Molecular biomarkers for objective assessment of symptomatic pulpitis: A systematic review and meta‐analysis

Abstract Background Inflammatory biomarkers are potentially useful targets for pulpal diagnostic tests that can identify pulp status and predict vital pulp treatment (VPT) outcome, however, their accuracy is unknown. Objectives (1) Calculate sensitivity, specificity and diagnostic odds ratio (DOR) of previously investigated pulpitic biomarkers; (2) Determine if biomarker levels discriminate between clinical diagnoses of pulpitis based on the presence or absence of spontaneous pain (3) Evaluate if biomarker level can predict VPT outcome. Methods Searches: PubMed/MEDLINE, Ovid SP, Cochrane Central Register of Controlled Trials (CENTRAL), International Clinical Trials Registry Platform (ICTRP), ClinicalTrials.gov, Embase, Web of Science and Scopus in May 2023. Inclusion: prospective and retrospective observational studies and randomized trials. Participants were humans with vital permanent teeth and a well‐defined pulpal diagnosis. Exclusion: deciduous teeth, in vitro and animal studies. Risk of bias was assessed with modified‐Downs and Black quality assessment checklist. Meta‐analysis was performed using bivariate random effect model in Meta‐DiSc 2.0 and RevMan and the quality of the evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation. Results Fifty‐six studies were selected, reporting >70 individual biomolecules investigating pulpal health and disease at the gene and protein level. Most studies were of low and fair quality. Among the biomolecules investigated, IL‐8 and IL‐6 demonstrated a level of diagnostic accuracy with high sensitivity, specificity and DOR to discriminate between healthy pulps and those exhibiting spontaneous pain suggestive of IRP (low‐certainty evidence). However, none was shown to have high DOR and the ability to discriminate between pulpitic states (very low certainty evidence). Limited data suggests high levels of matrix metalloproteinase 9 correlate with poorer outcomes of full pulpotomy. Discussion The inability of identified molecular inflammatory markers to discriminate between dental pulps with spontaneous and non‐spontaneous pain should shift the focus to improved study quality or the pursuit of other molecules potentially associated with healing and repair. Conclusions Low‐quality evidence suggests IL‐8 and IL‐6 demonstrated level of diagnostic accuracy to discriminate between healthy pulps and those exhibiting spontaneous pain. There is a need for standardized biomarker diagnostic and prognostic studies focusing on solutions that can accurately determine the degree of pulp inflammation. Registration PROSPERO CRD42021259305.