Objectives: Bone remodeling usually depends on complex molecular signaling, where receptor activator of NF-B ligand (RANKL) and osteoprotegerin (OPG) serve as key modulators that regulate osteoclastogenesis and overall bone metabolism process. This systematic review aimed to evaluate the influence of different graft materials on RANKL and OPG expression following alveolar ridge preservation. Methods: An electronic search of the literature was performed in Embase via Ovid, Medline via Ovid, CINAHL, Scopus and Web of Science databases, in addition to a manual search regarding all related articles. PRISMA guidelines and PICO framework were followed in this systematic review. The inclusion criteria were limited to English-published studies focusing on RANKL and/or OPG biomarkers’ outcomes in post-extraction dental sockets preserved with various types of bone grafts. The extracted data were synthesized in a standardized excel form including general study characteristics, graft interventional details, and RANKL/OPG expressions in addition to other outcomes regarding bone healing. Risk of bias, using ROBINS-I and RYRCLE tools, as well as certainty of evidence were assessed within included studies. Results: The initial search resulted in a total of 307 articles. After thorough screening and reviewing stages, 12 studies were finally selected to be included for comprehensive analysis. The findings revealed that socket preservation with different grafts demonstrated statistically significant differences in favor of RANKL downregulation and OPG upregulation compared to controls; the composite graft demonstrated superior outcomes to other types. The lowest RANKL/OPG ratio (0.11) was reported in the biologically enhanced autograft while synthetic graft alone showed the highest value (1.88). Conclusion: Bone substitutes that combine bioactive agents with scaffolds may offer potential benefits for socket preservation, possibly through modulation of the RANKL/OPG axis. However, their superiority over other grafts and the reliability of the RANKL/OPG ratio as a predictive biomarker remain uncertain, warranting further clinical investigation.
