TY  - JOUR
AU  - Đuran, Boris
AU  - Tatić, Zoran
AU  - Perunović, Neda
AU  - Pejčić, Nataša
AU  - Vuković, Jovana
AU  - Petković-Ćurčin, Aleksandra
AU  - Vojvodić, Danilo
AU  - Rakić, Mia
PY  - 2023
UR  - https://www.mdpi.com/1660-4601/20/1/477
UR  - http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC9819861
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5403
AB  - Peri-implant diseases are an emerging public health problem, and it's considered that limitations of standard diagnostics play the role herein. The study objective was the estimation of pathological bone resorption at clinical and biological level in patients with peri-implant mucositis (PIM) and peri-implantitis (PI) before and 6 months after standard treatment and to compare them with healthy controls (HC). The split-mouth interventional study included 60 patients affected with PIM or PI. Patients that also presented at least one more HC were enrolled in the study and underwent standard non-surgical and surgical treatment, respectively. Standard clinical parameters and soluble levels of RANKL were measured in peri-implant crevicular fluid baseline and 6 months following treatment. Clinical parameters and RANKL significantly decreased following treatment in PIM and PI. However, bleeding on probing and probing depth remained significantly increased when compared to HC. RANKL answered requests for biomarker of peri-implant diseases, its baseline levels were significantly increased in PIM and PI, they decreased following treatment and reached HC in peri-implantitis, while in PIM RANKL remained significantly increased. Presence of pathological bone resorption in patients lacked its clinical signs, and respective persistence following treatment suggest the need for biomarker-supported diagnosis for timely diagnosis of peri-implantitis and appropriate orientation of respective management strategies.
PB  - Basel: MDPI
T2  - International Journal of Environmental Research and Public Health
T1  - Underdiagnosis in Background of Emerging Public Health Challenges Related to Peri-Implant Diseases: An Interventional Split-Mouth Study
IS  - 1
VL  - 20
DO  - 10.3390/ijerph20010477
SP  - 477
ER  - 

@article{
author = "Đuran, Boris and Tatić, Zoran and Perunović, Neda and Pejčić, Nataša and Vuković, Jovana and Petković-Ćurčin, Aleksandra and Vojvodić, Danilo and Rakić, Mia",
year = "2023",
abstract = "Peri-implant diseases are an emerging public health problem, and it's considered that limitations of standard diagnostics play the role herein. The study objective was the estimation of pathological bone resorption at clinical and biological level in patients with peri-implant mucositis (PIM) and peri-implantitis (PI) before and 6 months after standard treatment and to compare them with healthy controls (HC). The split-mouth interventional study included 60 patients affected with PIM or PI. Patients that also presented at least one more HC were enrolled in the study and underwent standard non-surgical and surgical treatment, respectively. Standard clinical parameters and soluble levels of RANKL were measured in peri-implant crevicular fluid baseline and 6 months following treatment. Clinical parameters and RANKL significantly decreased following treatment in PIM and PI. However, bleeding on probing and probing depth remained significantly increased when compared to HC. RANKL answered requests for biomarker of peri-implant diseases, its baseline levels were significantly increased in PIM and PI, they decreased following treatment and reached HC in peri-implantitis, while in PIM RANKL remained significantly increased. Presence of pathological bone resorption in patients lacked its clinical signs, and respective persistence following treatment suggest the need for biomarker-supported diagnosis for timely diagnosis of peri-implantitis and appropriate orientation of respective management strategies.",
publisher = "Basel: MDPI",
journal = "International Journal of Environmental Research and Public Health",
title = "Underdiagnosis in Background of Emerging Public Health Challenges Related to Peri-Implant Diseases: An Interventional Split-Mouth Study",
number = "1",
volume = "20",
doi = "10.3390/ijerph20010477",
pages = "477"
}

Đuran, B., Tatić, Z., Perunović, N., Pejčić, N., Vuković, J., Petković-Ćurčin, A., Vojvodić, D.,& Rakić, M.. (2023). Underdiagnosis in Background of Emerging Public Health Challenges Related to Peri-Implant Diseases: An Interventional Split-Mouth Study. in International Journal of Environmental Research and Public Health
Basel: MDPI., 20(1), 477.
https://doi.org/10.3390/ijerph20010477

Đuran B, Tatić Z, Perunović N, Pejčić N, Vuković J, Petković-Ćurčin A, Vojvodić D, Rakić M. Underdiagnosis in Background of Emerging Public Health Challenges Related to Peri-Implant Diseases: An Interventional Split-Mouth Study. in International Journal of Environmental Research and Public Health. 2023;20(1):477.
doi:10.3390/ijerph20010477 .

Đuran, Boris, Tatić, Zoran, Perunović, Neda, Pejčić, Nataša, Vuković, Jovana, Petković-Ćurčin, Aleksandra, Vojvodić, Danilo, Rakić, Mia, "Underdiagnosis in Background of Emerging Public Health Challenges Related to Peri-Implant Diseases: An Interventional Split-Mouth Study" in International Journal of Environmental Research and Public Health, 20, no. 1 (2023):477,
https://doi.org/10.3390/ijerph20010477 . .

TY  - JOUR
AU  - Paunović, Zoran
AU  - Stanojević, Ivan
AU  - Abazović, Džihan
AU  - Rakić, Mia
AU  - Stanković, Nikola
AU  - Đukić, Mirjana
AU  - Milutinović, Sanja
AU  - Starčević, Srđan
AU  - Šupić, Gordana
AU  - Vojvodić, Danilo
AU  - Jović, Milena
AU  - Marić, Dusan
PY  - 2021
UR  - http://www.doiserbia.nb.rs/Article.aspx?ID=0042-84501900062P
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4185
AB  - Background/Aim. Recent studies indicate that adipokines have an important role in bone physiology and pathology. Recent data indicate that adipokine leptin functions as a regulator of bone growth at multiple levels, systemically and locally. So far, it has been shown that leptin influences bone volume and bone mineral density in a population with metabolic and/or hormonal abnormality. Data concerning leptin values in non-obese children with fractures are scarce. Methods. This study included 93 non-obese children with long bone fractures (LBF), 14 children with short bone fractures (SBF), and 19 healthy children. Leptin concentration was determined in two blood samples (day 0 and day 21) and analyzed according to gender, fracture type, anatomical localization of the fracture, fracture topography, callus formation, and the healing outcome. Results. Children with LBF demonstrated significantly increased leptin levels compared to the control group (both day 0/day 21). In the control group, girls had significantly more leptin than boys. Leptin value was significantly influenced by anatomical localization since boys and girls with humerus fracture and girls with femur fracture had the highest average leptin concentration in the initial sample. Boys with incomplete callus formation had the highest leptin concentration (both day 0 /day 21), significantly elevated compared to boys? samples in the control group, boys? samples with an intermediary and well-formed callus, and also increased compared to the initial samples of girls with incomplete callus. Better callus formation in girls was associated with an increment of leptin concentrations in the second over the initial sample. Girls with partially and satisfactorily formed callus had significantly increased leptin concentration in the second sample (day 21) compared to the boys? group. Conclusion. Leptin concentration was significantly increased (both samples) in children with LBF compared to children with SBF and corresponding controls. Leptin concentration was highly influenced by gender. High blood leptin concentrations in boys or low leptin concentrations in girls immediately upon fracture could be used to identify groups of children with incomplete callus formation.
T2  - Vojnosanitetski pregled
T2  - Vojnosanitetski pregled
T1  - Association of bone fracture type and degree of callus formation with leptin concentration in children with long bone fractures
T1  - Povezanost tipa preloma kosti i stepena formiranja kalusa sa koncentracijom leptina kod dece sa prelomima dugih kostiju
IS  - 2
VL  - 78
DO  - 10.2298/VSP190314062P
SP  - 192
EP  - 201
ER  - 

@article{
author = "Paunović, Zoran and Stanojević, Ivan and Abazović, Džihan and Rakić, Mia and Stanković, Nikola and Đukić, Mirjana and Milutinović, Sanja and Starčević, Srđan and Šupić, Gordana and Vojvodić, Danilo and Jović, Milena and Marić, Dusan",
year = "2021",
abstract = "Background/Aim. Recent studies indicate that adipokines have an important role in bone physiology and pathology. Recent data indicate that adipokine leptin functions as a regulator of bone growth at multiple levels, systemically and locally. So far, it has been shown that leptin influences bone volume and bone mineral density in a population with metabolic and/or hormonal abnormality. Data concerning leptin values in non-obese children with fractures are scarce. Methods. This study included 93 non-obese children with long bone fractures (LBF), 14 children with short bone fractures (SBF), and 19 healthy children. Leptin concentration was determined in two blood samples (day 0 and day 21) and analyzed according to gender, fracture type, anatomical localization of the fracture, fracture topography, callus formation, and the healing outcome. Results. Children with LBF demonstrated significantly increased leptin levels compared to the control group (both day 0/day 21). In the control group, girls had significantly more leptin than boys. Leptin value was significantly influenced by anatomical localization since boys and girls with humerus fracture and girls with femur fracture had the highest average leptin concentration in the initial sample. Boys with incomplete callus formation had the highest leptin concentration (both day 0 /day 21), significantly elevated compared to boys? samples in the control group, boys? samples with an intermediary and well-formed callus, and also increased compared to the initial samples of girls with incomplete callus. Better callus formation in girls was associated with an increment of leptin concentrations in the second over the initial sample. Girls with partially and satisfactorily formed callus had significantly increased leptin concentration in the second sample (day 21) compared to the boys? group. Conclusion. Leptin concentration was significantly increased (both samples) in children with LBF compared to children with SBF and corresponding controls. Leptin concentration was highly influenced by gender. High blood leptin concentrations in boys or low leptin concentrations in girls immediately upon fracture could be used to identify groups of children with incomplete callus formation.",
journal = "Vojnosanitetski pregled, Vojnosanitetski pregled",
title = "Association of bone fracture type and degree of callus formation with leptin concentration in children with long bone fractures, Povezanost tipa preloma kosti i stepena formiranja kalusa sa koncentracijom leptina kod dece sa prelomima dugih kostiju",
number = "2",
volume = "78",
doi = "10.2298/VSP190314062P",
pages = "192-201"
}

Paunović, Z., Stanojević, I., Abazović, D., Rakić, M., Stanković, N., Đukić, M., Milutinović, S., Starčević, S., Šupić, G., Vojvodić, D., Jović, M.,& Marić, D.. (2021). Association of bone fracture type and degree of callus formation with leptin concentration in children with long bone fractures. in Vojnosanitetski pregled, 78(2), 192-201.
https://doi.org/10.2298/VSP190314062P

Paunović Z, Stanojević I, Abazović D, Rakić M, Stanković N, Đukić M, Milutinović S, Starčević S, Šupić G, Vojvodić D, Jović M, Marić D. Association of bone fracture type and degree of callus formation with leptin concentration in children with long bone fractures. in Vojnosanitetski pregled. 2021;78(2):192-201.
doi:10.2298/VSP190314062P .

Paunović, Zoran, Stanojević, Ivan, Abazović, Džihan, Rakić, Mia, Stanković, Nikola, Đukić, Mirjana, Milutinović, Sanja, Starčević, Srđan, Šupić, Gordana, Vojvodić, Danilo, Jović, Milena, Marić, Dusan, "Association of bone fracture type and degree of callus formation with leptin concentration in children with long bone fractures" in Vojnosanitetski pregled, 78, no. 2 (2021):192-201,
https://doi.org/10.2298/VSP190314062P . .

TY  - JOUR
AU  - Taso, Ervin
AU  - Rakić, Mia
AU  - Stefanović, Vladimir
AU  - Petković-Ćurčin, Aleksandra
AU  - Stanojević, Ivan
AU  - Đukić, Mirjana
AU  - Struillou, Xavier
AU  - Vojvodić, Danilo
AU  - Banović, Tatjana
AU  - Kanjevac, Tatjana
PY  - 2020
UR  - https://content.sciendo.com/doi/10.2478/sjecr-2019-0015
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4167
AB  - Profiling of biomarkers of physiological process represents an integrative part in optimisation of diagnostic markers in order to adjust the diagnostic ranges to the potential effects of the local factors such occlusal forces in case of periodontal tissues. The objective of this study was estimation of IL-1β, IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12, IL-13, IL-17, IL-22, TNFα and IFNγ concentrations in gingival crevicular fluid samples (GCF) between different groups of teeth. Two hundred fifty-nine systemically healthy non-smokers having at least one vital tooth without restorations, with healthy periodontal tissues, were clinically examined and the GCF sample was retrieved. The cytokine levels were estimated using flow cytometry and compared between central incisors (CI), lateral incisors, canines, first premolars, second premo-lars, first molars and second molars. Cytokine profiles varied between different groups of teeth with tendency of increase in pro-inflammatory cytokines from anterior teeth toward molars. Molars might be considered teeth with natural predisposition for faster bone resorption while the adjustment of diagnostic range of periodontal biomarkers for anterior or posterior teeth should be considered within diagnostic context. Cytokine profiles varied between different groups of teeth with tendency of increase in pro-inflammatory cytokines from anterior teeth toward molars. Molars might be considered teeth with natural predisposition for faster bone resorption while the adjustment of diagnostic range of periodontal biomarkers for anterior or posterior teeth should be considered within diagnostic context.
AB  - Profilisanje biomarkera fiziološkog procesa predstavlja integrativni deo optimalizacije dijagnostičkih markera, kako bi se dijagnostički rasponi prilagodili potencijalnim uticajima lokalnih faktora poput okluzijskih sila u slučaju parodontalnih tkiva. Cilj ove studije bila je procena koncentracija IL-1b, IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12, IL-13, IL-17, IL- 22, TNFα i IFNγ u uzorcima gingivalne tečnosti (GT) kod različitih grupa zuba. Klinički je pregledano dvesta pedeset devet sistemski zdravih nepušača sa najmanje jednim vitalnim zubom bez restauracija, sa zdravim parodontalnim tkivima, i uzet je GT uzorak. Nivoi citokina procenjeni su protočnom citometrijom i upoređeni između centralnih sekutića (CS), bočnih sekutića, očnjaka, prvih i drugih premolara, kao i prvih i drugih kutnjaka. Profil citokina varirao je između različitih grupa zuba sa tendencijom povećanja pro-upalnih citokina od prednjih zuba do kutnjaka. Molari se mogu smatrati zubima sa prirodnom predispozicijom za bržu resorpciju kosti, dok bi podešavanje dijagnostičkog raspona parodontalnih biomarkera za prednje ili zadnje zube trebalo razmotriti unutar dijagnostičkog konteksta.
PB  - Walter de Gruyter GmbH
T2  - Serbian Journal of Experimental and Clinical Research
T1  - Variation of the Cytokine Profiles in Gingival Crevicular Fluid Between Different Groups of Periodontally Healthy Teeth
T1  - Varijacija profila citokina u gingivalnoj zglobnoj tečnosti između različitih grupa parodontalno zdravih zuba
IS  - 4
VL  - 21
DO  - 10.2478/sjecr-2019-0015
SP  - 333
EP  - 341
ER  - 

@article{
author = "Taso, Ervin and Rakić, Mia and Stefanović, Vladimir and Petković-Ćurčin, Aleksandra and Stanojević, Ivan and Đukić, Mirjana and Struillou, Xavier and Vojvodić, Danilo and Banović, Tatjana and Kanjevac, Tatjana",
year = "2020",
abstract = "Profiling of biomarkers of physiological process represents an integrative part in optimisation of diagnostic markers in order to adjust the diagnostic ranges to the potential effects of the local factors such occlusal forces in case of periodontal tissues. The objective of this study was estimation of IL-1β, IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12, IL-13, IL-17, IL-22, TNFα and IFNγ concentrations in gingival crevicular fluid samples (GCF) between different groups of teeth. Two hundred fifty-nine systemically healthy non-smokers having at least one vital tooth without restorations, with healthy periodontal tissues, were clinically examined and the GCF sample was retrieved. The cytokine levels were estimated using flow cytometry and compared between central incisors (CI), lateral incisors, canines, first premolars, second premo-lars, first molars and second molars. Cytokine profiles varied between different groups of teeth with tendency of increase in pro-inflammatory cytokines from anterior teeth toward molars. Molars might be considered teeth with natural predisposition for faster bone resorption while the adjustment of diagnostic range of periodontal biomarkers for anterior or posterior teeth should be considered within diagnostic context. Cytokine profiles varied between different groups of teeth with tendency of increase in pro-inflammatory cytokines from anterior teeth toward molars. Molars might be considered teeth with natural predisposition for faster bone resorption while the adjustment of diagnostic range of periodontal biomarkers for anterior or posterior teeth should be considered within diagnostic context., Profilisanje biomarkera fiziološkog procesa predstavlja integrativni deo optimalizacije dijagnostičkih markera, kako bi se dijagnostički rasponi prilagodili potencijalnim uticajima lokalnih faktora poput okluzijskih sila u slučaju parodontalnih tkiva. Cilj ove studije bila je procena koncentracija IL-1b, IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12, IL-13, IL-17, IL- 22, TNFα i IFNγ u uzorcima gingivalne tečnosti (GT) kod različitih grupa zuba. Klinički je pregledano dvesta pedeset devet sistemski zdravih nepušača sa najmanje jednim vitalnim zubom bez restauracija, sa zdravim parodontalnim tkivima, i uzet je GT uzorak. Nivoi citokina procenjeni su protočnom citometrijom i upoređeni između centralnih sekutića (CS), bočnih sekutića, očnjaka, prvih i drugih premolara, kao i prvih i drugih kutnjaka. Profil citokina varirao je između različitih grupa zuba sa tendencijom povećanja pro-upalnih citokina od prednjih zuba do kutnjaka. Molari se mogu smatrati zubima sa prirodnom predispozicijom za bržu resorpciju kosti, dok bi podešavanje dijagnostičkog raspona parodontalnih biomarkera za prednje ili zadnje zube trebalo razmotriti unutar dijagnostičkog konteksta.",
publisher = "Walter de Gruyter GmbH",
journal = "Serbian Journal of Experimental and Clinical Research",
title = "Variation of the Cytokine Profiles in Gingival Crevicular Fluid Between Different Groups of Periodontally Healthy Teeth, Varijacija profila citokina u gingivalnoj zglobnoj tečnosti između različitih grupa parodontalno zdravih zuba",
number = "4",
volume = "21",
doi = "10.2478/sjecr-2019-0015",
pages = "333-341"
}

Taso, E., Rakić, M., Stefanović, V., Petković-Ćurčin, A., Stanojević, I., Đukić, M., Struillou, X., Vojvodić, D., Banović, T.,& Kanjevac, T.. (2020). Variation of the Cytokine Profiles in Gingival Crevicular Fluid Between Different Groups of Periodontally Healthy Teeth. in Serbian Journal of Experimental and Clinical Research
Walter de Gruyter GmbH., 21(4), 333-341.
https://doi.org/10.2478/sjecr-2019-0015

Taso E, Rakić M, Stefanović V, Petković-Ćurčin A, Stanojević I, Đukić M, Struillou X, Vojvodić D, Banović T, Kanjevac T. Variation of the Cytokine Profiles in Gingival Crevicular Fluid Between Different Groups of Periodontally Healthy Teeth. in Serbian Journal of Experimental and Clinical Research. 2020;21(4):333-341.
doi:10.2478/sjecr-2019-0015 .

Taso, Ervin, Rakić, Mia, Stefanović, Vladimir, Petković-Ćurčin, Aleksandra, Stanojević, Ivan, Đukić, Mirjana, Struillou, Xavier, Vojvodić, Danilo, Banović, Tatjana, Kanjevac, Tatjana, "Variation of the Cytokine Profiles in Gingival Crevicular Fluid Between Different Groups of Periodontally Healthy Teeth" in Serbian Journal of Experimental and Clinical Research, 21, no. 4 (2020):333-341,
https://doi.org/10.2478/sjecr-2019-0015 . .

TY  - JOUR
AU  - Rakić, Mia
AU  - Monje, Alberto
AU  - Radovanović, Sandro
AU  - Petković-Ćurčin, Aleksandra
AU  - Vojvodić, Danilo
AU  - Tatić, Zoran
PY  - 2020
UR  - https://pubmed.ncbi.nlm.nih.gov/31773730/
UR  - http://www.ncbi.nlm.nih.gov/pubmed/31773730
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3828
AB  - BACKGROUND Study objectives were 1) to estimate diagnostic capacity of clinical parameters, receptor activator of nuclear factor kappa-B (RANKL) and osteoprotegerin (OPG) to diagnose healthy peri-implant condition (HI), peri-implant mucositis (PIM) and peri-implantitis (PIMP) by assessing respective diagnostic accuracy, sensitivity, specificity and diagnostic ranges 2) to develop personalized diagnostic model (PDM) for implant monitoring. METHODS Split-mouth study included 126 patients and 252 implants (HI = 126, PIM = 57, and PIMP = 69). RANKL and OPG concentrations were estimated in peri-implant crevicular fluid using enzyme-linked immunosorbent assay method and assessed with clinical parameters using routine statistics, while the diagnostic capacity of individual parameters and overall clinical diagnosis were estimated using classifying algorithms. PDM was developed using decision trees. RESULTS Bleeding on probing (BOP), plaque index, and probing depth (PD) were confirmed reliable discriminants between peri-implant health and disease, while increase in PD (PD > 4 mm) and suppuration were good discriminants amongst PIM/PIMP. Bone turnover markers (BTMs) demonstrated presence of bone resorption in PIM; between comparable diagnostic ranges PIM/PIMP, PIMP was clinically distinguished from PIM in about 60% of patients while 40% remained diagnosed as false negatives. PDM demonstrated highest diagnostic capacity (accuracy: 96.27%, sensitivity: 95.00%, specificity: 100%) and defined HI: BOP ≤0.25%; PIM: BOP >0.25%, PD ≤4.5 mm; PIMP: BOP >0.25%, PD >4.5 mm and RANKL ≤19.9 pg/site; PIM: BOP >0.25%, PD >4.5 mm, and RANKL >19.9 pg/site. CONCLUSIONS BTMs demonstrated capacity to substantially improve clinical diagnosis of peri-implant conditions. Considering lack of difference in BTMs between PIM/PIMP and cluster of PIM with exceeding BTMs, a more refined definition of peri-implant conditions according to biological characteristics is required for further BTMs validation and appropriate PIMP management.
PB  - Wiley-Blackwell
T2  - Journal of Periodontology
T1  - Is the personalized approach the key to improve clinical diagnosis of peri-implant conditions? The role of bone markers.
IS  - 7
VL  - 91
DO  - 10.1002/JPER.19-0283
SP  - 859
EP  - 869
ER  - 

@article{
author = "Rakić, Mia and Monje, Alberto and Radovanović, Sandro and Petković-Ćurčin, Aleksandra and Vojvodić, Danilo and Tatić, Zoran",
year = "2020",
abstract = "BACKGROUND Study objectives were 1) to estimate diagnostic capacity of clinical parameters, receptor activator of nuclear factor kappa-B (RANKL) and osteoprotegerin (OPG) to diagnose healthy peri-implant condition (HI), peri-implant mucositis (PIM) and peri-implantitis (PIMP) by assessing respective diagnostic accuracy, sensitivity, specificity and diagnostic ranges 2) to develop personalized diagnostic model (PDM) for implant monitoring. METHODS Split-mouth study included 126 patients and 252 implants (HI = 126, PIM = 57, and PIMP = 69). RANKL and OPG concentrations were estimated in peri-implant crevicular fluid using enzyme-linked immunosorbent assay method and assessed with clinical parameters using routine statistics, while the diagnostic capacity of individual parameters and overall clinical diagnosis were estimated using classifying algorithms. PDM was developed using decision trees. RESULTS Bleeding on probing (BOP), plaque index, and probing depth (PD) were confirmed reliable discriminants between peri-implant health and disease, while increase in PD (PD > 4 mm) and suppuration were good discriminants amongst PIM/PIMP. Bone turnover markers (BTMs) demonstrated presence of bone resorption in PIM; between comparable diagnostic ranges PIM/PIMP, PIMP was clinically distinguished from PIM in about 60% of patients while 40% remained diagnosed as false negatives. PDM demonstrated highest diagnostic capacity (accuracy: 96.27%, sensitivity: 95.00%, specificity: 100%) and defined HI: BOP ≤0.25%; PIM: BOP >0.25%, PD ≤4.5 mm; PIMP: BOP >0.25%, PD >4.5 mm and RANKL ≤19.9 pg/site; PIM: BOP >0.25%, PD >4.5 mm, and RANKL >19.9 pg/site. CONCLUSIONS BTMs demonstrated capacity to substantially improve clinical diagnosis of peri-implant conditions. Considering lack of difference in BTMs between PIM/PIMP and cluster of PIM with exceeding BTMs, a more refined definition of peri-implant conditions according to biological characteristics is required for further BTMs validation and appropriate PIMP management.",
publisher = "Wiley-Blackwell",
journal = "Journal of Periodontology",
title = "Is the personalized approach the key to improve clinical diagnosis of peri-implant conditions? The role of bone markers.",
number = "7",
volume = "91",
doi = "10.1002/JPER.19-0283",
pages = "859-869"
}

Rakić, M., Monje, A., Radovanović, S., Petković-Ćurčin, A., Vojvodić, D.,& Tatić, Z.. (2020). Is the personalized approach the key to improve clinical diagnosis of peri-implant conditions? The role of bone markers.. in Journal of Periodontology
Wiley-Blackwell., 91(7), 859-869.
https://doi.org/10.1002/JPER.19-0283

Rakić M, Monje A, Radovanović S, Petković-Ćurčin A, Vojvodić D, Tatić Z. Is the personalized approach the key to improve clinical diagnosis of peri-implant conditions? The role of bone markers.. in Journal of Periodontology. 2020;91(7):859-869.
doi:10.1002/JPER.19-0283 .

Rakić, Mia, Monje, Alberto, Radovanović, Sandro, Petković-Ćurčin, Aleksandra, Vojvodić, Danilo, Tatić, Zoran, "Is the personalized approach the key to improve clinical diagnosis of peri-implant conditions? The role of bone markers." in Journal of Periodontology, 91, no. 7 (2020):859-869,
https://doi.org/10.1002/JPER.19-0283 . .

TY  - JOUR
AU  - Taso, Ervin
AU  - Stefanović, Vladimir
AU  - Gaudin, Alexis
AU  - Grujić, Jovan
AU  - Maldonado, Estela
AU  - Petković-Curcin, Aleksandra
AU  - Vojvodić, Danilo
AU  - Sculean, Anton
AU  - Rakić, Mia
PY  - 2019
UR  - https://www.sciencedirect.com/science/article/pii/S0003996919309392?via%3Dihub
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3550
AB  - OBJECTIVE This controlled split-mouth study aimed to estimate the effect of caries and related treatment on concentrations of interleukin (IL)-2, interferon (IFN)-γ, IL-12, IL-17A, IL-13, IL-10, IL-6, IL-5, IL-4, IL-22, tumor necrosis factor (TNF)-α, and IL1-β in gingival crevicular fluid (GCF) of caries affected teeth before (B), 7 (7D) and 30 (30D) days post-treatment and to compare them with concentrations from healthy teeth. DESIGN Study population included 81 systemically and periodontally healthy non-smokers exhibiting at least one shallow occlusal/ inter-proximal caries and one healthy tooth from the same morphologic group at the contralateral position. Following clinical exam, the GCF samples were collected baseline as well as 7D and 30D, while the biomarker measurement was performed using multiplex flowcytometry. RESULTS Caries affected teeth exhibited significantly higher levels of IFN-γ, IL-1β, IL-2, IL-4 and IL-6 when compared to healthy teeth. Post-treatment cytokines levels showed general trend of increase when compared to baseline, that was significant for IL-22 and IL-17 at 7D, while IFN-γ was significantly increased at 7D compared to the healthy teeth. At 30D, IFN-γ, TNF-α, IL-17 and IL-4 levels were significantly increased when compared to healthy teeth, while IL-2 levels were significantly higher than baseline levels. CONCLUSION Considering significantly increased periodontal levels of inflammatory markers in caries affected teeth and in response to performed treatment, it seems that dental caries and related restorative treatment might contribute to periodontal inflammation via additive effects already in early-stage caries.
PB  - Pergamon
T2  - Archives of Oral Biology
T1  - Effect of dental caries on periodontal inflammatory status: A split-mouth study.
VL  - 110
DO  - 10.1016/j.archoralbio.2019.104620
SP  - 104620
ER  - 

@article{
author = "Taso, Ervin and Stefanović, Vladimir and Gaudin, Alexis and Grujić, Jovan and Maldonado, Estela and Petković-Curcin, Aleksandra and Vojvodić, Danilo and Sculean, Anton and Rakić, Mia",
year = "2019",
abstract = "OBJECTIVE This controlled split-mouth study aimed to estimate the effect of caries and related treatment on concentrations of interleukin (IL)-2, interferon (IFN)-γ, IL-12, IL-17A, IL-13, IL-10, IL-6, IL-5, IL-4, IL-22, tumor necrosis factor (TNF)-α, and IL1-β in gingival crevicular fluid (GCF) of caries affected teeth before (B), 7 (7D) and 30 (30D) days post-treatment and to compare them with concentrations from healthy teeth. DESIGN Study population included 81 systemically and periodontally healthy non-smokers exhibiting at least one shallow occlusal/ inter-proximal caries and one healthy tooth from the same morphologic group at the contralateral position. Following clinical exam, the GCF samples were collected baseline as well as 7D and 30D, while the biomarker measurement was performed using multiplex flowcytometry. RESULTS Caries affected teeth exhibited significantly higher levels of IFN-γ, IL-1β, IL-2, IL-4 and IL-6 when compared to healthy teeth. Post-treatment cytokines levels showed general trend of increase when compared to baseline, that was significant for IL-22 and IL-17 at 7D, while IFN-γ was significantly increased at 7D compared to the healthy teeth. At 30D, IFN-γ, TNF-α, IL-17 and IL-4 levels were significantly increased when compared to healthy teeth, while IL-2 levels were significantly higher than baseline levels. CONCLUSION Considering significantly increased periodontal levels of inflammatory markers in caries affected teeth and in response to performed treatment, it seems that dental caries and related restorative treatment might contribute to periodontal inflammation via additive effects already in early-stage caries.",
publisher = "Pergamon",
journal = "Archives of Oral Biology",
title = "Effect of dental caries on periodontal inflammatory status: A split-mouth study.",
volume = "110",
doi = "10.1016/j.archoralbio.2019.104620",
pages = "104620"
}

Taso, E., Stefanović, V., Gaudin, A., Grujić, J., Maldonado, E., Petković-Curcin, A., Vojvodić, D., Sculean, A.,& Rakić, M.. (2019). Effect of dental caries on periodontal inflammatory status: A split-mouth study.. in Archives of Oral Biology
Pergamon., 110, 104620.
https://doi.org/10.1016/j.archoralbio.2019.104620

Taso E, Stefanović V, Gaudin A, Grujić J, Maldonado E, Petković-Curcin A, Vojvodić D, Sculean A, Rakić M. Effect of dental caries on periodontal inflammatory status: A split-mouth study.. in Archives of Oral Biology. 2019;110:104620.
doi:10.1016/j.archoralbio.2019.104620 .

Taso, Ervin, Stefanović, Vladimir, Gaudin, Alexis, Grujić, Jovan, Maldonado, Estela, Petković-Curcin, Aleksandra, Vojvodić, Danilo, Sculean, Anton, Rakić, Mia, "Effect of dental caries on periodontal inflammatory status: A split-mouth study." in Archives of Oral Biology, 110 (2019):104620,
https://doi.org/10.1016/j.archoralbio.2019.104620 . .

TY  - JOUR
AU  - Canullo, Luigi
AU  - Pesce, Paolo
AU  - Botticelli, Daniele
AU  - Covani, Ugo
AU  - Janković, Saša
AU  - Jovanović, Tanja
AU  - Rakić, Mia
PY  - 2018
UR  - http://quintpub.com/journals/omi/abstract.php?iss2_id=1499&article_id=17993
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3002
AB  - PURPOSE To compare the qualitative and quantitative profile of Epstein-Barr virus (EBV) at external and internal implant surfaces between participants with peri-implantitis and healthy peri-implant tissues and to quantitatively assess the relation between EBV and periopathogens inside the microbiologic profile associated with peri-implantitis. MATERIALS AND METHODS Microbiologic specimens were retrieved from 84 patients wearing 190 implants to estimate the levels of EBV and 10 periopathogens in the peri-implant pocket and internal-implant connection using quantitative polymerase chain reaction. RESULTS The study sample consisted of 113 healthy and 77 peri-implantitis-affected implants. Statistical significance was not reached in EBV prevalence between peri-implantitis and healthy controls. EBV-positive participants demonstrated higher levels of Prevotella intermedia (Pi) and Campylobacter rectus (Cr) compared with EBV-negative participants. A positive correlation was demonstrated among EBV and Tannerella forsythia (Tf), Parvimonas micra (Pm), Fusobacterium nucleatum (Fn), and Cr levels in peri-implantitis-affected implants, while healthy controls demonstrated a positive correlation between EBV and Aggregatibacter actinomycetemcomitans (Aa), Pi, and Pm. CONCLUSION EBV cannot be considered as a microbiologic marker of peri-implantitis. However, EBV could be considered as a risk factor and a peri-implantitis enhancer based on its positive correlations with pathogens associated with peri-implantitis.
T2  - The International Journal of Oral and Maxillofacial Implants
T1  - What is the Impact of Epstein-Barr Virus in Peri-implant Infection?
IS  - 1
VL  - 33
DO  - 10.11607/jomi.5972
SP  - 58
EP  - 63
ER  - 

@article{
author = "Canullo, Luigi and Pesce, Paolo and Botticelli, Daniele and Covani, Ugo and Janković, Saša and Jovanović, Tanja and Rakić, Mia",
year = "2018",
abstract = "PURPOSE To compare the qualitative and quantitative profile of Epstein-Barr virus (EBV) at external and internal implant surfaces between participants with peri-implantitis and healthy peri-implant tissues and to quantitatively assess the relation between EBV and periopathogens inside the microbiologic profile associated with peri-implantitis. MATERIALS AND METHODS Microbiologic specimens were retrieved from 84 patients wearing 190 implants to estimate the levels of EBV and 10 periopathogens in the peri-implant pocket and internal-implant connection using quantitative polymerase chain reaction. RESULTS The study sample consisted of 113 healthy and 77 peri-implantitis-affected implants. Statistical significance was not reached in EBV prevalence between peri-implantitis and healthy controls. EBV-positive participants demonstrated higher levels of Prevotella intermedia (Pi) and Campylobacter rectus (Cr) compared with EBV-negative participants. A positive correlation was demonstrated among EBV and Tannerella forsythia (Tf), Parvimonas micra (Pm), Fusobacterium nucleatum (Fn), and Cr levels in peri-implantitis-affected implants, while healthy controls demonstrated a positive correlation between EBV and Aggregatibacter actinomycetemcomitans (Aa), Pi, and Pm. CONCLUSION EBV cannot be considered as a microbiologic marker of peri-implantitis. However, EBV could be considered as a risk factor and a peri-implantitis enhancer based on its positive correlations with pathogens associated with peri-implantitis.",
journal = "The International Journal of Oral and Maxillofacial Implants",
title = "What is the Impact of Epstein-Barr Virus in Peri-implant Infection?",
number = "1",
volume = "33",
doi = "10.11607/jomi.5972",
pages = "58-63"
}

Canullo, L., Pesce, P., Botticelli, D., Covani, U., Janković, S., Jovanović, T.,& Rakić, M.. (2018). What is the Impact of Epstein-Barr Virus in Peri-implant Infection?. in The International Journal of Oral and Maxillofacial Implants, 33(1), 58-63.
https://doi.org/10.11607/jomi.5972

Canullo L, Pesce P, Botticelli D, Covani U, Janković S, Jovanović T, Rakić M. What is the Impact of Epstein-Barr Virus in Peri-implant Infection?. in The International Journal of Oral and Maxillofacial Implants. 2018;33(1):58-63.
doi:10.11607/jomi.5972 .

Canullo, Luigi, Pesce, Paolo, Botticelli, Daniele, Covani, Ugo, Janković, Saša, Jovanović, Tanja, Rakić, Mia, "What is the Impact of Epstein-Barr Virus in Peri-implant Infection?" in The International Journal of Oral and Maxillofacial Implants, 33, no. 1 (2018):58-63,
https://doi.org/10.11607/jomi.5972 . .

TY  - JOUR
AU  - Monje, Alberto
AU  - Insua, Angel
AU  - Rakić, Mia
AU  - Nart, Jose
AU  - Moyano-Cuevas, Jose Luis
AU  - Wang, Hom-Lay
PY  - 2018
UR  - http://doi.wiley.com/10.1002/JPER.18-0081
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3210
AB  - BACKGROUND Lack of consensus on the clinical parameters of peri-implantitis may complicate accurate diagnosis of the disorder. Furthermore, the lack of reliable estimates of the diagnostic capacity of the clinical endpoints precludes the definition of an effective treatment protocol for peri-implantitis. The present canine study assesses the diagnostic accuracy of the clinical parameters for monitoring the peri-implant tissues in a controlled ligature-induced peri-implantitis model followed by a spontaneous progression phase. METHODS Six beagle dogs were followed-up on during three episodes of ligature-induced peri-implantitis and a further episode of spontaneous progression. Probing depth (PD), bleeding on probing (BOP), mucosal recession (MR), and suppuration (SUP) were recorded at four sites per implant and at four study timepoints. Moreover, the implant mucosal index (IMI) was calculated at implant level. Marginal bone loss (MBL) was determined using computed tomography at four sites per implant. A linear regression model was used to estimate clinical and radiological parameters during peri-implantitis progression. RESULTS Progressive peri-implant bone loss is characterized by an increase in PD, more profuse BOP, MR, and SUP in advanced cases (p < 0.001). However, even in the presence of severe bone loss, SUP was not a common finding, with an incidence of approximately 10% at the last timepoint. These clinical parameters were significantly correlated to MBL at most of the timepoints. The IMI, in turn, showed a positive correlation to MBL and the peri-implant inflammatory signs (r = 0.39; p < 0.001), with a tendency to exhibit higher scores during ligature-induced peri-implantitis, followed by a slight decrease during the spontaneous progression period. CONCLUSION The clinical features of peri-implantitis and spontaneous progression of the disorder may facilitate an accurate monitoring of peri-implant pathologic bone loss.
T2  - Journal of Periodontology
T1  - Estimation of the diagnostic accuracy of clinical parameters for monitoring peri-implantitis progression: An experimental canine study.
IS  - 12
VL  - 89
DO  - 10.1002/JPER.18-0081
SP  - 1442
EP  - 1451
ER  - 

@article{
author = "Monje, Alberto and Insua, Angel and Rakić, Mia and Nart, Jose and Moyano-Cuevas, Jose Luis and Wang, Hom-Lay",
year = "2018",
abstract = "BACKGROUND Lack of consensus on the clinical parameters of peri-implantitis may complicate accurate diagnosis of the disorder. Furthermore, the lack of reliable estimates of the diagnostic capacity of the clinical endpoints precludes the definition of an effective treatment protocol for peri-implantitis. The present canine study assesses the diagnostic accuracy of the clinical parameters for monitoring the peri-implant tissues in a controlled ligature-induced peri-implantitis model followed by a spontaneous progression phase. METHODS Six beagle dogs were followed-up on during three episodes of ligature-induced peri-implantitis and a further episode of spontaneous progression. Probing depth (PD), bleeding on probing (BOP), mucosal recession (MR), and suppuration (SUP) were recorded at four sites per implant and at four study timepoints. Moreover, the implant mucosal index (IMI) was calculated at implant level. Marginal bone loss (MBL) was determined using computed tomography at four sites per implant. A linear regression model was used to estimate clinical and radiological parameters during peri-implantitis progression. RESULTS Progressive peri-implant bone loss is characterized by an increase in PD, more profuse BOP, MR, and SUP in advanced cases (p < 0.001). However, even in the presence of severe bone loss, SUP was not a common finding, with an incidence of approximately 10% at the last timepoint. These clinical parameters were significantly correlated to MBL at most of the timepoints. The IMI, in turn, showed a positive correlation to MBL and the peri-implant inflammatory signs (r = 0.39; p < 0.001), with a tendency to exhibit higher scores during ligature-induced peri-implantitis, followed by a slight decrease during the spontaneous progression period. CONCLUSION The clinical features of peri-implantitis and spontaneous progression of the disorder may facilitate an accurate monitoring of peri-implant pathologic bone loss.",
journal = "Journal of Periodontology",
title = "Estimation of the diagnostic accuracy of clinical parameters for monitoring peri-implantitis progression: An experimental canine study.",
number = "12",
volume = "89",
doi = "10.1002/JPER.18-0081",
pages = "1442-1451"
}

Monje, A., Insua, A., Rakić, M., Nart, J., Moyano-Cuevas, J. L.,& Wang, H.. (2018). Estimation of the diagnostic accuracy of clinical parameters for monitoring peri-implantitis progression: An experimental canine study.. in Journal of Periodontology, 89(12), 1442-1451.
https://doi.org/10.1002/JPER.18-0081

Monje A, Insua A, Rakić M, Nart J, Moyano-Cuevas JL, Wang H. Estimation of the diagnostic accuracy of clinical parameters for monitoring peri-implantitis progression: An experimental canine study.. in Journal of Periodontology. 2018;89(12):1442-1451.
doi:10.1002/JPER.18-0081 .

Monje, Alberto, Insua, Angel, Rakić, Mia, Nart, Jose, Moyano-Cuevas, Jose Luis, Wang, Hom-Lay, "Estimation of the diagnostic accuracy of clinical parameters for monitoring peri-implantitis progression: An experimental canine study." in Journal of Periodontology, 89, no. 12 (2018):1442-1451,
https://doi.org/10.1002/JPER.18-0081 . .

TY  - JOUR
AU  - Monje, Alberto
AU  - Caballé-Serrano, Jordi
AU  - Nart, Jose
AU  - Peñarrocha, David
AU  - Wang, Hom-Lay
AU  - Rakić, Mia
PY  - 2018
UR  - http://doi.wiley.com/10.1002/JPER.17-0454
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3148
AB  - BACKGROUND The aim of this case-control study was to estimate the diagnostic accuracy of the standard clinical parameters in diagnosing healthy peri-implant tissues, peri-implant mucositis, and peri-implantitis. METHODS A case-control study was designed to compare the clinical parameters used in the diagnosis of peri-implant diseases such as: probingdepth (PD), bleeding on probing (BOP), mucosal redness (MR), suppuration (SUP), and plaque index (PI). Furthermore, the influence of patient- (sex, age) and implant-related variables (implant neck configuration, time in function after loading) were evaluated to investigate the association with the clinical findings. The inferential analysis consisted of estimation by generalized estimating equations (GEE) of multilevel logistic regression models. RESULTS In total, 1,572 sites were evaluated around 262 implants from 141 patients. Sites with implant mucositis showed significant levels of BOP (OR = 3.56), MR (OR = 7.66) and PD (OR = 1.48) compared to healthy sites. The specificity was 90.3% while the sensitivity was only 43.6%. Likewise, sites exhibiting peri-implantitis showed significant levels of BOP (OR = 2.32), MR (OR = 7.21), PD (OR = 2.43) and SUP (OR = 6.81) compared to healthy sites. Again, the multiple logistic regressions showed high specificity (92.1%) but modest sensitivity (52.5%). PD was the only diagnostic marker displaying significance comparing peri-implant mucositis and peri-implantitis sites (OR = 1.76). Moreover, tissue-level compared to bone-level implants were less associated with SUP+ (OR = 0.20), and PI (OR = 0.36) and demonstrated statistical significance. In addition, age, sex, and function time significantly influenced the tested clinical parameters. CONCLUSIONS The diagnosis of peri-implant diseases cannot rely solely upon individual clinical parameters but rather require a combination of criteria. The clinical parameters, particularly probing depth, might accurately discern between diagnoses among peri-implant conditions. Nevertheless, the specificity of the clinical parameters surpasses the sensitivity in the detection of peri-implant diseases, validating its potential use as a diagnostic tool.
T2  - Journal of Periodontology
T1  - Diagnostic accuracy of clinical parameters to monitor peri-implant conditions: A matched case-control study.
IS  - 4
VL  - 89
DO  - 10.1002/JPER.17-0454
SP  - 407
EP  - 417
ER  - 

@article{
author = "Monje, Alberto and Caballé-Serrano, Jordi and Nart, Jose and Peñarrocha, David and Wang, Hom-Lay and Rakić, Mia",
year = "2018",
abstract = "BACKGROUND The aim of this case-control study was to estimate the diagnostic accuracy of the standard clinical parameters in diagnosing healthy peri-implant tissues, peri-implant mucositis, and peri-implantitis. METHODS A case-control study was designed to compare the clinical parameters used in the diagnosis of peri-implant diseases such as: probingdepth (PD), bleeding on probing (BOP), mucosal redness (MR), suppuration (SUP), and plaque index (PI). Furthermore, the influence of patient- (sex, age) and implant-related variables (implant neck configuration, time in function after loading) were evaluated to investigate the association with the clinical findings. The inferential analysis consisted of estimation by generalized estimating equations (GEE) of multilevel logistic regression models. RESULTS In total, 1,572 sites were evaluated around 262 implants from 141 patients. Sites with implant mucositis showed significant levels of BOP (OR = 3.56), MR (OR = 7.66) and PD (OR = 1.48) compared to healthy sites. The specificity was 90.3% while the sensitivity was only 43.6%. Likewise, sites exhibiting peri-implantitis showed significant levels of BOP (OR = 2.32), MR (OR = 7.21), PD (OR = 2.43) and SUP (OR = 6.81) compared to healthy sites. Again, the multiple logistic regressions showed high specificity (92.1%) but modest sensitivity (52.5%). PD was the only diagnostic marker displaying significance comparing peri-implant mucositis and peri-implantitis sites (OR = 1.76). Moreover, tissue-level compared to bone-level implants were less associated with SUP+ (OR = 0.20), and PI (OR = 0.36) and demonstrated statistical significance. In addition, age, sex, and function time significantly influenced the tested clinical parameters. CONCLUSIONS The diagnosis of peri-implant diseases cannot rely solely upon individual clinical parameters but rather require a combination of criteria. The clinical parameters, particularly probing depth, might accurately discern between diagnoses among peri-implant conditions. Nevertheless, the specificity of the clinical parameters surpasses the sensitivity in the detection of peri-implant diseases, validating its potential use as a diagnostic tool.",
journal = "Journal of Periodontology",
title = "Diagnostic accuracy of clinical parameters to monitor peri-implant conditions: A matched case-control study.",
number = "4",
volume = "89",
doi = "10.1002/JPER.17-0454",
pages = "407-417"
}

Monje, A., Caballé-Serrano, J., Nart, J., Peñarrocha, D., Wang, H.,& Rakić, M.. (2018). Diagnostic accuracy of clinical parameters to monitor peri-implant conditions: A matched case-control study.. in Journal of Periodontology, 89(4), 407-417.
https://doi.org/10.1002/JPER.17-0454

Monje A, Caballé-Serrano J, Nart J, Peñarrocha D, Wang H, Rakić M. Diagnostic accuracy of clinical parameters to monitor peri-implant conditions: A matched case-control study.. in Journal of Periodontology. 2018;89(4):407-417.
doi:10.1002/JPER.17-0454 .

Monje, Alberto, Caballé-Serrano, Jordi, Nart, Jose, Peñarrocha, David, Wang, Hom-Lay, Rakić, Mia, "Diagnostic accuracy of clinical parameters to monitor peri-implant conditions: A matched case-control study." in Journal of Periodontology, 89, no. 4 (2018):407-417,
https://doi.org/10.1002/JPER.17-0454 . .

TY  - JOUR
AU  - Rakić, Mia
AU  - Galindo-Moreno, Pablo
AU  - Monje, Alberto
AU  - Radovanović, Sandro
AU  - Wang, Hom-Lay
AU  - Cochran, David
AU  - Sculean, Anton
AU  - Canullo, Luigi
PY  - 2017
UR  - http://link.springer.com/10.1007/s00784-017-2276-y
UR  - http://www.ncbi.nlm.nih.gov/pubmed/29218422
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2941
AB  - OBJECTIVES The objective of this study is to estimate the overall prevalence of peri-implantitis (PI) and the effect of different study designs, function times, and implant surfaces on prevalence rate reported by the studies adhering to the case definition of Sanz & Chapple 2012. MATERIAL AND METHODS Following electronic and manual searches of the literature published up to February 2016, data were extracted from the studies fitting the study criteria. Meta-analysis was performed for estimation of overall prevalence of PI while the effects of the study design, function time, and implant surface type on prevalence rate were investigated using meta-regression method. RESULTS Twenty-nine articles were included in this study. The prevalence rate in all subset meta-analyses was always higher at patient level when compared to the prevalence rate at the implant level. Prevalence of PI was 18.5% at the patient level and 12.8% at the implant level. Meta-regression analysis did not identify any association for different study designs and function times while it was demonstrated the significant association between moderately rough surfaces with lower prevalence rate of PI (p = 0.011). CONCLUSIONS The prevalence rate of PI remains highly variable even following restriction to the clinical case definition and it seems to be affected by local factors such as implant surface characteristics. The identification of adjuvant diagnostic markers seems necessary for more accurate disease classification. CLINICAL RELEVANCE The occurrence of PI is affected by local factors such as implant surface characteristics hence the careful assessment of the local factors should be performed within treatment planning.
T2  - Clinical Oral Investigations
T2  - Clinical Oral Investigations
T1  - How frequent does peri-implantitis occur? A systematic review and meta-analysis.
DO  - 10.1007/s00784-017-2276-y
ER  - 

@article{
author = "Rakić, Mia and Galindo-Moreno, Pablo and Monje, Alberto and Radovanović, Sandro and Wang, Hom-Lay and Cochran, David and Sculean, Anton and Canullo, Luigi",
year = "2017",
abstract = "OBJECTIVES The objective of this study is to estimate the overall prevalence of peri-implantitis (PI) and the effect of different study designs, function times, and implant surfaces on prevalence rate reported by the studies adhering to the case definition of Sanz & Chapple 2012. MATERIAL AND METHODS Following electronic and manual searches of the literature published up to February 2016, data were extracted from the studies fitting the study criteria. Meta-analysis was performed for estimation of overall prevalence of PI while the effects of the study design, function time, and implant surface type on prevalence rate were investigated using meta-regression method. RESULTS Twenty-nine articles were included in this study. The prevalence rate in all subset meta-analyses was always higher at patient level when compared to the prevalence rate at the implant level. Prevalence of PI was 18.5% at the patient level and 12.8% at the implant level. Meta-regression analysis did not identify any association for different study designs and function times while it was demonstrated the significant association between moderately rough surfaces with lower prevalence rate of PI (p = 0.011). CONCLUSIONS The prevalence rate of PI remains highly variable even following restriction to the clinical case definition and it seems to be affected by local factors such as implant surface characteristics. The identification of adjuvant diagnostic markers seems necessary for more accurate disease classification. CLINICAL RELEVANCE The occurrence of PI is affected by local factors such as implant surface characteristics hence the careful assessment of the local factors should be performed within treatment planning.",
journal = "Clinical Oral Investigations, Clinical Oral Investigations",
title = "How frequent does peri-implantitis occur? A systematic review and meta-analysis.",
doi = "10.1007/s00784-017-2276-y"
}

Rakić, M., Galindo-Moreno, P., Monje, A., Radovanović, S., Wang, H., Cochran, D., Sculean, A.,& Canullo, L.. (2017). How frequent does peri-implantitis occur? A systematic review and meta-analysis.. in Clinical Oral Investigations.
https://doi.org/10.1007/s00784-017-2276-y

Rakić M, Galindo-Moreno P, Monje A, Radovanović S, Wang H, Cochran D, Sculean A, Canullo L. How frequent does peri-implantitis occur? A systematic review and meta-analysis.. in Clinical Oral Investigations. 2017;.
doi:10.1007/s00784-017-2276-y .

Rakić, Mia, Galindo-Moreno, Pablo, Monje, Alberto, Radovanović, Sandro, Wang, Hom-Lay, Cochran, David, Sculean, Anton, Canullo, Luigi, "How frequent does peri-implantitis occur? A systematic review and meta-analysis." in Clinical Oral Investigations (2017),
https://doi.org/10.1007/s00784-017-2276-y . .

TY  - JOUR
AU  - Canullo, Luigi
AU  - Tallarico, Marco
AU  - Radovanovic, Sandro
AU  - Delibasic, Boris
AU  - Covani, Ugo
AU  - Rakić, Mia
PY  - 2016
UR  - http://doi.wiley.com/10.1111/clr.12738
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2527
AB  - Objective: To investigate whether specific predictive profiles for patient-based risk assessment/diagnostics can be applied in different subtypes of peri-implantitis. Materials and methods: This study included patients with at least two implants (one or more presenting signs of peri-implantitis). Anamnestic, clinical, and implant-related parameters were collected and scored into a single database. Dental implant was chosen as the unit of analysis, and a complete screening protocol was established. The implants affected by peri-implantitis were then clustered into three subtypes in relation to the identified triggering factor: purely plaque-induced or prosthetically or surgically triggered peri-implantitis. Statistical analyses were performed to compare the characteristics and risk factors between peri-implantitis and healthy implants, as well as to compare clinical parameters and distribution of risk factors between plaque, prosthetically and surgically triggered peri-implantitis. The predictive profiles for subtypes of peri-implantitis were estimated using data mining tools including regression methods and C4.5 decision trees. Results: A total of 926 patients previously treated with 2812 dental implants were screened for eligibility. Fifty-six patients (6.04%) with 332 implants (4.44%) met the study criteria. Data from 125 peri-implantitis and 207 healthy implants were therefore analyzed and included in the statistical analysis. Within peri-implantitis group, 51 were classified as surgically triggered (40.8%), 38 as prosthetically triggered (30.4%), and 36 as plaque-induced (28.8%) peri-implantitis. For peri-implantitis, 51 were associated with surgical risk factor (40.8%), 38 with prosthetic risk factor (30.4%), 36 with purely plaque-induced risk factor (28.8%). The variables identified as predictors of peri-implantitis were female sex (OR = 1.60), malpositioning (OR = 48.2), overloading (OR = 18.70), and bone reconstruction (OR = 2.35). The predictive model showed 82.35% of accuracy and identified distinguishing predictive profiles for plaque, prosthetically and surgically triggered peri-implantitis. The model was in accordance with the results of risk analysis being the external validation for model accuracy. Conclusions: It can be concluded that plaque induced and prosthetically and surgically triggered peri-implantitis are different entities associated with distinguishing predictive profiles; hence, the appropriate causal treatment approach remains necessary. The advanced data mining model developed in this study seems to be a promising tool for diagnostics of peri-implantitis subtypes.
PB  - Blackwell Munksgaard
T2  - Clinical Oral Implants Research
T1  - Distinguishing predictive profiles for patient-based risk assessment and diagnostics of plaque induced, surgically and prosthetically triggered peri-implantitis
IS  - 10
VL  - 27
DO  - 10.1111/clr.12738
SP  - 1243
EP  - 1250
ER  - 

@article{
author = "Canullo, Luigi and Tallarico, Marco and Radovanovic, Sandro and Delibasic, Boris and Covani, Ugo and Rakić, Mia",
year = "2016",
abstract = "Objective: To investigate whether specific predictive profiles for patient-based risk assessment/diagnostics can be applied in different subtypes of peri-implantitis. Materials and methods: This study included patients with at least two implants (one or more presenting signs of peri-implantitis). Anamnestic, clinical, and implant-related parameters were collected and scored into a single database. Dental implant was chosen as the unit of analysis, and a complete screening protocol was established. The implants affected by peri-implantitis were then clustered into three subtypes in relation to the identified triggering factor: purely plaque-induced or prosthetically or surgically triggered peri-implantitis. Statistical analyses were performed to compare the characteristics and risk factors between peri-implantitis and healthy implants, as well as to compare clinical parameters and distribution of risk factors between plaque, prosthetically and surgically triggered peri-implantitis. The predictive profiles for subtypes of peri-implantitis were estimated using data mining tools including regression methods and C4.5 decision trees. Results: A total of 926 patients previously treated with 2812 dental implants were screened for eligibility. Fifty-six patients (6.04%) with 332 implants (4.44%) met the study criteria. Data from 125 peri-implantitis and 207 healthy implants were therefore analyzed and included in the statistical analysis. Within peri-implantitis group, 51 were classified as surgically triggered (40.8%), 38 as prosthetically triggered (30.4%), and 36 as plaque-induced (28.8%) peri-implantitis. For peri-implantitis, 51 were associated with surgical risk factor (40.8%), 38 with prosthetic risk factor (30.4%), 36 with purely plaque-induced risk factor (28.8%). The variables identified as predictors of peri-implantitis were female sex (OR = 1.60), malpositioning (OR = 48.2), overloading (OR = 18.70), and bone reconstruction (OR = 2.35). The predictive model showed 82.35% of accuracy and identified distinguishing predictive profiles for plaque, prosthetically and surgically triggered peri-implantitis. The model was in accordance with the results of risk analysis being the external validation for model accuracy. Conclusions: It can be concluded that plaque induced and prosthetically and surgically triggered peri-implantitis are different entities associated with distinguishing predictive profiles; hence, the appropriate causal treatment approach remains necessary. The advanced data mining model developed in this study seems to be a promising tool for diagnostics of peri-implantitis subtypes.",
publisher = "Blackwell Munksgaard",
journal = "Clinical Oral Implants Research",
title = "Distinguishing predictive profiles for patient-based risk assessment and diagnostics of plaque induced, surgically and prosthetically triggered peri-implantitis",
number = "10",
volume = "27",
doi = "10.1111/clr.12738",
pages = "1243-1250"
}

Canullo, L., Tallarico, M., Radovanovic, S., Delibasic, B., Covani, U.,& Rakić, M.. (2016). Distinguishing predictive profiles for patient-based risk assessment and diagnostics of plaque induced, surgically and prosthetically triggered peri-implantitis. in Clinical Oral Implants Research
Blackwell Munksgaard., 27(10), 1243-1250.
https://doi.org/10.1111/clr.12738

Canullo L, Tallarico M, Radovanovic S, Delibasic B, Covani U, Rakić M. Distinguishing predictive profiles for patient-based risk assessment and diagnostics of plaque induced, surgically and prosthetically triggered peri-implantitis. in Clinical Oral Implants Research. 2016;27(10):1243-1250.
doi:10.1111/clr.12738 .

Canullo, Luigi, Tallarico, Marco, Radovanovic, Sandro, Delibasic, Boris, Covani, Ugo, Rakić, Mia, "Distinguishing predictive profiles for patient-based risk assessment and diagnostics of plaque induced, surgically and prosthetically triggered peri-implantitis" in Clinical Oral Implants Research, 27, no. 10 (2016):1243-1250,
https://doi.org/10.1111/clr.12738 . .

TY  - GEN
AU  - Canullo, Luigi
AU  - Radovanović, Sandro
AU  - Delibasic, Boris
AU  - Blaya, Juan Antonio
AU  - Penarrocha, David
AU  - Rakić, Mia
PY  - 2016
UR  - http://www.scopus.com/inward/record.url?eid=2-s2.0-84963502806&partnerID=tZOtx3y1
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2526
AB  - AIM: The primary aim of this study was to evaluate 23 pathogens associated with peri-implantitis at inner part of implant connections, in peri-implant and periodontal pockets between patients suffering peri-implantitis and participants with healthy peri-implant tissues; the secondary aim was to estimate the predictive value of microbiological profile in patients wearing dental implants using data mining methods. MATERIAL AND METHODS: Fifty participants included in the present case─control study were scheduled for collection of plaque samples from the peri-implant pockets, internal connection, and periodontal pocket. Real-time polymerase chain reaction was performed to quantify 23 pathogens. Three predictive models were developed using C4.5 decision trees to estimate the predictive value of microbiological profile between three experimental sites. RESULTS: The final sample included 47 patients (22 healthy controls and 25 diseased cases), 90 implants (43 with healthy peri-implant tissues and 47 affected by peri-implantitis). Total and mean pathogen counts at inner portions of the implant connection, in peri-implant and periodontal pockets were generally increased in peri-implantitis patients when compared to healthy controls. The inner portion of the implant connection, the periodontal pocket and peri-implant pocket, respectively, presented a predictive value of microbiologic profile of 82.78%, 94.31%, and 97.5% of accuracy. CONCLUSION: This study showed that microbiological profile at all three experimental sites is differently characterized between patients suffering peri-implantitis and healthy controls. Data mining analysis identified Parvimonas micra as a highly accurate predictor of peri-implantitis when present in peri-implant pocket while this method generally seems to be promising for diagnosis of such complex infections.
PB  - Blackwell Munksgaard
T2  - Clinical oral implants research
T1  - The predictive value of microbiological findings on teeth, internal and external implant portions in clinical decision making.
DO  - 10.1111/clr.12828
ER  - 

@misc{
author = "Canullo, Luigi and Radovanović, Sandro and Delibasic, Boris and Blaya, Juan Antonio and Penarrocha, David and Rakić, Mia",
year = "2016",
abstract = "AIM: The primary aim of this study was to evaluate 23 pathogens associated with peri-implantitis at inner part of implant connections, in peri-implant and periodontal pockets between patients suffering peri-implantitis and participants with healthy peri-implant tissues; the secondary aim was to estimate the predictive value of microbiological profile in patients wearing dental implants using data mining methods. MATERIAL AND METHODS: Fifty participants included in the present case─control study were scheduled for collection of plaque samples from the peri-implant pockets, internal connection, and periodontal pocket. Real-time polymerase chain reaction was performed to quantify 23 pathogens. Three predictive models were developed using C4.5 decision trees to estimate the predictive value of microbiological profile between three experimental sites. RESULTS: The final sample included 47 patients (22 healthy controls and 25 diseased cases), 90 implants (43 with healthy peri-implant tissues and 47 affected by peri-implantitis). Total and mean pathogen counts at inner portions of the implant connection, in peri-implant and periodontal pockets were generally increased in peri-implantitis patients when compared to healthy controls. The inner portion of the implant connection, the periodontal pocket and peri-implant pocket, respectively, presented a predictive value of microbiologic profile of 82.78%, 94.31%, and 97.5% of accuracy. CONCLUSION: This study showed that microbiological profile at all three experimental sites is differently characterized between patients suffering peri-implantitis and healthy controls. Data mining analysis identified Parvimonas micra as a highly accurate predictor of peri-implantitis when present in peri-implant pocket while this method generally seems to be promising for diagnosis of such complex infections.",
publisher = "Blackwell Munksgaard",
journal = "Clinical oral implants research",
title = "The predictive value of microbiological findings on teeth, internal and external implant portions in clinical decision making.",
doi = "10.1111/clr.12828"
}

Canullo, L., Radovanović, S., Delibasic, B., Blaya, J. A., Penarrocha, D.,& Rakić, M.. (2016). The predictive value of microbiological findings on teeth, internal and external implant portions in clinical decision making.. in Clinical oral implants research
Blackwell Munksgaard..
https://doi.org/10.1111/clr.12828

Canullo L, Radovanović S, Delibasic B, Blaya JA, Penarrocha D, Rakić M. The predictive value of microbiological findings on teeth, internal and external implant portions in clinical decision making.. in Clinical oral implants research. 2016;.
doi:10.1111/clr.12828 .

Canullo, Luigi, Radovanović, Sandro, Delibasic, Boris, Blaya, Juan Antonio, Penarrocha, David, Rakić, Mia, "The predictive value of microbiological findings on teeth, internal and external implant portions in clinical decision making." in Clinical oral implants research (2016),
https://doi.org/10.1111/clr.12828 . .

TY  - THES
AU  - Rakić, Mia
PY  - 2012
UR  - http://eteze.bg.ac.rs/application/showtheses?thesesId=584
UR  - https://fedorabg.bg.ac.rs/fedora/get/o:6743/bdef:Content/download
UR  - http://vbs.rs/scripts/cobiss?command=DISPLAY&base=70036&RID=1024187278
UR  - http://nardus.mpn.gov.rs/123456789/2684
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2443
AB  - Uvod. Peri-implantitis predstavlja inflamatorni proces koji se karakteriše gubitkom potporne
kosti opterećenog oralnog implantata. Osnovna patološka karakteristika peri-implantitisa je
gubitak potporne kosti implantata u funkciji. Ovaj proces je zasnovan na inflamatornoj
osteoklastogenezi koja ujedno predstavlja centralni patološki proces peri-implantitisa.
Inflamatorna osteoklastogeneza predstavlja proces sazrevanja pre-osteoklasta i pojačavanje
aktivnosti zrelih osteoklasta pod uticajem kritičnih koncentracija pro-inflamatornih
medijatora. Kliničke karakteristike peri-implantitisa nisu strogo definisane i variraju iz
prostog razloga jer dubina peri-implantnog sulkusa značajno varira s'toga dubina džepa
predstavlja individualnu determinantu. Istovremeno, proces gubitka marginalne kosti
predstavlja fiziološku pojavu koja je najintezivnija u prvoj godini opterećenja, i istraživanja su
pokazala da iznosi -0.78mm mezijalno i -0.85mm distalno, a zatim se kontinurano odvija i na
godišnjem nivou iznosi oko 0.2mm. Pomenuta vrednost iznosi prosečnu vrednost ali ona
takođe individualno varira i uslovljena je tipom implantata, dizajnom abatmenta i mnogim
drugim faktorima. Iz tog razloga se relativni nivo pripojnog epitela (rCAL) kao ni radiološki
evidentan gubitak kosti ne mogu usvojiti kao apsolutni indikatori patološkog gubitka kosti. U
dijagnostici stanja peri-implantnih tkiva koristi se nekoliko tipova metoda i najčešće u
kombinaciji radi što potpunijeg postavljanja dijagnoze. Dijagnostičke metode uključuju:
određivanje kliničkih parametara, radiološke analize, mikrobiološke analize i kvalitativne i
kvantitativne analize peri-implantnte krevikularne tečnosti (PICF). Analiza PICF predstavlja
jednu od najatraktivnijih metoda u savremenoj implantologiji, pri čemu je njena najveća
vrednost u tome što daje direktne informacije o stanju peri-implantinh tkiva i zasnovano na
tome poseduje mogućnost da pokaže rane znake oboljenja peri-implantnih tkiva u fazi gde su
tkivne promene reverzibilne. Ovo ograničenje kliničkih metoda rezultira u propuštanju
vremena od momenta pojave bolesti koje proporcijonalno umanjuje uspeh terapije, a često i u
izboru neadekvatnog terapijskog plana. Zasnovano na tome, metoda merenja specifičnih
biomarkera u uzorku PICF nadomešćuje ograničenja konvencionalnih kliničkih dijagnostičkih
metoda koje daju informacije u stadijumu razvijene bolesti. Brojne studije se sprovode u cilju
identifikacije biomolekula koji pouzdano reflektuje stanje peri-implantnih tkiva, ali kako je
patologija lokalnog meatbolizma kompleksna, a metoda evaluacije visoko-osetljiva,
standardizacija ove metode je još uvek u toku. Cilj istraživanja bio je da se ispIta potencijal
RANK-a, sRANKL-a, OPG-a, Katepsina-K, Sklerostina i VEGF-a kao biomarkera gubitka
potporne kosti implantata. Materijal i metode. Studija je obuhvatila tri grupe sistemski
zdravih nepušača sa ugrađenim endoesealnim oralnim implantatima, opterećenih tokom
najmanje godinu dana (35 sa peri-implantitisom, 30 sa peri-mukozitisom i 30 sa zdravim periimplantnim
tkivima). Kriterijum isključenja su bili: upotreba antibiotika u predhodna tri
meseca i upotreba antiinflamatorika u predhodna dva meseca od trenutka uzorkovanja,
menstrualni ciklus, trudnoća i laktacija, pušenje i tretiranost parodontalnih/peri-implantnih
tkiva u poslednjih godinu dana. Klinička merenja su obavljena u 6 tačaka (buko-mezijalna,
buko-medijalna, buko-distalna, oro-distalna, oro-medijalna i oro-mezijalna) i uključiće
određivanje: krvarenja na probu (BOP) odsustvo-0, prisustvo-1, 15 sekundi nakon sondiranja,
indeks akumulacije plaka (PI) odsustvo-0, prisustvo-1 duž marginalne ivice, PD i rNPE
graduisanom sondom (North Carolina–Hu-Friedy, Chicago, IL, USA). U slučaju prisustva
više peri-implantitisa ili peri-mukozitisa kod jednog pacijenta, zapaljenje sa većim defektom
je bilo uključeno u studiju, a u slučaju sličnih karakteristika defekta u 6 tačaka, najdostupnije,
odnosno anterijorno mesto je birano kao reprezentativno. Uzorak peri-implantne tečnosti
sakupljan je sa mezijalne površine reprezentativnog implantata participanta studije. Uzorci su
uzimani 24 časa nakon kliničkih merenja kako bi se izbegla kontaminacija uzorka krvlju, u
grupama sa zapaljenjem sa mesta sa najvećom dubinom sondiranja, a u grupi zdravih periimplantnih
tkiva sa najdostupnijeg mesta. Uzorci PCF su uzimani sa reprezentativnog mesta
metodom filter papira, a dobijeni volumen tečnosti iz tračica je određivan pomoću
kalibrisanog aparata Periotron 6000 (Interstate Drug Exchange, Amityville, NY, USA).
Komercijalni "enzyme-linked immunosorbent assay" (ELISA) kitovi su korišćeni za
evaluaciju koštanih biomarkera u uzorku PICF: 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). Rezultati. U svim analiziranim
uzorcima PICF-a su dokazane koncentracije RANK-a, sRANKL-a, OPG-a, katepsina-K i
VEGF-a iznad detekcionog limita, pri čemu je za sklerostin samo 6% uzoraka bilo pozitivno.
Koncentracija RANK-a je bila značajno veća kod peri-implantitisa u odnosu na zdrava periimplantna
tkiva (p=0.002), takođe je bila veća i kod peri-mukozitisa u odnosu na zdrave
implantate (p=0.021). Vrednosti sRANKL-a bile su značajno veće u grupi peri-implantitisa u
odnosu na zdrava peri-implantna tkiva (p=0.010), ali ne i u odnosu na peri-mukozitise, kao ni
između peri-mukozitisa i zdravih peri-implantnih tkiva, gde nije postignuta statistička
značajnost. Koncentracija OPG-a je bila značajno veća kod peri-implantitisa u odnosu na
zdrava peri-implantna tkiva (p=0.031), i to je ujedno bila jedina značajnost za ovaj marker.
Vrednosti katepsina-K su bile više na mestima zapaljenja, ali je jedina značajnost uočena
između peri-mukozitisa i zdravih peri-implantnih tkiva (p=0.039). Sklerostin je dokazan u
izuzetno malom broju uzoraka, ali su razlike bile upadljive pa su vrednosti bile značajno veće
u grupi peri-implantitisa u odnosu na druge dve grupe. Koncentracija VEGF-a je bila
značajno veća kod peri-implantitisa u odnosu na druge dve grupe, i grupu peri-mukozitisa
(p=0.014) i zdravih peri-implantnih tkiva (p=0.000). RANK i sRANKL su pokazali značajno
pozitivnu korelaciju sa svim merenim kliničkim parametrima, a OPG je pokazao takođe
značajnu pozitivnu korelaciju sa gotovo svim merenim kliničkim parametrima, izuzev sa PI
(p=0.121), a identičan slučaj je bio sa sklerostinom. VEGF nije pokazao nijednu značajnu
korelaciju sa merenim kliničkim parametrima. Zaključak. RANK, sRANKL, OPG, skelrostin i
VEGF su biomarkeri koji su udruženi sa peri-implantitisom. Katepsin-K predstavlja
biomarker svosjtven peri-mukozitisu. Evaluirani biomarkeri su drugačije distribuirani u
različitim regionima vilica i u PICF implantata različitih dijametara. RANK i OPG su
značajno povišeni u frontalnom regionu maksile, što ujedno ukazuje na intezivnije
osteolitičke procese u ovom regionu. RANK i katepsin-K su značajno povišeni u grupi
implantata sa najvećim dijametrom, što na molekularnom nivou potvrđuje predhodne
rezultate kliničkih studija da su dijametar implantata i gubitak implantata u pozitivnoj
korelaciji.
AB  - 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.
PB  - Belgrade: University of Belgrade, Faculty of Dental Medicine
T2  - University of Belgrade, Faculty of Dental Medicine
T1  - Određivanje biomarkera gubitka alveolarne kosti kod pacijenata sa peri-implantitisom
T1  - Determination of alveolar bone loss biomarkers related to peri-implantitis
SP  - 1
EP  - 70
UR  - https://hdl.handle.net/21.15107/rcub_nardus_2684
ER  - 

@phdthesis{
author = "Rakić, Mia",
year = "2012",
abstract = "Uvod. Peri-implantitis predstavlja inflamatorni proces koji se karakteriše gubitkom potporne
kosti opterećenog oralnog implantata. Osnovna patološka karakteristika peri-implantitisa je
gubitak potporne kosti implantata u funkciji. Ovaj proces je zasnovan na inflamatornoj
osteoklastogenezi koja ujedno predstavlja centralni patološki proces peri-implantitisa.
Inflamatorna osteoklastogeneza predstavlja proces sazrevanja pre-osteoklasta i pojačavanje
aktivnosti zrelih osteoklasta pod uticajem kritičnih koncentracija pro-inflamatornih
medijatora. Kliničke karakteristike peri-implantitisa nisu strogo definisane i variraju iz
prostog razloga jer dubina peri-implantnog sulkusa značajno varira s'toga dubina džepa
predstavlja individualnu determinantu. Istovremeno, proces gubitka marginalne kosti
predstavlja fiziološku pojavu koja je najintezivnija u prvoj godini opterećenja, i istraživanja su
pokazala da iznosi -0.78mm mezijalno i -0.85mm distalno, a zatim se kontinurano odvija i na
godišnjem nivou iznosi oko 0.2mm. Pomenuta vrednost iznosi prosečnu vrednost ali ona
takođe individualno varira i uslovljena je tipom implantata, dizajnom abatmenta i mnogim
drugim faktorima. Iz tog razloga se relativni nivo pripojnog epitela (rCAL) kao ni radiološki
evidentan gubitak kosti ne mogu usvojiti kao apsolutni indikatori patološkog gubitka kosti. U
dijagnostici stanja peri-implantnih tkiva koristi se nekoliko tipova metoda i najčešće u
kombinaciji radi što potpunijeg postavljanja dijagnoze. Dijagnostičke metode uključuju:
određivanje kliničkih parametara, radiološke analize, mikrobiološke analize i kvalitativne i
kvantitativne analize peri-implantnte krevikularne tečnosti (PICF). Analiza PICF predstavlja
jednu od najatraktivnijih metoda u savremenoj implantologiji, pri čemu je njena najveća
vrednost u tome što daje direktne informacije o stanju peri-implantinh tkiva i zasnovano na
tome poseduje mogućnost da pokaže rane znake oboljenja peri-implantnih tkiva u fazi gde su
tkivne promene reverzibilne. Ovo ograničenje kliničkih metoda rezultira u propuštanju
vremena od momenta pojave bolesti koje proporcijonalno umanjuje uspeh terapije, a često i u
izboru neadekvatnog terapijskog plana. Zasnovano na tome, metoda merenja specifičnih
biomarkera u uzorku PICF nadomešćuje ograničenja konvencionalnih kliničkih dijagnostičkih
metoda koje daju informacije u stadijumu razvijene bolesti. Brojne studije se sprovode u cilju
identifikacije biomolekula koji pouzdano reflektuje stanje peri-implantnih tkiva, ali kako je
patologija lokalnog meatbolizma kompleksna, a metoda evaluacije visoko-osetljiva,
standardizacija ove metode je još uvek u toku. Cilj istraživanja bio je da se ispIta potencijal
RANK-a, sRANKL-a, OPG-a, Katepsina-K, Sklerostina i VEGF-a kao biomarkera gubitka
potporne kosti implantata. Materijal i metode. Studija je obuhvatila tri grupe sistemski
zdravih nepušača sa ugrađenim endoesealnim oralnim implantatima, opterećenih tokom
najmanje godinu dana (35 sa peri-implantitisom, 30 sa peri-mukozitisom i 30 sa zdravim periimplantnim
tkivima). Kriterijum isključenja su bili: upotreba antibiotika u predhodna tri
meseca i upotreba antiinflamatorika u predhodna dva meseca od trenutka uzorkovanja,
menstrualni ciklus, trudnoća i laktacija, pušenje i tretiranost parodontalnih/peri-implantnih
tkiva u poslednjih godinu dana. Klinička merenja su obavljena u 6 tačaka (buko-mezijalna,
buko-medijalna, buko-distalna, oro-distalna, oro-medijalna i oro-mezijalna) i uključiće
određivanje: krvarenja na probu (BOP) odsustvo-0, prisustvo-1, 15 sekundi nakon sondiranja,
indeks akumulacije plaka (PI) odsustvo-0, prisustvo-1 duž marginalne ivice, PD i rNPE
graduisanom sondom (North Carolina–Hu-Friedy, Chicago, IL, USA). U slučaju prisustva
više peri-implantitisa ili peri-mukozitisa kod jednog pacijenta, zapaljenje sa većim defektom
je bilo uključeno u studiju, a u slučaju sličnih karakteristika defekta u 6 tačaka, najdostupnije,
odnosno anterijorno mesto je birano kao reprezentativno. Uzorak peri-implantne tečnosti
sakupljan je sa mezijalne površine reprezentativnog implantata participanta studije. Uzorci su
uzimani 24 časa nakon kliničkih merenja kako bi se izbegla kontaminacija uzorka krvlju, u
grupama sa zapaljenjem sa mesta sa najvećom dubinom sondiranja, a u grupi zdravih periimplantnih
tkiva sa najdostupnijeg mesta. Uzorci PCF su uzimani sa reprezentativnog mesta
metodom filter papira, a dobijeni volumen tečnosti iz tračica je određivan pomoću
kalibrisanog aparata Periotron 6000 (Interstate Drug Exchange, Amityville, NY, USA).
Komercijalni "enzyme-linked immunosorbent assay" (ELISA) kitovi su korišćeni za
evaluaciju koštanih biomarkera u uzorku PICF: 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). Rezultati. U svim analiziranim
uzorcima PICF-a su dokazane koncentracije RANK-a, sRANKL-a, OPG-a, katepsina-K i
VEGF-a iznad detekcionog limita, pri čemu je za sklerostin samo 6% uzoraka bilo pozitivno.
Koncentracija RANK-a je bila značajno veća kod peri-implantitisa u odnosu na zdrava periimplantna
tkiva (p=0.002), takođe je bila veća i kod peri-mukozitisa u odnosu na zdrave
implantate (p=0.021). Vrednosti sRANKL-a bile su značajno veće u grupi peri-implantitisa u
odnosu na zdrava peri-implantna tkiva (p=0.010), ali ne i u odnosu na peri-mukozitise, kao ni
između peri-mukozitisa i zdravih peri-implantnih tkiva, gde nije postignuta statistička
značajnost. Koncentracija OPG-a je bila značajno veća kod peri-implantitisa u odnosu na
zdrava peri-implantna tkiva (p=0.031), i to je ujedno bila jedina značajnost za ovaj marker.
Vrednosti katepsina-K su bile više na mestima zapaljenja, ali je jedina značajnost uočena
između peri-mukozitisa i zdravih peri-implantnih tkiva (p=0.039). Sklerostin je dokazan u
izuzetno malom broju uzoraka, ali su razlike bile upadljive pa su vrednosti bile značajno veće
u grupi peri-implantitisa u odnosu na druge dve grupe. Koncentracija VEGF-a je bila
značajno veća kod peri-implantitisa u odnosu na druge dve grupe, i grupu peri-mukozitisa
(p=0.014) i zdravih peri-implantnih tkiva (p=0.000). RANK i sRANKL su pokazali značajno
pozitivnu korelaciju sa svim merenim kliničkim parametrima, a OPG je pokazao takođe
značajnu pozitivnu korelaciju sa gotovo svim merenim kliničkim parametrima, izuzev sa PI
(p=0.121), a identičan slučaj je bio sa sklerostinom. VEGF nije pokazao nijednu značajnu
korelaciju sa merenim kliničkim parametrima. Zaključak. RANK, sRANKL, OPG, skelrostin i
VEGF su biomarkeri koji su udruženi sa peri-implantitisom. Katepsin-K predstavlja
biomarker svosjtven peri-mukozitisu. Evaluirani biomarkeri su drugačije distribuirani u
različitim regionima vilica i u PICF implantata različitih dijametara. RANK i OPG su
značajno povišeni u frontalnom regionu maksile, što ujedno ukazuje na intezivnije
osteolitičke procese u ovom regionu. RANK i katepsin-K su značajno povišeni u grupi
implantata sa najvećim dijametrom, što na molekularnom nivou potvrđuje predhodne
rezultate kliničkih studija da su dijametar implantata i gubitak implantata u pozitivnoj
korelaciji., 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.",
publisher = "Belgrade: University of Belgrade, Faculty of Dental Medicine",
journal = "University of Belgrade, Faculty of Dental Medicine",
title = "Određivanje biomarkera gubitka alveolarne kosti kod pacijenata sa peri-implantitisom, Determination of alveolar bone loss biomarkers related to peri-implantitis",
pages = "1-70",
url = "https://hdl.handle.net/21.15107/rcub_nardus_2684"
}

Rakić, M.. (2012). Određivanje biomarkera gubitka alveolarne kosti kod pacijenata sa peri-implantitisom. in University of Belgrade, Faculty of Dental Medicine
Belgrade: University of Belgrade, Faculty of Dental Medicine., 1-70.
https://hdl.handle.net/21.15107/rcub_nardus_2684

Rakić M. Određivanje biomarkera gubitka alveolarne kosti kod pacijenata sa peri-implantitisom. in University of Belgrade, Faculty of Dental Medicine. 2012;:1-70.
https://hdl.handle.net/21.15107/rcub_nardus_2684 .

Rakić, Mia, "Određivanje biomarkera gubitka alveolarne kosti kod pacijenata sa peri-implantitisom" in University of Belgrade, Faculty of Dental Medicine (2012):1-70,
https://hdl.handle.net/21.15107/rcub_nardus_2684 .