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Journal of Prosthetic Dentistry

Immediate versus early or conventional loading dental implants with fixed prostheses: A systematic review and meta-analysis of randomized controlled clinical trials

  • Jie Chen
    Affiliations
    Postgraduate student, Department of Prosthodontics, Guanghua School of Stomatology & Hospital of Stomatology, Guangdong Key Laboratory of Stomatology, Sun Yat-Sen University, Guangzhou, PR China
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  • Min Cai
    Affiliations
    Predoctoral student, Department of Prosthodontics, Guanghua School of Stomatology & Hospital of Stomatology, Guangdong Key Laboratory of Stomatology, Sun Yat-Sen University, Guangzhou, PR China
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  • Jiajun Yang
    Affiliations
    Postgraduate student, Department of Prosthodontics, Guanghua School of Stomatology & Hospital of Stomatology, Guangdong Key Laboratory of Stomatology, Sun Yat-Sen University, Guangzhou, PR China
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  • Taghrid Aldhohrah
    Affiliations
    Postgraduate student, Department of Prosthodontics, Guanghua School of Stomatology & Hospital of Stomatology, Guangdong Key Laboratory of Stomatology, Sun Yat-Sen University, Guangzhou, PR China
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  • Yan Wang
    Correspondence
    Corresponding author: Dr Yan Wang, No. 56, Ling Yuan Xi Road, Guangzhou, Guangdong, PR CHINA
    Affiliations
    Professor, Department of Prosthodontics, Guanghua School of Stomatology & Hospital of Stomatology, Guangdong Key Laboratory of Stomatology, Sun Yat-Sen University, Guangzhou, PR China
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Open AccessPublished:August 14, 2019DOI:https://doi.org/10.1016/j.prosdent.2019.05.013

      Abstract

      Statement of problem

      Immediate loading of dental implants has gained widespread popularity because of its advantages in shortening treatment duration and improving esthetics and patient acceptance. However, whether immediate loading can achieve clinical outcomes comparable with those of early or conventional delayed loading is still unclear.

      Purpose

      The purpose of this systematic review and meta-analysis was to compare the efficacy of immediate loading versus early or conventional loading implants in patients rehabilitated with fixed prostheses.

      Material and methods

      Electronic searches of CENTRAL, EMBASE, and MEDLINE were supplemented by manual searches up to October 2018. Only human randomized controlled trials (RCTs) comparing immediate with early or conventional loading dental implants were included. Quality assessment was performed by using the Cochrane Collaboration tool. For the meta-analysis, the dichotomous and continuous variables were pooled and analyzed by using risk ratios (RRs) and weighted mean differences (WMDs), with 95% confidence intervals (95% CIs). The outcomes assessed included survival rate, marginal bone level changes, peri-implant gingival level, probing depth, and implant stability. The subgroup analyses included healing methods, implant time, occlusal contact, number of missing teeth, and tooth position.

      Results

      Thirty-nine trials (49 articles) were included from the initial 763 references evaluated. When compared with conventional loading, with implants regarded as a statistical unit, a statistically significant lower survival rate was observed in the immediate loading dental implant (RR=0.974; 95% CI, 0.954, 0.994; P=.012). Regarding other outcomes, including marginal bone level changes, peri-implant gingival level, probing depth, and implant stability, no statistically significant differences were observed when comparing immediate versus early or conventional loading (P>.05).

      Conclusions

      Compared with early loading, immediate loading could achieve comparable implant survival rates and marginal bone level changes. Compared with conventional loading, immediate loading was associated with a higher incidence of implant failure.
      Clinical Implications
      Loading implants conventionally rather than immediately is advised. Based on the currently available randomized clinical trials, immediate loading achieved the same clinical efficacy as early loading.
      The conventional approach dictates that to achieve proper osseointegration, implants need to be submerged without any load for 3 to 4 months in the mandible and 6 to 8 months in the maxilla.
      • Branemark P.I.
      • Hansson B.O.
      • Adell R.
      • Breine U.
      • Lindstrom J.
      • Hallen O.
      • et al.
      Osseointegrated implants in the treatment of the edentulous jaw. Experience from a 10-year period.
      However, shortening the treatment period is beneficial for patients and dentists.
      Recently, immediate and early implant loading protocols have become popular.
      • Strub J.R.
      • Jurdzik B.A.
      • Tuna T.
      Prognosis of immediately loaded implants and their restorations: a systematic literature review.
      • De Bruyn H.
      • Raes S.
      • Ostman P.O.
      • Cosyn J.
      Immediate loading in partially and completely edentulous jaws: a review of the literature with clinical guidelines.
      • Galli F.
      • Capelli M.
      • Zuffetti F.
      • Testori T.
      • Esposito M.
      Immediate non-occlusal vs. early loading of dental implants in partially edentulous patients: a multicentre randomized clinical trial. Peri-implant bone and soft-tissue levels.
      • Cannizzaro G.
      • Leone M.
      • Torchio C.
      • Viola P.
      • Esposito M.
      Immediate versus early loading of 7-mm-long flapless-placed single implants: a split-mouth randomised controlled clinical trial.
      The first clinical trial on immediately or early loaded Brånemark System (Nobelpharma) implants was conducted in 1990.
      • Schnitman P.A.
      • Wohrle P.S.
      • Rubenstein J.E.
      Immediate fixed interim prostheses supported by two-stage threaded implants: methodology and results.
      The 10-year results of this study showed that the failure rate for immediately loaded implants was significantly higher than that of the conventional submerged technique implants.
      • Schnitman P.A.
      • Wohrle P.S.
      • Rubenstein J.E.
      • DaSilva J.D.
      • Wang N.H.
      Ten-year results for Branemark implants immediately loaded with fixed prostheses at implant placement.
      With the development of clinical techniques and implant surface modifications, a number of good-quality randomized controlled trials (RCTs) have reported high survival rates for immediate loading implants, some of which even showed no implant failure.
      • Assad A.S.
      • Hassan S.A.
      • Shawky Y.M.
      • Badawy M.M.
      Clinical and radiographic evaluation of implant-retained mandibular overdentures with immediate loading.
      • Romeo E.
      • Chiapasco M.
      • Lazza A.
      • Casentini P.
      • Ghisolfi M.
      • Iorio M.
      • et al.
      Implant-retained mandibular overdentures with ITI implants.
      • Cannizzaro G.
      • Leone M.
      • Esposito M.
      Immediate versus early loading of two implants placed with a flapless technique supporting mandibular bar-retained overdentures: a single-blinded, randomised controlled clinical trial.
      • Crespi R.
      • Capparé P.
      • Gherlone E.
      • Romanos G.E.
      Immediate versus delayed loading of dental implants placed in fresh extraction sockets in the maxillary esthetic zone: A clinical comparative study.
      • Merli M.
      • Moscatelli M.
      • Mariotti G.
      • Piemontese M.
      • Nieri M.
      Immediate versus early non-occlusal loading of dental implants placed flapless in partially edentulous patients: a 3-year randomized clinical trial.
      • Merli M.
      • Merli A.
      • Bernardelli F.
      • Lombardini F.
      • Esposito M.
      Immediate versus early non-occlusal loading of dental implants placed flapless in partially edentulous patients. One-year results from a randomised controlled trial.
      • Romanos G.E.
      • Aydin E.
      • Locher K.
      • Nentwig G.H.
      Immediate vs. delayed loading in the posterior mandible: a split-mouth study with up to 15 years of follow-up.
      • Romanos G.E.
      • Nentwig G.H.
      Immediate versus delayed functional loading of implants in the posterior mandible: a 2-year prospective clinical study of 12 consecutive cases.
      • Cannizzaro G.
      • Leone M.
      • Consolo U.
      • Ferri V.
      • Esposito M.
      Immediate functional loading of implants placed with flapless surgery versus conventional implants in partially edentulous patients: a 3-year randomized controlled clinical trial.
      • Degidi D.M.
      • Nardi D.
      • Piattelli A.
      Immediate versus one-stage restoration of small-diameter implants for a single missing maxillary lateral incisor: A 3-year randomized clinical trial.
      • Danza M.
      • Tortora P.
      • Quaranta A.
      • Perrotti V.
      • Vozza I.
      • Piattelli A.
      Randomised study for the 1-year crestal bone maintenance around modified diameter implants with different loading protocols: a radiographic evaluation.
      • Barewal R.M.
      • Stanford C.
      • Weesner T.C.
      A randomized controlled clinical trial comparing the effects of three loading protocols on dental implant stability.
      • Meloni S.M.
      • De Riu G.
      • Pisano M.
      • De Riu N.
      • Tullio A.
      Immediate versus delayed loading of single mandibular molars. One-year results from a randomised controlled trial.
      • Jokstad A.
      • Alkumru H.
      Immediate function on the day of surgery compared with a delayed implant loading process in the mandible: a randomized clinical trial over 5 years.
      • Esposito M.
      • Siormpas K.
      • Mitsias M.
      • Bechara S.
      • Trullenque-Eriksson A.
      • Pistilli R.
      Immediate, early (6 weeks) and delayed loading (3 months) of single implants: 4-month post-loading from a multicenter pragmatic randomised controlled trial.
      • Vercruyssen M.
      • Cox C.
      • Naert I.
      • Jacobs R.
      • Teughels W.
      • Quirynen M.
      Accuracy and patient-centered outcome variables in guided implant surgery: a RCT comparing immediate with delayed loading.
      • Chidagam P.
      • Gande V.
      • Yadlapalli S.
      • Venkata R.
      • Kondaka S.
      • Chedalawada S.
      Immediate versus delayed loading of implant for replacement of missing mandibular first molar: a randomized prospective six years clinical study.
      • Giacomel M.
      • Camati P.
      • Souza J.
      • Deliberador T.
      Comparison of marginal bone level changes of immediately loaded implants, delayed loaded nonsubmerged implants, and delayed loaded submerged implants: a randomized clinical trial.
      • Grandi T.
      • Garuti G.
      • Guazzi P.
      • Tarabini L.
      • Forabosco A.
      Survival and success rates of immediately and early loaded implants: 12-month results from a multicentric randomized clinical study.
      • Grandi T.
      • Guazzi P.
      • Samarani R.
      • Grandi G.
      A 3-year report from a multicentre randomised controlled trial: immediately versus early loaded implants in partially edentulous patients.
      • Kokovic V.
      • Jung R.
      • Feloutzis A.
      • Todorovic V.S.
      • Jurisic M.
      • Hämmerle C.H.
      Immediate vs. early loading of SLA implants in the posterior mandible: 5-year results of randomized controlled clinical trial.
      • Rieder D.
      • Eggert J.
      • Krafft T.
      • Weber H.-P.
      • Wichmann M.
      • Heckmann S.
      Impact of placement and restoration timing on single-implant esthetic outcome-a randomized clinical trial.
      Systematic reviews have concluded that clinically significant differences in implant failure associated with different loading times are lacking.
      • Esposito M.
      • Grusovin M.G.
      • Maghaireh H.
      • Worthington H.V.
      Interventions for replacing missing teeth: different times for loading dental implants.
      • Kern J.S.
      • Kern T.
      • Wolfart S.
      • Heussen N.
      A systematic review and meta-analysis of removable and fixed implant-supported prostheses in edentulous jaws: post-loading implant loss.
      • Engelhardt S.
      • Papacosta P.
      • Rathe F.
      • Ozen J.
      • Jansen J.A.
      • Junker R.
      Annual failure rates and marginal bone-level changes of immediate compared to conventional loading of dental implants. A systematic review of the literature and meta-analysis.
      However, meta-analyses have concluded that immediate loading has resulted in reduced implant survival rates.
      • Sanz-Sanchez I.
      • Sanz-Martin I.
      • uero E.
      • Sanz M.
      Clinical efficacy of immediate implant loading protocols compared to conventional loading depending on the type of the restoration: a systematic review.
      • Zhang S.
      • Wang S.
      • Song Y.
      Immediate loading for implant restoration compared with early or conventional loading: A meta-analysis.
      • Chrcanovic B.R.
      • Albrektsson T.
      • Wennerberg A.
      Immediately loaded non-submerged versus delayed loaded submerged dental implants: a meta-analysis.
      Moreover, controversy also exists among these systematic reviews in regard to marginal bone level changes, implant stability, and probing depth.
      • Sanz-Sanchez I.
      • Sanz-Martin I.
      • uero E.
      • Sanz M.
      Clinical efficacy of immediate implant loading protocols compared to conventional loading depending on the type of the restoration: a systematic review.
      • Zhang S.
      • Wang S.
      • Song Y.
      Immediate loading for implant restoration compared with early or conventional loading: A meta-analysis.
      • Chrcanovic B.R.
      • Albrektsson T.
      • Wennerberg A.
      Immediately loaded non-submerged versus delayed loaded submerged dental implants: a meta-analysis.
      • Suarez F.
      • Chan H.L.
      • Monje A.
      • Galindo-Moreno P.
      • Wang H.L.
      Effect of the timing of restoration on implant marginal bone loss: a systematic review.
      The authors are unaware of a meta-analysis of these issues, presumably because of the high heterogeneity in the description of soft-tissue status, the subjective feeling of patients, and other variables.
      • Sanz-Sanchez I.
      • Sanz-Martin I.
      • uero E.
      • Sanz M.
      Clinical efficacy of immediate implant loading protocols compared to conventional loading depending on the type of the restoration: a systematic review.
      Therefore, the differences between immediate, early, and delayed loading are unclear.
      In addition, the systematic reviews performed by Esposito et al
      • Esposito M.
      • Grusovin M.G.
      • Maghaireh H.
      • Worthington H.V.
      Interventions for replacing missing teeth: different times for loading dental implants.
      and Sanz-Sanchez et al
      • Sanz-Sanchez I.
      • Sanz-Martin I.
      • uero E.
      • Sanz M.
      Clinical efficacy of immediate implant loading protocols compared to conventional loading depending on the type of the restoration: a systematic review.
      noted a high or moderate risk of bias in most included RCTs, the influence of statistical units going unnoticed (patient or implant), high heterogeneity shown in meta-analyses, and a significant number of RCTs published or data updated in recent years. Additionally, factors that were not investigated included the healing method, implant time, tooth position, use of surgery guide, and the flap or flapless approach.
      The effects of the following elements were evaluated in subgroup analyses: number of missing teeth, immediately functional or nonfunctional loading during the osseointegration period, healing methods in the control group (submerged or transmucosal), implant time (immediate, early, or delayed), tooth position, surgery guide (used or not), definitive or interim prostheses as the initial restoration, and surgery protocols (flap or flapless).
      The purpose of this systematic review was to determine the impact of immediate loading implants on the clinical outcomes of fixed restorations when compared with early or conventionally loaded implants.

      Material and methods

      A prospective protocol was developed a priori according to the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analyses) and the Meta-analysis of Observational Studies in Epidemiology recommendations.
      • Liberati A.
      • Altman D.G.
      • Tetzlaff J.
      • Mulrow C.
      • Gotzsche P.C.
      • Ioannidis J.P.
      • et al.
      The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration.
      • Stroup D.F.
      • Berlin J.A.
      • Morton S.C.
      • Olkin I.
      • Williamson G.D.
      • Rennie D.
      • et al.
      Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group.
      The PICOS strategy was used for the search: P (population)=patients requiring at least 1 dental implant; I (intervention)=restoration within 1 week of implant placement
      • Esposito M.
      • Grusovin M.G.
      • Willings M.
      • Coulthard P.
      • Worthington H.V.
      The effectiveness of immediate, early, and conventional loading of dental implants: a Cochrane systematic review of randomized controlled clinical trials.
      ; C (comparison)=delayed (also termed “conventional”) loading defined as restorations 8 weeks after insertion, early loading between 1 and 8 weeks
      • Weber H.P.
      • Morton D.
      • Gallucci G.O.
      • Roccuzzo M.
      • Cordaro L.
      • Grutter L.
      Consensus statements and recommended clinical procedures regarding loading protocols.
      ; O (outcome)=implant survival rate, marginal bone level changes, peri-implant gingival level, plaque index, probing depth, implant stability, the rate of peri-implantitis or peri-implant mucositis, and subjective feeling of patients; S (study design)=randomized controlled trials (RCTs). The focus question was “Is there a difference in postoperative outcomes when an immediate implant loading protocol is compared with early or conventional loading in fixed restoration(s)?”
      From inception until October 2018, a comprehensive electronic search was conducted in CENTRAL (The Cochrane Central Register of Controlled Trials), EMBASE, and MEDLINE via PubMed (The National Library of Medicine). The search strategy is shown in Table 1, and the results filter was set to humans and randomized controlled trials.
      Table 1Strategy of electronic search
      DatabaseSearch Terms
      CENTRAL and MEDLINEEMBASE
      Population((("Dental Implants"[Mesh]) OR "Dental Implantation"[Mesh]) OR dental implant*[Title/Abstract]) OR oral implant*[Title/Abstract](‘tooth implant’/exp) OR (‘tooth implantation’/exp) OR (dental AND implant*: ab, kw, ti) OR (oral AND implant*: ab, kw, ti)
      Intervention("Immediate Dental Implant Loading"[Mesh]) OR ((immediate*[Title/Abstract]) AND ((((((load*[Title/Abstract]) OR crown*[Title/Abstract]) OR bridge*[Title/Abstract]) OR prosthes*[Title/Abstract]) OR restoration*[Title/Abstract]) OR rehabilitat*[Title/Abstract]))((immediate*: ab, kw, ti) AND ((((((load*: ab, kw, ti) OR crown*: ab, kw, ti) OR bridge*: ab, kw, ti) OR prosthes*: ab, kw, ti) OR restoration*: ab, kw, ti) OR rehabilitat*: ab, kw, ti))
      There were no restrictions on regions or languages. The computer search was supplemented with a manual search of the reference lists in all retrieved literature. In addition, a search of the online databases in the following journals was performed: British Journal of Oral and Maxillofacial Surgery, Clinical Implant Dentistry and Related Research, Clinical Oral Implants Research, European Journal of Oral Implantology, Implant Dentistry, The International Journal of Oral & Maxillofacial Implants, International Journal of Oral and Maxillofacial Surgery, International Journal of Periodontics and Restorative Dentistry, International Journal of Prosthodontics, Journal of Clinical Periodontology, Journal of Dental Implantology, Journal of Dental Research, Journal of Oral Implantology, Journal of Oral and Maxillofacial Surgery, Journal of Periodontology, Journal of Periodontal Research, Journal of Prosthetic Dentistry.
      Two reviewers (J.C., M.C.) selected studies by independently screening the titles and abstracts of search results based on the following inclusion criteria: at least 1 dental implant with a fixed prosthesis; at least 15 participants; studies on immediate loading versus early or conventional loading; at least 1 of those aforementioned outcomes reported; and randomized controlled trials (RCTs). There was no restriction on the follow-up period. Animal studies or studies involving zygomatic implants or implants used for orthodontic anchorage were excluded. Additionally, review studies, case reports, case series, and meeting abstracts were also excluded. The full text of potential articles was reconfirmed and evaluated for data extraction. Any disagreement was resolved by further discussion or an additional author's (Y.W.) evaluation. When multiple articles reported the same trial, the most recent one with completed data was included. Authors of studies were contacted by e-mail when data were found to be incomplete or not reported.
      Two authors (T.A.A., J.Y.) independently assessed the risk of bias in the included studies. The quality assessment of the included RCTs was performed by using the Cochrane Collaboration's tool.
      • Higgins J.P.
      • Altman D.G.
      • Gotzsche P.C.
      • Juni P.
      • Moher D.
      • Oxman A.D.
      • et al.
      The Cochrane Collaboration's tool for assessing risk of bias in randomised trials.
      Seven criteria were assessed: random sequence generation (selection bias), allocation concealment (selection bias), blinding of participants and personnel (performance bias), blinding of outcome assessment (detection bias), incomplete outcome data (attrition bias), selective reporting (reporting bias), and other bias. Studies were classified as low risk if all criteria were met, moderate risk if 1 criterion is missed, and high risk if 2 or more were missed.
      For this meta-analysis, the dichotomous variables (such as, implant survival rate) were pooled and analyzed by using risk ratios (RRs) and 95% confidence intervals (95% CIs). As for continuous outcomes (such as, marginal bone level changes), weighted mean differences (WMDs) with 95% CI were used. The Q-test estimated heterogeneity, with significance set at α=.1 and quantified with the I2 index (high heterogeneity: I2>75%; low heterogeneity: I2<25%). The random-effect model was used when significant heterogeneity was found between the test and control study. Otherwise, the fixed-effect model was applied. Subgroup analyses were carried out based on items listed in the introduction. All analyses were performed by using a statistical software program (STATA-12; StataCorp LP) (α=.05). Forest plots were used to illustrate the effects of the intervention, and funnel plots were created to screen for publication bias.

      Results

      The screening process is depicted in Figure 1. Eighty-nine articles were selected for full-text analysis after the evaluation of titles and abstracts (agreement=87.4%; kappa=0.63). Forty-nine articles met inclusion criteria and were assessed for reliability (Table 2). After evaluation, 49 full-text articles that belonged to 39 trials were identified. Of the 39 studies, 18 belonged to 8 trials, which were divided into the following 8 series: In the first series, 2 articles reported the data at 2 years and 15 years, respectively.
      • Romanos G.E.
      • Aydin E.
      • Locher K.
      • Nentwig G.H.
      Immediate vs. delayed loading in the posterior mandible: a split-mouth study with up to 15 years of follow-up.
      • Romanos G.E.
      • Nentwig G.H.
      Immediate versus delayed functional loading of implants in the posterior mandible: a 2-year prospective clinical study of 12 consecutive cases.
      In the second series, 3 articles showed results at varying time periods.
      • Galli F.
      • Capelli M.
      • Zuffetti F.
      • Testori T.
      • Esposito M.
      Immediate non-occlusal vs. early loading of dental implants in partially edentulous patients: a multicentre randomized clinical trial. Peri-implant bone and soft-tissue levels.
      • Testori T.
      • Galli F.
      • Capelli M.
      • Zuffetti F.
      • Esposito M.
      Immediate nonocclusal versus early loading of dental implants in partially edentulous patients: 1-Year results from a multicenter, randomized controlled clinical trial.
      • Capelli M.
      • Esposito M.
      • Zuffetti F.
      • Galli F.
      • Fabbro M.
      • Testroi T.
      A 5-year report from a multicentre randomised clinical trial: immediate non-occlusal versus early loading of dental implants in partially edentulous patients.
      In the third series, 2 articles reported the outcomes at 1 year and 5 years.
      • Donati M.
      • Scala V.
      • Raimondo R.
      • Speroni S.
      • Testi M.
      • Berglundh T.
      Marginal bone preservation in single-tooth replacement: a 5-year prospective clinical multicenter study.
      • Donati M.
      • Scala V.
      • Billi M.
      • Dino B.
      • Torrisi P.
      • Berglundh T.
      Immediate functional loading of implants in single tooth replacement: a prospective clinical multicenter study.
      In the fourth series, 2 articles reported the data at 9 months and 4 years.
      • Cannizzaro G.
      • Leone M.
      • Torchio C.
      • Viola P.
      • Esposito M.
      Immediate versus early loading of 7-mm-long flapless-placed single implants: a split-mouth randomised controlled clinical trial.
      • Cannizzaro G.
      • Felice P.
      • Leone M.
      • Ferri V.
      • Viola P.
      • Esposito M.
      Immediate versus early loading of 6.5 mm-long flapless-placed single implants: a 4-year after loading report of a split-mouth randomised controlled trial.
      In the fifth series, 3 articles showed the results at 5 months, 1 year, and 3 years.
      • Ganeles J.
      • Zöllner A.
      • Jackowski J.
      • Ten Bruggenkate C.
      • Beagle J.
      • Guerra F.
      Immediate and early loading of Straumann implants with a chemically modified surface (SLActive) in the posterior mandible and maxilla: 1-Year results from a prospective multicenter study.
      • Zöllner A.
      • Ganeles J.
      • Korostoff J.
      • Guerra F.
      • Krafft T.
      • Brägger U.
      Immediate and early non-occlusal loading of Straumann implants with a chemically modified surface (SLActive) in the posterior mandible and maxilla: Interim results from a prospective multicenter randomized-controlled study.
      • Nicolau P.
      • Korostoff J.
      • Ganeles J.
      • Jackowski J.
      • Krafft T.
      • Neves M.
      • et al.
      Immediate and early loading of chemically modified implants in posterior jaws: 3-year results from a prospective randomized multicenter study.
      In the sixth series, 2 articles reported the data at 1 and 3 years.
      • Merli M.
      • Moscatelli M.
      • Mariotti G.
      • Piemontese M.
      • Nieri M.
      Immediate versus early non-occlusal loading of dental implants placed flapless in partially edentulous patients: a 3-year randomized clinical trial.
      • Merli M.
      • Merli A.
      • Bernardelli F.
      • Lombardini F.
      • Esposito M.
      Immediate versus early non-occlusal loading of dental implants placed flapless in partially edentulous patients. One-year results from a randomised controlled trial.
      In the seventh series, 2 articles showed the results at 1 and 2 years.
      • Shibly O.
      • Patel N.
      • Albandar J.M.
      • Kutkut A.
      Bone regeneration around implants in periodontally compromised patients: a randomized clinical trial of the effect of immediate implant with immediate loading.
      • Shibly O.
      • Kutkut A.
      • Patel N.
      • Albandar J.M.
      Immediate implants with immediate loading vs. conventional loading: 1-year randomized clinical trial.
      In the eighth series, 2 articles reported the data at 1 and 3 years.
      • Grandi T.
      • Garuti G.
      • Guazzi P.
      • Tarabini L.
      • Forabosco A.
      Survival and success rates of immediately and early loaded implants: 12-month results from a multicentric randomized clinical study.
      • Grandi T.
      • Guazzi P.
      • Samarani R.
      • Grandi G.
      A 3-year report from a multicentre randomised controlled trial: immediately versus early loaded implants in partially edentulous patients.
      Figure thumbnail gr1
      Figure 1Flow diagram of studies identified, included, and excluded.
      Table 2Characteristics of included studies
      StudyCountryDesign (RCT)Follow-up (mo)Age: Mean (Minimum, Maximum) Test/Control
      Data of both test and control group.
      Global
      Patients (Implant), No. (Test/Control)ImplantLoading Time of the Control Group (wk)
      InitialFinal
      Testori et al (2003)
      • Testori T.
      • Bianchi F.
      • Fabbro M.
      • Szmukler-Moncler S.
      • Francetti L.
      • Weinstein R.
      Immediate non-occlusal loading vs. early loading in partially edentulous patients.
      ItalyParallel2456/54.214 (52)/18 (49)14 (50)/18 (48)Osseotite and Osseotite NT; Implant Innovations Inc8
      Hall et al (2006, 2007)
      • Hall J.A.G.
      • Payne A.G.T.
      • Purton D.G.
      • Torr B.
      A randomized controlled clinical trial of conventional and immediately loaded tapered implants with screw-retained crowns.
      • Hall J.A.G.
      • Payne A.G.T.
      • Purton D.G.
      • Torr B.
      • Duncan W.J.
      • De Silva R.K.
      Immediately restored, single-tapered implants in the anterior maxilla: Prosthodontic and aesthetic outcomes after 1 year.
      New ZealandParallel1243.25 (23, 71)
      Data of both test and control group.
      14 (14)/14 (14)14 (13)/12 (12)Southern Implants Ltd26
      Oh et al (2006)
      • Oh T.J.
      • Shotwell J.L.
      • Billy E.J.
      • Wang H.L.
      Effect of flapless implant surgery on soft tissue profile: a randomized controlled clinical trial.
      USAParallel645.2/47.312 (12)/12 (12)9 (9)/12 (12)Zimmer Dental16
      Romanos et al (2006, 2016)
      • Romanos G.E.
      • Aydin E.
      • Locher K.
      • Nentwig G.H.
      Immediate vs. delayed loading in the posterior mandible: a split-mouth study with up to 15 years of follow-up.
      • Romanos G.E.
      • Nentwig G.H.
      Immediate versus delayed functional loading of implants in the posterior mandible: a 2-year prospective clinical study of 12 consecutive cases.
      GermanySplit mouth18050.75
      Data of both test and control group.
      12 (36)/12 (36)10 (30)/10 (30)Ankylos implants; Dentsply Sirona Ceramed12
      Testori et al (2007),
      • Testori T.
      • Galli F.
      • Capelli M.
      • Zuffetti F.
      • Esposito M.
      Immediate nonocclusal versus early loading of dental implants in partially edentulous patients: 1-Year results from a multicenter, randomized controlled clinical trial.
      Galli et al (2008),
      • Galli F.
      • Capelli M.
      • Zuffetti F.
      • Testori T.
      • Esposito M.
      Immediate non-occlusal vs. early loading of dental implants in partially edentulous patients: a multicentre randomized clinical trial. Peri-implant bone and soft-tissue levels.
      Capelli et al (2010)
      • Capelli M.
      • Esposito M.
      • Zuffetti F.
      • Galli F.
      • Fabbro M.
      • Testroi T.
      A 5-year report from a multicentre randomised clinical trial: immediate non-occlusal versus early loading of dental implants in partially edentulous patients.
      ItalyParallel6051.6 (27, 74)/51.3 (34, 73)25 (52)/27 (52)24 (51)/26 (NR)Full OSSEOTITE Tapered Implants (FOSS); Biomet 3i8
      Cannizzaro et al (2008)
      • Cannizzaro G.
      • Leone M.
      • Consolo U.
      • Ferri V.
      • Esposito M.
      Immediate functional loading of implants placed with flapless surgery versus conventional implants in partially edentulous patients: a 3-year randomized controlled clinical trial.
      ItalyParallel3640.1 (18, 62)/37.4 (19, 64)20 (52)/20 (56)20 (52)/20 (56)Tapered SwissPlus; Zimmer Dental12(L); 16(U)
      Cannizzaro et al (2008, 2012)
      • Cannizzaro G.
      • Leone M.
      • Torchio C.
      • Viola P.
      • Esposito M.
      Immediate versus early loading of 7-mm-long flapless-placed single implants: a split-mouth randomised controlled clinical trial.
      • Cannizzaro G.
      • Felice P.
      • Leone M.
      • Ferri V.
      • Viola P.
      • Esposito M.
      Immediate versus early loading of 6.5 mm-long flapless-placed single implants: a 4-year after loading report of a split-mouth randomised controlled trial.
      ItalySplit mouth935 (18, 57)
      Data of both test and control group.
      15 (30)/15 (30)15 (29)/15 (29)Biomet 3i6
      Cannizzaro et al (2008)
      • Cannizzaro G.
      • Torchio C.
      • Leone M.
      • Esposito M.
      Immediate versus early loading of flapless-placed implants supporting maxillary full-arch prostheses: a randomised controlled clinical trial.
      ItalyParallel1262 (45, 65)/56 (42, 69)15 (90)/15 (87)15 (89)/15 (84)Tapered SwissPlus; Zimmer Dental8
      Crespi et al (2008)
      • Crespi R.
      • Capparé P.
      • Gherlone E.
      • Romanos G.E.
      Immediate versus delayed loading of dental implants placed in fresh extraction sockets in the maxillary esthetic zone: A clinical comparative study.
      ItalyParallel2445.6 (24, 62)/48.8 (27, 68)20 (20)/20 (20)20 (20)/20 (20)Outlink; Sweden & Martina12
      Donati et al (2008, 2015)
      • Donati M.
      • Scala V.
      • Raimondo R.
      • Speroni S.
      • Testi M.
      • Berglundh T.
      Marginal bone preservation in single-tooth replacement: a 5-year prospective clinical multicenter study.
      • Donati M.
      • Scala V.
      • Billi M.
      • Dino B.
      • Torrisi P.
      • Berglundh T.
      Immediate functional loading of implants in single tooth replacement: a prospective clinical multicenter study.
      ItalyThree armed6045.4
      Data of both test and control group.
      NR (104)/NR (57)NR (89)/NR (51)OsseoSpeed; Astra Tech Dental12
      Ganeles et al (2008),
      • Ganeles J.
      • Zöllner A.
      • Jackowski J.
      • Ten Bruggenkate C.
      • Beagle J.
      • Guerra F.
      Immediate and early loading of Straumann implants with a chemically modified surface (SLActive) in the posterior mandible and maxilla: 1-Year results from a prospective multicenter study.
      Zollner et al (2008),
      • Zöllner A.
      • Ganeles J.
      • Korostoff J.
      • Guerra F.
      • Krafft T.
      • Brägger U.
      Immediate and early non-occlusal loading of Straumann implants with a chemically modified surface (SLActive) in the posterior mandible and maxilla: Interim results from a prospective multicenter randomized-controlled study.
      Nicolau et al (2013)
      • Nicolau P.
      • Korostoff J.
      • Ganeles J.
      • Jackowski J.
      • Krafft T.
      • Neves M.
      • et al.
      Immediate and early loading of chemically modified implants in posterior jaws: 3-year results from a prospective randomized multicenter study.
      Several countriesParallel3646.3
      Data of both test and control group.
      138 (197)/128 (186)124 (178)/115 (162)SLActive; Institut Straumann AG4
      Guncu et al (2008)
      • Güncü M.B.
      • Aslan Y.
      • Tümer C.
      • Güncü G.N.
      • Uysal S.
      In-patient comparison of immediate and conventional loaded implants in mandibular molar sites within 12 months.
      TurkeySplit mouth1241.1 (30, 55)/41.1 (30, 55)12 (12)/12 (12)12 (11)/12 (12)Branemark System, TiUnite, Mk III; Nobel BiocareGothenburg12
      Merli et al (2008, 2012)
      • Merli M.
      • Moscatelli M.
      • Mariotti G.
      • Piemontese M.
      • Nieri M.
      Immediate versus early non-occlusal loading of dental implants placed flapless in partially edentulous patients: a 3-year randomized clinical trial.
      • Merli M.
      • Merli A.
      • Bernardelli F.
      • Lombardini F.
      • Esposito M.
      Immediate versus early non-occlusal loading of dental implants placed flapless in partially edentulous patients. One-year results from a randomised controlled trial.
      ItalyParallel3650.3 (28, 72)/48.7 (19, 68)30 (35)/30 (34)29 (34)/27 (31)ELEMENT; Thommen Medical6
      Schincaglia et al (2008)
      • Schincaglia G.P.
      • Marzola R.
      • Giovanni G.F.
      • Chiara C.S.
      • Scotti R.
      Replacement of mandibular molars with single-unit restorations supported by wide-body implants: immediate versus delayed loading. A randomized controlled study.
      ItalyParallel1251.9 (31, 75)/49.2 (35, 68)15 (15)/15 (15)15 (14)/15 (15)Mk III WP TiUnite implant Nobel BiocareGothenburg12-16
      De Rouck et al (2009)
      • Rouck T.
      • Collys K.
      • Wyn I.
      • Cosyn J.
      Instant provisionalization of immediate single-tooth implants is essential to optimize esthetic treatment outcome.
      BelgiumParallel1255/5224 (24)/25 (25)24 (23)/25 (23)NobelReplace tapered TiUnite; Nobel BiocareGothenburg12
      Degidi et al (2009)
      • Degidi D.M.
      • Nardi D.
      • Piattelli A.
      Immediate versus one-stage restoration of small-diameter implants for a single missing maxillary lateral incisor: A 3-year randomized clinical trial.
      ItalyParallel3631.5 (18, 55)
      Data of both test and control group.
      30 (30)/30 (30)30 (30)/30 (30)XiVE Plus; Dentsply Sirona24
      Guncu et al (2009)
      • Güncü G.N.
      • Tözüm T.F.
      • Güncü M.B.
      • Yamalik N.
      • Tümer C.
      A 12-month evaluation of nitrite oxide metabolism around immediate and conventionally loaded dental implants.
      TurkeySplit mouth1240 (27, 56)/40 (27, 56)12 (12)/12 (12)11 (11)/11 (11)Branemark System, TiUnite, Mk III; Nobel Biocare AB Gothenburg12
      Shibly et al (2010, 2012)
      • Shibly O.
      • Patel N.
      • Albandar J.M.
      • Kutkut A.
      Bone regeneration around implants in periodontally compromised patients: a randomized clinical trial of the effect of immediate implant with immediate loading.
      • Shibly O.
      • Kutkut A.
      • Patel N.
      • Albandar J.M.
      Immediate implants with immediate loading vs. conventional loading: 1-year randomized clinical trial.
      USAParallel24(25, 94)*30 (30)/30 (30)26 (26)/29 (28)NR12-16
      Danza et al (2010)
      • Danza M.
      • Tortora P.
      • Quaranta A.
      • Perrotti V.
      • Vozza I.
      • Piattelli A.
      Randomised study for the 1-year crestal bone maintenance around modified diameter implants with different loading protocols: a radiographic evaluation.
      ItalyParallel12NRNR (20)/NR (20)NR (20)/NR (20)SFB screw internal hex implant; Alpha Bio Ltd12(L); 24(U)
      Prosper et al (2010)
      • Prosper L.
      • Crespi R.
      • Valenti E.
      • Capparé P.
      • Gherlone E.
      Five-year follow-up of wide-diameter implants placed in fresh molar extraction sockets in the mandible: immediate versus delayed loading.
      ItalyParallel6058.3 (26, 72)*36 (60)/35 (60)36 (58)/35 (58)Bioactive Covering; Winsix12
      Velde et al (2010)
      • Velde T.
      • Sennerby L.
      • Bruyn H.
      The clinical and radiographic outcome of implants placed in the posterior maxilla with a guided flapless approach and immediately restored with a provisional rehabilitation: a randomized clinical trial.
      BelgiumSplit mouth1855.7 (39, 75)
      Data of both test and control group.
      13 (36)/13 (34)12 (32)/12 (32)Straumann SLA TE implants; Straumann AG6
      Zembić et al (2010)
      • Zembic A.
      • Glauser R.
      • Khraisat A.
      • Hammerle C.H.
      Immediate vs. early loading of dental implants: 3-year results of a randomized controlled clinical trial.
      SwitzerlandSplit mouth3654.8 (37.8, 68.6)
      Data of both test and control group.
      11 (22)/11 (22)10 (19)/10 (20)Branemark MK IV, TiUnite; Nobel Biocare AB6
      den Hartog et al (2011)
      • Den Hartog L.
      • Raghoebar G.M.
      • Stellingsma K.
      • Vissink A.
      • Meijer H.J.A.
      Immediate non-occlusal loading of single implants in the aesthetic zone: A randomized clinical trial.
      NetherlandsParallel1838.4 (18, 66)/40.1 (18, 67)31 (31)/31 (31)31 (30)/31 (31)NobelReplace Tapered Groovy; Nobel Biocare AB, Goteborg12
      Barewal et al (2012) (1)
      • Barewal R.M.
      • Stanford C.
      • Weesner T.C.
      A randomized controlled clinical trial comparing the effects of three loading protocols on dental implant stability.
      USAParallel36NR (20, 82)
      Data of both test and control group.
      8 (8)/15 (15)7 (7)/14 (14)Astra Tech6
      Barewal et al (2012) (2)
      • Barewal R.M.
      • Stanford C.
      • Weesner T.C.
      A randomized controlled clinical trial comparing the effects of three loading protocols on dental implant stability.
      8 (8)/15 (15)7 (7)/14 (13)12
      Grandi et al (2012, 2013)
      • Grandi T.
      • Garuti G.
      • Guazzi P.
      • Tarabini L.
      • Forabosco A.
      Survival and success rates of immediately and early loaded implants: 12-month results from a multicentric randomized clinical study.
      • Grandi T.
      • Guazzi P.
      • Samarani R.
      • Grandi G.
      A 3-year report from a multicentre randomised controlled trial: immediately versus early loaded implants in partially edentulous patients.
      ItalyMulti-center Parallel3651.8 (39, 65)/55.3 (43, 65)40 (81)/40 (80)38 (77)/39 (78)JDEvolution; JDentalCare8
      Margossian et al (2012) (1)
      • Margossian P.
      • Mariani P.
      • Stephan G.
      • Margerit J.
      • Jorgensen C.
      Immediate loading of mandibular dental implants in partially edentulous patients: a prospective randomized comparative study.
      FranceThree armed24NR40 (105)/37 (98)40 (105)/37 (98)First-generation full Osseotite NT certain; Biomet 3i20
      Margossian et al (2012) (2)
      • Margossian P.
      • Mariani P.
      • Stephan G.
      • Margerit J.
      • Jorgensen C.
      Immediate loading of mandibular dental implants in partially edentulous patients: a prospective randomized comparative study.
      40 (104)/37 (98)40 (97)/37 (98)
      Meloni et al (2012)
      • Meloni S.M.
      • De Riu G.
      • Pisano M.
      • De Riu N.
      • Tullio A.
      Immediate versus delayed loading of single mandibular molars. One-year results from a randomised controlled trial.
      ItalySplit mouth1246 (28, 70)/46 (28, 70)20 (20)/20 (20)20 (20)/20 (20)NobelReplace Tapered Groovy; Nobel Biocare, Goteborg16-20
      Alfadda et al (2014)
      • Alfadda S.A.
      A randomized controlled clinical trial of edentulous patients treated with immediately loaded implant-supported mandibular fixed prostheses.
      CanadaParallel1261.5
      Data of both test and control group.
      20 (80)/22 (88)16 (64)/24 (96)TiUnite dental implants; Nobel Biocare, Goteborg12
      Gothberg et al (2014)
      • Göthberg C.
      • André U.
      • Gröndahl K.
      • Ljungquist B.
      • Thomsen P.
      • Slotte C.
      Immediately loaded implants with or without abutments supporting fixed partial dentures: 1-year results from a prospective, randomized, clinical trial.
      SwedenParallel1268.0/66.126 (78)/24 (72)23 (74)/22 (70)Branemark TiUnite implants; Nobel Biocare, Goteborg12
      Jokstad et al (2014)
      • Jokstad A.
      • Alkumru H.
      Immediate function on the day of surgery compared with a delayed implant loading process in the mandible: a randomized clinical trial over 5 years.
      CanadaParallel6062 (42, 82)/62 (47, 78)21 (84)/21 (84)17 (68)/18 (71)Branemark System Mk III or Mk IV TiUnite; Nobel Biocare AB, Goteborg12-16
      Kokovic et al (2014)
      • Kokovic V.
      • Jung R.
      • Feloutzis A.
      • Todorovic V.S.
      • Jurisic M.
      • Hämmerle C.H.
      Immediate vs. early loading of SLA implants in the posterior mandible: 5-year results of randomized controlled clinical trial.
      UAESplit mouth6049 (20, 62)
      Data of both test and control group.
      12 (36)/12 (36)12 (36)/12 (36)SLA Straumann TE; Straumann AG6
      Grandi et al (2015) (1)
      • Grandi T.
      • Guazzi P.
      • Samarani R.
      • Tohme H.
      • Khoury S.
      • Sbricoli L.
      • et al.
      Immediate, early (3 weeks) and conventional loading (4 months) of single implants: preliminary data at 1 year after loading from a pragmatic multicenter randomised controlled trial.
      ItalyThree armed1251.4 (22, 73)/45.5 (21, 66)35 (35)/35 (35)33 (32)/35 (34)JDEvolution; JDentalCare tapered thread titanium implants and double acid-etched treated surface3
      Grandi et al (2015) (2)
      • Grandi T.
      • Guazzi P.
      • Samarani R.
      • Tohme H.
      • Khoury S.
      • Sbricoli L.
      • et al.
      Immediate, early (3 weeks) and conventional loading (4 months) of single implants: preliminary data at 1 year after loading from a pragmatic multicenter randomised controlled trial.
      51.4 (22, 73)/46.1 (24, 75)33 (32)/35 (35)16
      Cesaretti et al (2016)
      • Cesaretti G.
      • Botticelli D.
      • Renzi A.
      • Rossi M.
      • Rossi R.
      • Lang N.P.
      Radiographic evaluation of immediately loaded implants supporting 2-3 units fixed bridges in the posterior maxilla: a 3-year follow-up prospective randomized controlled multicenter clinical study.
      CubaParallel3664.5 (51, 76)/58.9 (41, 79)15 (36)/15 (35)14 (34)/14 (33)SLA surface; Institute Straumann AG and a polished neck of 2.8 mm12
      Esposito et al (2016) (1)
      • Esposito M.
      • Siormpas K.
      • Mitsias M.
      • Bechara S.
      • Trullenque-Eriksson A.
      • Pistilli R.
      Immediate, early (6 weeks) and delayed loading (3 months) of single implants: 4-month post-loading from a multicenter pragmatic randomised controlled trial.
      SwedenThree armed451.3 (35, 67.6)/55.1 (42.5, 67.7)27 (84)/27 (82)27 (84)/27 (82)AnyRidge Xpeed; Megagen Implant12
      Esposito et al (2016) (2)
      • Esposito M.
      • Siormpas K.
      • Mitsias M.
      • Bechara S.
      • Trullenque-Eriksson A.
      • Pistilli R.
      Immediate, early (6 weeks) and delayed loading (3 months) of single implants: 4-month post-loading from a multicenter pragmatic randomised controlled trial.
      51.3 (35, 67.6)/54.3 (40.1, 68.5)27 (84)/27 (83)27 (84)/27 (83)6
      Rieder et al (2016) (1)
      • Rieder D.
      • Eggert J.
      • Krafft T.
      • Weber H.-P.
      • Wichmann M.
      • Heckmann S.
      Impact of placement and restoration timing on single-implant esthetic outcome-a randomized clinical trial.
      GermanyFour armed844.8 (17, 76)
      Data of both test and control group.
      12 (12)/12 (12)11 (11)/12 (12)SLActivea surface; Straumann AG4-6
      Rieder et al (2016) (2)
      • Rieder D.
      • Eggert J.
      • Krafft T.
      • Weber H.-P.
      • Wichmann M.
      • Heckmann S.
      Impact of placement and restoration timing on single-implant esthetic outcome-a randomized clinical trial.
      12 (12)/10 (10)
      Vercruyssen et al (2016)BelgiumParallel0.3(45, 71)/(49, 70)7 (42)/8 (48)7 (42)/8 (47)Ankylos implants; Dentsply Sirona12
      Zuffetti et al (2016)
      • Zuffetti F.
      • Esposito M.
      • Galli F.
      • Capelli M.
      • Grandi G.
      • Testori T.
      A 10-year report from a multicentre randomised controlled trial: immediate non-occlusal versus early loading of dental implants in partially edentulous patients.
      ItalySplit mouth12051.6 (27, 74)/51.3 (34, 73)25 (52)/27 (52)21 (43)/25 (49)FOSS; Zimmer Biomet 3iFL8
      Chidagam et al (2017)
      • Chidagam P.
      • Gande V.
      • Yadlapalli S.
      • Venkata R.
      • Kondaka S.
      • Chedalawada S.
      Immediate versus delayed loading of implant for replacement of missing mandibular first molar: a randomized prospective six years clinical study.
      IndiaParallel7223.1 (19, 31)
      Data of both test and control group.
      10 (10)/10 (10)10 (10)/10 (10)NR12
      Giacomel et al (2017)
      • Giacomel M.
      • Camati P.
      • Souza J.
      • Deliberador T.
      Comparison of marginal bone level changes of immediately loaded implants, delayed loaded nonsubmerged implants, and delayed loaded submerged implants: a randomized clinical trial.
      BrazilThree armed947.7 (30, 61)/47.7 (30, 61)15 (15)/15 (30)15 (15)/15 (28)NR12
      L, in mandible; U, in maxilla.
      (1) and (2) mean different comparisons from same trial.
      Data of both test and control group.
      Table 2 shows the methodological characteristics of the selected studies. Nine of 39 articles were split-mouth trials, and 30 studies were parallel studies. Seven of 30 parallel trials had 2 test groups that met the inclusion criteria; therefore, each comparison was regarded independently.
      • Barewal R.M.
      • Stanford C.
      • Weesner T.C.
      A randomized controlled clinical trial comparing the effects of three loading protocols on dental implant stability.
      • Esposito M.
      • Siormpas K.
      • Mitsias M.
      • Bechara S.
      • Trullenque-Eriksson A.
      • Pistilli R.
      Immediate, early (6 weeks) and delayed loading (3 months) of single implants: 4-month post-loading from a multicenter pragmatic randomised controlled trial.
      • Giacomel M.
      • Camati P.
      • Souza J.
      • Deliberador T.
      Comparison of marginal bone level changes of immediately loaded implants, delayed loaded nonsubmerged implants, and delayed loaded submerged implants: a randomized clinical trial.
      • Rieder D.
      • Eggert J.
      • Krafft T.
      • Weber H.-P.
      • Wichmann M.
      • Heckmann S.
      Impact of placement and restoration timing on single-implant esthetic outcome-a randomized clinical trial.
      • Donati M.
      • Scala V.
      • Raimondo R.
      • Speroni S.
      • Testi M.
      • Berglundh T.
      Marginal bone preservation in single-tooth replacement: a 5-year prospective clinical multicenter study.
      • Donati M.
      • Scala V.
      • Billi M.
      • Dino B.
      • Torrisi P.
      • Berglundh T.
      Immediate functional loading of implants in single tooth replacement: a prospective clinical multicenter study.
      • Grandi T.
      • Guazzi P.
      • Samarani R.
      • Tohme H.
      • Khoury S.
      • Sbricoli L.
      • et al.
      Immediate, early (3 weeks) and conventional loading (4 months) of single implants: preliminary data at 1 year after loading from a pragmatic multicenter randomised controlled trial.
      • Margossian P.
      • Mariani P.
      • Stephan G.
      • Margerit J.
      • Jorgensen C.
      Immediate loading of mandibular dental implants in partially edentulous patients: a prospective randomized comparative study.
      This systematic review pooled data from 1868 participants (914 in a test group and 954 in control), and a total of 3746 implants were inserted (1880 in an experimental group and 1866 in control) at baseline. A total of 1785 participants were followed up (864 in the experimental group and 921 in the control group), and 3486 implants (1749 in the experimental group and 1737 in control group) were reported at the end of the trial. The maximum follow-up period was 180 months,
      • Romanos G.E.
      • Aydin E.
      • Locher K.
      • Nentwig G.H.
      Immediate vs. delayed loading in the posterior mandible: a split-mouth study with up to 15 years of follow-up.
      and the minimum was 10 days
      • Vercruyssen M.
      • Cox C.
      • Naert I.
      • Jacobs R.
      • Teughels W.
      • Quirynen M.
      Accuracy and patient-centered outcome variables in guided implant surgery: a RCT comparing immediate with delayed loading.
      Figure 2 depicts the risk of bias for RCTs. Six studies showed a low risk of bias,
      • Cannizzaro G.
      • Leone M.
      • Torchio C.
      • Viola P.
      • Esposito M.
      Immediate versus early loading of 7-mm-long flapless-placed single implants: a split-mouth randomised controlled clinical trial.
      • Cannizzaro G.
      • Leone M.
      • Consolo U.
      • Ferri V.
      • Esposito M.
      Immediate functional loading of implants placed with flapless surgery versus conventional implants in partially edentulous patients: a 3-year randomized controlled clinical trial.
      • Danza M.
      • Tortora P.
      • Quaranta A.
      • Perrotti V.
      • Vozza I.
      • Piattelli A.
      Randomised study for the 1-year crestal bone maintenance around modified diameter implants with different loading protocols: a radiographic evaluation.
      • Cannizzaro G.
      • Felice P.
      • Leone M.
      • Ferri V.
      • Viola P.
      • Esposito M.
      Immediate versus early loading of 6.5 mm-long flapless-placed single implants: a 4-year after loading report of a split-mouth randomised controlled trial.
      • Grandi T.
      • Guazzi P.
      • Samarani R.
      • Tohme H.
      • Khoury S.
      • Sbricoli L.
      • et al.
      Immediate, early (3 weeks) and conventional loading (4 months) of single implants: preliminary data at 1 year after loading from a pragmatic multicenter randomised controlled trial.
      • Alfadda S.A.
      A randomized controlled clinical trial of edentulous patients treated with immediately loaded implant-supported mandibular fixed prostheses.
      • Cannizzaro G.
      • Torchio C.
      • Leone M.
      • Esposito M.
      Immediate versus early loading of flapless-placed implants supporting maxillary full-arch prostheses: a randomised controlled clinical trial.
      8 trials showed medium risk of bias,
      • Degidi D.M.
      • Nardi D.
      • Piattelli A.
      Immediate versus one-stage restoration of small-diameter implants for a single missing maxillary lateral incisor: A 3-year randomized clinical trial.
      • Meloni S.M.
      • De Riu G.
      • Pisano M.
      • De Riu N.
      • Tullio A.
      Immediate versus delayed loading of single mandibular molars. One-year results from a randomised controlled trial.
      • Esposito M.
      • Siormpas K.
      • Mitsias M.
      • Bechara S.
      • Trullenque-Eriksson A.
      • Pistilli R.
      Immediate, early (6 weeks) and delayed loading (3 months) of single implants: 4-month post-loading from a multicenter pragmatic randomised controlled trial.
      • Kokovic V.
      • Jung R.
      • Feloutzis A.
      • Todorovic V.S.
      • Jurisic M.
      • Hämmerle C.H.
      Immediate vs. early loading of SLA implants in the posterior mandible: 5-year results of randomized controlled clinical trial.
      • Den Hartog L.
      • Raghoebar G.M.
      • Stellingsma K.
      • Vissink A.
      • Meijer H.J.A.
      Immediate non-occlusal loading of single implants in the aesthetic zone: A randomized clinical trial.
      • Göthberg C.
      • André U.
      • Gröndahl K.
      • Ljungquist B.
      • Thomsen P.
      • Slotte C.
      Immediately loaded implants with or without abutments supporting fixed partial dentures: 1-year results from a prospective, randomized, clinical trial.
      • Güncü G.N.
      • Tözüm T.F.
      • Güncü M.B.
      • Yamalik N.
      • Tümer C.
      A 12-month evaluation of nitrite oxide metabolism around immediate and conventionally loaded dental implants.
      • Velde T.
      • Sennerby L.
      • Bruyn H.
      The clinical and radiographic outcome of implants placed in the posterior maxilla with a guided flapless approach and immediately restored with a provisional rehabilitation: a randomized clinical trial.
      and the remaining showed high risk of bias. Funnel plots and the Begg test were used to detect publication bias.
      Figure thumbnail gr2
      Figure 2Risk of bias summary for selected randomized controlled trials.
      According to previous systematic reviews, the patient
      • Esposito M.
      • Ardebili Y.
      • Worthington H.V.
      Interventions for replacing missing teeth: different types of dental implants.
      and implant
      • Sanz-Sanchez I.
      • Sanz-Martin I.
      • uero E.
      • Sanz M.
      Clinical efficacy of immediate implant loading protocols compared to conventional loading depending on the type of the restoration: a systematic review.
      are regarded as statistical units in the current meta-analysis. The results of the 2 methods are as follows: for implant as a statistical unit, the mean survival rates were 96.8% in the test and 98.6% in the control group. In 9 of 29 included trials, the survival rate of implants was 100%.
      • Crespi R.
      • Capparé P.
      • Gherlone E.
      • Romanos G.E.
      Immediate versus delayed loading of dental implants placed in fresh extraction sockets in the maxillary esthetic zone: A clinical comparative study.
      • Romanos G.E.
      • Aydin E.
      • Locher K.
      • Nentwig G.H.
      Immediate vs. delayed loading in the posterior mandible: a split-mouth study with up to 15 years of follow-up.
      • Romanos G.E.
      • Nentwig G.H.
      Immediate versus delayed functional loading of implants in the posterior mandible: a 2-year prospective clinical study of 12 consecutive cases.
      • Cannizzaro G.
      • Leone M.
      • Consolo U.
      • Ferri V.
      • Esposito M.
      Immediate functional loading of implants placed with flapless surgery versus conventional implants in partially edentulous patients: a 3-year randomized controlled clinical trial.
      • Degidi D.M.
      • Nardi D.
      • Piattelli A.
      Immediate versus one-stage restoration of small-diameter implants for a single missing maxillary lateral incisor: A 3-year randomized clinical trial.
      • Danza M.
      • Tortora P.
      • Quaranta A.
      • Perrotti V.
      • Vozza I.
      • Piattelli A.
      Randomised study for the 1-year crestal bone maintenance around modified diameter implants with different loading protocols: a radiographic evaluation.
      • Meloni S.M.
      • De Riu G.
      • Pisano M.
      • De Riu N.
      • Tullio A.
      Immediate versus delayed loading of single mandibular molars. One-year results from a randomised controlled trial.
      • Esposito M.
      • Siormpas K.
      • Mitsias M.
      • Bechara S.
      • Trullenque-Eriksson A.
      • Pistilli R.
      Immediate, early (6 weeks) and delayed loading (3 months) of single implants: 4-month post-loading from a multicenter pragmatic randomised controlled trial.
      • Chidagam P.
      • Gande V.
      • Yadlapalli S.
      • Venkata R.
      • Kondaka S.
      • Chedalawada S.
      Immediate versus delayed loading of implant for replacement of missing mandibular first molar: a randomized prospective six years clinical study.
      • Margossian P.
      • Mariani P.
      • Stephan G.
      • Margerit J.
      • Jorgensen C.
      Immediate loading of mandibular dental implants in partially edentulous patients: a prospective randomized comparative study.
      The results from the meta-analyses of the remaining 20 studies are reported in Figure 3. The meta-analysis resulted in a statistically significant lower survival rate for the test (immediate loading) group compared with that for the conventional group (RR=0.974; 95% CI, 0.954, 0.994; P=.012). No publication bias was detected by the Begg test (P=.261; Fig. 4). In the subgroup analyses, a lower survival rate was shown in the immediately loaded implants than in conventional loading in regard to the following: nonsubmerged technique (RR=0.969; 95% CI, 0.946, 0.994; P=.013), delayed implant (RR=0.974; 95% CI, 0.953, 0.996; P=.020), occlusal contact (RR=0.969; 95% CI, 0.947, 0.992; P=.009), single missing tooth (RR=0.958; 95% CI, 0.921, 0.998; P=.038), several missing teeth (RR=0.955; 95% CI, 0.920, 0.991; P=.015), surgical guide stent (RR=0.953; 95% CI, 0.920, 0.988; P=.009), operative area not only restricted in the maxillary nonmolar or mandibular posterior region (RR=0.972; 95% CI, 0.951, 0.995; P=.015), flap operations in both groups (RR=0.972; 95% CI, 0.950, 0.994; P=.015), and interim prostheses used for immediate loading while definitive restorations placed in the control group (RR=0.966; 95% CI, 0.943, 0.991; P=.007) (Table 3).
      Figure thumbnail gr3
      Figure 3Forest plot of implant survival rate compared with delayed loading, for implant as statistical unit.
      Figure thumbnail gr4
      Figure 4Funnel plot illustrating meta-analysis of implant survival rate compared with delayed loading, for implant as statistical unit.
      Table 3Results of meta-analyses on implant survival rate compared with delayed loading, for implant as statistical unit
      VariableSubgroupN (Excluded)
      Excluded: number of studies with 100% implant survival rates in both groups.
      RR95% CIPHeterogeneity PHeterogeneity I2 (%)
      Overall20 (9)0.9740.954, 0.994.012.5350.0
      Healing methodSubmerged7 (5)0.9840.946, 1.023.405.6270.0
      Nonsubmerged13 (3)0.9690.946, 0.994.013.31413.0
      Both0 (1)
      Implant timeDelay16 (7)0.9740.953, 0.996.020.4650.0
      Immediate3 (1)0.9900.930, 1.055.761.5710.0
      Both1 (1)0.9150.817, 1.026.129
      OcclusionOcclusion12 (5)0.9690.947, 0.992.009.26318.4
      Nonocclusion4 (3)0.9620.904, 1.024.225.5690.0
      NR4 (1)<.0010.946, 1.057<.001.6190.0
      Missing teethSingle13 (4)0.9580.921, 0.998.038.8260.0
      Several3 (2)0.9550.920, 0.991.015.5110.0
      Full3 (0)1.0100.980, 1.040.532.8810.0
      Any1 (3)<.0010.936, 1.069<.001
      Surgery guideGuide8 (5)0.9530.920, 0.988.009.32313.6
      Free hand12 (4)0.9850.960, 1.010.237.680.0
      Tooth positionMaxillary nonmolar region4 (2)0.9510.877, 1.031.221.34110.5
      Mandibular posterior6 (3)0.9930.938, 1.050.801.7640.0
      Other10 (4)0.9720.951, 0.995.015.22823.4
      Surgery: test/controlFlap/flap17 (8)0.9720.950, 0.994.015.6640.0
      Flapless/flapless2 (0)0.9570.885, 1.035.276.06770.1
      Flapless/flap0 (0)
      NR1 (0)1.0200.961, 1.082.522
      First restorations: test/controlProvisional/definitive13 (5)0.9660.943, 0.991.007.28116.1
      Provisional/provisional4 (4)0.9670.922, 1.013.160.9200.0
      Definitive/definitive1 (0)1.0200.961, 1.082.522
      Unclear2 (0)1.0690.941, 1.214.306<.0010.0
      Bold text indicates statistically significant differences.
      Excluded: number of studies with 100% implant survival rates in both groups.
      For patient as a statistical unit, the mean survival rate was 95.0% in the test group and 97.3% in the control group. Of the 27 included studies, there was no implant failure in 8 studies.
      • Crespi R.
      • Capparé P.
      • Gherlone E.
      • Romanos G.E.
      Immediate versus delayed loading of dental implants placed in fresh extraction sockets in the maxillary esthetic zone: A clinical comparative study.
      • Romanos G.E.
      • Aydin E.
      • Locher K.
      • Nentwig G.H.
      Immediate vs. delayed loading in the posterior mandible: a split-mouth study with up to 15 years of follow-up.
      • Romanos G.E.
      • Nentwig G.H.
      Immediate versus delayed functional loading of implants in the posterior mandible: a 2-year prospective clinical study of 12 consecutive cases.
      • Cannizzaro G.
      • Leone M.
      • Consolo U.
      • Ferri V.
      • Esposito M.
      Immediate functional loading of implants placed with flapless surgery versus conventional implants in partially edentulous patients: a 3-year randomized controlled clinical trial.
      • Degidi D.M.
      • Nardi D.
      • Piattelli A.
      Immediate versus one-stage restoration of small-diameter implants for a single missing maxillary lateral incisor: A 3-year randomized clinical trial.
      • Danza M.
      • Tortora P.
      • Quaranta A.
      • Perrotti V.
      • Vozza I.
      • Piattelli A.
      Randomised study for the 1-year crestal bone maintenance around modified diameter implants with different loading protocols: a radiographic evaluation.
      • Meloni S.M.
      • De Riu G.
      • Pisano M.
      • De Riu N.
      • Tullio A.
      Immediate versus delayed loading of single mandibular molars. One-year results from a randomised controlled trial.
      • Esposito M.
      • Siormpas K.
      • Mitsias M.
      • Bechara S.
      • Trullenque-Eriksson A.
      • Pistilli R.
      Immediate, early (6 weeks) and delayed loading (3 months) of single implants: 4-month post-loading from a multicenter pragmatic randomised controlled trial.
      • Chidagam P.
      • Gande V.
      • Yadlapalli S.
      • Venkata R.
      • Kondaka S.
      • Chedalawada S.
      Immediate versus delayed loading of implant for replacement of missing mandibular first molar: a randomized prospective six years clinical study.
      • Margossian P.
      • Mariani P.
      • Stephan G.
      • Margerit J.
      • Jorgensen C.
      Immediate loading of mandibular dental implants in partially edentulous patients: a prospective randomized comparative study.
      The overall effect of the meta-analyses showed a higher rate of implant failure in the test group but without a statistically significant difference (RR=0.963; 95% CI, 0.927, 1.001; P=.059) (Fig. 5). No publication bias was detected by the Begg test (P=.780; Fig. 6). The subgroup analyses resulted in a higher rate of failure for immediate loading implants than for conventional loading implants in regard to the following conditions: a nonsubmerged technique was used (RR=0.951; 95% CI, 0.907, 0.997; P=.037), several missing teeth (RR=0.903; 95% CI, 0.820, 0.993; P=.036), surgical guide used (RR=0.921; 95% CI, 0.864, 0.983; P=.014), and interim prostheses used for immediate loading while definitive restorations were placed in the control group (RR=0.949; 95% CI, 0.905, 0.995; P=.030). In the immediately loaded group, a relatively higher failure rate was identified for delayed implant (RR=0.958; 95% CI, 0.913, 1.005; P=.081), occlusal contact (RR=0.948; 95% CI, 0.897, 1.003; P=.064), single missing tooth (RR=0.957; 95% CI, 0.911, 1.006; P=.087), operative area not only restricted in the maxillary nonmolar or mandibular posterior region (RR=0.949; 95% CI, 0.896, 1.004; P=.070), and flap operations in both groups (RR=0.961; 95% CI, 0.922, 1.001; P=.058), without statistically significant differences (P>.05) (Table 4).
      Figure thumbnail gr5
      Figure 5Forest plot of implant survival rate compared with delayed loading, for patient as statistical unit.
      Figure thumbnail gr6
      Figure 6Funnel plot illustrating meta-analysis of implant survival rate compared with delayed loading, for patient as statistical unit.
      Table 4Results of meta-analyses on implant survival rate compared with delayed loading, for patient as statistical unit
      SubgroupN (Excluded)
      Excluded: number of studies with 100% implant survival rates in both groups.
      RR95% CIPHeterogeneity PHeterogeneity I2 (%)
      Overall19 (8)0.9630.927, 1.001.059.6730.0
      Healing methodSubmerged6 (4)0.9910.927, 1.059.793.7290.0
      Nonsubmerged13 (3)0.9510.907, 0.997.037.4580.0
      Both0 (1)
      Implant timeDelay15 (6)0.9580.913, 1.005.081.6780.0
      Immediate3 (1)<.0010.925, 1.081.995.4910.0
      Both1 (1)0.9150.817, 1.026.129
      OcclusionOcclusion11 (4)0.9480.897, 1.003.064.4222.1
      Nonocclusion4 (3)0.9620.904, 1.024.225.5690.0
      NR4 (1)1.0050.919, 1.100.907.6230.0
      Missing teethSingle12 (4)0.9570.911, 1.006.087.7600.0
      Several3 (2)0.9030.820, 0.993.036.5150.0
      Full3 (0)1.0530.941, 1.180.367.8820.0
      Any1 (2)1.0310.934, 1.138.542
      Surgery guideGuide8 (4)0.9210.864, 0.983.014.5460.0
      Free hand11 (4)0.9900.943, 1.038.669.7670.0
      Tooth positionMaxillary nonmolar region4 (2)0.9510.877, 1.031.221.34110.5
      Mandibular posterior6 (3)1.0010.936, 1.071.972.7110.0
      Other9 (3)0.9490.896, 1.004.070.5500.0
      Surgery: test/controlFlap/flap16 (7)0.9610.922, 1.001.058.7860.0
      Flapless/flapless2 (0)0.9570.856, 1.071.448.04974.2
      Flapless/flap0 (0)
      NR1 (0)1.1250.799, 1.585.500
      First restorations: test/controlProvisional/definitive12 (5)0.9490.905, 0.995.030.4093.6
      Provisional/provisional4 (3)0.9580.885, 1.037.288.8770.0
      Definitive/definitive1 (0)1.1250.799, 1.585.500
      Unclear2 (0)1.0690.941, 1.214.306<.0010.0
      Bold text indicates statistically significant differences.
      Excluded: number of studies with 100% implant survival rates in both groups.
      The change of crestal bone level was reported in all except 5 trials.
      • Cannizzaro G.
      • Leone M.
      • Consolo U.
      • Ferri V.
      • Esposito M.
      Immediate functional loading of implants placed with flapless surgery versus conventional implants in partially edentulous patients: a 3-year randomized controlled clinical trial.
      • Esposito M.
      • Siormpas K.
      • Mitsias M.
      • Bechara S.
      • Trullenque-Eriksson A.
      • Pistilli R.
      Immediate, early (6 weeks) and delayed loading (3 months) of single implants: 4-month post-loading from a multicenter pragmatic randomised controlled trial.
      • Vercruyssen M.
      • Cox C.
      • Naert I.
      • Jacobs R.
      • Teughels W.
      • Quirynen M.
      Accuracy and patient-centered outcome variables in guided implant surgery: a RCT comparing immediate with delayed loading.
      • Güncü G.N.
      • Tözüm T.F.
      • Güncü M.B.
      • Yamalik N.
      • Tümer C.
      A 12-month evaluation of nitrite oxide metabolism around immediate and conventionally loaded dental implants.
      • Oh T.J.
      • Shotwell J.L.
      • Billy E.J.
      • Wang H.L.
      Effect of flapless implant surgery on soft tissue profile: a randomized controlled clinical trial.
      Most investigations used periapical radiographs except 1 using panoramic radiographs. To avoid high heterogeneity among studies, studies that used periapical radiographs to evaluate the crestal bone were combined in the independent meta-analyses. The loss of marginal bone level ranged from −1.32 mm (loss) to 0 mm in the test group and from −1.25 mm to −0.10 mm in the control group. The result shows no statistically significant differences in the crestal bone loss between the test and control groups (WMD=0.016; 95% CI, −0.052, 0.084; P=.645) when the data at all sites of implants were combined (Fig. 7). For any of the subgroup analyses, no statistically significant differences were found between groups, except in trials with occlusal contact (WMD=0.083; 95% CI, 0.003, 0.163; P=.043) and flapless operations in both groups (WMD=−0.3; 95% CI, −0.489, −0.111; P=.002), despite the high heterogeneity within some items (Table 5). For the study evaluating the change of marginal bone with panoramic radiography,
      • Romanos G.E.
      • Aydin E.
      • Locher K.
      • Nentwig G.H.
      Immediate vs. delayed loading in the posterior mandible: a split-mouth study with up to 15 years of follow-up.
      • Romanos G.E.
      • Nentwig G.H.
      Immediate versus delayed functional loading of implants in the posterior mandible: a 2-year prospective clinical study of 12 consecutive cases.
      the differences in crestal bone loss between the 2 groups were not statistically significant (P>.05).
      Figure thumbnail gr7
      Figure 7Forest plot of marginal bone level change compared with delayed loading.
      Table 5Results of meta-analyses on marginal bone level change compared with delayed loading
      SubgroupNWMD95% CIPHeterogeneity PHeterogeneity I2 (%)
      Overall170.016-0.052, 0.084.645.07435.5
      Healing methodSubmerged6-0.050-0.208, 0.109.540.07450.3
      Nonsubmerged110.048-0.011, 0.107.111.4222.1
      Implant timeDelay12-0.002-0.090, 0.086.965.02549.8
      Immediate30.111-0.017, 0.238.091.9760.0
      Mixed2-0.019-0.240, 0.203.869.6070.0
      OcclusionOcclusion70.0830.003, 0.163.043.24424.3
      Nonocclusion6-0.063-0.215, 0.09.420.12242.4
      NR4-0.051-0.155, 0.054.343.9380.0
      Missing teethSingle110.022-0.079, 0.122.672.02052.8
      Several20.066-0.051, 0.183.269.5850.0
      Full2-0.080-0.260, 0.100.382.8770.0
      Any20.084-0.082, 0.250.320.4310.0
      Surgery guideGuide60.023-0.136, 0.181.779.00471.4
      Free hand110.013-0.056, 0.081.721.6980.0
      Tooth positionMaxillary nonmolar region5-0.039-0.255, 0.177.725.04459.2
      Mandibular posterior50.099-0.048, 0.246.185.05756.4
      Other70.022-0.044, 0.089.514.8660.0
      Surgery: test/controlFlap/flap160.036-0.014, 0.087.156.5660.0
      Flapless/flapless1-0.300-0.489, -0.111.002
      First restorations: test/controlProvisional/definitive110.026-0.032, 0.084.384.01853.6
      Provisional/provisional50.024-0.098, 0.147.695.7270.0
      Unclear1-0.050-0.175, 0.075.435
      Bold text indicates statistically significant differences.
      Implant stability was assessed using 2 methods: the implant stability quotient (ISQ) measured by resonance frequency analysis (RFA) with the Osstell device (Integration Diagnostics Ltd) and the implant Periotest (Siemens AG) value (PTV) with the periotest device. The Osstell was used in 7 trials. The data were reported as Figures in 2 studies,
      • Barewal R.M.
      • Stanford C.
      • Weesner T.C.
      A randomized controlled clinical trial comparing the effects of three loading protocols on dental implant stability.
      • Göthberg C.
      • André U.
      • Gröndahl K.
      • Ljungquist B.
      • Thomsen P.
      • Slotte C.
      Immediately loaded implants with or without abutments supporting fixed partial dentures: 1-year results from a prospective, randomized, clinical trial.
      whereas 1 reported the minimum and maximum values.
      • Hall J.A.G.
      • Payne A.G.T.
      • Purton D.G.
      • Torr B.
      A randomized controlled clinical trial of conventional and immediately loaded tapered implants with screw-retained crowns.
      • Hall J.A.G.
      • Payne A.G.T.
      • Purton D.G.
      • Torr B.
      • Duncan W.J.
      • De Silva R.K.
      Immediately restored, single-tapered implants in the anterior maxilla: Prosthodontic and aesthetic outcomes after 1 year.
      The remaining 4 studies presented the mean and standard deviation. However, 1 of them did not show the sample size.
      • Margossian P.
      • Mariani P.
      • Stephan G.
      • Margerit J.
      • Jorgensen C.
      Immediate loading of mandibular dental implants in partially edentulous patients: a prospective randomized comparative study.
      Based on the last 3 studies,
      • Cannizzaro G.
      • Leone M.
      • Consolo U.
      • Ferri V.
      • Esposito M.
      Immediate functional loading of implants placed with flapless surgery versus conventional implants in partially edentulous patients: a 3-year randomized controlled clinical trial.
      • Degidi D.M.
      • Nardi D.
      • Piattelli A.
      Immediate versus one-stage restoration of small-diameter implants for a single missing maxillary lateral incisor: A 3-year randomized clinical trial.
      • Güncü M.B.
      • Aslan Y.
      • Tümer C.
      • Güncü G.N.
      • Uysal S.
      In-patient comparison of immediate and conventional loaded implants in mandibular molar sites within 12 months.
      the ISQ ranged between 69.4 and 77.1 in the test group and between 69.8 and 78.6 in the control group. Regarding the result of the meta-analysis, there was no statistically significant difference (WMD=−0.436; 95% CI, −1.469, 0.598; P=.409).
      In the 3 studies reporting PTV,
      • Romanos G.E.
      • Aydin E.
      • Locher K.
      • Nentwig G.H.
      Immediate vs. delayed loading in the posterior mandible: a split-mouth study with up to 15 years of follow-up.
      • Romanos G.E.
      • Nentwig G.H.
      Immediate versus delayed functional loading of implants in the posterior mandible: a 2-year prospective clinical study of 12 consecutive cases.
      • Cannizzaro G.
      • Leone M.
      • Consolo U.
      • Ferri V.
      • Esposito M.
      Immediate functional loading of implants placed with flapless surgery versus conventional implants in partially edentulous patients: a 3-year randomized controlled clinical trial.
      • Chidagam P.
      • Gande V.
      • Yadlapalli S.
      • Venkata R.
      • Kondaka S.
      • Chedalawada S.
      Immediate versus delayed loading of implant for replacement of missing mandibular first molar: a randomized prospective six years clinical study.
      the mean ranged between −1.8 and 4.07 in the test group and between −1.3 and 4.0 in control. The meta-analysis found insufficient evidence to determine whether there was a difference between immediate and delayed loading (WMD=−0.233; 95% CI, −0.707, 0.241; P=.335).
      Gingival inflammation was reported in 12 studies, and 5 indexes were used. The percentage of sites with positive bleeding on probing (BOP [%]) was reported in 5 studies. However, in 1 study,
      • Donati M.
      • Scala V.
      • Raimondo R.
      • Speroni S.
      • Testi M.
      • Berglundh T.
      Marginal bone preservation in single-tooth replacement: a 5-year prospective clinical multicenter study.
      • Donati M.
      • Scala V.
      • Billi M.
      • Dino B.
      • Torrisi P.
      • Berglundh T.
      Immediate functional loading of implants in single tooth replacement: a prospective clinical multicenter study.
      the author without exact data stated there was no significant statistical difference between the 2 groups. In the remaining 4 trials,
      • Degidi D.M.
      • Nardi D.
      • Piattelli A.
      Immediate versus one-stage restoration of small-diameter implants for a single missing maxillary lateral incisor: A 3-year randomized clinical trial.
      • Danza M.
      • Tortora P.
      • Quaranta A.
      • Perrotti V.
      • Vozza I.
      • Piattelli A.
      Randomised study for the 1-year crestal bone maintenance around modified diameter implants with different loading protocols: a radiographic evaluation.
      • Chidagam P.
      • Gande V.
      • Yadlapalli S.
      • Venkata R.
      • Kondaka S.
      • Chedalawada S.
      Immediate versus delayed loading of implant for replacement of missing mandibular first molar: a randomized prospective six years clinical study.
      • Rouck T.
      • Collys K.
      • Wyn I.
      • Cosyn J.
      Instant provisionalization of immediate single-tooth implants is essential to optimize esthetic treatment outcome.
      BOP (%) varied from 0% to 40% in the test group and 0% to 36% in the control group. Modified sulcus bleeding index (mBI)
      • Mombelli A.
      • van Oosten M.A.
      • Schurch Jr., E.
      • Land N.P.
      The microbiota associated with successful or failing osseointegrated titanium implants.
      was presented in 4 trials. One
      • Hall J.A.G.
      • Payne A.G.T.
      • Purton D.G.
      • Torr B.
      A randomized controlled clinical trial of conventional and immediately loaded tapered implants with screw-retained crowns.
      • Hall J.A.G.
      • Payne A.G.T.
      • Purton D.G.
      • Torr B.
      • Duncan W.J.
      • De Silva R.K.
      Immediately restored, single-tapered implants in the anterior maxilla: Prosthodontic and aesthetic outcomes after 1 year.
      reported the change of mBI, and no significant statistical difference was shown in the Student t test (P>.05). In the other 3 studies,
      • Meloni S.M.
      • De Riu G.
      • Pisano M.
      • De Riu N.
      • Tullio A.
      Immediate versus delayed loading of single mandibular molars. One-year results from a randomised controlled trial.
      • Den Hartog L.
      • Raghoebar G.M.
      • Stellingsma K.
      • Vissink A.
      • Meijer H.J.A.
      Immediate non-occlusal loading of single implants in the aesthetic zone: A randomized clinical trial.
      • Oh T.J.
      • Shotwell J.L.
      • Billy E.J.
      • Wang H.L.
      Effect of flapless implant surgery on soft tissue profile: a randomized controlled clinical trial.
      the mean of mBI varied from 0.5 to 1.3 and from 0.67 to 1.4 in the test and control groups, respectively. Gingival index (GI)
      • Loe H.
      • Silness J.
      Periodontal disease in pregnancy. I. Prevalence and severity.
      was used in 2 studies.
      • Güncü G.N.
      • Tözüm T.F.
      • Güncü M.B.
      • Yamalik N.
      • Tümer C.
      A 12-month evaluation of nitrite oxide metabolism around immediate and conventionally loaded dental implants.
      • Güncü M.B.
      • Aslan Y.
      • Tümer C.
      • Güncü G.N.
      • Uysal S.
      In-patient comparison of immediate and conventional loaded implants in mandibular molar sites within 12 months.
      The GI ranged from 0.29 to 0.32 in the test group and from 0.25 to 0.29 in the other group. For these 3 indexes, the result of the meta-analyses showed insufficient evidence to determine whether statistically significant differences existed.
      For 2 studies reporting gingival bleeding time index (GBTI),
      • Nowicki D.
      • Vogel R.I.
      • Melcer S.
      • Deasy M.J.
      The gingival bleeding time index.
      no meta-analysis was performed because the mean of 1 study
      • Güncü M.B.
      • Aslan Y.
      • Tümer C.
      • Güncü G.N.
      • Uysal S.
      In-patient comparison of immediate and conventional loaded implants in mandibular molar sites within 12 months.
      was 0 in both groups. However, the other study
      • Güncü G.N.
      • Tözüm T.F.
      • Güncü M.B.
      • Yamalik N.
      • Tümer C.
      A 12-month evaluation of nitrite oxide metabolism around immediate and conventionally loaded dental implants.
      presented GBTI with a decreasing trend, reaching their lowest values at 12 months in both groups. Sulcus bleeding index (SBI)
      • Muhlemann H.R.
      • Son S.
      Gingival sulcus bleeding--a leading symptom in initial gingivitis.
      was used in only 1 trial.
      • Güncü M.B.
      • Aslan Y.
      • Tümer C.
      • Güncü G.N.
      • Uysal S.
      In-patient comparison of immediate and conventional loaded implants in mandibular molar sites within 12 months.
      No statistically significant difference was found between the test and control subjects (P>.05).
      For peri-implant gingival level, change in papilla, free gingiva, and keratinized mucosa were reported. For the height of papilla, 5 trials use the papilla index (PPI).
      • Jemt T.
      Regeneration of gingival papillae after single-implant treatment.
      Three of them reported the mean, standard deviation, and sample size in both groups.
      • Shibly O.
      • Patel N.
      • Albandar J.M.
      • Kutkut A.
      Bone regeneration around implants in periodontally compromised patients: a randomized clinical trial of the effect of immediate implant with immediate loading.
      • Shibly O.
      • Kutkut A.
      • Patel N.
      • Albandar J.M.
      Immediate implants with immediate loading vs. conventional loading: 1-year randomized clinical trial.
      • Den Hartog L.
      • Raghoebar G.M.
      • Stellingsma K.
      • Vissink A.
      • Meijer H.J.A.
      Immediate non-occlusal loading of single implants in the aesthetic zone: A randomized clinical trial.
      • Oh T.J.
      • Shotwell J.L.
      • Billy E.J.
      • Wang H.L.
      Effect of flapless implant surgery on soft tissue profile: a randomized controlled clinical trial.
      The meta-analysis, with low heterogeneity (P=.751, I2=0.0%), presents insufficient evidence of statistically significant differences between the 2 groups (WMD=0.061; 95% CI, −0.169, 0.292; P=.602). One publication recorded the Jemt-index frequency,
      • Degidi D.M.
      • Nardi D.
      • Piattelli A.
      Immediate versus one-stage restoration of small-diameter implants for a single missing maxillary lateral incisor: A 3-year randomized clinical trial.
      and there was no statistically significant difference (P>.05) for the 2 procedures. One
      • Hall J.A.G.
      • Payne A.G.T.
      • Purton D.G.
      • Torr B.
      A randomized controlled clinical trial of conventional and immediately loaded tapered implants with screw-retained crowns.
      • Hall J.A.G.
      • Payne A.G.T.
      • Purton D.G.
      • Torr B.
      • Duncan W.J.
      • De Silva R.K.
      Immediately restored, single-tapered implants in the anterior maxilla: Prosthodontic and aesthetic outcomes after 1 year.
      reported that papilla index at all sites, both groups combined, either remained unchanged (28.5%) or improved (63%). The other 3 studies use the height of interproximal papillae. However, 1 investigation
      • Donati M.
      • Scala V.
      • Raimondo R.
      • Speroni S.
      • Testi M.
      • Berglundh T.
      Marginal bone preservation in single-tooth replacement: a 5-year prospective clinical multicenter study.
      • Donati M.
      • Scala V.
      • Billi M.
      • Dino B.
      • Torrisi P.
      • Berglundh T.
      Immediate functional loading of implants in single tooth replacement: a prospective clinical multicenter study.
      did not report the sample size, and the meta-analysis result of the remaining 2
      • Den Hartog L.
      • Raghoebar G.M.
      • Stellingsma K.
      • Vissink A.
      • Meijer H.J.A.
      Immediate non-occlusal loading of single implants in the aesthetic zone: A randomized clinical trial.
      • Rouck T.
      • Collys K.
      • Wyn I.
      • Cosyn J.
      Instant provisionalization of immediate single-tooth implants is essential to optimize esthetic treatment outcome.
      showed insufficient evidence to determine the difference between the test and control procedure (WMD=0.078; 95% CI, −0.115, 0.271; P=.429).
      Regarding free gingiva change, which was reported in 5 included studies, 3 investigations showed the recession of the mid-buccal site,
      • Den Hartog L.
      • Raghoebar G.M.
      • Stellingsma K.
      • Vissink A.
      • Meijer H.J.A.
      Immediate non-occlusal loading of single implants in the aesthetic zone: A randomized clinical trial.
      • Hall J.A.G.
      • Payne A.G.T.
      • Purton D.G.
      • Torr B.
      A randomized controlled clinical trial of conventional and immediately loaded tapered implants with screw-retained crowns.
      • Hall J.A.G.
      • Payne A.G.T.
      • Purton D.G.
      • Torr B.
      • Duncan W.J.
      • De Silva R.K.
      Immediately restored, single-tapered implants in the anterior maxilla: Prosthodontic and aesthetic outcomes after 1 year.
      • Rouck T.
      • Collys K.
      • Wyn I.
      • Cosyn J.
      Instant provisionalization of immediate single-tooth implants is essential to optimize esthetic treatment outcome.
      the change ranging from −0.67 mm to 0.06 mm in the test group and from −1.16 mm to −0.09 mm in the control. The meta-analysis, with high heterogeneity among trials, showed insufficient evidence with a statistically significant difference (WMD=0.204; 95% CI, −0.297, 0.704; P=.425). The other 2 studies measured the gingival recession from the crown margin to the gingival margin,
      • Romanos G.E.
      • Aydin E.
      • Locher K.
      • Nentwig G.H.
      Immediate vs. delayed loading in the posterior mandible: a split-mouth study with up to 15 years of follow-up.
      • Romanos G.E.
      • Nentwig G.H.
      Immediate versus delayed functional loading of implants in the posterior mandible: a 2-year prospective clinical study of 12 consecutive cases.
      with a reference line connecting the highest free gingival margins of adjacent dentition.
      • Oh T.J.
      • Shotwell J.L.
      • Billy E.J.
      • Wang H.L.
      Effect of flapless implant surgery on soft tissue profile: a randomized controlled clinical trial.
      Evidence of a statistically significant difference was lacking between the test and control participants regarding gingival recession (P>.05).
      For assessing the width of the keratinized mucosa (WKM), 2 studies registered the data of the last visit.
      • Romanos G.E.
      • Aydin E.
      • Locher K.
      • Nentwig G.H.
      Immediate vs. delayed loading in the posterior mandible: a split-mouth study with up to 15 years of follow-up.
      • Romanos G.E.
      • Nentwig G.H.
      Immediate versus delayed functional loading of implants in the posterior mandible: a 2-year prospective clinical study of 12 consecutive cases.
      • Oh T.J.
      • Shotwell J.L.
      • Billy E.J.
      • Wang H.L.
      Effect of flapless implant surgery on soft tissue profile: a randomized controlled clinical trial.
      The meta-analysis results found insufficient evidence to determine whether there was a statistically significant difference between the test and control groups (WMD=−0.186; 95% CI, −0.750, 0.387; P=.517), and 1 study reported the alteration from baseline to 1-year recall.
      • Hall J.A.G.
      • Payne A.G.T.
      • Purton D.G.
      • Torr B.
      A randomized controlled clinical trial of conventional and immediately loaded tapered implants with screw-retained crowns.
      • Hall J.A.G.
      • Payne A.G.T.
      • Purton D.G.
      • Torr B.
      • Duncan W.J.
      • De Silva R.K.
      Immediately restored, single-tapered implants in the anterior maxilla: Prosthodontic and aesthetic outcomes after 1 year.
      The mean ±standard deviation loss from definitive crown placement to 1 year was 0.83 ±1.59 mm and 1.08 ±1.31 mm for the immediate and conventional groups, respectively. There was no statistically significant difference between the 2 groups.
      Probing depth (PD) was measured in 11 investigations. One,
      • Hall J.A.G.
      • Payne A.G.T.
      • Purton D.G.
      • Torr B.
      A randomized controlled clinical trial of conventional and immediately loaded tapered implants with screw-retained crowns.
      • Hall J.A.G.
      • Payne A.G.T.
      • Purton D.G.
      • Torr B.
      • Duncan W.J.
      • De Silva R.K.
      Immediately restored, single-tapered implants in the anterior maxilla: Prosthodontic and aesthetic outcomes after 1 year.
      conducted by the same authors, reported the changes of PD in the 2 loading groups, from 4 weeks after definitive crown placement to 1 year, which showed no significant statistical difference. The other 10 studies evaluated the PD on the last visit
      • Romanos G.E.
      • Aydin E.
      • Locher K.
      • Nentwig G.H.
      Immediate vs. delayed loading in the posterior mandible: a split-mouth study with up to 15 years of follow-up.
      • Romanos G.E.
      • Nentwig G.H.
      Immediate versus delayed functional loading of implants in the posterior mandible: a 2-year prospective clinical study of 12 consecutive cases.
      • Degidi D.M.
      • Nardi D.
      • Piattelli A.
      Immediate versus one-stage restoration of small-diameter implants for a single missing maxillary lateral incisor: A 3-year randomized clinical trial.
      • Danza M.
      • Tortora P.
      • Quaranta A.
      • Perrotti V.
      • Vozza I.
      • Piattelli A.
      Randomised study for the 1-year crestal bone maintenance around modified diameter implants with different loading protocols: a radiographic evaluation.
      • Meloni S.M.
      • De Riu G.
      • Pisano M.
      • De Riu N.
      • Tullio A.
      Immediate versus delayed loading of single mandibular molars. One-year results from a randomised controlled trial.
      • Chidagam P.
      • Gande V.
      • Yadlapalli S.
      • Venkata R.
      • Kondaka S.
      • Chedalawada S.
      Immediate versus delayed loading of implant for replacement of missing mandibular first molar: a randomized prospective six years clinical study.
      • Den Hartog L.
      • Raghoebar G.M.
      • Stellingsma K.
      • Vissink A.
      • Meijer H.J.A.
      Immediate non-occlusal loading of single implants in the aesthetic zone: A randomized clinical trial.
      • Güncü G.N.
      • Tözüm T.F.
      • Güncü M.B.
      • Yamalik N.
      • Tümer C.
      A 12-month evaluation of nitrite oxide metabolism around immediate and conventionally loaded dental implants.
      • Oh T.J.
      • Shotwell J.L.
      • Billy E.J.
      • Wang H.L.
      Effect of flapless implant surgery on soft tissue profile: a randomized controlled clinical trial.
      • Güncü M.B.
      • Aslan Y.
      • Tümer C.
      • Güncü G.N.
      • Uysal S.
      In-patient comparison of immediate and conventional loaded implants in mandibular molar sites within 12 months.
      • Rouck T.
      • Collys K.
      • Wyn I.
      • Cosyn J.
      Instant provisionalization of immediate single-tooth implants is essential to optimize esthetic treatment outcome.
      and reported data as mean, standard deviation, and sample size. The meta-analysis showed no significant statistical difference in PD when comparing immediate with conventional loading technique (WMD=−0.004; 95% CI, −0.123, 0.115; P=.944; Fig. 8). In the analysis of subgroup, despite high heterogeneity shown in some items (nonocclusion, freehand, maxillary nonmolar region), a statistically significant difference was not found in any subgroup comparison (Table 6).
      Figure thumbnail gr8
      Figure 8Forest plot of probing depth compared with delayed loading.
      Table 6Results of meta-analyses on probing depth compared with delayed loading
      VariableSubgroupNWMD95% CIPHeterogeneity PHeterogeneity I2 (%)
      Overall10-0.004-0.123, 0.115.944.22823.4
      Healing methodSubmerged50.047-0.102, 0.196.540.3765.4
      Nonsubmerged5-0.094-0.291, 0.104.352.17936.4
      Implant timeDelay9-0.054-0.182, 0.073.406.5120.0
      Immediate10.330-0<.001, 0.660.050
      OcclusionOcclusion6-0.029-0.196, 0.138.733.6050.0
      Nonocclusion40.021-0.148, 0.191.805.04762.3
      Missing teethSingle80.022-0.116, 0.159.758.13037.5
      Several1-0.070-0.358, 0.218.634
      Any1-0.100-0.509, 0.309.632
      Surgery guideGuide5-0.092-0.271, 0.088.316.7650.0
      Free hand50.064-0.094, 0.223.427.08251.7
      Tooth positionMaxillary nonmolar region4-0.052-0.263, 0.158.625.02069.6
      Mandibular posterior50.035-0.119, 0.189.655.8740.0
      Posterior1-0.100-0.509, 0.309.632
      Surgery: test/controlFlap/flap90.011-0.109, 0.132.854.30615.3
      Flapless/flapless1-0.550-1.264, 0.164.131
      First restorations: test/controlProvisional/definitive60.104-0.052, 0.260.192.34610.8
      Provisional/provisional4-0.155-0.339, 0.029.099.6330.0
      The presence of plaque was reported in 7 trials. Three different indexes were used to assess the plaque accumulation: plaque index (PI),
      • Silness J.
      • Loe H.
      Periodontal disease in pregnancy. II. Correlation between oral hygiene and periodontal condition.
      modified plaque index (mPI),
      • Mombelli A.
      • van Oosten M.A.
      • Schurch Jr., E.
      • Land N.P.
      The microbiota associated with successful or failing osseointegrated titanium implants.
      and frequencies of the site with a plaque. Meta-analyses were performed for the studies by using the same indexes but without subgroup analysis being performed. For the PI, the mean change was 0.38 to 0.57 in the test group and 0.29 to 0.43 in the control group.
      • Romanos G.E.
      • Aydin E.
      • Locher K.
      • Nentwig G.H.
      Immediate vs. delayed loading in the posterior mandible: a split-mouth study with up to 15 years of follow-up.
      • Romanos G.E.
      • Nentwig G.H.
      Immediate versus delayed functional loading of implants in the posterior mandible: a 2-year prospective clinical study of 12 consecutive cases.
      • Güncü G.N.
      • Tözüm T.F.
      • Güncü M.B.
      • Yamalik N.
      • Tümer C.
      A 12-month evaluation of nitrite oxide metabolism around immediate and conventionally loaded dental implants.
      • Güncü M.B.
      • Aslan Y.
      • Tümer C.
      • Güncü G.N.
      • Uysal S.
      In-patient comparison of immediate and conventional loaded implants in mandibular molar sites within 12 months.
      No statistically significant difference was observed between the test and control groups (WMD=−0.078; 95% CI, −0.101, 0.258; P=.963).
      Three articles used mPI for assessment of plaque index, of them 2 articles stemmed from the same trial registering the mean changes
      • Hall J.A.G.
      • Payne A.G.T.
      • Purton D.G.
      • Torr B.
      A randomized controlled clinical trial of conventional and immediately loaded tapered implants with screw-retained crowns.
      • Hall J.A.G.
      • Payne A.G.T.
      • Purton D.G.
      • Torr B.
      • Duncan W.J.
      • De Silva R.K.
      Immediately restored, single-tapered implants in the anterior maxilla: Prosthodontic and aesthetic outcomes after 1 year.
      and 1 reported mPI on the last follow-up evaluation.
      • Oh T.J.
      • Shotwell J.L.
      • Billy E.J.
      • Wang H.L.
      Effect of flapless implant surgery on soft tissue profile: a randomized controlled clinical trial.
      The mean change was −0.26 (decrease) in the test group and −0.14 in the control group, while mPI was 0.57 and 0.43 in the test and control groups, respectively. Again, no statistically significant difference was detected between both groups (P>.05). This index was reported as a frequency of the site with plaque. A meta-analysis could not be performed because the sample size was not declared in this trial.
      • Donati M.
      • Scala V.
      • Raimondo R.
      • Speroni S.
      • Testi M.
      • Berglundh T.
      Marginal bone preservation in single-tooth replacement: a 5-year prospective clinical multicenter study.
      • Donati M.
      • Scala V.
      • Billi M.
      • Dino B.
      • Torrisi P.
      • Berglundh T.
      Immediate functional loading of implants in single tooth replacement: a prospective clinical multicenter study.
      The percentage of the site with plaque was 16% in the test group and 17% in the control group.
      • Rouck T.
      • Collys K.
      • Wyn I.
      • Cosyn J.
      Instant provisionalization of immediate single-tooth implants is essential to optimize esthetic treatment outcome.
      The subjective feeling of patients was evaluated in 4 studies. The first investigation
      • Oh T.J.
      • Shotwell J.L.
      • Billy E.J.
      • Wang H.L.
      Effect of flapless implant surgery on soft tissue profile: a randomized controlled clinical trial.
      showed patient satisfaction data regarding comfort level, appearance, and function. There was no statistically significant difference between the 2 groups. The second trial
      • Rouck T.
      • Collys K.
      • Wyn I.
      • Cosyn J.
      Instant provisionalization of immediate single-tooth implants is essential to optimize esthetic treatment outcome.
      reported patients' esthetic satisfaction, indicating on average 93% (range: 82% to 100%) for the test group and 91% (range: 80% to 96%) for the control group. The third study
      • Cannizzaro G.
      • Leone M.
      • Consolo U.
      • Ferri V.
      • Esposito M.
      Immediate functional loading of implants placed with flapless surgery versus conventional implants in partially edentulous patients: a 3-year randomized controlled clinical trial.
      registered the postoperative edema, pain, and use of analgesics. Immediate loading decreased the postoperative discomfort, with statistically significant differences (P<.05). The last one
      • Den Hartog L.
      • Raghoebar G.M.
      • Stellingsma K.
      • Vissink A.
      • Meijer H.J.A.
      Immediate non-occlusal loading of single implants in the aesthetic zone: A randomized clinical trial.
      showed patient satisfaction with function, esthetics, treatment procedure, and general satisfaction. The scores were high, and no statistically significant differences were found between the test and control groups.
      Two methods also evaluated the survival rate of the implant, with patient and implant regarded as the statistical unit. For implant as a statistical unit, the mean survival rate was 96.3% in both groups. Of the 16 included studies, there was no implant failure in 7.
      • Merli M.
      • Moscatelli M.
      • Mariotti G.
      • Piemontese M.
      • Nieri M.
      Immediate versus early non-occlusal loading of dental implants placed flapless in partially edentulous patients: a 3-year randomized clinical trial.
      • Merli M.
      • Merli A.
      • Bernardelli F.
      • Lombardini F.
      • Esposito M.
      Immediate versus early non-occlusal loading of dental implants placed flapless in partially edentulous patients. One-year results from a randomised controlled trial.
      • Barewal R.M.
      • Stanford C.
      • Weesner T.C.
      A randomized controlled clinical trial comparing the effects of three loading protocols on dental implant stability.
      • Esposito M.
      • Siormpas K.
      • Mitsias M.
      • Bechara S.
      • Trullenque-Eriksson A.
      • Pistilli R.
      Immediate, early (6 weeks) and delayed loading (3 months) of single implants: 4-month post-loading from a multicenter pragmatic randomised controlled trial.
      • Grandi T.
      • Garuti G.
      • Guazzi P.
      • Tarabini L.
      • Forabosco A.
      Survival and success rates of immediately and early loaded implants: 12-month results from a multicentric randomized clinical study.
      • Grandi T.
      • Guazzi P.
      • Samarani R.
      • Grandi G.
      A 3-year report from a multicentre randomised controlled trial: immediately versus early loaded implants in partially edentulous patients.
      • Kokovic V.
      • Jung R.
      • Feloutzis A.
      • Todorovic V.S.
      • Jurisic M.
      • Hämmerle C.H.
      Immediate vs. early loading of SLA implants in the posterior mandible: 5-year results of randomized controlled clinical trial.
      • Rieder D.
      • Eggert J.
      • Krafft T.
      • Weber H.-P.
      • Wichmann M.
      • Heckmann S.
      Impact of placement and restoration timing on single-implant esthetic outcome-a randomized clinical trial.
      The overall effect of the meta-analyses showed no statistical difference regarding the incidence of implant failure in both groups (RR=1.003; 95% CI, 0.974, 1.032; P=.851; Fig. 9). No publication bias was detected with the Begg test (P=.111; Fig. 10). The subgroup analysis also resulted in no statistically significant differences between the immediate and early loading groups, with acceptably low heterogeneity among studies (P>.1; I2<50%) (Table 7).
      Figure thumbnail gr9
      Figure 9Forest plot of implant survival rate compared with early loading, for implant as statistical unit.
      Figure thumbnail gr10
      Figure 10Funnel plot illustrating meta-analysis of implant survival rate compared with early loading, for implant as statistical unit.
      Table 7Results of meta-analyses on implant survival rate compared with early loading, for implant as statistical unit
      VariableSubgroupN (Excluded)
      Excluded: number of studies with 100% implant survival rates in both groups.
      RR95% CIPHeterogeneity PHeterogeneity I2 (%)
      Overall9 (7)1.0030.974, 1.032.851.6050.0
      Healing methodSubmerged9 (6)1.0030.974, 1.032.851.6050.0
      Nonsubmerged0 (1)
      Implant timeDelay2 (2)1.0260.965, 1.092.408.18044.4
      Immediate0 (1)
      Early0 (1)
      Both7 (3)0.9880.962, 1.015.372.5900.0
      OcclusionOcclusion4 (1)0.9900.952, 1.030.611.22730.9
      Nonocclusion5 (4)1.0090.971, 1.049.646.4790.0
      NR0 (2)
      Missing teethSingle3 (4)1.0270.972, 1.085.343.6580.0
      Several3 (1)0.9550.903, 1.010.104.4080.0
      Full1 (0)1.0240.979, 1.072.301
      Any2 (2)0.9790.940, 1.019.296.910.0
      Surgery guideGuide2 (3)1.0090.970, 1.051.652.26519.4
      Free hand7 (4)1.0010.966, 1.037.963.5810.0
      Tooth positionPosterior3 (2)1.0110.954, 1.072.712.13649.8
      Maxillary incisors0 (2)
      Maxillary1 (0)1.0240.979, 1.072.301
      Any5 (3)0.9850.956, 1.016.349.9890.0
      Surgery: test/controlFlap/flap4 (5)0.9680.930, 1.007.107.5340.0
      Flapless/flapless2 (1)1.0180.977, 1.061.396.6490.0
      Flapless/flap1 (0)0.9710.893, 1.055.485
      Unclear2 (1)1.0250.967, 1.085.408.19839.7
      First restorations: test/controlProvisional/definitive0 (1)
      Provisional/provisional9 (6)1.0030.974, 1.032.851.6050.0
      Excluded: number of studies with 100% implant survival rates in both groups.
      For patient as a statistical unit, the mean survival rate was 94.6% and 95.9% in the immediate loading and the early loading groups, respectively. In 7 of the 15 included trials, the survival rate of implants was 100%. The results of the meta-analysis of the remaining 8 studies are presented in Figure 11. The meta-analysis resulted in the same survival rate in both the groups (RR=0.984; 95% CI, 0.937, 1.033; P=.516). No publication bias was detected by the Begg test (P=.312) (Fig. 12). In the subgroup analyses, also no statistically significant difference was shown in the implant survival rate of either group (P>.05) (Table 8).
      Figure thumbnail gr11
      Figure 11Forest plot of implant survival rate compared with early loading, for patient as statistical unit.
      Figure thumbnail gr12
      Figure 12Funnel plot illustrating meta-analysis of implant survival rate compared with early loading, for patient as statistical unit.
      Table 8Results of meta-analyses on implant survival rate compared with early loading, for patient as statistical unit
      VariableSubgroupN (Excluded)
      Excluded: number of studies with 100% implant survival rates in both groups.
      RR95% CIPHeterogeneity PHeterogeneity I2 (%)
      Overall8 (7)0.9840.937, 1.033.516.9060.0
      Healing methodSubmerged0 (1)
      Nonsubmerged8 (6)0.9840.937, 1.033.516.9060.0
      Implant timeDelay2 (2)0.9930.920, 1.071.847.4910.0
      Immediate0 (1)
      Early0 (1)
      Both6 (3)0.9740.918, 1.034.395.8130.0
      OcclusionOcclusion4 (1)0.9630.855, 1.085.535.5740.0
      Nonocclusion4 (4)0.9890.938, 1.044.688.8560.0
      NR0 (2)
      Missing teethSingle2 (5)0.9990.921, 1.083.976.9860.0
      Several2 (1)0.8780.726, 1.060.176.5890.0
      Full1 (0)1.0770.847, 1.369.545
      Any3 (1)0.9870.928, 1.050.687.7110.0
      Surgery guideGuide2 (3)1.0000.848, 1.1801.000.3440.0
      Free hand6 (4)0.9820.933, 1.034.489.8670.0
      Tooth positionPosterior3 (2)0.9800.910, 1.056.594.4480.0
      Maxillary incisors0 (2)
      Maxillary1 (0)1.0770.847, 1.369.545
      Any4 (3)0.9770.923, 1.035.429.9020.0
      Surgery: test/controlFlap/flap4 (5)0.9560.898, 1.018.163.6140.0
      Flapless/flapless2 (1)1.0370.890, 1.208.641.6290.0
      Flapless/flap1 (0)0.9200.735, 1.151.466
      Unclear1 (1)1.0000.922, 1.084.998
      First restorations: test/controlProvisional/definitive0 (1)
      Provisional/provisional8 (6)0.9840.937, 1.033.516.9060.0
      Excluded: number of studies with 100% implant survival rates in both groups.
      The change of crestal bone level was reported in all trials, except 2.
      • Esposito M.
      • Siormpas K.
      • Mitsias M.
      • Bechara S.
      • Trullenque-Eriksson A.
      • Pistilli R.
      Immediate, early (6 weeks) and delayed loading (3 months) of single implants: 4-month post-loading from a multicenter pragmatic randomised controlled trial.
      • Rieder D.
      • Eggert J.
      • Krafft T.
      • Weber H.-P.
      • Wichmann M.
      • Heckmann S.
      Impact of placement and restoration timing on single-implant esthetic outcome-a randomized clinical trial.
      All 13 investigations used periapical radiographs for bone loss evaluation. One study did not register the standard deviation,
      • Testori T.
      • Bianchi F.
      • Fabbro M.
      • Szmukler-Moncler S.
      • Francetti L.
      • Weinstein R.
      Immediate non-occlusal loading vs. early loading in partially edentulous patients.
      so the remaining 12 were combined in the meta-analysis. The loss of marginal bone level ranged from −1.60 mm (loss) to −0.12 mm in the test group and from −1.54 mm to −0.17 mm in the controls. The result shows no statistically significant difference in crestal bone loss between the test and control groups (WMD=0.02; 95% CI, −0.138, 0.178; P=.809) when combining the data at all sites of implants (Fig. 13). For any of the subgroup analysis, no statistically significant difference was found between groups, except in trials that did not report definitive immediate occlusion (WMD=0.400; 95% CI, 0.240, 0.560; P<.001) and when interim prostheses were used for immediate loading while directly definitive restorations were used for early loading (WMD=0.240; 95% CI, 0.015, 0.465; P=.036) (Table 9).
      Figure thumbnail gr13
      Figure 13Forest plot of marginal bone level change compared with early loading.
      Table 9Results of meta-analyses on marginal bone level change compared with early loading
      VariableSubgroupNWMD95% CIPHeterogeneity PHeterogeneity I2 (%)
      Overall120.020-0.138, 0.178.809<.00177.0
      Healing methodSubmerged0
      Nonsubmerged120.020-0.138, 0.178.809<.00177.0
      Implant timeDelay4-0.065-0.476, 0.345.755<.00192.2
      Mixed80.076-0.035, 0.187.178.24822.7
      OcclusionOcclusion5-0.064-0.201, 0.073.361.25624.8
      Nonocclusion60.0490.189, 0.286.689.00175.1
      NR10.4000.240, 0.560<.001
      Missing teethSingle50.105-0.154, 0.365.426.00179.5
      Several3-0.105-0.569, 0.359.657.02573.0
      Full10.07-0.099, 0.239.416
      Any3-0.084-0.368, 0.200.562.03370.7
      Surgery guideGuide50.045-0.214, 0.305.732.00178.0
      Free hand70.000-0.196, 0.196.998.00173.3
      Tooth positionPosterior5-0.133-0.519, 0.252.498<.00190.2
      Maxillary10.070-0.099, 0.239.416
      Any60.095-0.029, 0.219.132.31215.8
      Surgery: test/controlFlap/flap60.095-0.136, 0.326.421.00471.3
      Flapless/flapless30.008-0.114, 0.131.892.5820.0
      Flapless/flap1-0.230-0.625, 0.165.254
      Unclear2-0.040-0.579, 0.499.885<.00193.0
      First restorations: test/controlProvisional/definitive10.2400.015, 0.465.036
      Provisional/provisional11-0.006-0.176, 0.165.947<.00177.7
      Bold text indicates statistically significant differences.
      The Osstell device was used in 5 trials for testing implants' stability. One reported data as Figures,
      • Barewal R.M.
      • Stanford C.
      • Weesner T.C.
      A randomized controlled clinical trial comparing the effects of three loading protocols on dental implant stability.
      and one showed the results by comparing cylindrical implants with tapered ones.
      • Testori T.
      • Bianchi F.
      • Fabbro M.
      • Szmukler-Moncler S.
      • Francetti L.
      • Weinstein R.
      Immediate non-occlusal loading vs. early loading in partially edentulous patients.
      The remaining 3 studies presented data as mean, standard deviation, and sample size.
      • Cannizzaro G.
      • Leone M.
      • Torchio C.
      • Viola P.
      • Esposito M.
      Immediate versus early loading of 7-mm-long flapless-placed single implants: a split-mouth randomised controlled clinical trial.
      • Kokovic V.
      • Jung R.
      • Feloutzis A.
      • Todorovic V.S.
      • Jurisic M.
      • Hämmerle C.H.
      Immediate vs. early loading of SLA implants in the posterior mandible: 5-year results of randomized controlled clinical trial.
      • Cannizzaro G.
      • Felice P.
      • Leone M.
      • Ferri V.
      • Viola P.
      • Esposito M.
      Immediate versus early loading of 6.5 mm-long flapless-placed single implants: a 4-year after loading report of a split-mouth randomised controlled trial.
      • Zembic A.
      • Glauser R.
      • Khraisat A.
      • Hammerle C.H.
      Immediate vs. early loading of dental implants: 3-year results of a randomized controlled clinical trial.
      The mean varied from 66.10 to 82.97 in the test group and from 70.40 to 81.14 in the control group. The meta-analysis results reported that there was no sufficient evidence to support the significant statistical difference between the 2 groups (WMD=−0.805; 95% CI, −3.309, 1.699; P=.529).
      Gingival inflammation was registered in 5 studies, and 2 indexes were used: modified sulcus bleeding index (mBI)
      • Mombelli A.
      • van Oosten M.A.
      • Schurch Jr., E.
      • Land N.P.
      The microbiota associated with successful or failing osseointegrated titanium implants.
      and peri-implant mucositis. Two methods also evaluated the peri-implant mucositis. Patients and implants were regarded as a statistical unit. For patient as a statistical unit, the rates were 2.5% and 0.8% in the test and control groups, respectively.
      • Esposito M.
      • Siormpas K.
      • Mitsias M.
      • Bechara S.
      • Trullenque-Eriksson A.
      • Pistilli R.
      Immediate, early (6 weeks) and delayed loading (3 months) of single implants: 4-month post-loading from a multicenter pragmatic randomised controlled trial.
      • Grandi T.
      • Garuti G.
      • Guazzi P.
      • Tarabini L.
      • Forabosco A.
      Survival and success rates of immediately and early loaded implants: 12-month results from a multicentric randomized clinical study.
      • Grandi T.
      • Guazzi P.
      • Samarani R.
      • Grandi G.
      A 3-year report from a multicentre randomised controlled trial: immediately versus early loaded implants in partially edentulous patients.
      • Grandi T.
      • Guazzi P.
      • Samarani R.
      • Tohme H.
      • Khoury S.
      • Sbricoli L.
      • et al.
      Immediate, early (3 weeks) and conventional loading (4 months) of single implants: preliminary data at 1 year after loading from a pragmatic multicenter randomised controlled trial.
      • Zuffetti F.
      • Esposito M.
      • Galli F.
      • Capelli M.
      • Grandi G.
      • Testori T.
      A 10-year report from a multicentre randomised controlled trial: immediate non-occlusal versus early loading of dental implants in partially edentulous patients.
      The meta-analysis for the 4 studies showed the same rate of peri-implant mucositis in both groups, with no significant difference observed between immediate and early loading (RR=1.922; 95% CI, 0.417, 8.866; P=.402). For implant as a statistical unit, the peri-implant mucositis rate was 3.2% in the test and 1.5% in the control group. The meta-analysis for the 4 studies
      • Cannizzaro G.
      • Leone M.
      • Torchio C.
      • Viola P.
      • Esposito M.
      Immediate versus early loading of 7-mm-long flapless-placed single implants: a split-mouth randomised controlled clinical trial.
      • Esposito M.
      • Siormpas K.
      • Mitsias M.
      • Bechara S.
      • Trullenque-Eriksson A.
      • Pistilli R.
      Immediate, early (6 weeks) and delayed loading (3 months) of single implants: 4-month post-loading from a multicenter pragmatic randomised controlled trial.
      • Cannizzaro G.
      • Felice P.
      • Leone M.
      • Ferri V.
      • Viola P.
      • Esposito M.
      Immediate versus early loading of 6.5 mm-long flapless-placed single implants: a 4-year after loading report of a split-mouth randomised controlled trial.
      • Grandi T.
      • Guazzi P.
      • Samarani R.
      • Tohme H.
      • Khoury S.
      • Sbricoli L.
      • et al.
      Immediate, early (3 weeks) and conventional loading (4 months) of single implants: preliminary data at 1 year after loading from a pragmatic multicenter randomised controlled trial.
      • Zuffetti F.
      • Esposito M.
      • Galli F.
      • Capelli M.
      • Grandi G.
      • Testori T.
      A 10-year report from a multicentre randomised controlled trial: immediate non-occlusal versus early loading of dental implants in partially edentulous patients.
      with low heterogeneity found insufficient evidence to determine whether differences existed between both groups (RR=1.845; 95% CI, 0.562, 6.056; P=.313). Modified sulcus bleeding index (mBI)
      • Mombelli A.
      • van Oosten M.A.
      • Schurch Jr., E.
      • Land N.P.
      The microbiota associated with successful or failing osseointegrated titanium implants.
      was presented in 1 trial,
      • Kokovic V.
      • Jung R.
      • Feloutzis A.
      • Todorovic V.S.
      • Jurisic M.
      • Hämmerle C.H.
      Immediate vs. early loading of SLA implants in the posterior mandible: 5-year results of randomized controlled clinical trial.
      which showed no significant statistical difference between the 2 groups (P>.05).
      For patient and implant as the statistical unit, the rates of peri-implantitis were 0 and 0.5% in the immediately loaded group and 2.6% and 2.3% in the early loaded group. According to the results of meta-analysis, evidence of a statistically significant difference was lacking in either method.
      As for peri-implant soft tissue, the pink esthetic score (PES),
      • Furhauser R.
      • Florescu D.
      • Benesch T.
      • Haas R.
      • Mailath G.
      • Watzek G.
      Evaluation of soft tissue around single-tooth implant crowns: the pink esthetic score.
      gingival recession, and attached mucosa height were registered. PES, consisting of 7 soft-tissue parameters, was used for the assessment in 1 trial.
      • Rieder D.
      • Eggert J.
      • Krafft T.
      • Weber H.-P.
      • Wichmann M.
      • Heckmann S.
      Impact of placement and restoration timing on single-implant esthetic outcome-a randomized clinical trial.
      No statistically significant difference was found between the immediately and early loaded groups in terms of the overall effect (P=.124). Gingival recession outcomes were reported in 2 studies.
      • Galli F.
      • Capelli M.
      • Zuffetti F.
      • Testori T.
      • Esposito M.
      Immediate non-occlusal vs. early loading of dental implants in partially edentulous patients: a multicentre randomized clinical trial. Peri-implant bone and soft-tissue levels.
      • Testori T.
      • Galli F.
      • Capelli M.
      • Zuffetti F.
      • Esposito M.
      Immediate nonocclusal versus early loading of dental implants in partially edentulous patients: 1-Year results from a multicenter, randomized controlled clinical trial.
      • Capelli M.
      • Esposito M.
      • Zuffetti F.
      • Galli F.
      • Fabbro M.
      • Testroi T.
      A 5-year report from a multicentre randomised clinical trial: immediate non-occlusal versus early loading of dental implants in partially edentulous patients.
      • Zuffetti F.
      • Esposito M.
      • Galli F.
      • Capelli M.
      • Grandi G.
      • Testori T.
      A 10-year report from a multicentre randomised controlled trial: immediate non-occlusal versus early loading of dental implants in partially edentulous patients.
      The meta-analysis was associated with low heterogeneity, and there was insufficient evidence to determine whether a statistically significant difference existed between the test and control subjects (WMD=−0.145; 95% CI, −0.330, 0.040; P=.124). For the height of attached mucosa, only 1 study reported the data at different time periods.
      • Velde T.
      • Sennerby L.
      • Bruyn H.
      The clinical and radiographic outcome of implants placed in the posterior maxilla with a guided flapless approach and immediately restored with a provisional rehabilitation: a randomized clinical trial.
      No statistically significant difference was found between the test and control groups at 3, 6, 12, and 18 months (P>.05).
      Plaque index was reported in 2 trials. In 1 study,
      • Kokovic V.
      • Jung R.
      • Feloutzis A.
      • Todorovic V.S.
      • Jurisic M.
      • Hämmerle C.H.
      Immediate vs. early loading of SLA implants in the posterior mandible: 5-year results of randomized controlled clinical trial.
      the mPI
      • Mombelli A.
      • van Oosten M.A.
      • Schurch Jr., E.
      • Land N.P.
      The microbiota associated with successful or failing osseointegrated titanium implants.
      was registered for the test and control groups at 1 and 5 years after loading. No statistically significant difference was shown at either time period (P>.05). The plaque control record (PCR)
      • O'Leary T.J.
      • Drake R.B.
      • Naylor J.E.
      The plaque control record.
      was used in another trial,
      • Zembic A.
      • Glauser R.
      • Khraisat A.
      • Hammerle C.H.
      Immediate vs. early loading of dental implants: 3-year results of a randomized controlled clinical trial.
      where only the percentage of plaque accumulation was reported.
      For subjective assessment, patients were asked to fill in a questionnaire with a visual analog scale (VAS) in 1 study.
      • Velde T.
      • Sennerby L.
      • Bruyn H.
      The clinical and radiographic outcome of implants placed in the posterior maxilla with a guided flapless approach and immediately restored with a provisional rehabilitation: a randomized clinical trial.
      There were no statistically significant differences in speech, function, esthetics, and self-confidence after loading with interim prostheses (6 weeks). A statistical difference was found between the test and control groups regarding pain, comfort, or overall satisfaction scores at any time point (P>.05). Another trial
      • Cannizzaro G.
      • Leone M.
      • Torchio C.
      • Viola P.
      • Esposito M.
      Immediate versus early loading of 7-mm-long flapless-placed single implants: a split-mouth randomised controlled clinical trial.
      • Cannizzaro G.
      • Felice P.
      • Leone M.
      • Ferri V.
      • Viola P.
      • Esposito M.
      Immediate versus early loading of 6.5 mm-long flapless-placed single implants: a 4-year after loading report of a split-mouth randomised controlled trial.
      showed no statistically significant difference when patients who preferred immediate versus early loading were compared after 3 months and 4 years of loading.

      Discussion

      The results showed that immediate loading represented a higher risk of implant failure than delayed loading, while presenting no difference in marginal bone level change or probing depth. When compared with early loading, immediate loading achieved similar implant survival rates and marginal bone level change.
      This systematic review included 39 RCTs, with a total of 1868 patients and 3746 implants, that compared immediate loading versus early or delayed loading in patients rehabilitated with a fixed prosthesis. Six of the studies had less than 1 year of follow-up duration.
      • Cannizzaro G.
      • Leone M.
      • Torchio C.
      • Viola P.
      • Esposito M.
      Immediate versus early loading of 7-mm-long flapless-placed single implants: a split-mouth randomised controlled clinical trial.
      • Esposito M.
      • Siormpas K.
      • Mitsias M.
      • Bechara S.
      • Trullenque-Eriksson A.
      • Pistilli R.
      Immediate, early (6 weeks) and delayed loading (3 months) of single implants: 4-month post-loading from a multicenter pragmatic randomised controlled trial.
      • Vercruyssen M.
      • Cox C.
      • Naert I.
      • Jacobs R.
      • Teughels W.
      • Quirynen M.
      Accuracy and patient-centered outcome variables in guided implant surgery: a RCT comparing immediate with delayed loading.
      • Giacomel M.
      • Camati P.
      • Souza J.
      • Deliberador T.
      Comparison of marginal bone level changes of immediately loaded implants, delayed loaded nonsubmerged implants, and delayed loaded submerged implants: a randomized clinical trial.
      • Rieder D.
      • Eggert J.
      • Krafft T.
      • Weber H.-P.
      • Wichmann M.
      • Heckmann S.
      Impact of placement and restoration timing on single-implant esthetic outcome-a randomized clinical trial.
      • Cannizzaro G.
      • Felice P.
      • Leone M.
      • Ferri V.
      • Viola P.
      • Esposito M.
      Immediate versus early loading of 6.5 mm-long flapless-placed single implants: a 4-year after loading report of a split-mouth randomised controlled trial.
      • Oh T.J.
      • Shotwell J.L.
      • Billy E.J.
      • Wang H.L.
      Effect of flapless implant surgery on soft tissue profile: a randomized controlled clinical trial.
      Esposito et al
      • Esposito M.
      • Grusovin M.G.
      • Maghaireh H.
      • Worthington H.V.
      Interventions for replacing missing teeth: different times for loading dental implants.
      reported on a relatively short period (4 months to 1 year), but the time was sufficient to determine the impact of loading on the establishment of osseointegration as the first several months of immediate or early loading is the key period for osseointegration. As the influence of the loading method on the outcomes after osseointegration is reduced, it is reasonable to include these 6 trials.
      Compared with conventional loading, immediately loaded implants had a statistically significant lower survival rate (implant as statistical unit), and this finding was similar to the result reported in previously published systematic reviews of fixed restorations.
      • Sanz-Sanchez I.
      • Sanz-Martin I.
      • uero E.
      • Sanz M.
      Clinical efficacy of immediate implant loading protocols compared to conventional loading depending on the type of the restoration: a systematic review.
      • Zhang S.
      • Wang S.
      • Song Y.
      Immediate loading for implant restoration compared with early or conventional loading: A meta-analysis.
      The survival rate in the immediate group showed no significant difference, although it was relatively lower with patients considered as the statistical unit. The discrepancy caused by the statistical unit can be explained thus: the patient unit increases the implant failure rate to some extent as the failure of a multiunit prosthesis may be caused by the loss of only 1 implant. Additionally, this method has decreased the relative sample size of implant-supported fixed prostheses for meta-analysis.
      No statistically significant difference in MBL was shown in the overall effects of the meta-analysis when immediate loading was compared with the delayed protocol. This was also consistent with previously published systematic reviews.
      • Esposito M.
      • Grusovin M.G.
      • Maghaireh H.
      • Worthington H.V.
      Interventions for replacing missing teeth: different times for loading dental implants.
      • Chrcanovic B.R.
      • Albrektsson T.
      • Wennerberg A.
      Immediately loaded non-submerged versus delayed loaded submerged dental implants: a meta-analysis.
      • Suarez F.
      • Chan H.L.
      • Monje A.
      • Galindo-Moreno P.
      • Wang H.L.
      Effect of the timing of restoration on implant marginal bone loss: a systematic review.
      This result indicated that different loading protocols behaved similarly after osseointegration because only successful treatments were included in the meta-analysis. Sanz-Sanchez et al
      • Sanz-Sanchez I.
      • Sanz-Martin I.
      • uero E.
      • Sanz M.
      Clinical efficacy of immediate implant loading protocols compared to conventional loading depending on the type of the restoration: a systematic review.
      reported statistically significant lower bone loss in the immediate loading group than that in the conventionally loaded group. These discrepancies may be explained by previous systematic reviews combining both fixed and removable implant-supported prostheses,
      • Esposito M.
      • Grusovin M.G.
      • Maghaireh H.
      • Worthington H.V.
      Interventions for replacing missing teeth: different times for loading dental implants.
      • Kern J.S.
      • Kern T.
      • Wolfart S.
      • Heussen N.
      A systematic review and meta-analysis of removable and fixed implant-supported prostheses in edentulous jaws: post-loading implant loss.
      • Sanz-Sanchez I.
      • Sanz-Martin I.
      • uero E.
      • Sanz M.
      Clinical efficacy of immediate implant loading protocols compared to conventional loading depending on the type of the restoration: a systematic review.
      • Zhang S.
      • Wang S.
      • Song Y.
      Immediate loading for implant restoration compared with early or conventional loading: A meta-analysis.
      • Suarez F.
      • Chan H.L.
      • Monje A.
      • Galindo-Moreno P.
      • Wang H.L.
      Effect of the timing of restoration on implant marginal bone loss: a systematic review.
      while the current meta-analysis focused on only fixed restorations. Additionally, the Cochrane review made comparisons at 4 to 12 months after loading,
      • Esposito M.
      • Grusovin M.G.
      • Maghaireh H.
      • Worthington H.V.
      Interventions for replacing missing teeth: different times for loading dental implants.
      while the others assessed data at the last visit.
      • Kern J.S.
      • Kern T.
      • Wolfart S.
      • Heussen N.
      A systematic review and meta-analysis of removable and fixed implant-supported prostheses in edentulous jaws: post-loading implant loss.
      • Sanz-Sanchez I.
      • Sanz-Martin I.
      • uero E.
      • Sanz M.
      Clinical efficacy of immediate implant loading protocols compared to conventional loading depending on the type of the restoration: a systematic review.
      • Zhang S.
      • Wang S.
      • Song Y.
      Immediate loading for implant restoration compared with early or conventional loading: A meta-analysis.
      • Suarez F.
      • Chan H.L.
      • Monje A.
      • Galindo-Moreno P.
      • Wang H.L.
      Effect of the timing of restoration on implant marginal bone loss: a systematic review.
      The present review used the latter method. Because the MBL change is irreversible, it is reasonable to use the most recent data because of the longer follow-up time.
      In the subgroup analyses, the lower survival rate of implants was observed in the immediately loaded implants with items listed previously. Types of loading, tooth position, and unit number of prostheses caused the different outcomes between the test and control groups by influencing stabilization during the osseointegration period. Micromotion might hinder the proliferation of osteoblasts and lead to the formation of fibrous tissues at the bone-implant interface.
      • Javed F.
      • Romanos G.E.
      The role of primary stability for successful immediate loading of dental implants. A literature review.
      • Roberts W.E.
      • Smith R.K.
      • Zilberman Y.
      • Mozsary P.G.
      • Smith R.S.
      Osseous adaptation to continuous loading of rigid endosseous implants.
      Nonocclusal patterns reduced the masticatory force on immediately loaded implants, while cross-arch stabilization could be obtained from complete-arch restorations. It was concluded that controlled occlusal loads for complete-arch prostheses and nonocclusal loads for short-span prostheses and single-tooth replacements were important factors for a successful outcome.
      • Aparicio C.
      • Rangert B.
      • Sennerby L.
      Immediate/early loading of dental implants: a report from the Sociedad Espanola de Implantes World Congress consensus meeting in Barcelona, Spain, 2002.
      However, a systematic review, based on 10 RCTs, concluded that immediately and conventionally loaded single-implant crowns were clinically equal regarding implant survival, marginal bone loss, papilla height, and the recession of midfacial peri-implant mucosa.
      • Benic G.I.
      • Mir-Mari J.
      • Hammerle C.H.
      Loading protocols for single-implant crowns: a systematic review and meta-analysis.
      A similar conclusion was also drawn by Moraschini and Barboza
      • Moraschini V.
      • Porto Barboza E.
      Immediate versus conventional loaded single implants in the posterior mandible: a meta-analysis of randomized controlled trials.
      on single posterior mandibular implants. For partially edentulous situations, Schrott et al
      • Schrott A.
      • Riggi-Heiniger M.
      • Maruo K.
      • Gallucci G.O.
      Implant loading protocols for partially edentulous patients with extended edentulous sites--a systematic review and meta-analysis.
      concluded that there was no statistically significant difference in implant survival rate among immediate, early, or delayed loading. The result of another meta-analysis concluded that the differences in occlusal loading might not have significant effects on implant survival rate and marginal bone loss.
      • Chrcanovic B.R.
      • Albrektsson T.
      • Wennerberg A.
      Immediate nonfunctional versus immediate functional loading and dental implant failure rates: a systematic review and meta-analysis.
      A consensus meeting, based on systematic reviews, reported no increased risk of implant loss in immediate loading with occlusal contact or complete-arch fixed restorations and a lower implant survival rate and less marginal bone level change in the test group.
      • Sanz-Sanchez I.
      • Sanz-Martin I.
      • uero E.
      • Sanz M.
      Clinical efficacy of immediate implant loading protocols compared to conventional loading depending on the type of the restoration: a systematic review.
      • Schwarz F.
      • Sanz-Martin I.
      • Kern J.S.
      • Taylor T.
      • Schaer A.
      • Wolfart S.
      • et al.
      Loading protocols and implant supported restorations proposed for the rehabilitation of partially and fully edentulous jaws. Camlog Foundation Consensus Report.
      In regard to tooth position, a potential problem of installing implants in poor-quality bone is the difficulty in obtaining adequate primary implant stability.
      • Javed F.
      • Romanos G.E.
      The role of primary stability for successful immediate loading of dental implants. A literature review.
      • Chow J.
      • Hui E.
      • Liu J.
      • Li D.
      • Wat P.
      • Li W.
      • et al.
      The Hong Kong Bridge Protocol. Immediate loading of mandibular Branemark fixtures using a fixed provisional prosthesis: preliminary results.
      • Chung S.
      • McCullagh A.
      • Irinakis T.
      Immediate loading in the maxillary arch: evidence-based guidelines to improve success rates: a review.
      Relatively lower survival rate in immediate loading groups was also caused by the delayed implant, implant guide plate, and flap surgery. This could be explained by the predictable clinical outcomes with conventionally standardized therapy. Another statistically significant difference was shown in marginal bone level as compared with delayed loading, depending on the occlusal contact of immediately loaded implants (WMD=0.083; 95% CI, 0.003, 0.163; P=.043).
      The implant survival rate might be influenced by many other elements including insertion torque, implant surface and design modifications, bone density, alveolar ridge augmentation, load, infection, and smoking.
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      However, comparing the outcomes between the test and control groups was impossible based on the RCTs included in this article because the related data were obtained in an inconsistent manner.
      According to the results of the current meta-analysis, immediate and early loaded implants were equally successful regarding implant survival and marginal bone loss. Zhang et al