Effectiveness of revitalization in treating apical periodontitis: A systematic review and meta-analysis

Background Revitalization procedures primarily aim to eliminate clinical symptoms and heal periapical lesions. Objectives The objective of the study was to elucidate the effectiveness of revitalization in treating apical periodontitis in necrotic mature and immature permanent teeth based on the following PICO question: In patients with permanent immature or mature teeth and pulp necrosis with or without signs of apical periodontitis (P) what is the effectiveness of revitalization (I) in comparison with calcium hydroxide apexification, apical plug and root canal treatment (C) in terms of tooth survival, pain, tenderness, swelling, need for medication (analgesics and antibiotics), radiographic evidence of reduction of apical lesion size, radiographic evidence of normal periodontal ligament space, radiographic evidence of increased root thickness and length (not for mature teeth), tooth function (fracture and restoration longevity), need for further intervention, adverse effects (including exacerbation, restoration integrity, allergy and discolouration), oral health-related quality of life (OHRQoL), presence of sinus tract and response to sensibility testing (O). (T) = Defined as a minimum of 1 year and maximum of as long as possible for all outcome measures, except 'pain, tenderness, swelling, need for medication (analgesics)', which is a minimum of 7 days and maximum of 3 months and OHRQoL which is minimum of 6 months and a maximum of as long as possible. Methods Three databases (PubMed, Embase and Cochrane Library) were searched for human, experimental and observational studies in English, complemented with hand search, until 31/10/2021. Studies recruiting teeth with pulp necrosis (with/without apical periodontitis), with minimum 10 teeth/arm at the end of the study and with a follow-up of at least 1 year, were included. Records without an abstract and a full text were excluded. The qualitative analysis of the included (non-) randomized controlled clinical trials was performed with the Revised Cochrane risk-of-bias tools (RoB 2 and ROBINS-I). Meta-analysis for survival and success (including a subgroup analysis for mature/immature permanent teeth) was performed using the Mantel-Haenszel method. The certainty of evidence was assessed using GRADE (Grades of Recommendation, Assessment, Development and Evaluation). Results From the 365 identified records, five met the inclusion criteria. The 12 months survival rate was 100% for all (im)mature permanent teeth in all groups (3 studies). The success rate at 12 months was 100% for immature permanent teeth for I and C (1 study), however, reduced to 92% and 80% for mature teeth in I and C respectively (1 study, p > .05). The risk of bias for the most critical outcome (survival) was high for two studies and low for one. For the critical outcome success, all assessed studies were highly biased. Meta-analyses provided pooled relative risk with no statistically significant difference between I and C for both survival (RR = 1.00, 95%CI = 0.96-1.04, p = 1.00) and success (RR = 1.06; 95%CI = 0.83-1.35, p = .66). The evidence level for survival was kept 'low' and for success was downgraded to 'very low' due to inconsistency and imprecision. Discussion The survival and success rates were favourable in all included studies and for all groups; however, these outcomes are not reliable due to the low certainty level. Clinically, the most reported adverse event was tooth discolouration, hence the application of bismuth oxide containing calcium silicate cements should be avoided in revitalization. Radiographically, caution is needed when assessing periapical bone healing and further root development with periapical radiographs, due to multifactorial inaccuracies of this imaging technique. Methodological and assessment concerns need to be addressed in future clinical trials. Long-term results are necessary for studies reporting revitalization of mature permanent teeth, as they seem to be experimental so far. Conclusions No robust evidence was discovered to support that revitalization is effective to treat apical periodontitis in (im)mature permanent teeth. The success and survival rates of revitalized and fully pulpectomized (im)mature permanent teeth did not differ significantly. Registration Prospero: CRD42021262466.