Peri-Implantitis Diagnosis and Prognosis Using Biomarkers in Peri-Implant Crevicular Fluid: A Narrative Review

Abstract

Dental implant diseases, peri-implantitis (PI) and peri-implant mucositis (PIM), have shown wide prevalence in recent studies. Despite the prevalence, diagnosing peri-implant disease (PID) remains challenging as common diagnostic methods of periodontal probing and radiographs may be inaccurate. These methods only document pre-existing destruction rather than current disease activity. Furthermore, there is no current model to predict the progression of PID. Though a predictive model is lacking, biomarkers may offer some potential. Biomarkers are commonly used in medicine to objectively determine disease state, or responses to a therapeutic intervention. Gingival crevicular fluid (GCF) biomarkers have moderate diagnostic validity in periodontitis. Biomarkers in peri-implant crevicular fluid (PICF) also show promising results in regard to their diagnostic and prognostic value. The aim of this review is to summarize the current knowledge of PICF biomarkers in the diagnosis of PID and evaluate their validity to predict disease progression. This review found that PICF studies utilize different methods of sampling and interpretation with varying validity (sensitivity and specificity). A number of promising diagnostic techniques were identified. Commercially available chair-side tests for MMP-8 to diagnose periodontal disease and PID activity are now available. Future directions include proteomics and metabolomics for accurate, site-specific diagnosis and prediction of PID progression. Although more research is needed, this review concludes that the assessment of proinflammatory cytokines (IL-1β, TNFα, MMP-8) in the PICF may be of value to diagnose PI and PIM but current research remains insufficient to indicate whether biomarkers predict peri-implant disease progression.

Gingival Response to Dental Implant: Comparison Study on the Effects of New Nanopored Laser-Treated vs. Traditional Healing Abutments

“…It has been already reported that the upregulation of MMP-9, a regulatory factor in neutrophil migration across the basement membrane, is linked to the irreversible destruction of peri-implant tissue [ 14 ] and that low levels of TIMP-1 are associated with peri-implant disease progression [ 14 ]. Indeed, in healthy conditions, MMP-9 and TIMP-1 are in balance, but in many diseases and inflammatory processes, MMP-9 levels become higher, without a concomitant increase in TIMP-1.…”

“…This unbalanced condition leads to tissue damage [ 40 ]. TIMP-1, in particular, is barely expressed in periodontitis in comparison with healthy subjects; on the other hand, its overproduction contributes to inhibiting the inflammation and tissue damage, due to the hyperactivation of MMP-9 [ 16 ], in the wound area after healing abutment implantation, suggesting that it exerts a pivotal role in controlling peri-implant disease progression [ 14 , 17 ]. The important role of MMP-9 in inflammation entails strict control of its expression.…”

“…Modification of its expression reflects local differences in cell populations and their state of activation [ 41 ]. In soft tissue facing the machined surface, we observed an increased expression in TNF-α, a proteases activator that induces fibroblasts apoptosis and osteoclasts proliferation, leading, consequently, to bone resorption together with reduced repair capacity of peri-implant tissues [ 14 ]. TNF-α, produced by macrophages, lymphocytes, and activated neutrophils [ 42 ] would induce the release of the neutrophil chemoattractant ICAM-1 and MMP-9, by establishing a self-maintenance loop that cannot be compensated for by the too-low levels of IL-10 and TIMP-1.…”

“…Therefore, regulation of ICAM-1 expression and differences in ICAM-1 levels in JE might depend not only on bacteria-derived lipopolysaccharides, but also on local inflammatory factors [ 12 ]. TNF-α is one of the main culprits in the progression of the gingival inflammation and bone resorption, stimulating both the osteoclast activity and the release of Matrix Metalloproteinases (MMPs), which, in turn, catalyze the degradation of extracellular matrix, connective tissue and alveolar bone [ 14 ]. MMP-9, in particular, appears to be a regulatory factor in neutrophil migration across the basement membrane [ 15 ] and its activity is negatively regulated by the Tissue Inhibitor of Metalloproteinase-1 (TIMP-1) [ 16 ], that, when regularly expressed, inhibits inflammation and tissue damage in the wound area after healing abutment implantation [ 14 , 17 ].…”

“…TNF-α is one of the main culprits in the progression of the gingival inflammation and bone resorption, stimulating both the osteoclast activity and the release of Matrix Metalloproteinases (MMPs), which, in turn, catalyze the degradation of extracellular matrix, connective tissue and alveolar bone [ 14 ]. MMP-9, in particular, appears to be a regulatory factor in neutrophil migration across the basement membrane [ 15 ] and its activity is negatively regulated by the Tissue Inhibitor of Metalloproteinase-1 (TIMP-1) [ 16 ], that, when regularly expressed, inhibits inflammation and tissue damage in the wound area after healing abutment implantation [ 14 , 17 ]. Among the landscape of anti-inflammatory mediators, Interleukin-10 (IL-10) has been reported to have a more powerful anti-inflammatory activity, with a pivotal role in the modulation of the inflammatory cascade in peri-implant tissues [ 10 ].…”