Calprotectin (S100A8/S100A9) is an inflammation-related protein that is produced in leukocytes, macrophages/monocytes, and epithelial cells, and its level increases in several inflammatory diseases including ulcerative colitis, rheumatoid arthritis, and cystic fibrosis [14, 15]. Calprotectin was previously detected in GCF, and its level was significantly higher in GCF from periodontal disease sites than in that from healthy non-diseased sites [16, 17]. Furthermore, GCF calprotectin levels correlated with clinical indicator levels, such as PD, GI, and BOP [17, 18], and was shown to predict periodontal disease activity [19]. These findings indicate that calprotectin is a useful inflammatory biomarker for periodontal diseases. Calprotectin was also detected in PICF, but its levels in PICF samples from healthy and peri-implant disease sites were not compared [20].

Cross-linked N-telopeptide of type I collagen (NTx) is a product of bone type I collagen degradation by cathepsin K in osteoclasts, is released into blood and urine, and is a specific biomarker of bone resorption [21,22,23]. NTx levels have been shown to increase in the blood and urine of patients with osteoporosis, hyperparathyroidism, and bone metastasis of cancer and are used as a diagnostic marker for these bone metabolism diseases [23, 24]. GCF contains NTx, and significant differences were not detected in its levels in GCF between healthy and periodontitis sites [25,26,27]. In contrast, Aruna [28] examined NTx in GCF samples from periodontitis sites and did not detect NTx in GCF from healthy sites. Although Friedmann et al. [20] measured NTx amounts in PICF and GCF, its levels in PICF did not correlated with changes of alveolar bone levels.

This pilot study aims to investigate whether calprotectin and NTx levels in PICF reflect inflammation and alveolar BL in peri-implant tissues, respectively, and also if these proteins are useful biomarkers for the diagnosis of peri-implant diseases.