INTRODUCTION

Conventional orthodontic tooth movement is defined as the outcome of biological cascades of resorption and apposition brought on by various mechanical stimuli.[1] External apical root resorption, or orthodontically induced root resorption (OIRR), is considered a common sequela of orthodontic tooth movement. It can be characterized as an iatrogenic condition that occurs when a tooth is moved in orthodontics and mineralized cementum and dentine are lost; the resorbed section of the root is then replaced with healthy bone.[2] The most common method of detecting root resorption is with the help of radiographs. Nevertheless, bidimensional radiographs are unable to detect buccal or labial surface resorption of the roots and cannot accurately detect root resorption at an early stage. Thus, there is a critical need for non-invasive methods to identify root resorption early in patients who are at risk.[3]

In contrast to X-rays, the gingival crevicular fluid (GCF) could be used as an easy diagnostic technique that is not invasive and comparatively easy with increased repeatability. The ability to learn more about the activity and stage of root resorption, the ability to recognize high-risk patients and diagnose them early, and the ability to forecast the outcomes and lack of exposure to ionizing radiation are additional benefits. Early identification of resorption is necessary due to the harmful effects of root resorption on tooth mobility. Determining the biomarkers requires a thorough understanding of root resorption in relation to the periodontal ligament and surrounding bone, which contain a variety of cells, matrices, and biological messengers.[4] Although the GCF biomarkers secreted in the paracrine environment during orthodontic tooth movement have been thoroughly examined, there is a lack of comprehensive research on all body fluid biomarkers, such as GCF, saliva, and blood, around the resorbing tooth structures.[5] The ease of reproducibility, collection, and early resorption detection offered by GCF over other mediums for biomarker collection are of advantage. Moreover, saliva is easier to reach and less specialized for the underlying periodontal problem.

Proinflammatory cytokines (interleukin [IL], tumor necrosis factor, etc.) or matrix metalloproteinases, which are involved in osteoclastogenesis or extracellular matrix destruction, have also been linked to the degree of resorption.[6] Alkaline phosphatase, an enzyme associated with early mineral deposition and tissue calcification, is associated with pulpal repair and healing after acute shocks or injury, which could also lead to varying expression of root resorption.[7-12] Numerous markers are specifically associated with root resorption, including those found in tissue damage, tissue repair, and various stages of resorption. Precious research has been done on analyzing numerous cytokines and their effect in detecting root resorption. However, the results have been non-homogenous without standardized methods.[13-25]

Among these, dentin sialophosphoprotein (DSPP) exhibits continuous expression during dentinogenesis and amelogenesis and is regarded as a powerful resorption marker.[26-30] The concentrations of certain biomarkers associated with mineralization, such as dentin matrix protein 1 and DPP, are higher in patients with OIIRR than in controls without OIRR, according to prior studies. Moreover, patients with severe OIRR have greater DPP concentrations than patients with mild OIRR.[31-38] This systematic review aimed to determine whether root resorption in adult and adolescent orthodontic patients could be detected by changes in the DSPP biomarker concentration found in the GCF. By systematically reviewing and analyzing the existing literature on this topic, the review can provide valuable insights into the efficacy of DSPP as a biomarker in detecting orthodontically induced root resorption.

MATERIAL AND METHODS

A comprehensive search of electronic databases, i.e., PubMed Central, Cochrane, Scopus, and Web of Science, was made for relevant articles. The search was performed up to April 2023 using the search items and a combination of the PubMed search builder. All peer-reviewed, potentially relevant articles were screened and identified using the search strategy. Studies were included based on the eligibility criteria and assessed. The was used to rate the studies’ quality and draw attention to any methodological errors.

Protocol registration

The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 statement’s reporting guidelines for systematic reviews and meta-analyses served as the basis for conducting the systematic review. It was also registered with the PROSPERO database, the International Prospective Register of Systematic Reviews, with the registration number CRD42023416507. The research question was as follows: Can root resorption in adult and adolescent orthodontic patients receiving fixed appliance therapy be detected using changes in DSPP biomarker concentration in the GCF? The included studies were presented based on the PICO format.

Eligibility criteria

Prior to the literature search, the inclusion and exclusion criteria were established. The PICO question was formulated as if root resorption in adult and adolescent orthodontic patients receiving fixed appliance therapy could be detected using changes in DSPP biomarker concentration in the GCF. The population (P) consisted of human subjects, such as adolescent and adult patients undergoing orthodontic treatment. The intervention (I) involved the use of fixed appliance therapy for treatment. The comparison (C) was made between individuals who have not received treatment or who have received treatment but have not displayed any evidence of root resorption. The outcome (O) was the changes in the concentration of DSPP biomarkers in GCF.

The following criteria were used to select the studies: Inclusion criteria

Clinical trials and prospective research, both randomized and non-randomized, were considered

Studies conducted on either adult or adolescent patients receiving fixed appliances for orthodontic treatment

Studies assessing root resorption using DSPP biomarker level in GCF samples with micropipettes or Periopaper.

Exclusion criteria

Exclusion criteria were in vitro, animal research, meta-analyses, case reports, reviews, narrative reviews, and systematic reviews

Studies pertaining to other analyses of gingival biomarkers

Studies using various GCF sampling techniques.

Information sources and search strategy

The following electronic databases, including PubMed, Embase, Scopus, and Web of Science, were thoroughly searched up until April 2023. Using the terms root resorption, DSPP, dentin, biomarker, GCF, and orthodontic treatment, a thorough literature search was carried out. Two investigators independently chose which studies to include (RR and AK). Before being chosen as full-text papers, the studies were evaluated according to their titles and abstracts. Before being included in the review, the chosen articles were read. A discussion was used to settle the investigators’ discrepancies. [Table 1] lists the search approach, which includes MeSH terms, keywords, and several database queries.

Table 1: Search strategy.

Database Search strategy Results PubMed ((((Adult[Mesh]) OR (Orthodontic Appliances, Fixed [Mesh])) OR (Braces [Mesh])) OR (Orthodontic Brackets [Mesh])) OR (Orthodontic Appliances, Removable [Mesh]) Gingival Crevicular Fluid [Mesh] gingival exudate [Mesh] gingival exudates [Mesh] (((Biomarkers [Mesh]) OR (Biomarkers, Pharmacological [Mesh])) OR (dentin sialo phosphoprotein [Supplementary Concept])) OR (dentin sialo phosphoprotein human) ((((Root Resorption [Mesh]) OR (Tooth Resorption [Mesh])) OR (Tooth Root [Mesh])) OR (Orthodontic forces)) OR (Orthodontic force levels) 1620 Web of Science ((ALL=(adult)) OR ALL=(adolescent)) OR ALL=(orthodontic patients)) AND ALL=(orthodontic therapy)) OR ALL=(fixed appliance therapy)) OR ALL=(braces)) OR ALL=(orthodontic treatment)) AND ALL=(biomarkers)) OR ALL=(gingival crevicular fluid)) OR ALL=(dentin sialoprotein)) OR ALL=(dentin sialo phosphoprotein)) AND ALL=(root resorption)) OR ALL=(orthodontically induced root resorption)) OR ALL=(inflammatory root resorption) 921 SCOPUS (Orthodontic patients) AND (fixed appliance therapy) OR (orthodontic braces) OR (fixed orthodontic treatment) AND (dentin sialo phosphoprotein biomarker) OR (gingival exudate) AND (orthodontic root resorption) OR (inflammatory root resorption) 35 Embase (adult orthodontic patients) OR (adolescent patients) OR (orthodontic patients) AND (fixed appliance therapy) OR (orthodontic therapy) OR (fixed braces) AND (biomarkers) OR (gingival crevicular fluid) OR (dentin sialo phosphoprotein) AND (root resorption) OR (orthodontic root resorption) 37 Selection criteria Screening and selection of studies

The studies that met the eligibility requirements were all included. Two authors (RR and AK) separately selected the studies after initially screening the articles’ titles and abstracts. They then independently extracted the data from the chosen studies. All discrepancies were discussed with the third author (AM) to find a solution. The names of the authors, the study design, the patient types, and the preparations employed, as well as general information about each of the included studies, are specified in [Table 2].

Data extraction

RoB assessment was conducted by two reviewers (RR and AK) who reviewed the included studies independently. The extracted data were based on the type of study, population involved, sample collection, experimental and control groups, assessment protocol, detection method of root resorption, type of orthodontic force, magnitude of the force applied, duration of the study, biomarker involved, site of sample collection, type of sample, and time interval. Any conflict was resolved by discussion with the third author (AM).

Qualitative assessment of the included studies

The RoB assessment tool was used to conduct a qualitative analysis of the included studies (RoB version 2.0). The following categories were used to evaluate the bias risk: bias in result data, outcome evaluation, outcome reporting, and other biases. The results were tabulated and are shown in [Table 2]. Based on each individual study, scores were provided. The scores depicted “+” as “high risk,” “-” as “low risk,” and “?” as “unclear risk.” Based on this assessment, the studies were summarized and mentioned as given in [Table 3].

Table 2: Study characteristics involving the preparation method included in the studies.

Authors Study design Type of patients Mean age Preparation used Mah et al., 2004[39] Clinical trial Adolescent 10–15 years To collect GCF, the tooth was first carefully cleaned with water, dried, and isolated with cotton rollers to avoid saliva contamination. For 30 s, a paper collecting strip (Periopaper) was introduced 1 mm into the gingival crevice. A second collection was started after 1 min. Both strips were placed in a micro-centrifuge tube, immediately sealed and stored at –70°C for later analysis. Balducci et al., 2007[31] Clinical trial Mixed 12-44 years The central and lateral upper incisors’ mesial and distal sides were used to collect the GCF. Filter paper strips (Periopaper1, Oraflow, Plainview, NY) were inserted
1-2 mm into the gingival sulcus and left there for 30 s. At 1-min intervals, the identical procedure was repeated. Kereshanan et al., 2008[40] Clinical trial Adolescent 18.9±6.1
(study group)
28±5.3
(control group) GCF was obtained by capillary action during a 10-min period using 5 L micropipettes (Drummond Scientific Co., Broomall, Pennsylvania, USA). Prior to being analyzed in the laboratory, the samples were kept at 80°C. Thalanany et al., 2017[41] Clinical trial Adolescent and adults 13–22 years A total of two GCF samples were collected. First, just before and then two months after applying orthodontic intrusion force, respectively. Using single-use micro-capillary tubes with an internal diameter of 1.1 mm and a volume of 5 L, GCF was collected from the central and lateral incisors of the maxillary arch, with the right and left side being randomly selected (Raghavendra et al., 2012). (Ring Caps, Hirschmann Laborgerate, GmbH and Co., Germany). Over a 20-min period, almost 2 L of GCF were extracted from the gingival sulcus of the teeth. Uma and Ahmed, 2018[42] Clinical trial Adolescent and adults 16-22 years A calibrated volumetric disposable microcapillary tube with a capacity of 5 L and an internal diameter of 1.1 mm was used to collect GCF (Ring Caps, Hirschmann Laborgerate, GmbH & Co. Germany). Over the course of 20 min, 2 mL of GCF was extracted from the gingival sulcus of the central and lateral incisors, respectively. Huang et al., 2021[43] Split mouth study Adults 23.5 years In four locations (mesiolabial, distolabial, mesiolingual, and distolingual) of each chosen tooth, paper strips were placed into the gingival sulcus until light resistance was felt, and they were held in place for 30 s. Each of the four strips taken from each tooth after the GCF was collected was then put into a microtube (Axygen®, China). For each microtube, this process was repeated twice at 5-min intervals, yielding a total of twelve strips from each tooth. Ghaleb et al., 2021[44] Single blinded, split mouth RCT Adults and adolescents 15.8 years The strips were inserted into the gingival crevice until a slight resistance was felt, and then they were left in place for 60 s to collect samples of the GCF. After being removed, fresh strips were added at 1-min intervals to obtain four strips at each location. Each set of four filter paper strips was gathered from the same experimental site and placed in a separate Eppendorf tube containing 100 uL of phosphate-buffered saline. It was centrifuged at 3000 g for 10 min. and stored at 20°C for a subsequent analysis. Blood or saliva-contaminated samples were discarded, and fresh samples were taken in their place. Ravi et al., 2022[45] Split mouth study Adults 18–26 years Selected patients were instructed to thoroughly rinse their mouths with water. Cotton pellets were used to isolate the targeted tooth. The distobuccal and mesiobuccal aspects of the canines were employed to collect 1 mL of the GCF using a 1–5 L calibrated volumetric micro-capillary pipette. A standardized volume of GCF (1 L) was collected using a volumetric micropipette implanted extra crevicularly, before retraction (TO) and again after 90 days after retraction. Adiwirya et al., 2022[46] Clinical trial Adults 25.5±4.91 GCF was taken from both experimental groups immediately before orthodontic activation (T0), and again three and
12 weeks later (T1 and T2, respectively). The control group’s GCF collection followed the same schedule as that of the experimental groups, with T0 denoting the initial GCF collection and T1 and T2 denoting 3 and 12 weeks thereafter.

Table 3: Risk of bias chart of the included studies.

Authors Random sequence generation Allocation concealment Selective outcome reporting Blinding of participants and personnel Blinding of outcome assessment Incomplete outcome data Other bias Mah et al.[39] + + + + ? ? + Balducci et al.[31] + + − + ? ? + Kereshanan et al.[41] + + + + ? ? + Thalanany et al.[41] + + − + ? + + Uma and Ahmed[42] + + − + + + + Huang et al.[43] − − − − − ? − Ghaleb et al.[44] − − − − ? ? − Ravi et al.[45] + + + + ? ? + Adiwirya et al.[46] + + − + ? ? + Summary of synthesis

There was some variation among the included studies regarding the orthodontic force type, force magnitude, sample size, data collection location, and study duration. The compilation of the data for a meta-analysis was both methodologically difficult and statistically inappropriate due to the significant variability in study design, participant characteristics, intervention procedures, and outcome measurements that caused the gap between the studies. Hence, a qualitative analysis was performed, describing the results obtained from each of the included studies.

RESULTS Study selection

A total of 2613 articles from PubMed, Scopus, Web of Science, and Embase were returned via an electronic database search. There were 874 items left after the duplicates were eliminated. Less than 1737 of the remaining items were eliminated because they could not possibly be related. Twenty of the remaining abstracts were eliminated because of improper technique or failure to meet the criteria for inclusion. For a thorough evaluation, eleven full-text papers were evaluated. Due to their cross-sectional research or lack of a goal that matched the current systematic review, two papers were removed. In the end, the study included nine studies. [Figure 1] shows a PRISMA flowchart for the study selection procedure.

Figure 1: Preferred reporting items for systematic reviews and meta-analyses flowchart. GCF: Gingival crevicular fluid

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Study characteristics

The studies that were included comprised six clinical trials, two split-mouth studies, and one single-blinded split-mouth randomized controlled trial. The studies comprised the type of patients involved, their mean age, and the type of preparation used for the sample analysis. Among the studies that were taken into consideration, the mean age of the patients ranged from 17.3 to 26.07 years. The level of the DSPP biomarker in the GCF of the affected tooth served as the basis for all investigations that were included in the analysis of orthodontically induced root resorption. Filter paper strips or micropipettes were used to collect the samples, which were then promptly centrifuged and saved for subsequent examination. A detailed description of the preparation needed for each study is provided in [Table 2].

RoB of the included studies

The RoB tool was used to assess the RoB (version 2). The studies were given a high-risk, low-risk, or uncertain risk rating based on the numerous factors influencing design, conduct, and reporting of clinical trials. Only two of the nine included studies were considered to fall into the “low-risk” category. The included studies had a significant RoB related to randomization, blinding, and other factors, but the reporting of outcome measures had a very low risk. The RoB chart was formulated as given in [Table 3]. A graphical representation of the numerous bias risks is highlighted in [Figure 2].

Figure 2: Graphical representation of bias distribution.

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Overall percentage distribution of bias analysis included in our systematic review Findings of qualitative synthesis

To determine whether biochemical assays could be employed for the early detection of root resorption, Mah et al. measured the amounts of dentin phosphoprotein (DPP) in the primary, orthodontic, and control groups.[38] According to the study, DPP levels were highest in primary teeth that were exfoliating and lowest in control teeth.[39]

In a clinical trial by Balducci et al., the extracellular matrix proteins such as dentin matrix protein 1 (DMP1), and dentin sialoprotein (DSP) were identified and measured in GCF from patients receiving orthodontic treatment.[31] The study came to the conclusion that dentin phosphophoryn (PP) and DSP concentrations might be employed as a useful biomarker for monitoring root resorption during orthodontic treatment since they were higher in groups with severe and mild resorption, respectively.[31]

DSP, a dentine-specific matrix protein released into GCF during physiological root resorption and orthodontic tooth movement, was the focus of a clinical trial by Kereshanan et al.[40] In physiologically resorbing sites compared to nonresorbing control groups, the level of DSP was higher. Between groups with severe and minimum resorption, there was no difference.

Thalanany et al. examined the possibility of DSPP as a biomarker to identify root resorption and to measure the amount of DSPP produced into the GCF during orthodontic intrusion utilizing Ricketts’ simultaneous intrusion and retraction utility arch. The study’s findings showed that the levels of DSPP in GCF had significantly increased.[41]

By adopting Bhavna Shroff ’s three-piece intrusion arch for orthodontic intrusion, Uma and Ahmed conducted a clinical trial with adults and adolescents to evaluate the potential contribution of DSPP in GCF in root resorption.[42] No difference in DSPP levels before and after 2 months of intrusion was found between the experimental and control groups as a result of the investigation.[42]

Under constant buccal tipping force, Huang et al. looked at the relationship between changes in cementum protein-1 (CEMP-1), dentin phosphoprotein (DPP), and C-terminal cross-linked telopeptide of type I collagen levels in human GCF and external root resorption volume and amount of tooth movement. GCF samples were taken at the 1st week, the 4th week, and the 8th week.[43] Varying degrees of root resorption could be correlated with variations in CEMP-1 and DPP levels in human GCF.[43]

Dentin phosphoprotein levels in GCF were used by Ghaleb et al. to compare the effects of continuous and intermittent orthodontic force in a single-blinded, split-mouth, randomized controlled study to determine the degree of root resorption.[44] According to the study, continuous buccal tipping force groups had greater DPP concentrations than intermittent force groups (P = 0.04). Consequently, it was discovered that dentin phosphoprotein was a helpful early biomarker to identify and track root resorption and that intermittent forces were less likely to produce root resorption than continuous forces.[44]

In a split-mouth investigation, Ravi et al. measured the quantity of root resorption following canine retraction through a piezocision site, compared it to a site that had recently undergone extraction, and evaluated DSP levels in GCF.[45] The study’s findings showed elevated DSP levels on the piezocision side, but these findings were statistically insignificant.[45]

In a recent clinical trial by Adiwirya et al.,[46] patients receiving their first orthodontic treatment with self-ligating and traditional pre-adjusted brackets had their DSP concentration variations in GCF during orthodontically induced root resorption evaluated. The GCF was obtained from five proximal sites of the maxillary anterior teeth from three different time points: Before treatment (T0), 3 weeks (T1), and 12 weeks following intrusion. Three groups of identical size were involved (T2). Based on the type of fixed appliance therapy, the study demonstrated no discernible variations in DSP levels between the experimental and control groups.[46]

Outcome measures

A summary of the various outcome measures from the included studies is mentioned in [Table 4]. Hence, it is essential for future studies to have the DSPP biomarker regarded as a trustworthy biomarker that could aid in accurate identification of root resorption. According to studies by Mah[39], Balducci[31], Thalanany et al.,[41], Huang[43], Ghaleb, and Ravi et al.,[45] there has been a statistically significant shift in the levels of the DSPP biomarker with an increase in those levels in the GCF. The biomarker levels did not significantly change; in the studies carried out by Kereshanan, Uma, and Adiwirya et al.[40,42,46]

Table 4: Outcome data as reported in the included studies.

Authors Type of sample and method of collection Method of testing Outcome Mah et al., 2004[39] DPP gene using filter paper strips ELISA assay Examining the release of organic matrix proteins into the GCF Balducci et al., 2007[31] DMP 1, DPP and DSPP Using filter paper strips ELISA assay To calculate the amounts of dentin matrix protein 1, dentin phosphoprotein, and dentin sialoprotein in GCF. Kereshanan et al., 2008[40] DSPP using micropipettes ELISA assay Measure the dentin sialoprotein in GCF. Thalanany et al., 2017[41] DSPP using microcapillary tubes ELISA assay Determine the amount of DSPP released into the GCF during orthodontic intrusion Uma et al., 2018[42] DSPP using microcapillary tubes ELISA assay Using a three-piece intrusion arch, quantify the DSPP in root resorption during orthodontic intrusion. Huang et al., 2021[43] CEMP 1 and DPP using paper strips ELISA assay Compare the levels of tissue-specific biomarkers with the overall volume of root resorption using micro-CT. Ghaleb et al., 2021[44] DPP using filter paper strips ELISA assay Using DPP levels in GCF, compare the degree of root resorption between the continuous and intermittent orthodontic force groups. Ravi et al., 2022[45] DSPP using microcapillary pipette ELISA assay Determine the degree of root resorption during canine retraction using a piezocision site. Adiwirya et al., 2022[46] DSPP using paper points ELISA assay Compare the levels of DSPP in patients receiving orthodontic treatment at the beginning of the process. DISCUSSION

The studies included in the systematic review had some amount of heterogeneity which did not allow a quantitative synthesis of the results. However, the results confirmed the use of the DSPP biomarker as a potential biomarker for the assessment of orthodontic root resorption during various types of orthodontic tooth movement. DSPP was considered a potential biomarker for assessing root resorption initially by Balducci et al. and Kereshanan et al.[31,40] As a comparison to the control group, both the severe and mild root resorption groups in the study by Balducci et al. showed a markedly higher concentration of this cytokine.[31] Particularly in cases of severe root resorption, the peak was found to be higher. On the other hand, the study by Kereshanan et al. was based on a comparison of the DSP concentration in participants receiving orthodontic care and in subjects whose second primary molars were going through physiological root resorption.[40] Between the study groups and the control group, there was a statistically significant difference. Even though one of the study groups still had deciduous molars during the reabsorption phase, there was no statistically significant difference in the concentrations between the two groups . DSPP levels in GCF significantly increased as a result of a clinical trial Rahul et al. did to measure the quantity of DSPP released into the GCF after orthodontic intrusion.[41] In addition to CEMP-1, Huang et al. measured the levels of DPP and came to the conclusion that variations in CEMP-1 and DPP levels in human GCF might be related to various degrees of root resorption.[43] These findings were in line with those of the study by Ghaleb et al., which revealed a greater concentration of DPP in continuous force groups compared to intermittent force groups (P = 0.04).[44] The observations of a rise in DSPP during the retraction stages were also validated by Ravi et al.[45] However, in studies by Uma and Ahmed, and Adiwirya et al., no appreciable changes in the levels of the DSPP biomarker were discovered.[42,46]

Mah assessed the levels of DPP in the crevicular fluid of patients receiving orthodontic treatment, and the findings revealed a statistically significant difference between the control group and the orthodontic group as well as between the control group and the primary group.[39] The use of physiological root resorption as a good model to study pathological root resorption has been acknowledged by researchers based on a number of studies on the resorption of dentine.[47] It is recognized that the actual biochemical mechanism at work is basically similar, notwithstanding the possibility that the initiation process may vary. DSP may not be totally dentine-specific, according to some theories. In general, DSP and DPP are expressed as a single messenger RNA that codes for a substantial precursor protein known as DSPP, which is typically thought to be dentine-specific. Qin et al.[48] discovered that DSPP gene expression is present in both osteoblasts and odontoblasts, although at significantly lower levels. The information showed that both bone and teeth have various regulatory systems that control DSPP expression. Although at a low level, the presence of DSP in the bone may be a reflection of the presence of GCF in the control samples. Hence, it is possible that the cementum stores the dentin sialoprotein inside its matrix, releasing it into GCF as a natural result of the cementum’s resorption/repair process both during the physiological resorption of the root and during the movement caused by orthodontic therapy.[49] Because some sections of the cementum are resorbed and then regenerated during orthodontic movement, it appears that the proteins of dentine are the best markers for the diagnosis of root resorption. Cementum proteins, hence, do not strongly indicate the loss of root structure.

Based on the outcomes of the RoB evaluation, only two studies were found to have a low RoB. The investigations by Huang et al.[43] and Ghaleb et al.[44] mostly complied with all criteria, including randomization, allocation concealment, participant and staff blinding, and other biases. Hence, the systematic review may have come to the conclusion that both of these studies have a strong body of evidence.

Several research revealed a significant bias risk. In contrast to other protein matrices, the organic, non-collagenous DSPP of dentine is a sign of the permanent loss of root structure. Therefore, the creation of a DSPP-specific antibody is essential to use DSPPs as diagnostic tools for the clinical identification of root resorption in orthodontic patients. The majority of the included studies in this systematic review discovered an elevation in the DSPP biomarker in the GCF samples following the application of orthodontic force.

Hence, it is essential for future studies to have The DSPP Biomarker’s Dentin Phosphoprotein (DPP) and DSPP may therefore be regarded as trustworthy biomarkers that could aid in the accurate identification of root resorption. To improve the reliability and generalizability of the results, future research would substantially benefit from the application of more robust randomization procedures and a more advanced method to sample selection.

Limitation

The primary limitation of the included research was that the samples were evaluated at various points in time. Although the included studies used a similar ELISA technique for sample assessment, the types of groups, ages, and genetic variations among the subjects could have an impact on the levels of the DSPP biomarker. Therefore, additional research using a uniform technique and the same kind of orthodontic tooth movement is needed to verify the findings.

CONCLUSION

The DPP and DSP of the DSPP biomarker may be regarded as a reliable diagnostic for both adult and adolescent patients with orthodontically induced root resorption. This comprehensive review proved that the biomarker was present in the GCF. It may be used to quantify orthodontic root resorption rather than only cemental resorption because it is the primary organic and inorganic collagenous component of dentin. Therefore, additional clinical trials with improved standardization techniques and a bigger sample size are necessary to detect orthodontically induced root resorption early and avoid unjustified harm to the tooth structure during orthodontic tooth movement.

Availability of data and materials:

The data will be available on reasonable request from the corresponding author.