C3-targeted host-modulation approaches to oral inflammatory conditions.

Periodontitis is an inflammatory disease caused by biofilm accumulation and dysbiosis in subgingival areas surrounding the teeth. If not properly treated, this oral disease may result in tooth loss and consequently poor esthetics, deteriorated masticatory function and compromised quality of life. Epidemiological and clinical intervention studies indicate that periodontitis can potentially aggravate systemic diseases, such as, cardiovascular disease, type 2 diabetes mellitus, rheumatoid arthritis, and Alzheimer disease. Therefore, improvements in the treatment of periodontal disease may benefit not only oral health but also systemic health. The complement system is an ancient host defense system that plays pivotal roles in immunosurveillance and tissue homeostasis. However, complement has unwanted consequences if not controlled appropriately or excessively activated. Complement overactivation has been observed in patients with periodontitis and in animal models of periodontitis and drives periodontal inflammation and tissue destruction. This review places emphasis on a promising periodontal host-modulation therapy targeting the complement system, namely the complement C3-targeting drug, AMY-101. AMY-101 has shown safety and efficacy in reducing gingival inflammation in a recent Phase 2a clinical study. We also discuss the potential of AMY-101 to treat peri-implant inflammatory conditions, where complement also seems to be involved and there is an urgent unmet need for effective treatment.

Localized microbially induced inflammation influences distant healthy tissues in the human oral cavity.

Variation in human immune response to the same bacterial or viral pathogen is well established in the literature. Variation in immune response to microbial challenge has also been observed within the human oral cavity. Our recent study focused on characterizing observed variations in microbially induced gingival inflammation-resulting in three distinct clinical Inflammatory Responder Types (IRTs): High-IRT, Low-IRT, and Slow-IRT. Here, we applied a high-resolution temporal multiomic analysis during microbially induced inflammation in order to characterize the effects of localized oral inflammation on distant healthy tissues in young healthy adults. Our results highlight a nonlocalized subclinical effect with alterations in proinflammatory host mediators and an ecological shift toward dysbiosis within the subgingival microbiome in an IRT-dependent manner-despite maintained oral hygiene. Our results provide mechanistic insight into how healthy tissues within humans are influenced by distant localized inflammation and may ultimately become susceptible to disease.

Interdental oral hygiene interventions elicit varying compositional microbiome changes in naturally occurring gingivitis: Secondary data analysis from a clinical trial.

AIM: To evaluate the effect of different oral irrigators on the sub-gingival microbiome composition in patients with naturally occurring plaque-induced gingivitis. MATERIALS AND METHODS: Sub-gingival plaque was collected from adults participating in a clinical trial assessing the efficacy of oral hygiene with two different oral irrigators (Waterpik Water Flosser [Group 1] and Oral-B Water Flosser [Group 2]) versus dental flossing (Group 3) for microbiome analysis. Plaque samples were reflective of naturally occurring plaque-induced gingivitis at baseline and of gingival health at the endpoint (4 weeks). Clinical measures of gingival inflammation were collected, and the sub-gingival microbiome was analysed by 16S rRNA sequencing to identify amplicon sequence variants. RESULTS: Oral hygiene instruction with self-performed manual toothbrushing and water-jet irrigation led to significant reductions in inflammation for all groups; both oral irrigators outperformed flossing in bleeding-on-probing reduction (p < .001). Microbiome diversity of sub-gingival plaque remained relatively stable over time, but significant changes were noted in certain taxa, consistent with increases in the relative abundance of commensals and reductions in late colonizers and periodontal pathogens in the water-jet groups. CONCLUSIONS: Reduction in gingival inflammation at 4 weeks within the water-jet groups is accompanied by slight but critical changes in microbiome composition. Although biodiversity does not substantially change within 4 weeks during the resolution of naturally induced gingivitis, significant relative increases in commensal early colonizers such as Streptococcus, Veillonella and Fusobacterium were accompanied by a shift towards a less anaerobic microbiota associated with return to health. These changes were contingent upon the type of interdental hygiene, with Group 1 exhibiting more significant alterations in microbiome composition towards a periodontal-health-compatible community.

Human variation in gingival inflammation.

Oral commensal bacteria actively participate with gingival tissue to maintain healthy neutrophil surveillance and normal tissue and bone turnover processes. Disruption of this homeostatic host-bacteria relationship occurs during experimental gingivitis studies where it has been clearly established that increases in the bacterial burden increase gingival inflammation. Here, we show that experimental gingivitis resulted in three unique clinical inflammatory phenotypes (high, low, and slow) and reveal that interleukin-1ß, a reported major gingivitis-associated inflammatory mediator, was not associated with clinical gingival inflammation in the slow response group. In addition, significantly higher levels of Streptococcus spp. were also unique to this group. The low clinical response group was characterized by low concentrations of host mediators, despite similar bacterial accumulation and compositional characteristics as the high clinical response group. Neutrophil and bone activation modulators were down-regulated in all response groups, revealing novel tissue and bone protective responses during gingival inflammation. These alterations in chemokine and microbial composition responses during experimental gingivitis reveal a previously uncharacterized variation in the human host response to a disruption in gingival homeostasis. Understanding this human variation in gingival inflammation may facilitate the identification of periodontitis-susceptible individuals. Overall, this study underscores the variability in host responses in the human population arising from variations in host immune profiles (low responders) and microbial community maturation (slow responders) that may impact clinical outcomes in terms of destructive inflammation.

Comparison of antibacterial and antibiofilm activity of bioactive glass compounds S53P4 and 45S5.

BACKGROUND: Bone loss and deformation due to damage caused by injury or recurrent invasive infections presents a major clinical obstacle. While bone substitute biomaterials promote osseous tissue regeneration, their application in sites complicated by microbial infections such as osteomyelitis, is limited. Bioactive glass biomaterials (Bioglass) have been shown to have efficient mechanisms of repairing the integrity of bone, while inhibiting growth of a range of bacterial strains. There are several commercially available bioactive glass compounds, each with a unique chemical composition. One compound in particular, S53P4, has demonstrated antimicrobial effects in previous studies but the antimicrobial activity of the parent compound 45S5 has not been investigated. RESULTS: To assess whether antimicrobial activity is common among bioglass compounds, 45S5-the parent compound, was evaluated in comparison to S53P4 for antibacterial and antibiofilm effects against multiple strains of aerobic and anaerobic bacteria associated with various types of osteomyelitis. Experiments of antimicrobial effects in liquid cultures demonstrated that both compounds were antimicrobial against various microbial genera including S. gordonii, V. parvula, P. aeruginosa and MRSA; particles of the smallest size (32-125 µm) invariably showed the most robust antimicrobial capabilities. When employed against biofilms ecological biofilms grown on hydroxyapatite, 45S5 particles produced a stronger reduction in biofilm mass compared to S53P4 particles when considering small particle ranges. CONCLUSION: We found that 45S5 seems to be as effective as S53P4 and possibly even more capable of limiting bacterial infections. The efficacy of bioactive glass was not limited to inhibition of planktonic growth, as it also extended to bacterial biofilms. The increased antibacterial activity of 45S5 compared to S53P4 is true for a variety of size ranges.

Biological mechanisms underlying complications related to implant site preparation.

Implant site preparation is a critical stage of implant surgery that may underpin various complications related to implant surgery. This review discusses the latest available scientific information on risk factors related to implant site preparation. The role of the drilling process in relation to the density of the available alveolar bone, the effects of insertion torque on peri-implant osseous healing, and implant-related variables such as macrodesign and implant-abutment connection are all factors that can influence implant success. Novel information that links osteotomy characteristics (including methods to improve implant initial stability, the impact of drilling speed, and increase of the implant insertion torque modifying the bone-implant interface) with the appropriate instrumentation techniques will be discussed, as well as interactions at the bone-biomaterial interface that may lead to biologic complications mediated by implant dissolution products.

Peri-implantitis is not periodontitis: Scientific discoveries shed light on microbiome-biomaterial interactions that may determine disease phenotype.

Peri-implantitis is an immune-mediated biological complication that is attributed to bacterial biofilms on the implant surface. As both periodontitis and peri-implantitis have similar inflammatory phenotypes when assessed cross-sectionally, treatment protocols for peri-implantitis were modeled according to those used for periodontitis. However, lack of efficacy of antimicrobial treatments targeting periodontal pathogens coupled with recent discoveries from open-ended microbial investigation studies create a heightened need to revisit the pathogenesis of peri-implantitis compared with that of periodontitis. The tale of biofilm formation on intraoral solid surfaces begins with pellicle formation, which supports initial bacterial adhesion. The differences between implant- and tooth-bound biofilms appear as early as bacterial adhesion commences. The electrostatic forces and ionic bonding that drive initial bacterial adhesion are fundamentally different in the presence of titanium dioxide or other implant alloys vs mineralized organic hydroxyapatite, respectively. Moreover, the interaction between metal surfaces and the oral environment leads to the release of implant degradation products into the peri-implant sulcus, which exposes the microbiota to increased environmental stress and may alter immune responses to bacteria. Clinically, biofilms found in peri-implantitis are resistant to beta-lactam antibiotics, which are effective against periodontal communities even as monotherapies and demonstrate a composition different from that of biofilms found in periodontitis; these facts strongly suggest that a new model of peri-implant infection is required.

Dentist-Patient Communication of Treatment Outcomes in Periodontal Practice: A Need for Dental Patient-Reported Outcomes.

Periodontal practice has made tremendous progress toward evidence-based treatment over the past decade. Importantly, a new classification scheme for periodontal and peri-implant treatments has recently been devised that is incorporating current evidence and enabling patient-specific periodontal care. However, this important progress can be further accelerated with the availability of patient-perceived outcomes of periodontal and implant interventions. The majority of existing clinical studies assess treatment effects based on clinician-measured surrogate outcomes, such as probing depth and attachment levels which are easily communicated to or perceived by dental patients. As dental patient-reported outcomes (dPROs) gain momentum in dental practice, our understanding of the true outcome of dental therapies is vastly increasing. In periodontal research in particular, the utilization of dPROs has clearly demonstrated that periodontal disease contributes to an individual's burden of disease in a substantial manner. Correspondingly, disease treatment interventions seem to lead to varying levels of patient-perceived improvements. The present editorial aims to highlight the importance of patient communication of treatment outcomes in periodontal and implant research and to review the information on available measures for capturing dPROs.

Bayesian Network Meta-analysis of Multiple Outcomes in Dental Research.

OBJECTIVES: Dental research typically targets multiple outcomes. Interdental cleaning devices such as interdental brushes (IB) and water jet devices (WJ) share a sizable portion of the medical device market. However, recommendations for device selection are limited by the conflicting evidence from multiple outcomes in available studies and the lack of an appropriate synthesis approach to summarize evidences taken from multiple outcomes. In particular, both pairwise meta-analyses and single-outcome network meta-analyses can give discordant results. The purpose of this multioutcome, Bayesian network meta-analysis is to introduce this innovative method to the dental research community using data from interdental cleaning device studies for illustrative purposes. METHODS: We reanalyzed a network meta-analysis of interproximal oral hygiene methods in the reduction of clinical indices of inflammation, which included 22 trials assessing 10 interproximal oral hygiene aids. We focused on the primary outcome of gingival inflammation, which was measured by 2 correlated outcome variables, the Gingival Index (GI) and bleeding on probing (BOP). RESULTS: In our previous single-outcome analysis, we concluded that IB and WJ rank high for reducing gingival inflammation while toothpick and flossing rank last. In this multioutcome Bayesian network meta-analysis with equal weight on GI and BOP, the surface under the cumulative ranking curve was 0.87 for WJ and 0.85 for IB. WJ and IB remained ranked as the 2 best devices across different sets of weightings for the GI and BOP. CONCLUSION: In conclusion, multioutcome Bayesian network meta-analysis naturally takes the correlations among multiple outcomes into account, which in turn can provide more comprehensive evidence.

Minimizing risk of bias in clinical implant research study design.

The field of clinical implant research has been flourishing in recent years. The number of related publications has been on the rise, as has the number of dental journals. However, the information gathered from surveillance studies on the quality of reporting and methodologic quality of published studies is unsettling. An important challenge faced by researchers endeavoring to conduct implant studies is how to factor the differences between implant surfaces and dental surfaces in the study design. Given the considerable experience that has been gained in the research methodology of the study of teeth and periodontal tissues, clinical implant research studies have often been conducted without giving much consideration to the fundamental differences between implants and teeth. This article discusses study design related to implant research in view of these differences. Observational and interventional study design methodology is discussed, and guidelines are provided to inform researchers on how to minimize bias in the design and implementation of these clinical studies when implant-related outcomes are studied.

The Root Membrane Technique: A Retrospective Clinical Study With Up to 10 Years of Follow-Up.

PURPOSE: Immediate implant placement in conjunction with intentional root retention is a recently introduced technique, but the majority of existing documentation is limited to short-term reports with low level of evidence. Hence, the aim of this study was to document the long-term clinical and radiographic results of the root membrane technique. METHODS: This retrospective study reports on clinical results of the root membrane technique for periodontal ligament-mediated immediate implant placement with up to 10 years of follow-up from 3 private dental practices. Anterior implants placed with immediate loading from January 2006 to December 2016 were assessed. Kaplan-Meier estimators were computed for reporting of implant success and survival. RESULTS: A sample of 182 patients (82 men and 100 women, age range: 18-83 years) received 250 immediate implants (230 maxilla, 20 mandible) after the root membrane concept and followed-up for a mean of 49.94 months (±32.5). Overall, 5 implant failures were recorded for a 10-year cumulative patient-level implant survival rate of 96.5%. Considering mechanical and biological complications, the 10-year cumulative implant success rate was 87.9%. CONCLUSIONS: Within the limits of the retrospective design, the root membrane technique showed long-term success rates comparable to those of conventional immediate implants.

Personal oral hygiene and dental caries: A systematic review of randomised controlled trials.

OBJECTIVE: To conduct a systematic review of randomised trials assessing the association between personal oral hygiene and dental caries in the absence of the confounding effects of fluoride. BACKGROUND: Dental caries continues to affect close to 100% of the global population. There is a century-old conflict on whether dental caries is caused by poor oral hygiene or poorly formed teeth (ie, teeth with dental defects). Resolving this conflict is of significant public health importance as these two hypotheses on dental caries aetiology can lead to different prevention strategies. METHODS: A systematic search for randomised trials was conducted using predefined criteria in 3 databases. The impact of personal oral hygiene interventions on coronal dental caries incidence was evaluated using random-effects models. RESULTS: Three randomised studies involving a total of 743 participants were included. Personal oral hygiene interventions failed to influence the incidence of dental caries (Δ Decayed, Missing and Filled Surfaces (DFMS) = -0.11; 95% confidence interval: (-0.91, 0.69; P-value < .79)) despite meticulous deplaquing of teeth. There was no significant heterogeneity in the trial results (heterogeneity chi-squared = 1.88, P = .39). The findings were robust to sensitivity analyses, including consideration of the results of nonrandomised studies. CONCLUSION: Personal oral hygiene in the absence of fluorides has failed to show a benefit in terms of reducing the incidence of dental caries.

Network meta-analysis of studies included in the Clinical Practice Guideline on the nonsurgical treatment of chronic periodontitis.

AIM: The recent ADA-commissioned Clinical Practice Guideline on the nonsurgical treatment of chronic periodontitis has provided the most exhaustive library of clinical trials on scaling and root planing (SRP) with or without adjuncts. This network meta-analysis (NMA) compared the adjuncts against each other. MATERIALS AND METHODS: A star-shaped NMA was performed based on 36 indirect comparisons of clinical attachment-level (CAL) gains among nine adjuncts in 74 studies from the Clinical Practice Guideline. RESULTS: All pairwise differences were accompanied by wide confidence intervals, and none of the adjuncts were statistically significantly superior to another. Local doxycycline hyclate and photodynamic therapy with a diode laser had the highest probabilities for ranking first and second, respectively. Publication bias was evident, with fewer than expected studies with small effects. The lack of these studies inflated the treatment effects by an estimated by 20%. CONCLUSIONS: Adjuncts improve CAL gain by about a third of a mm over 6-12 months compared with SRP alone, but no significant differences were found among the adjuncts. The patient-perceived benefit of this gain is unclear because CAL is a physical measure made by the clinician and not a patient-oriented outcome. Publication bias inflated the observed treatment effects.

Effect of Growth Hormone Supplementation on Osseointegration: A Systematic Review and Meta-analyses.

OBJECTIVES: The aim of this study was to assess whether growth hormone (GH) replacement therapy can enhance implant osseointegration. MATERIALS AND METHODS: A systematic literature search was conducted from 1982 to March 2016. A structured search using the keywords "growth hormone," "implants," and "osseointegration" was performed to identify preclinical and clinical in vivo controlled studies and was followed by a 2-phase search strategy. Initially, 31 potentially relevant articles were identified. After removal of duplicates and screening by title and abstract, 10 potential studies were included. Studies were assessed for bias and data were synthesized using a random-effects meta-analysis model. RESULTS: All studies were preclinical animal trials, and the follow-up period ranged from 2 to 16 weeks. Seventy percent of the included studies reported an increase in bone-to-implant contact in animals receiving GH compared with controls. Meta-analysis showed a significant mean difference for bone to implant between GH groups versus controls (no GH supplementation) of 10.60% (95% confidence interval: 3.79%-17.41%) favoring GH administration. CONCLUSION: GH treatment seems to promote osseointegration around implants in preclinical studies; however, these findings must be assessed in highly controlled human clinical trials as a number of confounding factors may have influenced the outcomes of the included studies.

Association between low-dose aspirin and periodontal disease: results from the continuous national health and nutrition examination survey (NHANES) 2011-2012.

AIM: Low-dose aspirin has been hypothesized as being a potential host modulatory agent for periodontitis treatment. We investigated the relationship between low-dose aspirin use and periodontitis prevalence in the continuous National Health and Nutrition Examination Survey, 2011-2012. METHODS: We analysed n = 2335 adult men and women who received a full-mouth periodontal examination and responded to an aspirin use questionnaire. Periodontal disease was defined as severe, moderate or mild according to established case definitions. Mean full-mouth probing depth, attachment loss and tooth loss were also considered. Low-dose aspirin was defined by any self-reported, physician prescribed aspirin use of ≤162 mg/day. RESULTS: Participants had mean age (SE) 55.8 years (0.42). The prevalences of periodontitis and low-dose aspirin use were 49.5% and 25% respectively. In multivariable logistic regression models controlling for age, sex, race, socioeconomic variables and comorbidities, the odds ratios [95%CI] for moderate or severe periodontitis among low-dose aspirin users (versus non-users) were: 0.91 [0.56-1.50] and 1.06 [0.74-1.50] respectively. Results were unchanged among participants without diabetes or coronary heart disease. CONCLUSIONS: Within the limitations of this cross-sectional study we conclude that low-dose aspirin is not associated with prevalent periodontal status in a nationally representative sample of US adults.

Evaluation of the bone regeneration potential of bioactive glass in implant site development surgeries: a systematic review of the literature.

OBJECTIVES: The aim of this systematic review was to assess the efficacy of bioactive glass (BG) in bone regeneration for implant site development procedures. MATERIAL AND METHODS: The following specific question was formulated with reference to Population, Intervention, Control, Outcomes (PICO): "In persons that undergo bone regeneration surgeries for implant site development, what histological outcomes does the use of BG yield, alone or in combination with AB, compared to positive or negative controls?". RESULTS: The 1st phase of screening yielded 400 titles and abstracts. A total of 12 studies reporting on the use of bioactive glass were scrutinized for inclusion in the final analysis and 5 studies were selected for qualitative synthesis of the results. Data were divided into two categories: ridge preservation (n = 2) and sinus augmentation (n = 3). CONCLUSIONS: Within the limitations of this review, it can be concluded that (1) the combination of BG with AB chips in a 1:1 ratio is an efficacious treatment modality for direct sinus augmentation, with histological results comparable to 100 % AB. (2) When used for ridge preservation, BG yields a high percentage of true bone regeneration. (3) Currently, no reliable controlled studies report histological outcomes from the use of BG in ridge augmentation procedures. CLINICAL RELEVANCE: Clinicians may consider BG bone substitutes as efficacious alternatives for ridge preservation and sinus augmentation surgical procedures. Further controlled clinical studies are warranted to determine if bone-to-implant contact is improved in BG-grafted sites versus controls.

Clinical results of implant placement in resorbed ridges using simultaneous guided bone regeneration: a multicenter case series.

OBJECTIVES: The purpose of this case series was to evaluate the new bone formation following guided bone regeneration (GBR) with a calcium phosphosilicate (CPS), alloplastic bone putty at peri-implant dehiscence defects and to assess survival rate of implants placed in the augmented sites after 12 months of function. MATERIALS AND METHODS: Implants were placed in patients exhibiting Seibert class I ridge defects resulting in peri-implant dehiscence defects. The defects were treated following GBR principles with the use of a CPS alloplastic bone graft putty in combination either with a collagen membrane or a titanium mesh. The height of each bony dehiscence was clinically measured at the time of implant placement and again during second-stage surgery. The percentage of complete defect coverage, frequency of adverse events, and risk factors for residual defect were determined. RESULTS: Thirty-six implants were placed in 26 patients. Twenty-seven of the 36 sites employed a collagen membrane in conjunction with the CPS while the remaining nine sites utilized a titanium membrane. Mean gain in bone height was 3.23 ± 2.04 mm, with 75 % of the peri-implant defects achieving complete regeneration. A negative correlation was identified between patient age and complete coverage of the peri-implant defect (p = 0.026). The implant survival rate at 12 months was 97.22 %. CONCLUSION: Use of CPS bone putty during delayed implant placement at peri-implant dehiscence sites either in combination with a collagen membrane or a titanium mesh results in predictable defect coverage. CLINICAL RELEVANCE: The handling characteristics of CPS putty may simplify GBR protocol. Implants placed in conjunction with GBR have a very good survival rate after 1 year of follow-up.

Risk Indicators of Papillary Recession in the Anterior Maxilla.

PURPOSE: The interdental papilla is the portion of the gingiva that occupies the space between two adjacent teeth. When papillary recession occurs, an array of problems arises ranging from phonetics to food impaction and esthetic concerns. The aim of this study was to identify risk indicators for visible papillary recession in the anterior maxilla among a Caucasian population utilizing an advanced analytical approach. MATERIALS AND METHODS: A dataset of 211 adult dentate Caucasian patients that had undergone intraoral assessment of midline papillary recession and extra-oral assessment of visible papillary recession during maximum ("Duchenne") smile was utilized. An enhanced analytical approach was employed to identify risk indicators for papillary recession. RESULTS: Approximately one-third of the participants (38%) demonstrated papillary recession during maximum smile ("visible papillary recession"). An association between sex (male preference) and visible papillary recession was found in this sample population, while age was found to be a risk indicator for papillary recession in individuals over 65 years of age. CONCLUSIONS: Visible midline papillary recession in the maxilla is a highly prevalent clinical entity in Caucasian individuals, thus the development of efficacious treatment modalities for papillary regeneration is necessary. Findings of the present study on risk indicators for visible papillary absence, namely sex and age, may facilitate clinicians in treating patient with compromised interdental aesthetics as well as identifying patients that are in high risk for loss of interdental tissues. CLINICAL SIGNIFICANCE: Findings of the present study on risk indicators for visible papillary absence, namely sex and age, indicate the need for careful assessment and meticulous treatment planning with respect to preservation of the interdental tissues. The consideration of these risk indicators can help dentists to identify patients at risk for papillary recession.

Implants placed simultaneously with lateral window sinus augmentation using a putty alloplastic bone substitute for increased primary implant stability: a retrospective study.

INTRODUCTION: The aim of this retrospective study was to evaluate the primary stability of implants placed in significantly pneumatized maxillary sinuses with minimum residual bone height. MATERIALS AND METHODS: Seventeen patients who had been treated with simultaneous implant placement in sites with <5 mm of vertical bone height using a modified direct sinus lift technique were included. Implants placed in adjacent sites with at least 5 mm of bone height were included as quasi-controls. RESULTS: A total of 30 implants were inserted with a maximum insertion torque number >20 N/cm. Logistic regression analysis failed to show any association between residual bone height and primary implant stability. Implant survival was 96.67% (29/30) during a mean follow-up of 15.74 months postloading. CONCLUSIONS: The diminished preoperative vertical dimensions of the residual ridges did not seem to negatively influence the osseointegration of implants placed in this study. The prerequisite for simultaneous sinus augmentation and implant placement is an adequate primary stability of the implant and not a fixed minimum bone height level.

Patient-related and financial outcomes analysis of conventional full-arch rehabilitation versus the All-on-4 concept: a cohort study.

BACKGROUND: Patient-related variables such as cost of treatment, length of the treatment period, and comfort provided by the interim prosthesis when treatment planning for full-arch rehabilitation are often neglected in dental publications. METHODS: Two patient cohorts were followed up longitudinally in this study: the "All-on-4 treatment concept group" and the "historical group." The number of implants, total treatment time, number of surgical procedures, number of sinus grafts, necessity for immediate provisional implants, adjusted cost associated for treatment in each group, and the quality of interim prosthesis were compared. RESULTS: The total adjusted cost for patients receiving All-on-4 treatment concept averaged at $42,422 ± 3860 (&OV0556;31,392 ± 2856), whereas the mean total adjusted cost for the historical group was $57,944 ± 20,198 (&OV0556;42,879 ± 2113) (P = 0.01). The difference in cost had a mean value of $7307 (&OV0556;5407) per jaw. Factors associated with complexity of treatment and patient comfort, such as the quality of interim prosthesis, number of surgeries, and duration of treatment time, all significantly favored the All-on-4 treatment concept group in comparison with conventional treatment modalities. CONCLUSIONS: When implant rehabilitation of the total jaw is sought, the All-on-4 treatment concept should be considered the least costly and least time consuming treatment option.