Biomarkers in peri-implant crevicular fluid of healthy implants and those with peri-implant diseases: a systematic review and meta-analysis

Introduction: Several biomarkers in peri-implant crevicular fluid have been studied to diagnose peri-implant diseases with inconclusive results. This systematic review and meta-analysis aimed to comprehensively compare data on the levels of biological components in peri-implant crevicular fluid collected from healthy and diseased implants to identify reliable biomarkers for diagnosing and monitoring peri-implant disease. Materials and Methods: The search strategy included studies comparing biomarker levels in peri-implant crevicular fluid between healthy and diseased implants through electronic databases (MEDLINE/PubMed, Embase, Cochrane Library), grey literature, and hand-searching relevant journals and reference lists of pertinent papers. A two-stage screening was performed in duplicate and independently. In the first stage, titles and abstracts that fulfilled eligibility criteria were screened. In the second stage, a full-text analysis was conducted to verify eligibility. All articles meeting the inclusion criteria underwent data extraction and quality assessment. Meta-analyses were conducted on studies with similar comparisons and outcome measures. Results: After screening the titles and abstracts, out of 100 potentially relevant papers identified for full-text evaluation, 49 were excluded, 51 were included in the qualitative analysis, and 18 were included in the quantitative synthesis. Among 96 biomarkers assessed, the most studied were pro-inflammatory cytokines (IL-1ß, IL-6, TNF-α, and IL-17), osteoclastogenic-related factors (RANK, RANKL, and OPG), anti-inflammatory cytokines (IL-10), chemokines (IL-8, MIP-1α/CCL3, and MIP-3α/CCL-20), and enzymes (MMP-8, Cat-K, AST, and ALT). Conclusions: Meta-analyses comparing data from healthy patients and those with peri-implantitis or mucositis and between patients with mucositis and those with peri-implantitis showed a moderate predictive value of IL-1ß, VEGF, cortisol, and sRANKL/ OPG for peri-implantitis.