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Background and Objectives: Periodontitis can corroborate with development and progression of atherosclerosis and a possible bidirectional interaction between both pathologies has been hypothesized. The aim of this work was to study the interactions between diet-induced hypercholesterolemia and ligature-induced periodontitis in Wistar rats submitted to both conditions., Material and Methods: Animals were divided into four experimental groups: C (control: standard diet without periodontitis), Perio (periodontitis plus standard diet), HC (high cholesterol diet without periodontitis), and HC + Perio (high cholesterol diet plus periodontitis). The diets were offered for 45 days and a silk ligature was applied in the lower first molars of Perio and HC-Perio animals on day 34 and maintained for 11 days until euthanasia. The mandibles were excised, and alveolar bone loss was determined by macroscopic and micro-tomographic (µ-CT) imaging. Blood samples were obtained, and platelet aggregation was induced in plasma rich in platelets by adenosine diphosphate (ADP) and collagen. Endothelium-dependent vascular reactivity and protein expression of endothelial (eNOS), phosphorylated endothelial (peNOS), and inducible (iNOS) nitric oxide synthases were evaluated in aorta samples., Results: The HC diet combined with periodontitis (HC + Perio group) was associated with an increased alveolar bone loss, when compared to the other groups. Both in Perio and HC groups, platelet aggregation induced by ADP or collagen was increased, while maximum aortic relaxation induced by acetylcholine was decreased. Periodontitis or HC diet alone decreased the expression of peNOS and HC diet increased the expression of iNOS. In contrast, no additive or synergistic effects were found in vascular reactivity or in platelet aggregation when the two conditions were associated (HC + Perio group)., Conclusion: Hypercholesterolemia accelerated the process of bone loss induced by periodontitis while a high cholesterol diet or periodontitis individually increased platelet aggregation and vascular reactivity in rats without additive or synergistic effects, when associated., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The present study examined the hemodynamics [arterial pressure (AP), AP variability (APV), heart rate (HR), and heart rate variability (HRV)], cardiac function (echocardiographycally), and myocardial inflammation in Balb/c mice submitted to Periodontitis, through the ligation of the left first molar, or Sham surgical procedure. The first protocol indicated that the AP was similar (136 ± 2 vs. 132 ± 3 mmHg in Sham), while the HR was higher in mice with Periodontitis (475 ± 20 vs. 412 ± 18 bpm in Sham), compared to their Sham counterparts. The APV was higher in mice with Periodontitis when evaluated in the time domain (4.5 ± 0.3 vs. 3.4 ± 0.2 mmHg in Sham), frequency domain (power of the LF band of systolic AP), or through symbolic analysis (patterns 0V + 1V), indicating a sympathetic overactivity. The HRV was similar in the mice with Periodontitis, as compared to their Sham counterparts. In the second protocol, the mice with Periodontitis showed decreased cardiac output (10 ± 0.8 vs. 15 ± 1.4 mL/min in Sham) and ejection fraction (37 ± 3 vs. 47 ± 2% in Sham) associated with increased myocardial cytokines (Interleukin-17, Interleukin-6, and Interleukin-4). This study shows that experimental Periodontitis caused cardiac dysfunction, increased heart cytokines, and sympathetic overactivity, in line with epidemiological studies indicating an increased risk of cardiovascular events in clinical Periodontitis.

Background: Oral breathing can cause morphological changes in the oral and maxillofacial regions., Aims: To investigate whether oral breathing affected structural changes in bone tissues., Study Design: Animal experimentation., Methods: A total of 48 8-day-old male Sprague−Dawley rats were divided into two groups: a breathing group and a sham (control) group. All Sprague−Dawley rats were killed at 7 weeks after unilateral nostril obstruction modeling. Then, structural changes in bone tissues were detected by micro-computed tomography, and the expression levels of receptor activator of nuclear factor-κB, osteoprotegerin, and receptor activator of nuclear factor-κB ligand in the signal pathway of bone metabolism within the local alveolar bone and serum of rats were detected by reverse transcription-quantitative polymerase chain reaction and Western blotting., Results: The results showed that receptor activator of nuclear factor-κB ligand and receptor activator of nuclear factor-κB levels in bone tissues and serum in the oral breathing group were higher than those in the control group [Maxillary alveolar bone: receptor activator of nuclear factor-κB ligand (pRNA=0.009, pprotein=0.008), receptor activator of nuclear factor-κB (pRNA=0.008, pprotein=0.009); Mandibular alveolar bone: receptor activator of nuclear factor-κB ligand (pRNA=0.047, pprotein=0.042), receptor activator of nuclear factor-κB (pRNA=0.041, pprotein=0.007); Serum: receptor activator of nuclear factor-κB ligand (pRNA<0.001, pprotein<0.001), receptor activator of nuclear factor-κB (pRNA<0.001, pprotein<0.001)], along with decreased osteoprotegerin expression (Maxillary alveolar bone: pRNA=0.038, pprotein=0.048; Mandibular alveolar bone: pRNA<0.001, pprotein<0.001; Serum: pRNA=0.009, pprotein=0.006) and elevated receptor activator of nuclear factor-κB ligand/osteoprotegerin. Micro-computed tomography analysis indicated a significant difference in the level of bone volume fraction, as well as trabecular thickness in maxillary alveolar bone between the experimental and control groups (p=0.049, p=0.047). Meanwhile, trabecular thickness, and cortical thickness levels in mandibular alveolar bone also differed significantly between the experimental and control groups (p=0.043, p=0.024)., Conclusion: Structural changes of the respiratory system affect the alveolar bone structure and unilateral nasal obstruction may lead to a change in regional specific bone density.

Tyrosine-protein phosphatase non-receptor type 2 (PTPN2) is an important protection factor for diabetes and periodontitis, but the underlying mechanism remains elusive. This study aimed to identify the substrate of PTPN2 in mediating beneficial effects of 25-Hydroxyvitamin D 3 (25(OH)2D 3 ) on diabetic periodontitis. 25(OH)2D 3 photo-affinity probe was synthesized with the minimalist linker and its efficacy to inhibit alveolar bone loss, and inflammation was evaluated in diabetic periodontitis mice. The probe was used to pull down the lysates of primary gingival fibroblasts. We identified PTPN2 as a direct target of 25(OH)2D 3 , which effectively inhibited inflammation and bone resorption in diabetic periodontitis mice. In addition, we found that colony-stimulating factor 1 receptor (CSF1R) rather than JAK/STAT was the substrate of PTPN2 to regulate bone resorption. PTPN2 direct interacted with CSF1R and dephosphorylated Tyr807 residue. In conclusion, PTPN2 dephosphorylates CSF1R at Y807 site and inhibits alveolar bone resorption in diabetic periodontitis mice. PTPN2 and CSF1R are potential targets for the therapy of diabetic periodontitis or other bone loss-related diseases., (© 2019 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

Our goal was to evaluate alveolar bone healing in OVX mice, and to assess the functional utility of a WNT-based treatment to accelerate healing in mice with an osteoporotic-like bony phenotype., Introduction: Is osteoporosis a risk factor for dental procedures? This relatively simple question is exceedingly difficult to answer in a clinical setting, for two reasons. First, as an age-related disease, osteoporosis is frequently accompanied by age-related co-morbidities that can contribute to slower tissue repair. Second, the intervals at which alveolar bone repair are assessed in a clinical study are often measured in months to years. This study aimed to evaluate alveolar bone repair in ovariectomized (OVX) mice and provide preclinical evidence to support a WNT-based treatment to accelerate alveolar bone formation., Methods: OVX was performed in young mice to produce an osteoporotic-like bone phenotype. Thereafter, the rate of extraction socket healing and osteotomy repair was assessed. A liposomal WNT3A treatment was tested for its ability to promote alveolar bone formation in this OVX-induced model of bone loss., Results: Bone loss was observed throughout the murine skeleton, including the maxilla, and mirrored the pattern of bone loss observed in aged mice. Injuries to the alveolar bone, including tooth extraction and osteotomy site preparation, both healed significantly slower than the same injuries produced in young controls. Given sufficient time, however, all injuries eventually healed. In OVX mice, osteotomies healed significantly faster if they were treated with L-WNT3A., Conclusions: Alveolar bone injuries heal slower in OVX mice that exhibit an osteoporotic-like phenotype. The rate of alveolar bone repair in OVX mice can be significantly promoted with local delivery of L-WNT3A.

Background and Objective: Both chronic and aggressive periodontal disease are associated with vitamin D deficiency. The active form of vitamin D, 1,25(OH) 2 D 3 , induces the expression of the antimicrobial peptide LL-37 and innate immune mediators in cultured human gingival epithelial cells (GECs). The aim of this study was to further delineate the mechanism by which vitamin D enhances the innate defense against the development of periodontal disease (PD)., Materials and Methods: Wild-type C57Bl/6 mice were made deficient in vitamin D by dietary restriction. Cultured primary and immortalized GEC were stimulated with 1,25(OH) 2 D 3 , followed by infection with Porphyromonas gingivalis, and viable intracellular bacteria were quantified. Conversion of vitamin D 3 to 25(OH)D 3 and 1,25(OH) 2 D 3 was quantified by ELISA. Effect of vitamin D on basal IL-1α expression in mice was determined by topical administration to the gingiva of wild-type mice, followed by qRT-PCR., Results: Dietary restriction of vitamin D led to alveolar bone loss and increased inflammation in the gingiva in the mouse model. In primary human GEC and established human cell lines, treatment of GEC with 1,25(OH) 2 D 3 inhibited the intracellular growth of P. gingivalis. Cultured GEC expressed two 25-hydroxylases (CYP27A1 and CYP2R1), as well as 1-α hydroxylase, enabling conversion of vitamin D to both 25(OH)D 3 and 1,25(OH) 2 D 3 . Topical application of both vitamin D 3 and 1,25(OH) 2 D 3 to the gingiva of mice led to rapid inhibition of IL-1α expression, a prominent pro-inflammatory cytokine associated with inflammation, which also exhibited more than a 2-fold decrease from basal levels in OKF6/TERT1 cells upon 1,25(OH) 2 D 3 treatment, as determined by RNA-seq., Conclusion: Vitamin D deficiency in mice contributes to PD, recapitulating the association seen in humans, and provides a unique model to study the development of PD. Vitamin D increases the activity of GEC against the invasion of periodontal pathogens and inhibits the inflammatory response, both in vitro and in vivo. GEC can convert inactive vitamin D to the active form in situ, supporting the hypothesis that vitamin D can be applied directly to the gingiva to prevent or treat periodontal disease., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: Dental aplasia is an anomaly in which the number of teeth is reduced. It is the most commonly occurring dental anomaly during tooth development. Treatment management of patients with dental aplasia is challenging., Objectives: The aim of this retrospective clinical study was to analyze the survival and success rates of dental implants placed in hypodontic patients, rated with different criteria., Methods: Forty-three patients were diagnosed with dental aplasia and treated with dental implants between November 2000 and February 2016. The variables assessed included the plaque level, bleeding on probing, probing depth, implant mobility, implant stability, and implant loss. To analyze the peri-implant bone level, a panoramic X-ray of each patient was taken. The results were compared with X-rays taken immediately after implantation., Results: Thirty-seven patients (16 males; 21 females) participated in this study. In total, 155 implants (86 maxillary; 69 mandibular) were inserted. Two of the 155 implants failed; the in situ survival rate was 98.7%. The success rate according to the criteria of Buser et al. was 96.8%, and that according to the criteria of Albrektsson et al. was 88.4%., Conclusion: The survival and success rates of dental implants in patients with congenitally absent teeth were very high and did not differ significantly from results achieved in an unaffected population. Dental implants are a reliable therapy for patients with dental aplasia.

Apical periodontitis represents a chronic inflammatory process within periapical tissues, mostly caused by etiological agents of endodontic origin. Progressive bone resorption in the periapical region represents the hallmark of apical periodontitis and occurs as the consequence of interplay between polymicrobial infections and host response. The Notch signaling pathway is an evolutionary conserved cell-signaling system that plays an important role in a variety of cell functions including proliferation, differentiation and apoptosis. In recent years its involvement in bone homeostasis has attracted a significant consideration. We hypothesized that Notch signaling pathway, which has a complex interplay with proinflammatory cytokines and bone resorption regulators, contributes to alveolar bone resorption via increased Notch receptors on immune cell surface and stimulates Notch receptor intracellular domain (NICD) translocation into the nucleus. The potential benefit of medications aimed to down-regulate these pathways in apical periodontitis treatment remains to be assessed., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Purpose: To evaluate the effect of misfit at implant-level fixed partial dentures (ILFPDs) and marginal bone support on the generation of implant cracks., Materials and Methods: This in vitro study included a mechanical fatigue test and finite element analysis. A mechanical cycling loading test was performed using 16 experimental models, each consisting of two parallel implants subdivided into four groups based on the misfit and the supporting bone condition. The framework, firmly seated at implants, was dynamically loaded vertically with a force of 1,600/160 N and 15 Hz for 1 × 10 6 cycles. Optical microscope, scanning electron microscope (SEM), and computed tomography three-dimensional (CT-3D) analyses were performed to detect impairments. Finite element models, representing the setups in the mechanical fatigue test, were used to represent the fatigue life., Results: None of the mechanical components presented distortion or fracture at the macroscopic level during the test. In a microscopy evaluation, the fatigue test revealed scratches visible in the inner part of the conical portion of the implants regardless of the groups. SEM and CT-3D analysis revealed one implant from the misfit/no bone loss group with a microfracture in the inner part of the conical interface. The simulated effective stress levels in the coronal body were higher in the misfit groups compared with the no misfit groups. The misfit groups presented effective stress levels, above 375 MPa, that penetrated the entire wall thickness. The no bone loss group presented an effective stress level above 375 MPa along its axial direction. In the no misfit group, the area presenting effective stress levels above 375 MPa in the conical connection was larger for the bone loss group compared with the no bone loss group., Conclusion: This study confirmed that implant fracture is an unlikely adverse event. A clear pattern of effective distribution greater than fatigue limit stresses could be noticed when the misfit was present. The dynamic load simulation demonstrated that the crack is more likely to occur when implants are fully supported by marginal bone compared with a bone loss scenario. Within the limitations of this study, it is speculated that marginal bone loss might follow the appearance of an undetected crack. Further research is needed to develop safe clinical protocols with regard to ILFPD.

Postmenopausal osteoporosis (PMO) is a risk factor for periodontitis, and current therapeutics against PMO prevent the aggravated alveolar bone loss of periodontitis in estrogen-deficient women. Gut microbiota is recognized as a promising therapeutic target for PMO. Berberine extracted from Chinese medicinal plants has shown its effectiveness in the treatment of metabolic diseases such as obesity and diabetes via regulating gut microbiota. Here, we hypothesize that berberine ameliorates periodontal bone loss by improving the intestinal barriers by regulating gut microbiota under an estrogen-deficient condition. Experimental periodontitis was established in ovariectomized (OVX) rats, and the OVX-periodontitis rats were treated with berberine for 7 wk before sacrifice for analyses. Micro-computed tomography and histologic analyses showed that berberine treatment significantly reduced alveolar bone loss and improved bone metabolism of OVX-periodontitis rats as compared with the vehicle-treated OVX-periodontitis rats. In parallel, berberine-treated OVX-periodontitis rats harbored a higher abundance of butyrate-producing gut microbiota with elevated butyrate generation, as demonstrated by 16S rRNA sequencing and high-performance liquid chromatography analysis. Berberine-treated OVX-periodontitis rats consistently showed improved intestinal barrier integrity and decreased intestinal paracellular permeability with a lower level of serum endotoxin. In parallel, IL-17A-related immune responses were attenuated in berberine-treated OVX-periodontitis rats with a lower serum level of proinflammatory cytokines and reduced IL-17A + cells in alveolar bone as compared with vehicle-treated OVX-periodontitis rats. Our data indicate that gut microbiota is a potential target for the treatment of estrogen deficiency-aggravated periodontal bone loss, and berberine represents a promising adjuvant therapeutic by modulating gut microbiota.

This study aimed to investigate the possible influence of the regional acceleratory phenomenon (RAP) on dental implant osseointegration. Orthognathic surgery was set as an intervention for RAP, and a multicentre cohort study of two groups was undertaken. Group O included patients with single implant placement at least 4 months after orthognathic surgery and functional loading for more than 1 year, while controls (Group C) were without any major surgery. Clinical and radiographic assessments of implants, including changes in marginal bone levels, were analysed at baseline, 6- and 12-month follow-up. Bivariate analysis of two groups with propensity score matching was performed. After propensity score matching, all 10 confounding variables had acceptable standardised difference scores (<20%), indicating that the matching procedure had efficiently balanced the two groups. Following the propensity score adjustment, the marginal bone loss was significantly higher in Group O than the control at 6 months (1.66 ± 1.05 mm vs 0.59 ± 0.64 mm, P < 0.001) and 12 months (2.30 ± 1.27 mm vs 0.82 ± 0.78 mm, P < 0.001). Compared to Group C, subjects in Group O had a higher incidence of peri-implant mucositis and implantitis (11.8% vs 1.5%, P = 0.033). Impaired osseointegration of dental implants was associated with orthognathic surgery. Special considerations for peri-implant soft and hard tissue stability should be addressed to obtain ideal treatment results and prognosis for patients who have had prior orthognathic surgery., (© 2018 John Wiley & Sons Ltd.)

Aim: To evaluate, with three-dimensional analysis, the effectiveness of alveolar ridge preservation (ARP) after maxillary molar extraction in reducing alveolar bone resorption and maxillary sinus pneumatization when compared to unassisted socket healing., Methods: Patients were included in the study following inclusion criteria and underwent minimally traumatic maxillary molar extraction followed by ARP using synthetic nanohydroxyapatite (Fisiograft Bone, Ghimas, Italy) (test group) or unassisted socket healing (control group). Cone-beam computerized tomographies (CBCT) were performed immediately after tooth extraction (T0) and 6 months postoperatively (T1). CBCTs were superimposed by using a specific software (Amira, Thermo Fisher Scientific, USA) and the following items were analyzed in both groups: (i) postextractive maxillary sinus floor expansion in coronal direction and (ii) postextractive alveolar bone dimensional changes (both vertical and horizontal). All data were tested for normality and equality of variance and subsequently analyzed by independent samples T-test and Mann-Whitney test., Results: Thirty patients were treated by three centers and twenty-six (test n=13; control n=13) were included in the final analysis. Mean sinus pneumatization at T1 was 0.69±0.48 mm in the test group and 1.04±0.67 mm in the control group (p=0.15). Mean vertical reduction of the alveolar bone at T1 was 1.62±0.49 mm in the test group and 2.01±0.84 mm in the control group (p=0.08). Mean horizontal resorption of crestal bone at T1 was 2.73±1.68 mm in test group and 3.63±2.24 mm in control group (p=0.24)., Conclusions: It could be suggested that ARP performed after maxillary molar extraction may reduce the entity of sinus pneumatization and alveolar bone resorption, compared to unassisted socket healing. This technique could decrease the necessity of advanced regenerative procedures prior to dental implant placement in posterior maxilla.

Objective: Periodontitis is associated with endothelial dysfunction, which is clinically characterized by a reduction in endothelium-dependent relaxation. However, we have previously shown that impairment in endothelium-dependent relaxation is transient. Therefore, we evaluated which mediators are involved in endothelium-dependent relaxation recovery., Material and Methods: Rats were subjected to ligature-induced experimental periodontitis. Twenty-one days after the procedure, the animals were prepared for blood pressure recording, and the responses to acetylcholine or sodium nitroprusside were obtained before and 30 minutes after injection of a nitric oxide synthase inhibitor (L-NAME), cyclooxygenase inhibitor (Indomethacin, SC-550 and NS- 398), or calcium-dependent potassium channel blockers (apamin plus TRAM- 34). The maxilla and mandible were removed for bone loss analysis. Blood and gingivae were obtained for C-reactive protein (CRP) and myeloperoxidase (MPO) measurement, respectively., Results: Experimental periodontitis induces bone loss and an increase in the gingival MPO and plasmatic CRP. Periodontitis also reduced endothelium-dependent vasodilation, a hallmark of endothelial dysfunction, 14 days after the procedure. However, the response was restored at day 21. We found that endothelium-dependent vasodilation at day 21 in ligature animals was mediated, at least in part, by the activation of endothelial calcium-activated potassium channels., Conclusions: Periodontitis induces impairment in endothelial-dependent relaxation; this impairment recovers, even in the presence of periodontitis. The recovery is mediated by the activation of endothelial calcium-activated potassium channels in ligature animals. Although important for maintenance of vascular homeostasis, this effect could mask the lack of NO, which has other beneficial properties.

Splinted and unsplinted overdenture attachment systems have unique advantages and disadvantages. The aim of the present systematic review was to determine the influence of splinted and unsplinted overdenture attachment systems on the marginal bone loss, prosthetic complications and implant survival rate. PubMed/MEDLINE, Scopus and Cochrane databases were searched for articles published up to October 2017, using the following search terms: "overdenture AND attachment OR overdenture AND bar OR overdenture splinted." The PICO question "Do splinted overdenture attachment systems promote better clinical results in comparison to unsplinted systems?" was evaluated. Eligible studies included randomized controlled clinical trials, prospective studies with at least 10 participants and a minimum follow-up of 6 months, and studies published in English that compared splinted and unsplinted attachment systems within the same study. The 95% confidence interval (CI) was considered for all outcomes analysed. After completion of the different steps in the article selection process, nine articles were included in the qualitative and quantitative analyses. A total of 984 implants were placed in 380 patients (mean age: 62.8 years). The meta-analysis demonstrated no statistically significant differences between splinted and unsplinted attachment systems with regard to marginal bone loss (P = .39; MD: -0.11; 95% CI: -0.37 to 0.14), complications (P = .31; RR: 1.26; CI: 0.80-1.99) and implant survival rate (P = .14; RR: 0.37% CI: 0.10-1.36). In addition, splinted and unsplinted overdenture attachment systems achieved similar results with regard to marginal bone loss, prosthetic complications and implant survival rate., (© 2018 John Wiley & Sons Ltd.)

To evaluate peri-implant bone loss (PIBL) and stability around submerged and non-submerged dental implants in patients with and without type 2 diabetes mellitus (T2DM). Thirty-five T2DM and non-diabetic (NT2DM) patients were included in this study. Demographic data were recorded using a questionnaire and PIBL was measured on digital radiographs. Resonance frequency analysis (RFA) was carried out for each implant at the time of fixture placement and at 3 months in both groups. P values less than 0.05 were considered statistically significant. One hundred and eighteen dental implants with a mean height of 10 to 12 mm and 3.3 to 4.1 mm in diameter were placed. The comparison of the mean RFA values at baseline and at 3 months was statistically significant (p = 0.008) in T2DM patients. The inter-group mean RFA values at baseline and at 3 months were not significant (p > 0.05). PIBL was significantly high in T2DM as compared to NT2DM patients at each follow-up (p < 0.05). At 2, 3, and 7 years, non-submerged dental implants showed significantly high PIBL in T2DM patients as compared to NT2DM individuals (p<0.05). The results of the present clinical study demonstrate increased PIBL around non-submerged single-tooth implant-supported restorations in T2DM patients, which may be due to the immune inflammatory status.

Aging is associated with a function decline in tissue homeostasis and tissue repair. Aging is also associated with an increased incidence in osteopenia and osteoporosis, but whether these low bone mass diseases are a risk factor for delayed bone healing still remains controversial. Addressing this question is of direct clinical relevance for dental patients, since most implants are performed in older patients who are at risk of developing low bone mass conditions. The objective of this study was to assess how an osteopenic/osteoporotic phenotype affected the rate of new alveolar bone formation. Using an ovariectomized (OVX) rat model, the rates of tooth extraction socket and osteotomy healing were compared with age-matched controls. Imaging, along with molecular, cellular, and histologic analyses, demonstrated that OVX produced an overt osteoporotic phenotype in long bones, but only a subtle phenotype in alveolar bone. Nonetheless, the OVX group demonstrated significantly slower alveolar bone healing in both the extraction socket, and in the osteotomy produced in a healed extraction site. Most notably, osteotomy site preparation created a dramatically wider zone of dying and dead osteocytes in the OVX group, which was coupled with more extensive bone remodeling and a delay in the differentiation of osteoblasts. Collectively, these analyses demonstrate that the emergence of an osteoporotic phenotype delays new alveolar bone formation., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: During rapid maxillary expansion (RME), heavy forces are transmitted to the maxilla by the anchored teeth causing buccal inclination and buccal bone loss of posterior teeth., Objective: To systematically review the literature in order to investigate whether RME causes periodontal sequelae, assessed by cone-beam computed tomography (CBCT)., Search Methods: Fifteen electronic databases and reference lists of studies were searched up to March 2017., Selection Criteria: To be included in the systematic review, articles must be human studies on growing subjects, with transversal maxillary deficiency treated with RME and with assessment of buccal bone loss by CBCT images. Only randomized and non-randomized trials were included., Data Collection and Analysis: Two authors independently performed study selection, data extraction, and risk of bias assessment. Study characteristics (study design, sample size, age, sex, skeletal maturity, type of appliance, daily activation, evaluated linear measurements, observation period, CBCT settings), and study outcomes (loss of buccal bone thickness and marginal bone) were reported according to the PRISMA statement., Results: On the basis of the applied inclusion criteria, only six articles, three randomized clinical trials and three controlled clinical trials were included. An individual analysis of the selected articles was undertaken. The risks of bias of the six trials were scored as medium to low., Limitations: The results of the present systematic review are based on a limited number of studies and only one study included a control group., Conclusions and Implications: In all considered studies, significant loss of buccal bone thickness and marginal bone level were observed in anchored teeth, following RME. Further prospective studies correlating the radiological data of bone loss to the periodontal soft tissues reaction after RME are required. A preliminary evaluation of the patient-related risk factors for RR may be advisable when considering to administering RME., Registration: This systematic review was registered in the National Institute of Health Research database with an appropriate protocol number (http://www.crd.york.ac.uk/PROSPERO Protocol: CRD42017062645)., Funding: The present study has not received any contributions from private or public funding agencies.

Alveolar bone, together with the underlying trabecular bone, fulfils an important role in providing structural support against masticatory forces. Diseases such as osteoporosis or periodontitis cause alveolar bone resorption which weakens this structural support and is a major cause of tooth loss. However, the functional relationship between alveolar bone remodelling within the molar region and masticatory forces is not well understood. This study investigated this relationship by comparing mammalian species with different diets and functional loading (Felis catus, Cercocebus atys, Homo sapiens, Sus scrofa, Oryctolagus cuniculus, Ovis aries). We performed histomorphometric analyses of trabecular bone morphology (bone volume fraction, trabecular thickness and trabecular spacing) and quantified the variation of bone and tooth root volumes along the tooth row. A principal component analysis and non-parametric MANOVA showed statistically significant differences in trabecular bone morphology between species with contrasting functional loading, but these differences were not seen in sub-adult specimens. Our results support a strong, but complex link between masticatory function and trabecular bone morphology. Further understanding of a potential functional relationship could aid the diagnosis and treatment of mandibular diseases causing alveolar bone resorption, and guide the design and evaluation of dental implants.

Purpose: The objective of this study was to assess whether long-term implant survival rates and bone loss in patients with moderately controlled type 2 diabetes is similar to the rates reported in the nondiabetic population., Materials and Methods: This retrospective observational study utilized patient medical records from a general practitioner's dental office. The records of patients who had moderately controlled type 2 diabetes with hemoglobin A1C (HbA1c) up to 8% and glucose level below 150 mg/dL were reviewed, as patients with HbA1c up to 7% are considered to be well-controlled type 2 diabetes. Follow-up data were recorded and analyzed. Inclusion criteria were as follows: partially edentulous patients with missing teeth who were subsequently treated with implant-supported prosthetic restorations; patients were at least 18 years of age and demonstrated the ability to maintain oral hygiene. Exclusion criteria were as follows: patients did not present for annual follow-up visits; patients presented with a neglected periodontal status; patient records had incomplete surgical or restorative data or nondiagnostic radiographs; implants with external hexagonal and machined surfaces. All the restorations were cement-retained. Three different implant insertion/placement methods were used: (1) implants immediately inserted following tooth extraction; (2) implants inserted 6 to 8 weeks after tooth extraction to allow for primary healing; and (3) implants inserted 4 to 6 months after tooth extraction., Results: After review of more than 3,256 medical records, 169 patients were identified (with 1,112 implants) who met the inclusion criteria. The mean follow-up time was 8.7 years, with a minimum of 4.9 years. Sixty-seven implants failed, yielding a 94% overall implant survival rate. The overall mean bone loss around the implants was 1.98 (± 1.81) mm. Comparable to data published earlier, no statistical significance in survival rate was found between the nondiabetic and diabetic population. The delayed insertion protocol presented the least bone loss, compared with immediate insertion (P = .06), and compared with early insertion (P = .046)., Conclusion: The results show that implant survival and bone loss levels were comparable to reported outcomes in the nondiabetic population. The delayed insertion protocol presented less bone loss compared with other insertion methods. Likewise, less bone loss was found in implants placed in the posterior region.

Objective: To test whether or not the modified design of the test implant (intended to increase primary stability) has an equivalent effect on MBL compared to the control., Methods: Forty patients were randomly assigned to receive test or control implants to be installed in identically dimensioned bony beds. Implants were radiographically monitored at installation, at prosthetic delivery, and after one year. Treatments were considered equivalent if the 90% confidence interval (CI) for the mean difference (MD) in MBL was in between -0.25 and 0.25 mm. Additionally, several soft tissue parameters and patient-reported outcome measures (PROMs) were evaluated. Linear mixed models were fitted for each patient to assess time effects on response variables., Results: Thirty-three patients (21 males, 12 females; 58.2 ± 15.2 years old) with 81 implants (47 test, 34 control) were available for analysis after a mean observation period of 13.9 ± 4.5 months (3 dropouts, 3 missed appointments, and 1 missing file). The adjusted MD in MBL after one year was -0.13 mm (90% CI: -0.46-0.19; test group: -0.49; control group: -0.36; p = 0.507)., Conclusion: Both implant systems can be considered successful after one year of observation. Concerning MBL in the presented setup, equivalence of the treatments cannot be concluded., Registration: This trial is registered with the German Clinical Trials Register (ID: DRKS00007877).

Objective: This study aims to evaluate the effect of dentoalveolar distraction extraction (DDE) on site preservation, and to evaluate how the technique keeps the height and width of alveolar bones to a greater extent., Methods: 12 beagle dogs, randomly divided into three groups (DDE group, NH group, BOG group), were used. In the dogs of three groups, the root of the left or right third mandibular premolars were respectively extracted by three methods namely, DDE, traditional extraction with natural healing, and traditional extraction with Bio-Oss bone dust implanted and guided bone regeneration (GBR). Cone-beam computed tomography (CBCT) scans and X-rays were taken immediately and three months after the tooth extraction. The height and width of the alveolar ridges were compared among different groups., Results: Three months after tooth extraction, at the 1 mm level below the alveolar ridge crest, the amount and degree of buccal alveolar ridge width resorption in DDE group were significantly lower than that of NH and BOG group (P < 0.05). At the 2 mm and 3 mm level below the alveolar ridge crest, the amount and degree of buccal alveolar ridge width resorption in DDE group and BOG had no significant difference, and both were significant lower than that of NH group (P < 0.05). The height resorption of alveolar ridge in DDE group was significantly lower than NH and BOG groups (P < 0.05), while NH and BOG group had no statistically significant., Conclusions: To a greater extent, the alveolar ridge preservation through DDE could preserve the height and width of alveolar ridge crest.

Concentrated growth factor (CGF) is an autogenuous product that contains highly concentrated number of platelets and can be derived from venous blood by selective centrifugation. It has been speculated that local growth factors in human platelets (insulinlike growth factor, IGF; transforming growth factor, TGF-b; platelet derived growth factor, PDGF) would enhance healing of grafts and also counteract resorption. The osteogensis effect of CGF and acellular dermal matrix (ADM) for alveolar cleft defects was evaluated in this study. Twenty alveolar cleft patients were divided randomly into two groups. One group underwent guided bone regeneration (GBR) using acellular dermal matrix film combined with alveolar bone grafting using iliac crest bone grafts (GBR group), while the other group underwent alveolar bone grafting combined with CGF (CGF group). Cone beam computed tomography (CBCT) images were obtained at 1 week and 6 months following the procedure. Using Mimics 17.0 software, the bone resorption rate and bone density improvement rate were calculated and compared between the two groups. Although not significant between ADM and CGF in bone resorption rate, the bone density improvement in cases with CGF(61.62 ± 4.728%) was much better than in cases with ADM (27.05 ± 5.607%) (p = 0.0002). Thus, CGF could be recommended to patients with alveolar cleft as a better choice.

Dental arches areas with teeth presenting dentoalveolar ankylosis and replacement root resorption can be considered as presenting normal bone, in full physiological remodeling process; and osseointegrated implants can be successfully placed. Bone remodeling will promote osseointegration, regardless of presenting ankylosis and/or replacement root resorption. After 1 to 10 years, all dental tissues will have been replaced by bone. The site, angulation and ideal positioning in the space to place the implant should be dictated exclusively by the clinical convenience, associated with previous planning. One of the advantages of decoronation followed by dental implants placement in ankylosed teeth with replacement resorption is the maintenance of bone volume in the region, both vertical and horizontal. If possible, the buccal part of the root, even if thin, should be preserved in the preparation of the cavity for the implant, as this will maintain gingival tissues looking fully normal for long periods. In the selection of cases for decoronation, the absence of microbial contamination in the region - represented by chronic periapical lesions, presence of fistula, old unconsolidated root fractures and active advanced periodontal disease - is important. Such situations are contraindications to decoronation. However, the occurrence of dentoalveolar ankylosis and replacement resorption without contamination should neither change the planning for implant installation, nor the criteria for choosing the type and brand of dental implant to be used. Failure to decoronate and use dental implants has never been reported.

Periodontal diseases are initiated by pathogenic bacterial biofilm activity that induces a host inflammatory cells immune response, degradation of dento gingival fibrous tissue and its detachment from root cementum. It is well accepted, that osteoclastic alveolar bone loss is governed exclusively through secretion of proinflammatory cytokines. Nevertheless, our findings suggest that once degradation of collagen fibers by MMPs occurs, a drop of cellular strains cause immediate release of ATP from marginal gingival fibroblasts, cell deformation and influx of Ca+2. Increased extracellular ATP (eATP) by interacting with P2×7 purinoreceptors, present on fibroblasts and osteoblasts, induces generation of receptor activator of nuclear factor kB ligand (RANKL) that further activates osteoclastic alveolar bone resorption and bone loss. In addition, increased eATP levels may amplify inflammation by promoting leukocyte recruitment and NALP3-inflammasome activation via P2×7. Then, the inflammatory cells secrete cytokines, interleukin IL-1, TNF and RANKL that further trigger alveolar bone resorption. Moreover, eATP can be secreted from periodontal bacteria that may further contribute to inflammation and bone loss in periodontitis. It seems therefore, that eATP is a key modulator that initiates the pathway of alveolar bone resorption and bone loss in patients with periodontal disease. In conclusion, we propose that strain release in gingival fibroblasts aligned on collagen fibers, due to activity of MMP, activates release of ATP that triggers the pathway of alveolar bone resorption in periodontitis. We predict that by controlling the eATP interaction with its cellular purinoreceptors will reduce significantly bone loss in periodontitis., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Loss of alveolar ridge width and height after tooth extraction is well documented, but models to evaluate ridge preservation are neither standardized nor cost-effective. This rat model characterizes the pattern of bone turnover and inflammation after extraction and bone grafting with or without local simvastatin (SIM)., Methods: Fifty retired-breeder rats underwent extraction of the maxillary right first molar and standard surgical defect creation under inhalation/local anesthesia. The left side of each animal served as unmanipulated control. Untreated groups (n = 8 to 9 per group) were compared (analysis of variance, t test) at days 0, 7, 14, and 28 for alveolar ridge height and width and for markers of inflammation and bone turnover by microcomputed tomography, histology, and enzyme-linked immunosorbent assay. Seventeen additional specimens had defects grafted with either bone mineralized matrix (BMM) or a BMM+SIM conjugate., Results: Extraction-induced bone loss (BL) was noted on buccal, palatal, and interproximal height (P <0.05) and ridge width (P <0.01). Week 1 inflammation positively correlated with ridge height; thereafter, a more intense inflammatory reaction corresponded to reduction in alveolar bone height and density (r = 0.74; P <0.05; Spearman). BMM+SIM preserved the most interproximal bone height (P <0.01), increased ridge width and bone density (P <0.01), enhanced 7-day prostaglandin E2 (P <0.01), and reduced 28-day inflammation density (P <0.05)., Conclusions: The standard defect used in the current study paralleled human postextraction alveolar BL. Defect grafting, especially BMM+SIM, reduced inflammation and preserved bone.

Background and Objectives: It is recognized that orthodontic force (OF) has an aggravating effect on the progression of destructive periodontitis if periodontitis have not been well controlled. However, the underlying mechanism is not completely clear. This study was to investigate the effect of antibiotic administration on OF-aggravated, ligature-induced experimental periodontitis in mice., Material and Methods: C57BL/6 mice (male, 8 wk old) were divided into three groups (n = 8). Silk ligatures (SL) were tied around the maxillary right (group 1) or both (groups 2 and 3) first molars on day 0, removed on day 8 and systemic antibiotics was administered through drinking water (group 3) since day 8. OF was applied on the maxillary right first molars since day 13 (groups 2 and 3). All mice were killed on day 20., Results: Total oral bacteria load was significantly higher in group 2 when compared to group 1 on day 20, whereas such count was greatly reduced in group 3 when antibiotics were administered. Periodontal bone loss was significantly increased on SL side vs. control side in group 1. Periodontal bone loss was significantly increased on OF + SL side vs. SL side in group 2 (p < 0.05) but not in group 3 when systemic antibiotics were administered. Gingival mRNA and protein expressions of receptor activator of nuclear factor kappa-B ligand/osteoprotegerin were significantly increased on OF + SL side vs. SL side in group 2 (p < 0.01) but not in group 3. However, comparable levels of tartrate-resistant acid phosphatase-positive cell formation within periodontal space and tooth movement were observed on OF + SL side in groups 2 and 3., Conclusion: Our results suggest that reduction of oral bacterial load by antibiotic administration alleviate orthodontic force-aggravated periodontitis bone loss., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose: The purpose of this study was comparison of clinical and radiographic outcomes of immediate post-extraction implants with or without the use of pure platelet-rich plasma (P-PRP) in the short- and medium-term follow-up., Methods: A retrospective analysis was performed to assess soft tissue healing, implant and prosthesis survival, marginal bone level changes and biological complications., Results: A total of 109 partially edentulous patients with 126 implants were included in this analysis. At 4-5 years after loading, cumulative survival rate in test group was 97.4% and in control group was 97.8%, with no significant differences. After 5 years of function, marginal bone loss (MBL) in test group was 0.8 ± 0.35 and 1.02 ± 0.27 mm for immediate and delayed loading, respectively, and in control group was 0.6 ± 0.16 and 0.8 ± 0.89 mm for immediate and delayed loading, respectively. No significant differences in MBL were observed intragroups and intergroups at any time point considered. Soft tissue healing score was significantly higher in test group compared to the control at 3 and 7 days after surgery, with significant differences., Conclusions: P-PRP implant group showed a better soft tissue management and wound healing in the first 7 days after surgery compared to non-P-PRP implant group. In the medium-term follow-up, comparable clinical and radiographic outcomes were noticed between two groups.

Introduction: In order to understand the mechanical behavior of a weakened incisor, this study aimed to evaluate the stress distribution caused by different alveolar bone heights and cement layer thickness., Methods: A finite element analysis was conducted for this investigation. An intact maxillary central incisor was initially modeled, and the bone of the models was modified in order to simulate 4 levels of bone height: BL0 (no bone loss), BL1 (1/3 bone loss), BL2 (1/2 bone loss), and BL3 (2/3 bone loss). These teeth models were remodeled with a fiber post at 2 different cement thicknesses and restored with a ceramic crown; "A" refers to the well-adapted fiber post (0.3 mm) and "B" to the nonadapted fiber post (1 mm), resulting in 12 models. RelyX ARC (3M ESPE, St Paul, MN) cement was simulated for the cementation of the crowns and fiber posts for all groups. Numeric models received a load of 100 N on the lingual surface. All materials and structures were considered linear elastic, homogeneous, and isotropic. Numeric models were plotted and meshed with isoparametric elements, and results were expressed in maximum principal stress., Results: For fiberglass posts, cement, and dentin, the highest stress concentration occurred in the groups with increased bone loss. For cortical bone, the highest values were for the groups with 1/3 bone loss. A greater thickness of cement layer concentrates more stress., Conclusions: More bone loss and greater CLT were the influential factors in concentrating the stress., (Copyright © 2017 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Objective: To compare the effect of placing the definitive abutment at the time of implant placement versus at a later stage, on the soft and hard tissue changes around dental implants., Material and Methods: Platform-switched implants were placed in the posterior maxilla or mandible of partial edentulous patients and they were randomized to receive the definitive abutment at the moment of implant placement, or 6-12 weeks later. Final prostheses were delivered 2-4 weeks later. Radiographic assessment of vertical bone level changes (primary outcome), clinical status of peri-implant tissues, changes in soft tissues margin, papilla filling, patient-related outcomes and adverse events were assessed 6 and 12 months after loading., Results: 60 implants were placed in 40 patients, replacing single or multiple absent teeth. One implant was lost 1 week after insertion (overall survival rate: 98.3%). A statistically significant greater bone resorption from surgery to 6 months post-loading was observed for those implants subjected to abutment change (control group: -1.24 ± 0.79 mm; test group: -0.61 ± 0.40 mm; P = 0.028). Periodontal clinical parameters and patient-related outcomes, however, did not demonstrate significant differences between groups at any time point. A significant increase in papilla height was observed from loading to 12 months in all implants (control group: 1.17 ± 1.47 mm; test group: 0.98 ± 0.89 mm) and a slight but not significant coronal migration of the gingival margin., Conclusions: The connection and disconnection of healing abutments is associated with significantly increased bone loss during the healing period between implant placement and 6 months post-loading, when compared to one-time abutment placement., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: The aim of this study is to evaluate the effect of the surface modification and cervical implant design on the bone remodeling in implants installed at the crestal and subcrestal bone level., Methods: Ten American Fox Hound of approximately 1 year of age, each weighing approximately 14 to 15 kg, were used for this study. Two different dental implant macrodesign were used: cylindric-conical with 3.5 mm of diameter and 9 in length (implant A) and conical with 2.9 mm of diameter and 9 mm in length (implant B). Two surfaces were used: sandblasting and acid etching (surface 1) and sandblasting and acid etching, then maintained in an isotonic solution of 0.9% sodium chloride (surface 2). Four groups were performed (n = 20 implants): Group A1 (implant A with the surface 1), Group A2 (implant A with surface 2), Group B1 (implant B with surface 1), and Group B2 (implant B with surface 2). The mandibular premolars and molars (P1, P2, P3, M1) were removed and, after 2 months of healing, implants were inserted at the crestal and 2 mm subcrestal position related to the buccal bone level. Analysis was performed at 4 and 8 weeks. Histomorphometry with longitudinal measurements and bone implant contact, bone remodeling and implant stability quotient analysis were realized., Results: The surface 2 showed to get more close contact between implant and new bone formed after implant placement and more stability surrounding platform both at 4 and 8 weeks. Surface 2 groups and subrestally placed showed to have better results in terms of linear measurements, with less bone loss and soft tissue distance to the IS. The data showed significant differences among the groups (P < 0.001)., Conclusions: Surface modification (surface 2) has shown to be an effective alternative to conventional surface with better results in situations placed subcrestally and combined with implant design.

Objective: To compare the extent and time course of alveolar bone loss and osteoclast activation in two murine models of periodontal disease: molar ligation and Porphyromonas gingivalis (P. gingivalis) oral inoculation., Methods: A split-mouth design was applied to two groups of mice (C57BL6, 6-8 weeks old, n=24 in both groups), resulting in four treatment groups: (1) Control group: unligated upper right 2nd molars receiving CMC only, (2)Ligature group: ligation of a 9-0 suture around the upper left 2nd molar, (3) P. gingivalis group: unligated upper right 2nd molar receiving P. gingivalis challenge only, (4)Ligature+P.gingivalis group: ligation of the upper left 2nd molar in combination with oral inoculation with 109 colony-forming units(CFU) P. gingivalis. Alveolar bone loss was measured as the cementoenamel junction and alveolar bone crest (CEJ-ABC) distance. In the study, 48 C57BL6 mice were designed and treated as described above, and osteoclasts were counted on histological sections following tartrate-resistant acid phosphatase (TRAP) staining and counts were normalized to alveolar bone surface distance. Then 36 C57BL6 mice were investigated, of which 30 were ligated a 9-0 silk ligature around the 2nd molar in the left maxillary quadrant and 6 were not ligated. After ligation for 1 week, the ligatures in 12 mice were taken off for either 1 week or 2 weeks. The CEJ-ABC distance of the 6 mice without ligation was baseline. The CEJ-ABC distances were measured and analyzed. The data were analyzed with one-way ANOVA., Results: Molar ligation induced marked alveolar bone loss after 3, 6, 9 and 12 weeks [(0.16±0.04) mm, (0.16±0.02) mm, (0.18±0.03) mm, (0.17±0.02) mm], vs. corresponding controls [(0.09±0.03)mm,(0.10±0.01)mm,(0.12±0.04)mm,(0.12±0.01)mm] and P. gingivalis group [(0.09±0.03)mm, (0.12±0.01)mm,(0.12±0.02)mm,(0.10±0.01)mm], P<0.05. Combined treatment with molar ligation and P. gingivalis did not further increase the CEJ-ABC distance. Evidence for osteoclast activation was found one day after molar ligation, and TRAP-positive cell numbers peaked on day 3 (12±4 vs. control 2±2, P<0.01). After taking off ligature following ligation for 2 weeks, it showed significantly regrowth of alveolar bone compared with that before removal of the ligature on day 7 [(0.07±0.02)mm vs. (0.13±0.01)mm, P<0.01]., Conclusion: Molar ligation is a rapid and effective way to induce periodontal bone loss in mice. Osteoclast activation occurs within 24 hours of ligature placement, and the extent of bone loss well exceeds that of the P.gingivalis-induced bone loss. Removing ligature after periodontal disease might help bone regeneration by regrowth of the alveolar bone.

The clinical examination of 36 tobacco smokers with chronic generalized periodontitis of light, average and severe degree was carried out. The examination established poor hygienic condition of oral cavity, less expressed inflammatory reaction of tissues of periodont and predominance of occurrences of destruction of alveolar portion of bone as compared with the group of 59 non-smoking patients with chronic generalized periodontitis of light, average and severe degree. The study demonstrated higher rate of detection of T. forsythia in smokers as compared with non-smoking patients at all stages of of development of chronic generalized periodontitis. Under light stage of chronic generalized periodontitis increasing of rate of detection of T. forsythia more than twice was registered. P.gigngivalis and P.intermedia were detected in smoking patients with light stage of chronic generalized periodontitis either in the same values or more rarely as compared with non-smokers. In the group of smokers with average stage of chronic generalized periodontitis increasing of rate of occurrence of association of T. forsythia-P. gigngivalis-P. intermedia occurred more than five times in comparison with non-smokers. The obtained results indicate on relationship between alterations of microbiota and aggressive development of chronic generalized periodontitis in smoking patients and on development in periodontal recesses of smokers of favorable conditions for growth of T. forsythia. The presence of T. forsythia is a significant factor of development of destructive processes in tissues of periodont.

Residual ridge resorption is a rapid, progressive, irreversible, and inevitable process of bone resorption. Long-standing teeth and implants have been shown to have maintained the bone around them without resorption. Thus, overdenture therapy has been proven to be beneficial in situations where few remaining teeth are present. In addition to the various advantages seen with tooth-supported telescopic overdentures, a few shortcomings can also be expected, including unseating of the overdenture, increased bulk of the prosthesis, secondary caries, etc. The precise transfer of the secondary telescopic copings to maintain the spatial relationship, without any micromovement, remains the most critical step in ensuring the success of the tooth-supported telescopic prosthesis. Thus, a simple and innovative technique of splinting the secondary copings was devised to prevent distortion and micromovement and maintain its spatial relationship., (© 2015 by the American College of Prosthodontists.)

Ethnopharmacological Relevance: Zanthoxylum piperitum (ZP) has been used to prevent toothache in East Asia., Aim of Study: In this study, we investigated the effects of ZP on periodontitis along with alveolar bone loss., Materials and Methods: Twenty-eight male Sprague-Dawley rats were assigned into 4 groups; non-ligated (NOR), ligated and treated vehicle (CTR), ligated and treated 1mg/mL ZP (ZP1), and ligated and treated 100mg/mL ZP (ZP100). Sterilized 3-0 nylon ligature was placed into the subgingival sulcus around the both sides of mandibular first molar. After topical application of 1 and 100mg/mL ZP for 2 weeks, mandibles was removed for histology. In addition, SaOS-2 osteoblast cells were treated 1, 10 and 100μg/mL ZP for 24h to analyze the expressions of alveolar bone-related markers., Results: Several alveolar bone resorption pits, which indicate cementum demineralization were decreased by ZP treatment. Topical ZP treatment inhibited periodontitis-induced alveolar bone loss. In addition, there were significant reduction of osteoclastic activities following topical ZP treatment in periodontium. The expression of RANKL was decreased in SaOS-2 osteoblast cells by treating ZP, while that of OPG was increased. ZP treatment increased the expressions of Runx2 and Osterix in SaOS-2 cells., Conclusion: In summary, ZP treatment inhibited alveolar bone loss as well as maintained the integrity of periodontal structures via regulation of bone remodeling. ZP may be a therapeutic target for treating periodontitis., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Objective: The present study aimed to investigate the role of periapical diseases in inducing medication-related osteonecrosis of the jaws (MRONJ) using an ovariectomized (OVX) mice model., Materials and Methods: Twenty C57BL/6N female mice were randomly assigned to two groups. All mice were subjected to bilateral ovariectomy and then treated with oncologic dose of zoledronic acid (ZA) or vehicle for twelve weeks. Eight weeks after commence of drug administration, a pulpal exposure (PE) operation was performed on the first right lower molar to induce periapical periodontitis; the contralateral non-PE tooth was used as control. All animals were sacrificed four weeks after pulpal exposure, and the mandibles were harvested for radiological and histomorphometrical analysis., Results: Micro computed tomography ( μ -CT) examination demonstrated that periapical diseases significantly increased alveolar bone resorption, and the resorption was greatly attenuated by ZA treatment. Concurrent ZA therapy significantly increased bone density and histological osteocyte necrosis in the presence of periapical lesions., Conclusion: ZA treatment reduced bone absorption resulting from periapical disease but increased the risk of developing MRONJ in the ovariectomized mouse model.

Purpose: To evaluate the survival, success, and complication rates of tapered double-lead threads single implants, placed in fresh extraction sockets and healed sites of the posterior jaws., Methods: The enrolled patients were randomly divided into 2 groups: in the test group (TG), all implants were inserted at the time of tooth extraction; in the control group (CG), all implants were placed 3 months after extraction. The implants were followed for a period of 1 to 3 years after loading. The main outcomes were implant survival, complications, and implant-crown success., Results: Ninety-two patients had 97 installed implants (49 in the TG, 48 in the CG). Only two implants failed, in the TG; the survival rates were therefore 95.9% (47/49) and 100% (48/48) for TG and CG, respectively. In the surviving implants, no complications were reported, for an implant-crown success of 100%., Conclusions: Although a significant difference was found in the levels of primary stability between TG and CG, single implants placed in fresh extraction sockets and healed sites of the posterior jaws had similar survival and complication rates. Crestal bone levels and peri-implant bone resorption showed similar values. A longer follow-up period is however required, to confirm these positive outcomes.

The benefits and feasibility of platform switching have been discussed in several studies, reporting lesser crestal bone loss in platform-switched implants than in platform-matched implants. Objective. The aim of the present study was to observe the changes in vertical and horizontal marginal bone levels in platform-switched and platform-matched dental implants. Materials and Methods. 51 patients received 60 dental implants in the present study over a 1-year period. Measurement was performed between the implant shoulder and the most apical and horizontal marginal defect by periapical radiographs to examine the changes of peri-implant alveolar bone before and 12 months after prosthodontic restoration delivery. Results . These marginal bone measurements showed a bone gain of 0.23 ± 0.58 mm in the vertical gap and 0.22 ± 0.53 mm in the horizontal gap of platform matching, while in platform switching a bone gain of 0.93 ± 1 mm ( P < 0.05) in the vertical gap and 0.50 ± 0.56 mm in the horizontal gap was found. The average vertical gap reduction from the baseline until 12 months was 0.92 ± 1.11 mm in platform switching and 0.29 ± 0.85 mm in platform matching ( P < 0.05). Conclusions. Within the limitations of the present study, platform switching seemed to be more effective for a better peri-implant alveolar bone vertical and horizontal gap reduction at 1 year.

Aggregatibacter actinomycetemcomitans is associated with aggressive periodontal disease, which is characterized by inflammation-driven alveolar bone loss. A. actinomycetemcomitans activates the p38 mitogen-activated protein kinase (MAPK) and MAPK-activated protein kinase 2 (MK2) stress pathways in macrophages that are involved in host responses. During the inflammatory process in periodontal disease, chemokines are upregulated to promote recruitment of inflammatory cells. The objective of this study was to determine the role of MK2 signaling in chemokine regulation during A. actinomycetemcomitans pathogenesis. Utilizing a murine calvarial model, Mk2 +/+ and Mk2 -/- mice were treated with live A. actinomycetemcomitans bacteria at the midsagittal suture. MK2 positively regulated the following macrophage RNA: Emr1 (F4/80), Itgam (CD11b), Csf1r (M-CSF Receptor), Itgal (CD11a), Tnf, and Nos2 Additionally, RNA analysis revealed that MK2 signaling regulated chemokines CCL3 and CCL4 in murine calvarial tissue. Utilizing the chimeric murine air pouch model, MK2 signaling differentially regulated CCL3 and CCL4 in the hematopoietic and nonhematopoietic compartments. Bone resorption pits in calvaria, observed by micro-computed tomography, and osteoclast formation were decreased in Mk2 -/- mice compared to Mk2 +/+ mice after A. actinomycetemcomitans treatment. In conclusion, these data suggest that MK2 in macrophages contributes to regulation of chemokine signaling during A. actinomycetemcomitans-induced inflammation and bone loss., (Copyright © 2016 American Society for Microbiology.)

MicroRNAs (miRNAs) bind at the 3'UTR of their target mRNA to induce gene silencing. Through this mechanism, number of biological pathways implicated in developmental, physiological, and pathological processes, have been frequently found to involve miRNA functions. MiRNA functions in bone metabolism have also been reported, especially in association with receptor activator of nuclear factor kappa B ligand (RANKL)-induced osteoclastogenesis. Expression of RANKL has been related to several inflammatory mediators, and thus some miRNAs may be implicated in the regulatory mechanism of inflammatory-induced RANKL expression as shown in periodontal resident cells such as gingival fibroblasts or periodontal ligament cells. This review aims to review the current miRNA research relating periodontal tissue and its relevance in periodontal inflammation. In miRNA profiling studies of tissues isolated from individuals with periodontal disease, miR-223 has been consistently identified as a potential candidate miRNA to be further investigated in periodontitis-related processes. Although these studies point to an important role of miRNA-mediated epigenetic changes in tissue inflammation and alveolar bone loss, further investigation is still required to determine the function of miRNAs in the complex processes of periodontal tissue homeostasis and pathogenesis. Knowledge gained from future studies will be beneficial in developing alternative therapeutic approaches, especially ones that use miRNA delivery systems to treat periodontal disease., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Objective: To evaluate the effect of chronic continuous hypoxia (CCH) in alveolar bone and its correlation with the inflammatory markers which play a key role in the development of periodontitis., Material and Methods: Wistar rats were exposed to CCH (600mbar, 3 months). Macroscopic and histological analyses of alveolar bone were performed, together with measurement of oxidative stress and inflammatory parameters in gums and submandibular glands (SMG)., Results: HCC induced cortical alveolar bone loss, decreased interradicular bone volume and increased the periodontal ligament height compared to control rats (p<0.05). CCH enhanced iNOS activity in gums (from 2735,04±662,96 nmol/min/mg proteins to 4289,58±915,63 p<0.05) and in SMG (from 56,71±12,05 nmol/min/mg proteins to 90,15±21,78 p<0.05). PGE 2 did not change in gums or in SMG by means of CCH, while TNFα decreased in gums (p<0.05). Regarding oxidative stress, thiobarbituric acid reactive species concentration in CCH animals was higher both in gums as in SMG, and catalase activity was decreased in SMG., Conclusion: Higher iNOS activity both in gums and SMG under CCH could be associated with the alveolar bone loss observed. The increase in oxidative stress occurring in SMG and gums, together with a lower antioxidant capacity might indicate a deleterious effect of HX in oral health., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Objective: Crestal bone loss around dental implants is a criterion for success as this could prevent loss of implant and superstructure. The macrogeometry of the implant could influence bone remodelling when the implant-abutment connection is placed at crestal bone level or above. The aim of this study was to evaluate crestal bone remodelling in a randomized clinical prospective trial in macrogeometrically similar implants with the prosthetic connection at the crestal bone level and 2.5 mm above. The null hypothesis was that there was no difference in crestal bone loss after 1 year of early loading., Material and Methods: Patients were referred to Academic Centre of Dentistry Amsterdam for implant placement. Patients were subjected to inclusion and exclusion criteria and received a minimum of two implants: an implant with the prosthetic abutment connection at the crestal bone level (minimized collar [MC], bone level) and one with the prosthetic abutment connection 2.5 mm supracrestal (long collar [LC], tissue level). The mesial or distal location of each implant type was blinded for the patient and randomized. The implants were loaded splinted after 3 weeks of healing. The primary outcome was bone-level change assessed after 1 year of loading., Results: Thirty-three patients fulfilled the inclusion criteria. Thirty-nine Thommen SPI ELEMENT LC implants and 39 MC were placed, and each fixed dental prosthesis was supported by one LC and one MC implant. The intraclass correlation of measures performed by the first and second X-ray examiner was as follows: on the mesial side of the MC implant 0.990 (0.980-0.995; 95% confidence interval [CI]), 0.980 (0.962-0.990; 95% CI) on the distal side of the MC implant, 0.979 (0.959-0.989; 95% CI) and 0.988 (0.978-0.994; 95% CI) on the mesial and distal side of the LC implant, respectively. The mean bone loss of the MC implant was 0.4 ± 0.4 mm. The mean bone loss of the LC implant was 0.2 ± 0.5 mm. The paired samples t-test showed a statistically significant difference (P < 0.05) between the MC and LC implants., Conclusion: Dental implants at bone level show statistically significantly (P < 0.05) more crestal bone change after 1 year of loading than a tissue-level implant., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

microRNAs could be mechanosensitive and emerge as critical posttranscriptional regulators in the bone-remodeling process. During orthodontic tooth movement (OTM), the application of mechanical force induces alveolar bone remodeling, but whether microRNAs respond to orthodontic force and contribute to OTM is unknown. microRNA-21 (miR-21) has been previously reported in vitro to mediate stretch-induced osteogenic differentiation of periodontal ligament stem cells and support osteoclast differentiation. In this study, the authors show that miR-21 responded to orthodontic force in periodontal tissue in a dose- and time-dependent manner and regulated the osteogenesis of human periodontal ligament stem cells following OTM. Using mmu-miR-21-deficient (miR-21 -/- ) mice, the authors discovered that mmu-miR-21 deficiency inhibited OTM and prevented force-induced maxillary bone loss. The authors found that miR-21 -/- mice showed a normal skeletal phenotype in development and a similar alveolar bone formation rate to wild-type mice postnatally. During OTM, mmu-miR-21 regulated force-induced alveolar osteoblastogenesis in the tensile side, while no effects were detected in the compressive side. However, miR-21 -/- mice showed inhibited alveolar osteoclastogenesis when compared with wild-type mice. During OTM, mmu-miR-21 deficiency blocked alveolar bone resorption in both the compressive and tensile sides. To dissect the mechanism by which miR-21 regulates alveolar bone remodeling, the authors screened the reported functional targets of miR-21 and found that periodontal expression of programmed cell death 4 ( Pdcd4) was inhibited following OTM. Furthermore, mmu-miR-21 deficiency removed the suppression of Pdcd4 at both the mRNA and protein levels in the periodontium, resulting in upregulation of the downstream effector C-fos. Further analysis of OTM under lipopolysaccharide-induced periodontal inflammation showed that mmu-miR-21 mediated lipopolysaccharide (LPS)-accelerated OTM and that mmu-miR-21 deficiency blocked lipopolysaccharide-induced maxillary bone loss. In summary, these findings reveal a previously unrecognized mechanism that a microRNA can modulate OTM and alveolar bone remodeling under both normal and inflammatory microenvironments in vivo.

More studies evaluating the outcome of dental implant restorations in diabetics are needed. To investigate the outcome of immediate function implant rehabilitations in diabetic patients. This retrospective cohort study included 70 diabetic patients (type 1 = six patients; type 2 = 64 patients; 33 females and 37 males, mean age=59 years), rehabilitated with 352 implants. Primary outcome measure was implant survival estimated at 5 years through the Kaplan-Meier product limit estimator using the patient as unit of analysis (first implant failure as reference); secondary outcome measures were marginal bone loss and biological complications. Risk indicators associated with bone loss >2·0 mm were tested in a multivariate logistic regression model. The level of significance considered was 5%. Seven patients were lost to follow-up (10%). Seven patients lost ten implants rendering a global implant cumulative survival rate for diabetic patients of 89·8% (type 1 = 80·0%; type 2 = 90·5%). The average (95% confidence interval) marginal bone loss at 1 and 5 years was 1·64 mm (0·00;3·32) and 2·55 mm (1·38;3·72) for type 1 diabetic patients, 0·79 mm (0·59;1·00) and 1·45 mm (1·09;1·82) for type 2 diabetic patients and 0·88 mm (0·65;1·10) and 1·56 mm (1·21;1·91) overall. Biological complications occurred in seven patients. Female gender (OR = 28·1) and smoking habits (OR = 10·3) were risk indicators for marginal bone loss >2·0 mm at 5 years when controlled for other variables of interest. Implant rehabilitations represent a valid treatment for diabetic patients, with a good risk/benefit ratio. Female gender and smoking habits were risk indicators for a higher marginal bone resorption at 5 years., (© 2016 John Wiley & Sons Ltd.)

The host immune response plays a key role in bacteria-induced alveolar bone resorption. Endogenous control of the magnitude and duration of inflammatory signaling is considered an important determinant of the extent of periodontal pathology. Suppressor of cytokine signaling (SOCS) proteins are inhibitors of cytokine signaling pathways and may play a role in restraining periodontal inflammation. We hypothesized that SOCS-3 regulates alveolar bone loss in experimental periodontitis. Periodontal bone loss was induced in 16-wk-old myeloid-specific SOCS-3-knockout and wild-type (WT) C57Bl6-B.129 mice by oral inoculation 9 times with 10(9) colony-forming units of Porphyromonas gingivalis A7436 through an oral gavage model for periodontitis. Sham controls for both types of mice received vehicle without bacteria. The mice were euthanized 6 wk after the last oral inoculation. Increased bone loss was demonstrated in P. gingivalis-infected SOCS-3-knockout mice as compared with P. gingivalis-infected WT mice by direct morphologic measurements, micro-computed tomography analyses, and quantitative histology. Loss of SOCS-3 function resulted in an increased number of alveolar bone osteoclasts and increased RANKL expression after P. gingivalis infection. SOCS-3 deficiency in myeloid cells also promotes a higher P. gingivalis lipopolysaccharide-induced inflammatory response with higher secretion of IL-1β, IL-6, and KC (IL-8) by peritoneal macrophages as compared with WT controls. Our data implicate SOCS-3 as a critical negative regulator of alveolar bone loss in periodontitis., (© International & American Associations for Dental Research 2016.)

Tooth extraction causes bone resorption of the alveolar bone volume. Although recombinant human bone morphogenetic protein 2 (rhBMP-2) markedly promotes de novo bone formation after tooth extraction, the application of high-dose rhBMP-2 may induce side effects, such as swelling, seroma, and an increased cancer risk. Therefore, reduction of the necessary dose of rhBMP-2 which can still obtain sufficient bone mass is necessary by developing a new osteogenic reagent. Recently, we showed that the systemic administration of OP3-4 peptide, which was originally designed as a bone resorption inhibitor, had osteogenic ability both in vitro and in vivo. This study evaluated the ability of the local application of OP3-4 peptide to promote bone formation in a murine tooth extraction model with a very low-dose of BMP. The mandibular incisor was extracted from 10-week-old C57BL6/J male mice and a gelatin hydrogel containing rhBMP-2 with or without OP3-4 peptide (BMP/OP3-4) was applied to the socket of the incisor. Bone formation inside the socket was examined radiologically and histologically at 21 days after the extraction. The BMP/OP3-4-group showed significant bone formation inside the mandibular extraction socket compared to the gelatin-hydrogel-carrier-control group or rhBMP-2-applied group. The BMP/OP3-4-applied mice showed a lower reduction of alveolar bone and fewer osteoclast numbers, suggesting that the newly formed bone inside the socket may prevent resorption of the cortical bone around the extraction socket. Our data revealed that OP3-4 peptide promotes BMP-mediated bone formation inside the extraction socket of mandibular bone, resulting in preservation from the loss of alveolar bone., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Aggregatibacter actinomycetemcomitans is a perio-pathogenic bacteria that has long been associated with localized aggressive periodontitis. The mechanisms of its pathogenicity have been studied in humans and preclinical experimental models. Although different serotypes of A. actinomycetemcomitans have differential virulence factor expression, A. actinomycetemcomitans cytolethal distending toxin (CDT), leukotoxin, and lipopolysaccharide (LPS) have been most extensively studied in the context of modulating the host immune response. Following colonization and attachment in the oral cavity, A. actinomycetemcomitans employs CDT, leukotoxin, and LPS to evade host innate defense mechanisms and drive a pathophysiologic inflammatory response. This supra-physiologic immune response state perturbs normal periodontal tissue remodeling/turnover and ultimately has catabolic effects on periodontal tissue homeostasis. In this review, we have divided the host response into two systems: non-hematopoietic and hematopoietic. Non-hematopoietic barriers include epithelium and fibroblasts that initiate the innate immune host response. The hematopoietic system contains lymphoid and myeloid-derived cell lineages that are responsible for expanding the immune response and driving the pathophysiologic inflammatory state in the local periodontal microenvironment. Effector systems and signaling transduction pathways activated and utilized in response to A. actinomycetemcomitans will be discussed to further delineate immune cell mechanisms during A. actinomycetemcomitans infection. Finally, we will discuss the osteo-immunomodulatory effects induced by A. actinomycetemcomitans and dissect the catabolic disruption of balanced osteoclast-osteoblast-mediated bone remodeling, which subsequently leads to net alveolar bone loss., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Bone preservation is an essential issue in the context of last teeth extraction and complete edentulism. The intended treatment, whether a complete denture or an implant placement, is facilitated with a voluminous residual ridge. Bone resorption after multiple extractions has not been as well studied as the bone resorption that occurs after the extraction of a single tooth. Recent advances in bone substitute materials have revived this issue. The purpose of this study is to evaluate the interest in using bone substitute material to fill the socket after last teeth extraction in a maxillary immediate complete denture procedure compared with the conventional protocol without socket filling., Methods/design: A randomized, controlled, clinical trial was designed. The 34 participants eligible for maxillary immediate complete denture were divided into two groups. Complete dentures were prepared despite persistence of the last anterior teeth. The control group received a conventional treatment including denture placement immediately after extractions. In the experimental group, in addition to the immediate denture placement, a xenograft bone-substitute material (Bio-Oss Collagen®) was placed in the fresh sockets. The primary outcome of the study is to compare mean bone ridge height loss 1 year after maxillary immediate complete denture placement, with or without bone-substitute material, in incisor and canine sockets. The secondary outcomes are to compare the average bone ridge height and width loss for each extraction site. An original quantitative evaluation method using cone beam computed tomography was designed for reproducible measurements, with a radio-opaque denture duplicate. Two independent operators perform the radiologic measurements., Discussion: The immediate complete denture technique limits bone resorption in multiple extraction situations and thus allows better denture retention and better options for implant placement. To compare the benefit of using any bone socket-filling material, we proposed a quantitative evaluation protocol of resorption in the specific case of the last anterior maxillary teeth extraction with immediate denture placement., Trial Registration: ClinicalTrials.gov, NCT02120053 . Registered on 18 April 2014.

Background: A successful clinical outcome for implanted tissue-engineered bone is dependent on the establishment of a functional vascular network. Gene-enhanced tissue engineering represents a promising approach for vascularization and osteogenesis. In the present study, we tested the angiogenesis and osteogenesis efficacy of gelatin as the scaffold carrier in combination with a virus encoding the HIF-1α gene in a rat alveolar bone defect model., Methods: Three groups of 10 rats each were either left untreated, treated with adenovirus encoding hypoxia-inducible factor-1α (AdHIF-1α)/gelatin sponge or treated with gelatin sponge with adenovirus encoding red fluorescence protein, respectively. At 4 weeks, all samples were determined by micro-computed tomography, histological analyses and immunohistochemical studies., Results: Scaffolds loaded with AdHIF-1α were able to sustain the release of AdHIF-1α for up to 21 days and alveolar bone defects treated with scaffolds containing AdHIF-1α significantly induced new bone and new vessel formation in vivo., Conclusions: Overexpression of HIF-1α by gene therapy may be a useful method for enhancing alveolar bone defect osteogenesis and angiogenesis. Copyright © 2016 John Wiley & Sons, Ltd., (Copyright © 2016 John Wiley & Sons, Ltd.)

Purpose . To investigate peri-implant alveolar bone changes using periapical radiographs before and after prosthetic delivery in submerged and nonsubmerged dental implants. Methods . Digital periapical films of 60 ITI Straumann nonsubmerged dental implants and 60 Xive Dentsply submerged dental implants were taken before, immediately after, and 12 and 24 weeks after the prosthetic restoration was delivered. Results . The 60-nonsubmerged dental implant group showed mean marginal bone resorption at baseline of 0.10 ± 0.23 mm and 24 weeks later, marginal bone resorption was 0.16 ± 0.25 mm. The submerged dental implant group showed a significantly higher distal marginal bone resorption over the mesial side. Mean marginal bone resorption at baseline was 0.16 ± 0.32 on the mesial and 0.41 ± 0.56 on the distal side. Twenty-four weeks later, it was 0.69 ± 0.69 mm on the mesial and 0.99 ± 0.90 mm on the distal side. Conclusion . First, it was possible to determine that submerged implants had a higher mean marginal bone resorption and less bone-to-implant contact than nonsubmerged implants. And second, the distal side of submerged dental implants presented higher marginal bone loss than the mesial side., Competing Interests: The authors claim to have no financial interests, either directly or indirectly, in the products or information listed in the article.

Periodontal diseases are chronic oral inflammatory diseases that are polymicrobial in nature. The presence of specific bacteria in subgingival plaque such as Porphyromonas gingivalis is associated with microbial dysbiosis and the modulation of host immune response. Bacterially elicited innate immune activation and inflammation are key elements implicated in the destruction of soft and hard tissues supporting the teeth. Liver X receptors (LXRs) are nuclear hormone receptors with important function in lipid homeostasis, inflammation, and host response to infection; however, their contribution to chronic inflammatory diseases such as periodontal disease is not understood. The aim of this study was to define the contribution of LXRs in the development of immune response to P. gingivalis and to assess the roles that LXRs play in infection-elicited oral bone loss. Employing macrophages, we observed that P. gingivalis challenge led to reduced LXRα and LXRβ gene expression compared with that observed with unchallenged wild-type cells. Myeloid differentiation primary response gene 88 (MyD88)-independent, Toll/interleukin-1 receptor-domain-containing adapter-inducing interferon-β (TRIF)-dependent signaling affected P. gingivalis-mediated reduction in LXRα expression, whereas neither pathway influenced the P. gingivalis effect on LXRβ expression. Employing LXR agonist and mice deficient in LXRs, we observed functional effects of LXRs in the development of a P. gingivalis-elicited cytokine response at the level of the macrophage, and participation of LXRs in P. gingivalis-elicited oral bone loss. These findings identify novel importance for LXRs in the pathogenesis of P. gingivalis infection-elicited inflammation and oral bone loss., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)