inflammation and bone turnover. The goal of this study is to explore the association between sex hormone levels and periodontitis in men using data from the third National Health and Nutrition Examination Survey (NHANES III). METHODS: Data from 755 men (aged ≥ 30 years), including serum levels of testosterone, estradiol, sex hormone binding globulin, and androstenediol glucuronide, were analyzed. Calculated bioavailable testosterone (CBT) and estradiol-to-testosterone ratio were calculated. Periodontitis was defined using the latest classification of extent and severity of periodontitis for NHANES data (≥ 2 interproximal sites with ≥ 3 mm attachment loss, ≥ 2 interproximal sites with probing depth [PD] ≥ 4 mm not on the same tooth, or one site with PD ≥ 5 mm). Sex hormones were evaluated as categorized and continuous variables. Correlations between the presence and severity of periodontitis and levels of sex hormones were determined and expressed as odds ratios (ORs). RESULTS: When adjusted for confounding factors, high total testosterone (TT) and CBT levels correlated with both the prevalence (OR [95% confidence interval (CI)], 2.1 [1 to 4.5] and 3.9 [1 to 14.8], respectively) and severity (OR [95% CI], 2.1 [1 to 4.3] and 3.4 [1.2 to 9.8]) of periodontitis. When continuous variables were used, the ORs (95% CIs) for presence and severity of periodontitis were 1.4 (0.6 to 3.3) and 1.5 (0.6 to 3.6) for TT and 1.3 (0.9 to 1.9) and 1.3 (0.9 to 1.8) for CBT, respectively. CONCLUSIONS: These findings are consistent with the existence of an association of periodontitis with sex hormone levels, especially testosterone, in men.

Clopidogrel enhances periodontal repair in rats through decreased inflammation.

AIM: We hypothesized that platelet inactivation induced by drugs might interfere with periodontal repair in experimental periodontitis by suppressing the release of biological mediators from platelets at the site of injury. MATERIAL AND METHODS: Sixty rats were randomly assigned to six groups (n = 10) and ligatures were placed around lower first molars of three groups. The other three groups were used as negative controls. Ligatures were removed after 10 days of periodontitis induction and all groups were submitted to treatment with aspirin (Asp) (30 mg/kg), clopidogrel (Clop) (75 mg/kg) or NaCl 0.9% intra-gastrically once daily for 3 days. Periodontal tissue was assessed by the measurement of CXCL12, CXCL4, CCL5 and platelet-derived growth factor (PDGF) by enzyme-linked immunosorbent assay; histomorphometrical analysis of polymorphonuclear (PMN) infiltration, attachment loss, bone loss and osteoclast numbers and quantification of blood vessels by imunnohistochemistry. RESULTS: During periodontal repair and treatment with NaCl 0.9%, CCL5 was decreased and CXCL12 increased when compared with negative control groups. Asp and Clop did not affect CCL5 expression, decreased CXCL12 but only Clop decreased CXCL4 and PDGF content compared with saline-treated animals. Clop increased blood vessel number, reduced PMN count and decreased attachment and bone loss, also decreased osteoclast number in animals submitted or not to periodontal repair. CONCLUSION: Systemic administration of Clop for 3 days improved the repair process associated with experimental periodontal disease, suggesting that it may have therapeutic value under situations where tissues undergo a transition from inflammation to repair.

Influence of parstatin on experimental periodontal disease and repair in rats.

BACKGROUND: Parstatin is a 41-amino acid peptide, formed by proteolytic cleavage on activation of the protease activated receptor-1, with antiangiogenic properties. The purpose of this study is to evaluate the influence of synthetic parstatin on experimental periodontal disease and repair in rats. METHODS: Ligature-induced periodontitis was established in rats and the influence of parstatin administration was assessed after 8 and 15 days for periodontal disease and 24 hours and 8 days after repair after ligature removal. RESULTS: Parstatin administration significantly inhibited gingival myeloperoxidase activity, interleukin (IL)-1ß, tumor necrosis factor-α, and IL-6 levels and led to suppression of macrophages and collagen degradation. At periodontal tissues under repair, parstatin increased the gingival levels of endostatin and decreased vascular endothelial growth factor expression and blood vessel number but did not influence histologic healing. In addition, the tomographic linear bone loss was significantly reduced at 15 days of periodontitis when the rats were treated with parstatin compared to their respective phosphate-buffered saline-treated controls. CONCLUSIONS: Parstatin suppresses the periodontal tissue breakdown followed by experimental periodontitis in rats and did not impair periodontal tissue repair, despite its antiangiogenic effect. Parstatin may represent a novel approach to modulate host response in chronic periodontal disease.