Platelet-rich plasma: Its applications in orthodontics – A systematic review

Rationale

PRP has become a valuable adjunct in various fields of dentistry. PRP has been used to treat periodontal defects, healing of extraction sockets, sinus lift augmentation, periapical osseous defects, etc., but there is a limited literature available on the diverse uses of PRP in orthodontics. Thus, the aim of this systematic review is to evaluate the different outcomes with the use of PRP in orthodontics.

Objectives

This systematic review aims at the appraisal of discrete effects of PRP when used as adjunct with the standard orthodontic procedures and to evaluate the response of PRP on acceleration of OTM and the accompanying changes on the surrounding bone.

Protocol and registration

The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) was followed in reporting this systematic review. The protocol for this systematic review was registered on the National Institute of Health Research Database (www.crd.york.ac.uk/prospero, protocol: CRD42020179187).

Eligibility criteria

Information sources, search strategy, and study selection

A literature search was performed independently by two reviewers using the following databases:

PubMed, Central of the Cochrane library, and Google scholar.

To identify the articles reporting the effect of PRP on the rate of OTM and the changes in the bone, the database was searched from January 2000 to May 2020 with no specific filter applied during the search. All articles were found using the combination of keywords as PRP and orthodontics with Boolean characters “AND” and “OR” combination. Additional search was also carried out on review articles, bibliography, and related journals. Search strategy used in PubMed was using keywords as “Orthodontics AND platelet-rich plasma OR PRP.”

The titles and abstracts of all retrieved articles were screened by three independent reviewers (a, b, and c), and irrelevant studies were excluded from the study. Full text of the eligible studies was obtained and thoroughly assessed by all the three reviewers for inclusion; disagreements were resolved by discussion between the reviewers.

Data collection process and items

Data collection was performed using a customized data extraction form: (1) Title of the study, (2) author’s name, (3) duration of study year of publication, (4) study setting, (5) study design, (6) study population, (7) method of randomization used (if any), (8) types of intervention, (9) types of comparator, (10) characteristic of participants (age and gender), (11) inclusion and exclusion criteria, (12) indicators of acceptability of user, (13) times of measurement outcomes (primary and secondary), and (14) conclusion.

Risk of bias

To evaluate the risk of bias in individual studies, different tools were used for human studies randomized controlled trials (RCTs) and for animal studies.

Revised Cochrane risk-of-bias tool for RCTs (RoB 2)^[9] was used for human studies and for animal studies SYRCLE’s RoB tool.^[10]

Study selection

PRISMA guidelines were followed to scrutinize the articles as detailed in [Figure 1]. The total number of hits was 1375 in the databases: 57 in PubMed, 8 in Cochrane, and 1310 in Google Scholar search resources. After adjusting the duplicates, 1310 hits were scrutinized for inclusion in the study. The majority of them were excluded as they did not have relevant title and abstract, leaving 12 publications. After excluding two review article and two hypothetical articles, just eight original articles remained which were included in this systematic review.

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Figure 1:

PRISMA Flowchart.

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Study characteristics

Risk-of-bias/quality assessment in individual studies

Risk-of-bias assessment for animal trials done by SYRCLE’S risk-of-bias tool.^[10]

[Table 7] describes the criteria from the SYRCLE’S risk-of-bias tool, which were used for the assessment using RevMan 5.4 software and in [Figures 2 and 3] provide the risk-of-bias summary.

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Figure 2:

Risk-of-bias summary: Review authors’ judgments about each risk-of-bias item (animal studies).

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Figure 3:

Risk-of-bias graph: Review authors’ judgments about each risk-of-bias item presented as percentages (animal studies).

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Risk-of-bias assessment for human RCT done by revised Cochrane risk-of-bias tool for randomized trials (RoB 2) tool[9] shown in [Table 8, Figures 4 and 5].

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Figure 4:

Risk of bias summary - Review authors judgement about each risk-of-bias item(Human studies).

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Figure 5:

Risk of bias graph- Review authors judgement about each risk-of-bias item presented as percentages (Human studies).

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Each human study was graded based on the seven criteria for risk-of-bias assessment including random sequence generation, allocation concealment, blinding of participants and personnel, blinding of assessors, incomplete outcome data, selective reporting of outcomes, and other potential sources of bias. An overall assessment of risk of bias (high, unclear, and low) was made for each included trial using the Cochrane collaboration risk-of-bias tool. Overall risk of bias was regarded as high with even if one criterion having a high risk of bias.

Animal studies

Of the six animal studies described in this systematic review, three studies^[5,12,14] were of the view that there was an increase in the rate of tooth movement after application of PRP. One study^[13] concluded that PRP reduced rate of tooth movement in a relapse case. Two studies^[11,15] revealed that there was no change in the rate of tooth movement following PRP administration and therefore did not favor PRP as a beneficial adjunct in accelerating the rate of tooth movement in orthodontic treatment.

Güleç et al.^[5] conducted a split-mouth study and concluded that PRP had a concentration dependent effect on OTM and alveolar bone density. PRP was used in their study in two concentrations – high conc. (hPRP) and moderate conc. (mPRP) (high conc. had 2.12-fold more platelets than moderate platelet conc.). The hPRP experimental group showed a 1.7 times greater amount of tooth movement than the control group. The hPRP experimental group showed 1.4 times greater OTM than mPRP experimental group.

Similarly, Rashid et al.^[14] in his study on dogs found a positive effect of PRP injection on the rate of OTM and showed a significant increase in the rate of tooth movement at every week from 0 to 9 weeks.

Clinical findings in both the studies were backed by histological findings, Güleç et al.,^[5] evaluated the alveolar bone volume density and osteoclastic activity through histomorphic analysis, and found that the bone density decreased in experimental group at all observation periods, thus increasing the rate of OTM. Furthermore, there was an increase in the number of TRAP+ cells in accordance with alveolar bone changes. Güleç et al.^[5] hypothesized that PRP injection created a regional acceleratory phenomenon like effect on the basis of histological findings of early and rapid bone resorption in experimental group at both high and moderate concentrations. Rashid et al.^[14] in his histologic findings at the resorption side showed multiple osteoclast indicative of high resorptive activity in PRP group, also dilated blood vessels in the PDL due to the effect of inflammatory mediators released due to mechanical loading and those present in the PRP. In apposition side, new bone formation was observed with increased osteogenesis in PRP group than control group, thus overall accelerating the rate of OTM.

Nakornnoi et al.^[12] in his study used leukocyte PRP (L-PRP) injection as a method of acceleration of OTM. A cumulative increase in the rate of OTM was seen in L-PRP group compared to control group at all observation times, with a 1.2 times higher rate of OTM than the control group on day 21. Amount of OTM was significantly greater in the 1^st week with L-PRP, which was in contrast to the findings of Rashid et al.^[14] who used PRP without leukocytes. This difference was due to the presence of leukocytes in the L-PRP, which leads to initial burst release of pro-inflammatory cytokines in the early phase of OTM serving as initiating factor for cellular and molecular events. In histological findings, Theerasak Nakornnoi et al.^[12] found a significant increase in number of osteoclast and increased angiogenesis in L-PRP group in the 1^st and 2^nd weeks compared to control group.

In contrast to the above-mentioned studies, Akbulut et al.^[11] and Sufarnap et al.^[15] found no beneficial effect of PRP as an adjunct to OTM. Akbulut et al.^[11] evaluated the early effects of PRP both clinically and histologically, whereas Sufarnap et al.^[15] did only clinical evaluation. Akbulut et al.^[11] found no change in the rate of OTM, no effect on cell counts of osteoblast and osteoclast, and the expression of TRAP, ALP, and TGF-β when compared to the control group. These findings were contradictory to Rashid et al.^[14] who found increased osteoclast cell count at week 9 on the compression side and Güleç et al.^[5] who reported increased rate of OTM at all observation times despite decreased osteoclast cell count in compression side compared to the control group.

Abdel-Haffiez et al.^[13] used PRP to prevent relapse in orthodontically moved teeth. They concluded that PRP can be used as a biological retainer to prevent the relapse of orthodontically moved teeth by encouraging new bone formation (osteogenesis) and inhibiting bone resorption (osteoclastogenesis), thereby suggesting that PRP prevented relapse of orthodontically moved tooth by reducing the rate of tooth movement.

Human studies

Literature search revealed only two human trials. A split-mouth RCT by El-Timamy et al.^[16] to study the effect of PRP on rate of OTM and Alomari et al.^[17] who studied the effect of PRP on reducing alveolar bone resorption following rapid maxillary expansion.

El-Timamy et al.^[16] concluded that PRP group had a significant acceleration in the rate of OTM. This was the only study which evaluated the amount of pain associated with administration of PRP injection and found that pain scores increased following injections on both intervention and control side and PRP administration is not associated with pain.

Alomari et al.^[17] in his study of rapid maxillary expansion showed no difference between the interventional and control groups of the buccal bone plate thickness and buccal bone crest level of the anchoring teeth. Furthermore, the percentage of dehiscence and fenestrations was not significantly different between the two groups.

Strengths and limitations

There are relatively a smaller number of studies included in this systematic review with a substantial heterogeneity among the studies regarding the samples used, the concentration of the intervention used, comparator, and methods of measurement of tooth movements. The methodological flaws in some of the studies reflected high risk of bias resulting from improper randomization, allocation concealment, and blinding. There was a limited scope for meta-analysis because of the diversity of population, the range of different comparators, different types of tooth movements in studies, different concentrations of PRP, and different calculation methods of rate of tooth movement across the small number of existing trials. Despite these limitations, this systematic review has assessed the effects of PRP in orthodontics, with a view that PRP has a positive impact on the rate of OTM when used as an adjunct along with orthodontic treatment.