Određivanje biomarkera gubitka alveolarne kosti kod pacijenata sa peri-implantitisom
Determination of alveolar bone loss biomarkers related to peri-implantitis
2012
Authors:
Rakić, MiaContributors
Leković, VojislavAleksić, Zoran
Janković, Saša
Marković, Aleksa
Jovanović, Tanja
Document Type:
Doctoral thesis (Published version)
Metadata
Show full item recordAbstract:
Introduction. Peri-implantitis is inflammatory process characterized by supporting bone loss
of loaded oral implants. The pathognomonic characteristic of peri-implantitis is supporting
bone loss of the loaded implant. This process is based on inflammatory osteoclastogenesis
which simultaneously represent the central pathologic process of the disorder. Inflammatory
osteoclastogenesis implies maturation of pre-osteoclasts and enhancement of the activity of
maturated osteoclasts which are induced by achieving of the critical concentrations of proinflammatory
mediators. Clinical characteristics of the peri-implantitis are still not strictly
defined and they vary because in the physiological conditions the values of clinical
parameters varies among individuals, for example peri-implant sulcus depth represents the
individual determinant which could be from 0.5mm to 4mm as well. Simultaneously, the
marginal bone loss is the physiological characteristic around implants in function, which is
the most intensive in the first year of loading represented by the -0.78mm in the mesial sites
and -0.85mm at the distal sites, and after that the process is constant and bone loss at the year
level is approximately 0.2mm. The mentioned value is the average values that individually
vary and it depends of the implant type, abutments and numerous other factors. From that
reason the relative clinical attachment level (rCAL), nether radiological proof of bone loss
could be accepted as the absolute indicators of the pathological bone loss. In the peri-implant
diagnostics the most frequently are used the few different diagnostic procedures in the
combination to give the complete diagnostic view. These diagnostic methods include:
evaluation of clinical parameters, radiological analyses, microbiological analyses and
quantitative and qualitative analyses of PICF. The PICF analysis is one of the most attractive
methods in current implantology, where the one of the most precious values is providing of
the direct information on peri-implant tissues d based on that providing information on early
disease onset in the phase of reversible damage. This limitation of clinical methods results in
time loss proportionally decreasing treatment success, and frequently resulting in
inappropriate treatment planning. Based on that, evaluation of biomarkers in PICF sample
compensates limitations of conventional diagnostic procedures without capability to provide
accurate information on early disease. Numerous studies have been conducted to identify the
biomolecules accurately reflecting peri-implant tissue condition, but since the pathology of
local metabolism is complex, the method for evaluation is still under standardization.
Objective. The objective of the study was to investigate potential of RANK, sRANKL, OPG,
Cathepsin-K, Sclerostin and VEGF as biomarkers of implant supporting bone loss. Material
and methods. Study included three groups of systemically healthy non smokers with
osseointegrated endosseal implants loaded for at least one year (35 with peri-implantitis, 30
with peri-mucositis and 30 with healthy peri-implant tissues). Exclusion criteria were the
following: antibiotics usage in the preceding three months and anti-inflammatorics in
preceding two months from the moment of sampling, menstruation, pregnancy and lactation,
smoking and periodontal/peri-implant treatment during last year. The following clinical
measurements have been performed in 6 points (bucco-mesial, bucco -medial, bucco -distal,
oro-distal, oro-medial and oro-mesial): Bleeding on Probing (BOP) measured 15 seconds after
probing and recorded as presence (1) or absence (0), Visible plaque accumulation (PI)
measured along the mucosal margin and recorded as presence (1) or absence (0), Probing
Pocket Depths (PPD) in mm and Relative Clinical Attachment Level (rCAL) (expressed in
mm) using a periodontal probe graded in mm (North Carolina–Hu-Friedy, Chicago, IL, USA).
In the case of few similar pathological processes in the same patient, the site representing the
greatest defect was sampled, and in the case of defects showing similar clinical
characteristics, the most accessible was included. PICF samples were collected from the
mesial aspects of one representative implant site in each individual participating in the study.
The specimens were retrieved 24 h after the clinical examination to avoid any contamination
with blood, from both peri-implant and periodontal sites, selected from those demonstrating
the deepest probing depth. The samples were retrieved using the filter paper technique, and
obtained volume was evaluated using calibrated Periotron 6000 (Interstate Drug Exchange,
Amityville, NY, USA). Commercial enzyme linked immunosorbent kits (ELISA) were used
for evaluation of biomarkers in PICF samples: Human RANK/TNFRSF11A (DuoSet, R&D
Systems Inc., Minneapolis, MN, USA), ampli-sRANKL, OPG, cathepsin-K i sclerostin
(Biomedica Gruppe, Vienna, Austria) i VEGF (Human VEGF ELISA Development Kit,
Promokine, PromoCell GmbH, Heidelberg, Germany). Results. In all tested PICF samples
were detected RANK, sRANKL, OPG, cathepsin-K and VEGF, indicating the concentrations
above detection limit, but only 6% of the samples were positive on sclerostin. RANK
concentration was significantly higher in peri-implantitis when compared to healthy periimplant
tissues (p=0.002), and it was higher when compared to peri-mucositis as well
(p=0.021). sRANKL values were significantly higher in peri-implantitis when compared to
healthy peri-implant tissues (p=0.010), but not when compared to peri-mucositis, nether perimucositis
an healthy peri-implant tissues. OPG concentration was significantly higher in periimplantitis
when compared to healthy peri-implant tissues (p=0.031), and that was single
significance obtained for this marker. sRANKL/OPG relative ration did not show significant
difference in distribution between investigated groups. Cathepsin-K were in general higher in
inflammed sites, but the single significance was reached among peri-mucositis and healthy
peri-implant tissues (p=0.039). Sclerostin was detected in small sample size, but the
differences were clearly higher in peri-implantitis group when compared to both two groups.
VEGF concentration was significantly higher in peri-implantitis when compared to healthy
peri-implant tissues (p=0.000) and peri-mucositis as well (p=0.014). RANK and sRANKL
showed significantly positive correlation with all measured clinical parameters, and OPG
showed significantly positive correlation with all measured clinical parameters as well, with
exception of PI (p=0.121), and an identical case was with sclerostin. VEGF showed no
significant correlations with clinical parameters. Conclusion. RANK, sRANKL, OPG,
sclerostin and VEGF are biomarkers related to peri-implantitis. Cathepsin-K was the marker
related to peri-mucositis. Evaluated in this study are differently distributed in different jaws
regions and in PICF samples of implants with different diameter. RANK and OPG were
significantly elevated in frontal maxillary region, indicating more intensive osteolytic
processes in this region. RANK and cathepsin-K were significantly increased in the group o
implants with highest diameter, which supports on molecular level the previous results of
clinical studies that showed positive correlation between implant diameter and implant loss.
Keywords:
Peri-implantitis; Peri-mucositis; RANK; RANKL; OPG; Cathepsin-K; Sclerostin; VEGF; Biomarker; BoneSource:
University of Belgrade, Faculty of Dental Medicine, 2012, 1-70URI
http://eteze.bg.ac.rs/application/showtheses?thesesId=584https://fedorabg.bg.ac.rs/fedora/get/o:6743/bdef:Content/download
http://vbs.rs/scripts/cobiss?command=DISPLAY&base=70036&RID=1024187278
http://nardus.mpn.gov.rs/123456789/2684
https://radar.ibiss.bg.ac.rs/handle/123456789/2443