1 Review article 2 Comparative effectiveness of natural and synthetic bone grafts in oral 3 and maxillofacial surgery prior to insertion of dental implants: 4 Systematic review and network meta-analysis of parallel and cluster 5 randomized controlled trials 6 Spyridon N. Papageorgiou a,b, * Q1 , Panagiotis N. Papageorgiou c , James Deschner d , 7 Werner Götz a 8 a Department of Orthodontics, School of Dentistry, University of Bonn, Bonn 53111, Germany 9 b Department of Oral Technology, School of Dentistry, University of Bonn, Bonn 53111, Germany 10 c Department of Neurosurgery, Queen Elizabeth University Hospital, Glasgow G51 4TF, UK 11 d Section for Experimental Dento-Maxillo-Facial Medicine, School of Dentistry, University of Bonn, Bonn 53111, Germany A R T I C L E I N F O Article history: Received 29 December 2015 Received in revised form 21 February 2016 Accepted 17 March 2016 Available online xxx Keywords: Bone grafting Bone substitutes Alveolar ridge augmentation Tooth extraction Sinus floor augmentation Systematic review Network meta-analysis Randomized controlled trial A B S T R A C T Objectives: Bone grafts are often used to enhance bone volume/quality prior to implantation insertion. This systematic review compares the histomorphometric effectiveness of bone grafts in an evidence- based manner. Data: Randomized clinical trials comparing histomorphometrically the% of newly-formed bone between two grafts were included. Risk of bias within and across studies was assessed with the Cochrane tool and the GRADE approach, respectively. Random-effects pairwise meta-analyses were conducted, followed by network meta-analysis, network meta-regression and sensitivity analyses. Sources: Four electronic databases were searched from inception to June 2015 without limitations. Study selection: A total of 12 trials (5 parallel; 7 cluster) with a total of 231 patients (302 grafted sites) were included. No statistically significant differences were found in the% of new bone from pairwise comparisons between any two bone grafts. Treatment ranking based on the evidence network indicated that autografts presented the highest% of new bone, followed by synthetic grafts, xenografts, and allografts. No differences according to patient age, sex, healing time, membrane used or kind of surgical graft use were identified. Our confidence on pairwise comparisons was moderate to very low, due to study limitations, inconsistency, and imprecision; our confidence on graft ranking was moderate, due to study limitations. Conclusions: No significant differences were found in the% of new bone between any two grafts. Clinical significance: Synthetic bone substitutes or xenologous bone grafts can be used as an alternative to autologous graft, in order to overcome problems of additional surgeries or limited graft availability. ã 2016 Published by Elsevier Ltd. 12 1. Introduction 13 1.1. Background 14 Resorption of the edentulous or partially edentulous alveolar 15 ridge frequently compromises dental implant placement in a 16 prosthetically ideal position. Therefore, augmentation of an 17 insufficient bone volume is often indicated prior to or in 18 conjunction with implant placement to attain predictable long- 19 term functioning and an esthetic treatment outcome. Autogenous 20 bone grafts (AUTs) are considered the gold standard in bone 21 regeneration procedures [1]. However, donor site morbidity, 22 transmission of live viruses, unpredictable resorption, limited 23 quantities available, and the need to include additional surgical 24 sites are autografts-related drawbacks that have intensified the 25 search for suitable alternatives [2]. Q2 26 Bone-substitute materials have increased in popularity as 27 adjuncts to or replacements for AUTs in bone augmentation 28 procedures to overcome many of their limitations [3]. Bone- 29 substitute materials can be categorized in three groups: (1) 30 allogenic grafts (ALLs), from another individual within the same * Corresponding author at: Department of Orthodontics, School of Dentistry, University of Bonn, Welschnonnenstr. 17, 53111 Bonn, Germany. E-mail address: snpapage@gmail.com (S.N. Papageorgiou). http://dx.doi.org/10.1016/j.jdent.2016.03.010 0300-5712/ ã 2016 Published by Elsevier Ltd. Journal of Dentistry xxx (2015) xxx–xxx G Model JJOD 2600 1–8 Please cite this article in press as: S.N. Papageorgiou, et al., Comparative effectiveness of natural and synthetic bone grafts in oral and maxillofacial surgery prior to insertion of dental implants: Systematic review and network meta-analysis of parallel and cluster randomized controlled trials, Journal of Dentistry (2016), http://dx.doi.org/10.1016/j.jdent.2016.03.010 Contents lists available at ScienceDirect Journal of Dentistry journal homepage: www.intl.elsevierhea lt h.com/journa ls/jde n