Do osteoconductive bone substitutes result in similar bone regeneration for maxillary sinus augmentation when compared to osteogenic and osteoinductive bone grafts? A systematic review and frequentist network meta-analysis

The purpose of this network meta-analysis was to identify the most effective biomaterials producing higher new bone formation (NBF) and lower residual graft (RG) and connective tissue (CT) following maxillary sinus augmentation (MSA), and to generate a ranking based on their performance. The MEDLINE, Embase, and CENTRAL databases were searched to identify randomized controlled trials (RCTs) published until March 2018, evaluating histomorphometric outcomes after MSA. Predictor variables were autogenous bone (AB), allografts (AG), xenografts (XG), alloplastic bone (AP), AB + XG, AB + AP, AG + XG, XG + AP, and grafts combined with autologous platelet concentrates/recombinant growth factors, mesenchymal stem cells (MSCs), or recombinant bone morphogenetic proteins (BMPs). Outcome variables were NBF%, RG%, and CT%. Healing time was considered. The weighted mean difference (WMD) with 95% confidence interval (CI) was calculated via frequentist network meta-analysis using Stata software. Fifty-two RCTs (1483 biopsies) were included. At a healing time <6 months, AB was superior to AP (WMD 10.66%, 95% CI 16.38% to 4.94%) and XG (WMD 7.93%, 95% CI - 15.11% to -0.75%) for NBF. Regarding CT, AB was superior to XG + AP, AP, MSCs, and XG. At a healing time >= 6 months, NBF was higher for AB than AP (WMD - 7.06%, 95% CI - 12.59% to - 1.52%). RG was lower in AB than AP (WMD 12.03%, 95% CI - 3.04% to 21.03%), XG (WMD 14.62%, 95% CI 4.25% to 24.98%), and growth factors (WMD 12.32%, 95% CI 0.04% to 24.60%). The three highest ranked biomaterials for increasing NBF were AG + XG (95%, very low quality evidence), growth factors (69.9%, low quality evidence), and AB alone (69.8%, moderate quality evidence). The three highest ranked biomaterials for decreasing RG were BMPs (88.8%, very low quality evidence), AB alone (81.5%, moderate quality evidence), and AB + AP (58.9%, very low quality evidence). Finally, XG + AP (84.7%, low quality evidence), AP alone (77.7%, moderate quality evidence), and MSCs (76.1%, low quality evidence), were the three highest ranked biomaterials for decreasing the amount of CT. Network meta-analysis provided moderate quality evidence that AB alone is probably the best option to obtain greater NBF after MSA in the first 6 months after surgery. Additionally, the results of this network meta-analysis support the hypothesis that osteoconductive bone substitute materials should be combined with osteogenic or osteoinductive grafts for superior histomorphometric outcomes in MSA.