This study aimed to evaluate the effect of oral administration of probiotics as an adjunctive treatment to local intracanal medicaments, namely propolis and calcium hydroxide or empty canal, on the levels of receptor activator of nuclear factor kappa B ligand (RANKL) and osteoprotegerin (OPG), as well as on postoperative pain following root canal retreatment of teeth with chronic apical periodontitis

Post-treatment chronic apical periodontitis is an inflammatory condition caused by persistent microbial infection within the root canal system, characterized by progressive periapical bone destruction mediated by host immune-inflammatory mechanisms. Root canal retreatment remains the treatment of choice for failed endodontic cases; however, postoperative pain and incomplete resolution of inflammatory mediators remain common concerns. Clinical evidence demonstrates that postoperative pain following endodontic retreatment is influenced by microbial persistence, host inflammatory response, and intracanal medication protocols.

The RANK/RANKL/OPG axis is a key regulator of osteoclastic activity and periapical bone resorption. Elevated RANKL levels and altered RANKL/OPG ratio are associated with active periapical bone destruction. Modulation of this pathway may improve healing outcomes. Recent studies suggest that probiotics can regulate immune response, reduce inflammatory cytokines, and decrease RANKL expression.

This randomized clinical trial includes patients diagnosed with previously root-filled teeth presenting with chronic apical periodontitis indicated for non-surgical retreatment.

Standardized retreatment procedures are performed under aseptic conditions. Periapical exudate samples collected for biochemical analysis of RANKL and OPG levels at predetermined time points. Postoperative pain is assessed to investigate whether systemic probiotic administration can act as a host-modulating adjunct in endodontic retreatment and improve both symptomatic and biological healing outcomes.

Inclusion Criteria:

• Previously treated failed single rooted teeth with chronic apical periodontitis.
• No use of antibiotic three months before treatment.
• Patients are free of any systemic disease.
• Positive patient acceptance for participation

Exclusion Criteria:

• Teeth that are badly broken down with difficult isolation.
• Signs of acute infection, root fracture, root surface caries, swellings or ankylosis
• Periodontally affected teeth with pockets deeper than 4mm.
• Pregnant or lactating woman.
• Patients who needs any prophylactic antibiotic.
• Patients with allergy to pollen.

Masking was implemented at the participant and outcomes assessor levels. Randomization and allocation concealment were performed by an independent person not involved in treatment procedures or outcome assessment. For systemic probiotic, the probiotic and placebo capsules were prepared in identical opaque containers, and the allocation key was maintained by the independent allocator until completion of data collection. so, the principal investigator and care provider were blinded regarding probiotic/placebo allocation throughout the intervention period.

However, due to the nature of the intracanal medicament intervention (calcium hydroxide or propolis or left empty ), blinding of the principal investigator and care provider was not feasible at the stage of ICM placement. But allocation concealment for the intracanal medicament was maintained using sealed opaque envelopes, which were opened only after completion of all treatment procedures and immediately before placement of the ICM