Dental implants are an increasingly popular treatment choice in young individuals with dento-facial anomalies characterized by missing teeth such as oligodontia and cleft lip and palate. Although dental implants may represent a predictable treatment option in the short term, over the long term the risk of peri-implant disease cannot be overlooked due to its high prevalence rate of 22% to 43%.1 The risk of peri‐implantitis has been reported to be strongly influenced not only by individual patient‐related factors but also by the length of the observation period. Given that dental implants are being prescribed for replacement of missing teeth in ever-younger individuals, strategies for early detection of peri-implant disease must therefore be considered essential to prolonging the retention of implants through early adulthood and into old age.
Peri-implant diseases comprise peri-implant mucositis and peri-implantitis. Peri-implant mucositis is an inflammatory disease confined to soft tissues surrounding a dental implant with no loss of supporting bone; at this stage the disease is reversible. Peri-implantitis is a pathological condition around an implant characterized by soft tissue inflammation and subsequent progressive loss of supporting bone beyond the initial biological remodeling, and is thought to be irreversible.
Mirroring the progression of gingivitis to periodontitis, peri-implant mucositis is assumed to precede peri-implantitis.2 When compared to periodontitis, peri-implantitis progresses in a non-linear and accelerating pattern in the absence of treatment.3,4 Although several studies report the presence of a large number of inflammatory cells such as plasma cells, macrophages and polymorphonuclear neutrophils (PMNs) in a peri-implantitis lesion, the exact etiology and mechanism of disease progression is yet to be identified.5
Role of oral PMNs
Homeostasis in the gingival tissues is maintained by a constant influx of PMNs in response to commensal bacteria, indicating a protective role. PMNs are the most abundantly circulating leukocytes as well as the primary responders of the innate immune system. However, during chronic increase of pathogenic bacteria, the PMNs become hyperactive and undergo amplified recruitment, thus leading to gingival inflammation with progressive loss of periodontal attachment. This dual behavior of PMNs is often described as a double-edged sword, as it functions to protect and also destroy oral mucosal tissue.6
An increase in oPMN counts can be indicative of oral inflammatory conditions ranging from gingivitis and periodontitis to inflamed mucosal tissue around implants.7,8 A positive correlation has been reported between oPMN counts in saliva and the clinically determined severity of periodontal disease.7,9-11 Furthermore, responders to periodontal therapy demonstrate a significant decrease in oPMN counts. PMNs have shown potential in predicting periodontal disease progression.12 Consequently, it is important to understand PMN functions to comprehend better the nature of periodontitis or other inflammatory conditions in general, and in this case, peri-implant diseases.
Current use of diagnostic testing
A non-invasive oral rinse test is used to measure the oral PMN count.7,11 This count corresponds to the oral inflammatory load. A 10-fold increase in oral PMN counts was found in our experimental study for patients with peri-implant diseases indicating elevated oral inflammatory load. (Fig. 1) The underlying principle of this test is to quantify oral PMN levels in much the same way that a circulating neutrophil or white blood cell count is used in medicine to help screen for patients with infection in the body. Furthermore, these isolated PMNs undergo a flowcytometric analysis for understanding the exact activation markers involved in the inflammatory lesion.13,14
Diagnosis of peri-implant diseases using clinical parameters borrowed from the repertoire of clinical tests used to evaluate periodontal diseases has certain limitations. Although clinical probing and radiographs are used to evaluate the current status of peri-implant health, a predictive model for disease activity and progression of peri-implant disease is lacking.15 The use of biopsies, biomarkers and bone markers to analyze inflammatory infiltrates surrounding dental implants has proven to be invasive, expensive, and impractical for a clinical scenario.16,17
This oral rinse screening tool can be utilized practically in combination with clinical examination to better assess underlying peri-implant disease activity and disease progression in peri-implant tissues even before the appearance of radiographic changes in bone. These developments in understanding the immune response and the role of PMNs in that process will help develop disease-oriented treatment methods.11 This will allow clinicians to treat the specific disease mechanisms in each patient, resulting in improved treatment outcomes. Furthermore, this tool may aid in monitoring the effectiveness of treatment therapy in patients with peri-implant diseases. Major advantages of this test include its ease of use, cost-effectiveness and non-invasive nature.
The benefits of an oral rinse test apply to all individuals, but perhaps more so to young individuals with dento-facial anomalies and other special needs that have the right to expect many decades of service from dental implant-supported prostheses. Identification at an early age of increased peri-implant inflammatory cell counts could allow for the timely commencement of treatment to reduce complications later in life. It may even provide insight into establishing the nature and grading the severity of peri-implant diseases. With the numerous benefits of a non-invasive assessment of oPMN counts, it is critical that this area of research continues, encouraging the use of chair-side screening tests in young individuals that can be easily administered and interpreted by clinicians.
Oral Health welcomes this original article.
- Derks J, Tomasi C. Peri-implant health and disease. A systematic review of current epidemiology. Journal of clinical periodontology. 2015 Apr;42:S158-71.
- Jepsen S, Berglundh T, Genco R, Aass AM, Demirel K, Derks J, Figuero E, Giovannoli JL, Goldstein M, Lambert F, Ortiz-Vigon A. Primary prevention of peri-implantitis: Managing peri-implant mucositis. Journal of clinical periodontology. 2015 Apr;42:S152-7.
- Derks J, Schaller D, Håkansson J, Wennström JL, Tomasi C, Berglundh T. Peri-implantitis–onset and pattern of progression. Journal of clinical periodontology. 2016 Apr;43(4):383-8.
- Belibasakis GN. Microbiological and immuno-pathological aspects of peri-implant diseases. Archives of oral biology. 2014 Jan 1;59(1):66-72.
- Berglundh T, Armitage G, Araujo MG, Avila-Ortiz G, Blanco J, Camargo PM, Chen S, Cochran D, Derks J, Figuero E, Hämmerle CH. Peri-implant diseases and conditions: Consensus report of workgroup 4 of the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions. Journal of periodontology. 2018 Jun;89:S313-8.
- Rijkschroeff P, Loos BG, Nicu EA. Oral polymorphonuclear neutrophil contributes to oral health. Current Oral Health Reports. 2018 Dec 1;5(4):211-20.
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- Dutzan N, Konkel JE, Greenwell-Wild T, Moutsopoulos NM. Characterization of the human immune cell network at the gingival barrier. Mucosal immunology. 2016 Sep;9(5):1163-72.
- Bender JS, Thang H, Glogauer M. Novel rinse assay for the quantification of oral neutrophils and the monitoring of chronic periodontal disease. Journal of periodontal research. 2006 Jun;41(3):214-20.
- Bhadbhade SJ, Acharya AB, Thakur S. Correlation between probing pocket depth and neutrophil counts in dental plaque, saliva, and gingival crevicular fluid. Quintessence International. 2012 Feb. 1;43(2).
- Khoury W, Glogauer J, Tenenbaum HC, Glogauer M. Oral inflammatory load: Neutrophils as oral health biomarkers. Journal of Periodontal Research. 2020 May 6.
- Hirschfeld J. Neutrophil subsets in periodontal health and disease: a mini review. Frontiers in Immunology. 2019;10.
- Fine N, Hassanpour S, Borenstein A, Sima C, Oveisi M, Scholey J, Cherney D, Glogauer M. Distinct oral neutrophil subsets define health and periodontal disease states. Journal of dental research. 2016 Jul;95(8):931-8.
- Lakschevitz FS, Hassanpour S, Rubin A, Fine N, Sun C, Glogauer M. Identification of neutrophil surface marker changes in health and inflammation using high-throughput screening flow cytometry. Experimental cell research. 2016 Mar 15;342(2):200-9.
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- Rakic M, Monje A, Radovanovic S, Petkovic-Curcin A, Vojvodic D, Tatic Z. Is the personalized approach the key to improve clinical diagnosis of peri-implant conditions? The role of bone markers. Journal of periodontology. 2020 Jul;91(7):859-69.
- Berglundh T, Zitzmann NU, Donati M. Are peri-implantitis lesions different from periodontitis lesions?. Journal of clinical periodontology. 2011 Mar;38:188-202.
About the Authors
Dr. Ramandeep Sandhu is an ITI (International team for Implantology) Scholar at Holland Bloorview Kids Rehabilitation Hospital/ University of Toronto. She is also a research associate at Princess Margaret Hospital. She completed her post-graduate training in Prosthodontics in India. Her research focus is to develop a diagnostic tool that will help clinicians monitor the progression of peri-implant mucositis and peri-implantitis.
Dr. Michael Glogauer is a Professor at the University of Toronto and Head of Dental Oncology at Princess Margaret Hospital. His research and clinical interests focus on developing novel bone grafting approaches prior to implant placement and the role of the oral innate immune system in maintenance of health. He is a periodontist at OMGPerio.ca.
Dr. Robert Carmichael is Chief of Dentistry and Director, Ontario Cleft Lip and Palate/Craniofacial Dental Program at Holland Bloorview Kids Rehabilitation Hospital. He is also coordinator of prosthodontics, The Hospital for Sick Children and assistant professor, Faculty of Dentistry, University of Toronto. He supervises the care of children with cleft lip and palate and other craniofacial disorders in communities in northern Ontario.