The key role of RANKL and OPG as molecular biomarkers in bone remodeling associated with different grafts regarding socket preservation: A systematic review

Abstract

Objectives

Bone remodeling usually depends on complex molecular signaling, where receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG) are key modulators that regulate osteoclastogenesis and the overall bone metabolism process. The aims of this systematic review were to evaluate the effects of different graft materials on RANKL and OPG expression following alveolar ridge preservation.

Methods

Electronic literature searches were performed in Embase via Ovid, Medline via Ovid, CINAHL, Scopus, and Web of Science databases, in addition to manual searches regarding all related articles. The PRISMA guidelines and PICO framework were followed in this systematic review. The inclusion criteria were limited to studies published in English that focused on RANKL and/or OPG biomarker outcomes in post-extraction dental sockets preserved with various types of bone grafts. The extracted data were synthesized in a standardized MS Excel form, including general study characteristics, graft interventional details, and RANKL/OPG expression, in addition to other outcomes regarding bone healing. Risk of bias was assessed using ROBINS-I and RYRCLE tools, as well as certainty of evidence for the studies included.

Results

The initial search yielded 307 articles. After thorough screening and reviewing stages, 12 studies were finally selected for inclusion and comprehensive analysis. The findings showed that socket preservation with different grafts led to significant differences in promoting RANKL downregulation and OPG upregulation compared with controls, where composite grafts obtained superior outcomes than other types. The lowest RANKL/OPG ratio (0.11) was reported for a biologically enhanced autograft, whereas using a synthetic graft alone had the highest value (1.88).

Conclusion

Bone substitutes that combine bioactive agents with scaffolds may provide potential benefits for socket preservation, possibly through modulating the RANKL/OPG axis. However, their superior performance compared with other grafts and the reliability of using the RANKL/OPG ratio as a predictive biomarker remain uncertain, warranting further clinical investigation.