Background: Over the past decades, locally delivered host-modulating pharmacological agents have been extensively investigated to treat periodontitis. Although a small category of agents has been tested in clinical trials, most of them were reported in the animal experiments. This systematic review evaluates the efficacy of local application of currently available host-modulating agents, with or without mechanical removal of plaque, in animal models with periodontitis or periodontal defect. Methods: PubMed and Embase were searched on February 11, 2019. The inclusion criteria were as follows: (1) experiments were performed in healthy animals (all ages, sexes, and species) with periodontitis, and (2) outcome data for the local application of host-modulating approaches were presented for bone quantity, bone loss, and attachment loss and compared with a vehicle control group. Study characteristics and outcome data were extracted and internal validity was assessed. The efficacy of host-modulating agents was analyzed in a meta-analysis. A standardized mean difference (SMD) and its 95% confidence intervals for each individual comparison were calculated to estimate the overall effect. Subgroup analyses were conducted on animal species and different types of agents. Results: Forty-eight articles were included in the review, of which 42 were included in meta-analysis on bone quantity, bone loss, and attachment loss. The results showed that host-modulating therapy significantly increased bone formation (SMD: 2.200 [1.560-2.840], n = 24), and decreased bone loss (SMD: -1.659 [-1.969 to -1.348], n = 51) and attachment loss (SMD: -1.572 [-2.211 to -0.933], n = 17). No significant subgroup effects were identified, indicating that the effects are similar across species and drug types. Conclusions: The current scientific evidence supports the use of local host-modulation therapy in the treatment of periodontitis in experimental animals. Our findings seem robust for various animal models and designs included in this review, which increases our confidence of the translational value of the results to the clinical situation. Impact Statement Over the past decades, locally delivered host-modulating pharmacological agents have been extensively investigated for periodontal regeneration. Although a small category of agents has been tested in clinical trials, most of them were reported in the animal experiments. Considering the increasing amount of preclinical evidence and the need for future clinical trials, a systematic review and meta-analysis of all preclinical data was performed to determine the translational value of host-modulating drugs for human application. The results showed that host-modulating therapy significantly increased bone formation and decreased bone and attachment loss. This study contributes to researchers working on the periodontal translational research.
Keywords: animal models; dental and periodontal; inflammatory/immune response.