1) Be free from error or reliable
2) Measure what they are intended to measure or valid
3) Be sensitive to changes in the patient’s condition or be able to detect treatment differences and
4) Be interpretable or clinically meaningful.
Relevance of PRO in periodontal therapy: Treatment of periodontitis is challenging because of the complexity of the condition, lack of complete understanding of the best disease control method and the need for a determined hygiene care from the patient. Assessment of therapeutic success by traditional ways therefore is inappropriate. Though the advancement in diagnostic techniques allows the clinician or researcher to measure the clinical, symptomatic and biochemical aspects after periodontal therapy, some critical patient related aspects still remain undetected. Certain data such as impact on physical functions like chewing, smiling and speech, cognitive functioning, satisfaction with treatment, psychological and social well-being and changes in OHRQoL with treatment can be obtained only from the patients self-report. Studies have shown that periodontal disease negatively impacts on OHRQoL [ 10 , 11 ]. A correlation between extent and severity of periodontal disease and poorer OHRQoL has also been reported [ 12 , 13 ]. Patients are aware of some periodontal health indicators such as teeth with mobility, recession in the aesthetic zone, and Bleeding On Probing (BOP) and these are highly correlated with their self-reported QoL. But there are certain silent indicators about which the patient is unaware like number of teeth with deep pockets or furcation involvements that do not correlate with their self-reported health status [ 14 ]. Therefore, PRO measurement of periodontal status related to treatment needs to be carefully assessed.
Satisfaction is a multidimensional construct about which there is little or no consensus. Patient satisfaction about periodontal therapy is one of the desirable outcomes and should be a main objective of the clinician. In the 21 st century, assessment of patient satisfaction related to therapy has become pivotal; thanks to the increasing consumerism in health care. There is also a shift in practitioner-patient relationships from a medical model to a transformed interactive model [ 15 ]. PRO instruments are very effective in studying patient satisfaction to a particular treatment or technique. It is also a valuable tool in assessing the HRQoL. Certain OHRQoL tools like Oral Health Impact Profile-14 (OHIP 14) [ 16 ] and Xerostomia Related QoL Scale [ 17 ] have been used in many studies as a subjective indicator to assess oral health status. Other generic tools used as PRO measures of periodontal disease status include OHRQoL Model for Dental Hygiene [ 18 ] Child Perceptions Questionnaire (CPQ 11-14) [ 19 ] and Oral Impacts on Daily Performance (OIDP) [ 8 ]. If the context of use allows, one of these established generic scales can be used as a PRO measure. Otherwise the clinician or researcher has to develop a reliable and valid context specific PRO tool for their use. In 2003, AAP commissioned systematic review [ 20 ] on surgical therapies for the treatment of recession pointed out the lack of standardized PRO measures as a limitation of the studies reviewed. It recommended to incorporate PRO measures in future studies.
Minimally important difference (MID) and statistically significant change in OHRQoL score: Many studies evaluated the impact of periodontal therapy on PRO and most of them report statistically significant changes from baseline OHRQoL scores. But this does not guarantee the observed differences are clinically meaningful [ 20 ]. MID [ 21 , 22 ] denotes the smallest change in a score that can be perceived as beneficial. In MID assessment, no clinical measures are used rather it represents the smallest score or change in score that is likely to be important from the patients or clinicians perspective [ 22 ]. MID, therefore, is an important parameter in the study on the impact of periodontal therapy on PRO to determine whether the observed change in OHRQoL scores after treatment is clinically meaningful [ 6 , 7 , 23 ]. MID estimation is done by two methods- distributed based and anchor based methods [ 7 , 21 , 22 ]. Distributed based MID estimation utilizes two statistical parameters namely Effect Size (ES) and Standard Error of Measurement (SEM) [ 22 , 23 ]. According to Norman GR et al., MID can be assumed as 0.5 Standard Deviation (SD) of the baseline score or an ES of 0.5 [ 24 ]. Jonsson B and Ohrn K assessed MID one year after NSPT using two OHRQoL tools [ 23 ]. Therefore studies on the impact of periodontal therapy on patient centered outcomes need to estimate MID, ES or SEM along with the statistical significance in the change score of the OHRQoL tool post treatment compared to the baseline.
The review was registered with the Institutional Ethics Committee of Govt. Dental College Kottayam, Kerala, India (registration no.IEC/ M/13/2017/DCK).
Search strategy: An electronic search was done in Google, Google Scholar and Pubmed for articles in English language using the terms QoL or OHRQoL or PROs or patient centred outcome AND periodontal therapy. The search commenced on 1 st September 2016 and ended on 15 th December 2016. Reference sections of potential studies were also searched. Unpublished literature was not included.
Eligibility: Studies assessing OHRQoL in patients with periodontitis receiving surgical or NSPT were included. Only adults above 18 years as participants were included. Non surgical therapy include oral hygiene instructions, supra and subgingival scaling and root planning using hand or ultrasonic/piezo electric devices, antiplaque agents and local or systemic antimicrobial therapy. Surgical therapy include flap technique for pocket therapy with or without regenerative material and root coverage procedures. Change in the self reported OHRQoL score from baseline was the outcome of interest. Longitudinal studies and both controlled and non-controlled clinical trials were considered. Inclusion criteria were as follows: 1) Studies that employed one or more than one multi-item OHRQoL instrument to assess PROs related to either NSPT or surgical periodontal therapy; 2) proper case definition of ‘periodontitis/ periodontal disease’ for sample selection; 3) minimum follow up of one week after periodontal therapy.
The excluded studies are: 1) narrative reviews; 2) case reports; 3) OHRQoL reported by parents or care givers; 4) those with participant’s age below 18 years; and 5) those related to implant surgeries.
Titles/abstract screening was done by one reviewer and full text articles collected. Full text articles were independently assessed for eligibility by two reviewers. Observational studies were assessed for participant selection, case definition and outcome assessment criteria. Randomised controlled trials were screened for randomisation, allocation concealment and blinding. Both the reviewers independently analysed all full texts and agreement on eligibility for inclusion and quality assessment was arrived on discussion.
Results of the search: Initially 423 relevant articles were obtained, from which based on screening titles and abstracts 396 were excluded for not related to research objective. Full text of remaining 27 articles was retrieved. Nineteen clinical studies with 1345 participants and two systematic reviews met all the inclusion criteria. Reasons for exclusion after full text review were use of non validated QoL scale [ 25 - 29 ] and not providing any periodontal treatment as part of therapy [ 30 ]. Search process and study inclusion are given in [ Table/Fig-2 ].
Prisma flow chart.
General characteristics of the included studies: All the included studies have defined ‘periodontitis case’ based on clinical parameters such as PD, BOP, CAL or GR. Of the 21 studies included, six were longitudinal or before after comparisons [ 31 - 36 ] six prospective clinical studies [ 1 , 37 - 41 ] one controlled clinical trial [ 42 ], two pilot studies [ 18 , 43 ], four randomised controlled trials [ 23 , 44 - 46 ] and two systematic reviews [ 2 , 47 ]. Eleven studies assessed the effect of NSPT on QoL [ 23 , 32 - 34 , 38 , 39 , 41 - 43 , 45 , 47 ]. Four studies compared NSPT and periodontal pocket surgery on effecting QoL changes [ 1 , 18 , 31 , 44 ]. Three studies investigated the role of root coverage procedures on QoL [ 36 , 37 , 40 ] and one study estimated whether Type 2 diabetes influences QoL scores in periodontally healthy and diseased subjects [ 35 ]. Four studies were from UK [ 32 , 35 , 43 , 45 ], three each from Brazil [ 40 , 42 , 46 ] and Japan [ 1 , 18 , 38 ], two from India [ 33 , 41 ] and one each from US [ 37 ] Korea [ 31 ], Turkey [ 44 ], Hong Kong [ 34 ], Germany [ 39 ] and Sweden [ 23 ]. One was a multi centre multinational study [ 36 ]. A summary of the included clinical studies is given in [ Table/Fig-3 ].
Included PRO studies related to periodontal therapy.
Authors/ Study design | Participants | Periodontal disease defenition | Intervention/ Comparison | OHQoL Instrument |
---|---|---|---|---|
Lee JM et al., [ ] Korea (Longitudinal) | 33 patients Age = 24 to 61 years | Chronic periodontitis | Modified Widman flap surgery | OHQoL questionnaire |
D’Avila GB et al., [ ], Brazil (Contolled clinical trial) | 60 patients Age >34 years | Eight sites with a PD >5 mm and no deeper than 10 mm | Different NSPT , modalities 1. SRP , 2. SRP + Metronidazole, 3. SRP + Professional, plaque removal, 4. SRP +, Metronidazole + Professiona, plaque removal | OHQoL questionnaire |
Gamboa AB et al., [ ], UK (Prospective pilot study) | 33 patients Age =20 to 60 years | Minimum of two teeth with PD > 4 mm | NSPT | Emotional intelligence questionnaire by Cooper and Sawaf |
Ozcelik O et al., [ ], Turkey (Randomised controlled trial) | 182 patients | Minimum of eight teeth with attachment loss > 5 mm At least one deep intrabony defect | 1. NSPT 2. ST 3. ST + EMD | OHIP – 14 GOHAI |
Wessel JR et al., [ ] Ohio (Prospective Clinical) | 26 patients Age= 21 to 70 years | GR | CTG vs FGG | VAS |
Aslund M et al., [ ] UK (Randomised controlled trial) | 59 patients Age = 47 to 56 years | Minimum of four site with > 5 mm pockets with 2 mm attachment loss in different quadrants | NSPT Piezo ceramic vs Curettes | OHQoL – UK VAS SF-MPQ |
Jowett AK et al., [ ] UK (Longitudinal) | 27 patients Age= 21 to 61 years | PD > 4 mm in atleast one sextant | 24 hour root surface debridement | OHIP – 14 |
Saito A et al., [ ] Japan (Prospective Clinical) | 58 patients Mean age = 53.6 | Min four sites with PD > 4 mm, Radio graphic evidence of bone loss | SRP and oral hygiene Instructions Evaluation after three weeks | OHRQL (questionnaire) |
Shah M and Kumar S [ ] India (Prospective Clinical) | 50 dentate adults Mean age = 26 and 29 years respectively in control and study groups | At least one proximal site with PD >4 mm | SRP in test group oral hygiene instructions only in control | OHIP – 14 |
Saito A et al., [ ], Japan (Prospective Pilot study) | 21 patients Mean age = 56 | Moderate to severe periodontitis more than two sites with CAL >4 mm, or more than two sites with PD >5 mm | Phase 1 – baseline Phase 2 (NSPT ) – OHI, SRP under LA. Phase 3 (ST ) – OFD + antibiotic +NSAIDs. | OHQoL -J (Japanese version) |
Nagarajan S and Chandra RV [ ], India (Longitudinal) | 183 patients 18–55 years | Classified into low, moderate and high-risk groups based on PRA model | 1. NSPT – SRP 2. ST 3. Aggressive NSPT –SRP + local drug Delivery | OHQoL –UK (United Kingdom version) |
Wong RM et al., [ ], Hong Kong (Longitudinal) | 65 patients 35–65 years of age | Moderate to advanced chronic periodontitis More than two sites with >5 mm PD in each quadrant. | NSPT – OHI, supra-/ sub-gingival SRP | OHIP -4-S (questionnaire) |
Brauchle F et al., [ ] Germany (Prospective Clinical) | 93 patients Age =27-74 | Control group (PD < 4 mm, CPI score 0–2), patients with CPI score of 3 (PD = 4–5 mm) and patients with CPI score of 4 (PD > 5 mm) | NSPT | OHIP -German version |
Douglas de Oliviera DW et al., [ ] Brazil (Prospective Clinical) | 22 patients, 25 defects 20 to 49 years of age | Miller class I or II GR on maxillary canine or premolar. Presence of dentine hypersensitivity | CAF + CTG | OHIP - 14 |
Jonsson B and Ohrn K [ ] Sweden (Randomised Controlled Trial) | 87 patients 20 to 65 years of age | Moderate to advanced periodontitis | NSPT | GOHAI OHQoL - UK |
Irani FC et al., [ ] U K (Prospective) | 61 Type 2 diabetics 74 non diabetics | Grouped into healthy, gingivitis and periodontitis based on PD, bleeding and radiographic bone loss | NSPT comparison between diabetics and non diabetics | OHIP 49 |
Santuchi CC et al., [ ] Brazil (Randomised Controlled Trial) | 90 patients 35 to 60 years of age | Mild to moderate chronic periodontitis | SRP vs One stage full mouth disinfection | OIDP OHQoL |
Makino-Oi A et al., [ ] Japan (Prospective Clinical) | 76 patients above 20years old | Two or more interproximal sites with clinical attachment ≥ 4 mm, not on the same tooth or two or more interproximal sites with probing pocket depth (PD ) ≥ 5 mm, not on the same tooth, with radiographic evidence of bone loss | 1. Baseline 2. After initial therapy 3. After ST or supportive periodontal therapy | OHRQL (questionnaire) |
Stefanini M et al., [ ] Mutli national (Longitudinal) | 45 patients (90 gingival recessions) | Miller class I or II GR | CAF vs CAF + CMX | VAS |
Satisfaction to treatment after modified Widman flap surgery was assessed by Lee JM et al., in chronic periodontitis patients using PRO scale and found that satisfaction parameters related to expectation of treatment outcome decreased significantly after surgical therapy [ 31 ].
Ozcelik O et al., compared the immediate postoperative QoL of periodontitis patients after non surgical, surgical and surgical plus enamel matrix derivative treatments [ 44 ]. They report that surgery alone group experienced the worst OHRQoL in the immediate postoperative period.
Postoperative comfort after root coverage surgery was compared between connective tissue graft and Free Gingival Graft (FGG) using PRO measures and reports more discomfort and pain for FGG [ 37 ]. Douglas de Oliveria DW et al., attributes the reduction in dentinal hypersensitivity as the reason for the improvement of QoL after root coverage surgery [ 40 ]. Irrespective of the procedure used, root coverage surgery significantly improved QoL scores posttreatment [ 36 ].
Aslund M et al., supports the concept that periodontitis may negatively affect a patient’s QoL and that non surgical treatment may improve it [ 45 ]. D’Avila GB et al., and Santuchi CC et al., reported that regardless of the protocol used, non surgical periodontal treatment led to significant reduction of self perceived impacts [ 42 , 46 ].
Four more studies were in agreement that non-surgical therapy improves QoL in periodontitis patients [ 32 , 34 , 38 , 41 ]. Patients with severe periodontal disease showed better improvement in QoL after therapy when compared to those with mild or moderate disease [39]. Brauchle F et al., reported the influence of age, gender and tobacco consumption on OHRQoL [ 39 ].
One study compared the impact of periodontal surgery with that of initial therapy (non surgical therapy) on QoL [ 18 ]. Both treatments improved OHRQoL. But the QoL didn’t significantly improve in the interval between post initial therapy and after surgery. Makino-Oi A et al., also reported the positive effect of initial therapy in bringing about OHRQoL improvement compared to subsequent non surgical or surgical therapy [ 1 ].
Nagarajan S and Chandra RV et al., assessed the impact of various OHRQoL items among three risk groups based on periodontal risk assessment -PRA model and showed that in moderate and high risk groups surgical and non surgical treatment resulted in QoL improvement when compared to low risk groups [ 33 ].
Jonsson B and Ohrn K et al., reported that NSPT resulted in QoL improvements beyond the MID in 46%-50% of patients [ 23 ]. One study assessed the effect of Type 2 diabetes on OHRQoL [ 35 ]. The QoL of non diabetic patients improved after non surgical periodontal treatment significantly, but in diabetics, there was no statistically significant change on OHRQoL scores after periodontal therapy.
Two systematic reviews on the topic were obtained [ 2 , 47 ]. The focussed question of the systematic review by Shanbhag S et al., was “Does surgical or non surgical periodontal therapy improve the OHRQoL in adults with periodontal disease”? The results of 11 studies reviewed suggested that all forms of nonsurgical therapy can improve the OHRQoL immediately after treatment as well as at 12 months. The ES of improvement ranges from small, medium to large among the studies reviewed. The OHRQoL domains that improve after periodontal therapy are those of function, psychology and pain. Surgical therapy does not have significant additional benefit on those who have received non-surgical therapy [ 2 ].
Buset SL et al., investigated the effect of gingivitis and periodontitis on OHRQol in a recent systematic review [ 47 ]. Twenty eight studies reported a significant association between periodontal disease and QoL. Eight studies point to increasing impacts with increased disease severity. The review also included articles that assessed the effect of periodontal therapy on QoL, even though it was not the primary objective [ 2 , 18 , 32 , 38 , 39 , 45 ].
The results from the included studies suggested that both surgical and NSPT can potentially improve the QoL of patients. Root coverage procedures like connective tissue grafts improved OHRQoL of patients with recession irrespective of the amount of root coverage attained. Surgical therapy didn’t result in significant additional improvement in QoL scores when compared to initial therapy. Gingivitis and periodontitis are associated with reduced QoL compared to periodontal health. OHRQoL of patients with periodontal disease improved significantly after periodontal treatment. The only study on diabetic subjects suggested that Type 2 diabetes has no impact on OHRQoL [ 35 ].
Patient centred outcome assessment- advantages and disadvantages: Patients self-report is a simple, convenient and less expensive mechanism for getting primary information related to therapeutic success. However such measures are heavily influenced by their personal beliefs, cultural background, social, educational and environmental factors. They often provide contrasting assessment from those of clinically determined metrics. Generally patients are less likely to assess adequately their periodontal status than the condition of restoration or status of teeth. Therefore, the patients self-report of their periodontal health may not be corresponding to the clinically determined measures. There is enough evidence [ 48 , 49 ] to show that the self-reported periodontal status is less predictive and thus less reliable. Moreover, self-reported measures are subjected to participants reporting biases. But when used to assess success of periodontal therapy in a clinical and research setting, PRO measures offer several advantages. Patient-based outcomes were identified as a research priority at the 2003 World Workshop on Emerging Science in Periodontology [ 50 ]. A validated PRO measure calibrated to normative clinical indicators is highly useful [ 48 ]. In clinical research situations where full mouth periodontal examination is impractical, validated PRO instruments are useful in determining periodontal health status. A simple and accurate PRO instrument is inexpensive and highly practical in clinical trials. Thus, it can be used in resource poor settings where expense is a concern.
The search didn’t include articles from Embase due to inaccessibility. Articles only in English language were included. Due to the heterogenicity of the variables meta analysis could not be performed.
Until recently, PRO have been largely neglected in periodontal therapeutic research. Studies have shown that PRO measures like treatment satisfaction and QoL are more relevant to patients than clinical changes in PPD or CAL. Evidence suggests that PRO add value to periodontal clinical practice and research. Both non surgical and surgical periodontal treatment improved OHRQoL. However, the improvement affected by surgical therapy after initial therapy is not significant. There is a need for a specific PRO scale that could potentially tap the entire dimension of the change in patients perception brought about by periodontal therapy. More longitudinal studies using scales with good responsiveness are needed to strengthen the evidence.
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Periodontitis is a chronic inflammatory disease caused by dysbiotic biofilms and destructive host immune responses. Extracellular vesicles (EVs) are circulating nanoparticles released by microbes and host cells involved in cell-to-cell communication, found in body biofluids, such as saliva and gingival crevicular fluid (GCF). EVs are mainly involved in cell-to-cell communication, and may hold promise for diagnostic and therapeutic purposes. Periodontal research has examined the potential involvement of bacterial- and host-cell-derived EVs in disease pathogenesis, diagnosis, and therapy, but data remains scarce on immune cell- or microbial-derived EVs. In this narrative review, we first provide an overview of the role of microbial and host-derived EVs on disease pathogenesis. Recent studies reveal that Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans-derived outer membrane vesicles (OMVs) can activate inflammatory cytokine release in host cells, while M1 macrophage EVs may contribute to bone loss. Additionally, we summarised current in vitro and pre-clinical research on the utilisation of immune cell and microbial-derived EVs as potential therapeutic tools in the context of periodontal treatment. Studies indicate that EVs from M2 macrophages and dendritic cells promote bone regeneration in animal models. While bacterial EVs remain underexplored for periodontal therapy, preliminary research suggests that P. gingivalis OMVs hold promise as vaccine candidates. Finally, we acknowledge the current limitations present in the field of translating immune cell derived EVs and microbial derived EVs in periodontology. It is concluded that microbial and host immune cell-derived EVs have a role in periodontitis pathogenesis and hence may be useful for studying disease pathophysiology, and as diagnostic and treatment monitoring biomarkers.
Keywords: extracellular vesicles; immune cells derived EVs; inflammatory response; microbial EVs; pathogenesis; periodontitis; therapy.
Journal of Periodontal Research© 2024 The Authors. Journal of Periodontal Research published by John Wiley & Sons Ltd.
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Aditya, Vangara; Vandana, Kharidhi Laxman 1
Private Practitioner, Consultant Periodontist and Implantologist, Hyderabad, Telangana, India
1 Department of Periodontics, Former Associate Dean Academics, NAAC Editor, CODSJOD, College of Dental Sciences, Davanagere, Karnataka, India
Address for correspondence: Dr. Kharidhi Laxman Vandana, Department of Periodontics, Former Associate Dean Academics, NAAC Editor, CODSJOD, College of Dental Sciences, Davanagere, Karnataka, India. E-mail: [email protected]
This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 4.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
There are various conventional radiological parameters for measuring the periodontal pocket depth apart from clinical measurements such as intraoral periapical radiograph, orthopantomogram and digital such as radiovisiography (RVG), and cone-beam computed tomography (CBCT) to an extent. As CBCT is highly recommended in the field of dentistry, especially in periodontics for an accurate measurement of remaining alveolar bone present from crest to apical region three dimensionally. Many patients cannot afford CBCT due to its cost-effectiveness and time-consuming procedure, and hence, a software was introduced to limit radiation exposure, where all preoperative and postoperative RVGs were placed in a software to measure its osseous defect and bone formation. This technique is introduced to reduce the exposure time to patients as well as for diagnosis of osseous defects radiographically to clinicians. This software can also be used in other fields of dentistry also. The main objective of this short communication is to create awareness regarding the availability of such a tool and recommend its application in periodontal regeneration clinical trials.
The radiographic measurements in any periodontal pocket therapy serve as a useful adjunct to clinical measurements. The traditional intraoral periapical radiograph (IOPA) followed by orthopantomogram (OPG) and radiovisiography (RVG) is well utilised in a routine clinical trial. The present day cone-beam computed tomography (CBCT) is stepping into periodontics with mixed opinion on its usefulness due to high cost and heavy radiation. The measurements of the osseous defect changes must be made with a minimum amount of error, dependability, repeatability, and economic considerations are the main factors that control radiographic measurements regardless of the method of imaging employed. With advancements in digital dentistry, one of the software or tools available is ImageJ analyzer software (Version 1.38).
In the field of periodontics, the use of radiographs from simple IOPA, grid IOPA, RVG, subtraction radiography, and OPG are well utilized. The digital advancement introduced the RVG which helped the periodontists to comprehend the periodontal osseous changes better during clinical trials. Further enhancement allowed the periodontist to utilize CorelDRAW on the digitalized radiographic images to have radiographic measurements from the designated hard tissue landmarks during the clinical trial. The great advantage provided in CorelDRAW is the tools to measure the defect changes in millimeter and fraction of millimeters.
Currently, the radiographic periodontal parameters used are linear measurements which quantify the bone changes from designated landmarks such as cementoenamel junction (CEJ), alveolar crest, and base of the defect. The radiographic linear measurements can be considered quantitative in nature which include:
(1) The distance from CEJ to the alveolar crest that expresses any alveolar crestal changes before and after treatment, (2) the distance from CEJ to the base of the defect that expresses the amount of bone formed at the base of the defect before regenerative treatment, and (3) the distance from the alveolar crest to the base of the defect. From these three measurements, the defect will be expressed using a specific formula. These three linear measurements are further supported by two more measurements such as defect angle [ 1 ] and defect area measurements. [ 1 ] Various radiographic measurements in a single periodontal osseous defect using ImageJ software had been considered [ Table 1 ].
To confirm the new bone formation and its density changes, invasive reentry and histological methods are the traditional approaches to qualitatively measure the new bone regenerated. The reentry and histological methods cannot be utilized during clinical trials due to ethical issues and noncompliance by the patient. The quantitative radiographic periodontal linear measurements are recorded by manual methods using a ruler, vernier caliper, or by acceptance of a grid. Hence, these are subjected to human errors, not reproducible, and not so dependable. The qualitative bone density measurement using histological methods cannot be a part of the routine clinical trial as histologic evaluation requires removal of a tooth with periodontium after successful treatment.
These inherent drawbacks associated with traditional quantitative linear and qualitative radiographic periodontal parameters are overcome by the implication of a software tool called ImageJ. The National Institutes of Health and the Laboratory for Optical and Computational Instrumentation created the Java-based image processing software called ImageJ (LOCI, University of Wisconsin).
Bone healing is an important subject in various fields of dentistry such as prosthodontics, periodontics, surgery, and implants. Out of the aforementioned methods, clinical method (e.g., probing) and adjunctive radiographic method practically aid the clinician to evaluate the outcome of periodontal therapy, whereas histologic and surgical reentry are least embraced methods.
The complete set of radiographic periodontal parameters can be assessed using ImageJ analyzer. ImageJ is a user-friendly, cost-effective, reliable, and reproducible software useful in assessment of periodontal regeneration. It is less time-consuming compared to manual methods. The success of the therapy may be evaluated noninvasively with the use of linear measures and density changes that are simply computed using user-friendly software. [ 1 ] The linear measurements performed using ImageJ are presented in Figure 1 .
Area of the defect is being dealt with for the first time in periodontal regenerative techniques. The specific changes that occur in the base of the defect can be addressed using the changes in area at different intervals instead of linear measurements [ Figure 2 ].
An original RVGs had been put before sending it to ImageJ software at baseline and 1 year [ Figure 3 ].
The bone density changes which are shown in various intervals are an eye-opener for the measurement of periodontal regenerative techniques. The density measurements using a histogram are shown in Figure 4 .
The main objective of this short communication is to create awareness regarding the availability of such a tool and recommend its application in periodontal regeneration clinical trials.
Currently, ImageJ software is successfully utilized in two clinical studies that are as stem cell assistance in periodontal regeneration technique by Shalini HS and Vandan KL 2018 [ 1 ] and interdental papilla treatment by Singh S and Vandana KL 2019. [ 2 ] It is also been utilized to measure dentinal tubules by Neha M and Vandana KL 2015. [ 3 ]
Any clinical study where the bone is the target tissue to be evaluated at various time points should make use of this software. It can find clinical applications including endodontic periapical cyst therapy, implant, oral and maxillofacial surgery, and orthopedic surgeries. It serves as a simple and affordable objective tool for bone regeneration assessment.
Conflicts of interest.
There are no conflicts of interest.
Thanks to Dr. Shalini HS and Dr. Aswin PS for their academic support.
Dentists ; humans ; periodontal pocket ; radiography ; software
Journal of Translational Medicine volume 22 , Article number: 907 ( 2024 ) Cite this article
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Dear editor,
Periodontitis, particularly chronic periodontitis, is a common chronic inflammatory disease affecting both oral and systemic health, often leading to alveolar bone resorption and loss of periodontal attachment [ 1 , 2 ]. Recent studies have demonstrated a close relationship between periodontitis and the onset and progression of systemic diseases, making the prevention and treatment of periodontitis crucial for overall health [ 4 ]. Currently, periodontal treatment mainly relies on ultrasonic scaling and periodontal debridement [ 5 ]. However, with the development of stem cells, traditional Chinese medicine, and other biomedical approaches, many new interventions have emerged in recent years, challenging conventional invasive treatment methods [ 3 ].
The clinical trial landscape of periodontitis reflects the recent development and evaluation of clinical interventions, providing deep insights into the latest treatment strategies, research trends, and future directions. On September 1, 2024, we conducted a database search using the keyword “periodontitis,” excluding non-interventional clinical trials, and identified 248 clinical trials. These trials were categorized based on their phase, status, and treatment type to evaluate their development trends (Supplementary Table 1 ).
In recent years, the number of clinical trials has remained relatively stable, reaching a peak in 2024, although the decline over the past two years may be attributed to the impact of the COVID-19 pandemic. These clinical trials cover different research phases, particularly Phase II and beyond (Fig. 1 A), with Phase IV trials dominating, comprising 69 studies focused on post-market surveillance and safety. Phase III trials include 66 studies (17.5%) validating efficacy, while Phase II trials also represent a significant proportion (50 studies, 20.1%). The lower proportion of early-phase trials may indicate market saturation or the challenges of early research. The proportions of Phase I and Phase 0 trials are 9.6% (24 studies) and 7.2% (18 studies), respectively. Currently, most clinical trials have been completed and will soon enter clinical application, indicating a new breakthrough in periodontitis treatment (Fig. 1 B). The number of trials related to supplements (including dietary supplements) and natural products (81 trials, 32.66%) suggests an increasing interest in non-invasive or dietary interventions (Fig. 1 C). Meanwhile, traditional local treatment methods remain the mainstay of periodontitis treatment, accounting for 16.13% (47 trials) of the studies. Research on other categories is less common, reflecting a diverse yet non-dominant research landscape. Among all trials related to supplements and natural products, natural products continue to dominate (Fig. 1 D), particularly products such as curcumin, resveratrol, aloe vera, and so on. As research on oral microbiota deepens, studies on prebiotics, probiotics, and related products are gradually emerging, further highlighting their role in inflammation management.
The Clinical Trial Landscape for Periodontitis. ( A ) Distribution and status of clinical trials across different phases (A significant increase in clinical trials began after 2018). ( B ) Distribution and status of clinical trials across different phases from 2018 to 2024. ( C ) Interventional clinical trials for periodontitis categorized by treatment type. ( D ) Main components within the supplements and natural products category
However, this analysis has certain limitations, primarily due to incomplete and biased data in clinical trial databases, as not all trials are registered or detailed. To mitigate this issue, we also searched government databases. Nevertheless, the lack of start dates hindered the analysis of annual trends. Additionally, the challenge of separating drug effects in multi-drug trials complicates classification and data interpretation. In future research, advanced statistical methods and subgroup analysis can help clarify the contribution of each drug in combination therapies.
This evaluation reveals that the clinical trial landscape for periodontitis treatment is undergoing significant changes. Although traditional invasive local treatment methods still hold an important position, increasing research is focusing on non-invasive or natural product interventions, indicating that clinical practice is gradually shifting towards safer and more patient-friendly approaches. This trend challenges existing periodontitis treatment theories, necessitating a reassessment of current treatment models and consideration of how to integrate these emerging non-invasive interventions into standard care.
Although the number of studies on supplements and natural products is increasing, large-scale, long-term clinical trials are still needed to verify their efficacy and safety. These studies should focus on understanding the mechanisms of these interventions to better grasp how they affect the progression of periodontitis. Since the etiology and progression of periodontitis may be influenced by factors such as race, diet, and environment, multi-center and international clinical trials will help evaluate the treatment effects on different populations and determine the best treatment strategies worldwide. As combination therapies rise, future research should aim to optimize the combination of different drugs and interventions to maximize therapeutic effects while minimizing side effects. This may require the application of advanced statistical and machine learning methods to analyze complex datasets and determine the optimal treatment regimen.
All data used and/or analyzed in this manuscript are publicly available in the clinical trial database ( https://clinicaltrial.gov/ ).
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The present evaluation was supported by the University of Debrecen Program for Scientific Publication, Shanghai Stomatological Hospital, and Shanghai Jiao Tong University School of Medicine.
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School of Medicine, Shanghai Jiao Tong University, 227 Chongqing South Road, Huangpu District, Shanghai, 200000, China
Zhengrui Li
Shanghai Stomatological Hospital & School of Stomatology, Fudan University, Shanghai, 200001, China
Faculty of Dentistry, University of Debrecen, Egyetem ter 1, Debrecen, 4032, Hungary
Xufeng Huang
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Zhegnrui: Conceptualization; methodology; software; validation; formal analysis; investigation; data curation; writing – original draft; project administration. Jing Li: Conceptualization; methodology; software; validation; formal analysis; investigation; data curation; writing – original draft. Xufeng Huang: Funding acquisition; methodology; resources; writing – review and editing; supervision. All authors read and approved the final manuscript.
Correspondence to Zhengrui Li or Xufeng Huang .
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Li, Z., Li, J. & Huang, X. Clinical trial landscape for periodontitis treatment: Trend analysis and future perspectives. J Transl Med 22 , 907 (2024). https://doi.org/10.1186/s12967-024-05697-4
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Received : 07 September 2024
Accepted : 22 September 2024
Published : 07 October 2024
DOI : https://doi.org/10.1186/s12967-024-05697-4
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The ISSN (Online) of Journal of Periodontal Research is 1600-0765 . An ISSN is an 8-digit code used to identify newspapers, journals, magazines and periodicals of all kinds and on all media-print and electronic. Journal of Periodontal Research Key Factor Analysis
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The Journal of Periodontal Research is an international research periodical the purpose of which is to publish original clinical and basic investigations and review articles concerned with every aspect of periodontology and related sciences. Reports of scientific meetings in periodontology and related fields are also published.
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Established in 1930, the Journal of Periodontology publishes original papers of the highest scientific quality to support practice, education, and research in periodontics and implant dentistry. As the original peer-reviewed journal of the American Academy of Periodontology, the primary mission is to publish cutting-edge basic, translational, and clinical science in the fields of ...
The Journal of Periodontal Research has an SJR (SCImago Journal Rank) of 0.895, according to the latest data. It is computed in the year 2024. It is computed in the year 2024. In the past 10 years, this journal has recorded a range of SJR, with the highest being 1.310 in 2020 and the lowest being 0.816 in 2022.
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Research in the field of periodontology has witnessed a tremendous upsurge in the last two decades unveiling newer innovations in techniques, methodologies, and material science. The recent focus in periodontal research is an evidence-based approach which offers a bridge from science to clinical practice.
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This warrants further research. One way to investigate the strength of these correlations is to record periodontal status before and after the few months of the oral hygiene phase, 21, 22 including oral hygiene instructions and supragingival scaling, and then again after the NSPT. This would help estimate treatment effect heterogeneity much ...
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