Histopathological Verification of Osteoimmunological Mediators in Peri-Implantitis and Correlation to Bone Loss and Implant Functional Period
Peri-implantitis (PI) is characterized by inflammation and bone resorption eventually leading to implant failure, but the characteristic pathologic determinants are undefined to date. This study aims to elucidate the parameters involved in PI pathogenesis, including intraoral implant retention time, extent of bone loss, smoking history, and identification of osteoimmunological markers for inflammation and bone loss. Peri-implant tissues (n = 21) displaying clinically diagnosed PI from patients with vertical bone loss ranging from 0–12 mm and implant function period between 1 and 60 months were evaluated by histochemistry and immunohistochemistry for TRAP, CD3, RANK, RANKL, OPG, and TNF-α. Statistical analyses were performed with the Welch test and correlation coefficients were calculated. Most bone resorption occurred during the first 12 months of implant function and correlated with the extent of inflammation, although histological signs of inflammation strongly varied between samples from minimal appearance of inflammatory cells to extended infiltrates. Implant function period and smoking history did not significantly affect the degree of inflammation. Higher RANK levels emerged in the first 12 months of implant function compared to longer retention times and were negatively correlated to the occurrence of RANKL. Additionally, histological signs of inflammation were about two-fold higher in specimens with bone resorption up from 5 mm compared to under 5 mm. CD3+ cells were more prevalent in extensive inflammatory infiltrates and samples derived from smokers. Our analyses proved that PI-induced bone loss is differentially influenced by the parameters evaluated in this study, but a distinct interconnection between disease severity and implant retention time can be established.
Histological photomicrographs of healthy and diseased gingival structures. (a) Clinically healthy gingiva with stratified squamous epithelium (E) and subepithelial gingival connective tissue (G). Original magnification ×10. (b) Clinically healthy peri-implant gingiva with insular epithelial structures (E) and a dense subepithelial gingival connective tissue (G). Original magnification ×20. (c) Peri-implantitis (PI) tissue with stratified squamous epithelium (E) and subepithelial gingival connective tissue (G) with inflammatory cell infiltrates (I) and insular bony fragments (B). Original magnification ×5.
Histochemical photomicrograph of tartrate-resistant acid phosphatase (TRAP) stained gingival structures. TRAP positive cell populations comprising macrophages (arrows) and cells with osteoclast-like morphology (arrowheads) scattered in gingival structures. Original magnification ×20.
Immunohistochemical photomicrographs of healthy and diseased gingival structures. (a) CD3 staining in healthy gingiva comprising epithelium (E) and gingival connective tissue (G) revealed only few positive lymphocytes (arrowheads). Original magnification ×40. (b) CD3 positive cells (arrowheads) in extensive immune cells infiltrations of PI tissues. Original magnification ×20. (c) Moderate OPG verification in epithelial structures (E) of healthy gingiva and absence in gingival connective tissue (G). Original magnification ×40. (d) Intense OPG immunostaining in cells of inflammatory infiltrates (I) and in the extracellular matrix (E) in peri-implantitis (PI) tissues. Original magnification ×40. (e) RANK immunoreactivity in the subepithelial gingival connective tissue (G) and weakly in epithelial structures (E) of clinically healthy peri-implant tissues. Original magnification ×40. (f) Considerable confirmation of RANK in the subepithelial gingival connective tissue (G) and in bony fragments of a specimen with PI diagnosis. Original magnification ×20. (g) Focal RANKL verification in the epithelial layer (E) and absence in gingival connective tissue (G) of healthy gingiva. Original magnification ×20. (h) Distinct RANKL staining in the epihelium (E) and moderate verification in inflammatory cell infiltrates (I) of the subepithelial gingival connective tissue (G) affected by PI. Original magnification ×20. (i) Focal cellular and extracellular TNF-α staining in subepithelial gingival connective tissue (G) of peri-implant healthy gingiva. Original magnification ×20. (j) Strong TNF-α staining in the epithelium (E) and in inflammatory infiltrates (I) of PI tissues. Original magnification ×20.
(a) Bone loss around dental implants in PI specimens in relation to intraoral implant retention time. Amount of bone loss (y-axis) referring to the time period the implants were kept in situ (x-axis) illustrated as a dot plot of each specimen investigated. Data were obtained from 21 specimens.
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