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Aim: This systematic review was aimed at addressing the focused question: What is the protective potential of biological agents against alveolar bone resorption during the progression of experimental periodontitis (EP)? Material and Methods: The study protocol was registered in the Open Science Framework database (doi:10.17605/OSF.IO/3P2HY). A comprehensive literature search was conducted across PubMed, Web of Science, Cochrane Library, Scopus, and Embase databases up to December 2023. Inclusion criteria consisted of preclinical studies in animal models of EP that examined the effects of biological agents on preventing periodontal bone loss and reducing tissue inflammation. Studies were excluded if they (i) used non-EP animal models; (ii) focused on antimicrobial agents; (iii) centered on prebiotics or probiotics; (iv) evaluated compounds not classified as biologicals; or (v) included randomized clinical trials, clinical studies, or reviews. Eligibility was determined based on the PI/ECOs framework, and study quality was assessed using the SYRCLE risk-of-bias tool. Results: After screening an initial pool of 5236 records from databases, registries, and hand searches, 39 studies met the inclusion criteria. A total of 23 biological agents were evaluated across these studies. The majority of studies employed the ligature-induced model of EP to test the effectiveness of biologicals as preventive or therapeutic interventions. The dosage of biological agents and the duration of disease induction varied depending on the EP model. In all studies, the main outcome-alveolar bone loss, a hallmark of EP-was significantly inhibited by biological agents, which also reduced proinflammatory mediators when compared to untreated controls. A key strength of this review is the high number of studies included, most of which were classified as having low risk of bias. However, a notable limitation is the absence of a meta-analysis, the short follow-up periods in the included studies, and the heterogeneity among the compound dosages and route of administration. Conclusion: This systematic review demonstrates that biological agents are effective in reducing bone loss and mitigating inflammation during EP progression. Randomized clinical trials are needed to confirm these findings in human populations., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Gabriela Ezequiel Oliveira et al.)

Periodontitis, a highly prevalent multicausal chronic inflammatory and destructive disease, develops as a result of complex host-parasite interactions. Dysbiotic bacterial biofilm in contact with the gingival tissues initiates a cascade of inflammatory events, mediated and modulated by the host's immune response, which is characterized by increased expression of several inflammatory mediators such as cytokines and chemokines in the connective tissue. If periodontal disease (PD) is left untreated, it results in the destruction of the supporting tissues around the teeth, including periodontal ligament, cementum, and alveolar bone, which lead to a wide range of disabilities and poor quality of life, thus imposing significant burdens. This process depends on the differentiation and activity of osteoclasts, the cells responsible for reabsorbing the bone tissue. Therefore, the inhibition of differentiation or activity of these cells is a promising strategy for controlling bone resorption. Several pharmacological drugs that target osteoclasts and inflammatory cells with immunomodulatory and anti-inflammatory effects, such as bisphosphonates, anti-RANK-L antibody, strontium ranelate, cathepsin inhibitors, curcumin, flavonoids, specialized proresolving mediators, and probiotics, were already described to manage inflammatory bone resorption during experimental PD progression in preclinical studies. Meantime, a growing number of studies have described the beneficial effects of herbal products in inhibiting bone resorption in experimental PD. Therefore, this review summarizes the role of several pharmacological drugs used for PD prevention and treatment and highlights the targeted action of all those drugs with antiresorptive properties. In addition, our review provides a timely and critical appraisal for the scientific rationale use of the antiresorptive and immunomodulatory medications in preclinical studies, which will help to understand the basis for its clinical application., Competing Interests: The authors declare no conflicts of interest to report regarding the present study., (Copyright © 2022 Angelica Leticia Reis Pavanelli et al.)