Does the adjunctive use of platelet-rich plasma to bone graft during sinus augmentation reduce implant failure and complication? Systematic review and meta-analysis

Does the adjunctive use of platelet-rich plasma to bone graft during sinus augmentation reduce implant failure and complication? Systematic review and meta-analysis

MENA Dental Talents

17. January 2019

Rasha Imam Bayoumy Abdalla, Ahmed Yaseen Alqutaibi, Amal Kaddah

Background: Prosthetic treatment of the posterior edentulous maxilla may require bone augmentation to enable the placement and integration of dental implants. This constitutes a complex healing situation, and resorption of the grafted bone and failure of the implants often occurs. The application of platelet-rich plasma (PRP) has been suggested to improve incorporation and preservation of bone grafts. Objective: The objective was to assess the effectiveness of PRP on the implant failure and complication rate, when used as an adjunctive material with bone graft in sinus floor augmentation. Method and Materials: An electronic search of two databases (PubMed and Cochrane) was performed to identify randomized controlled trials (RCTs) in patients requiring sinus augmentation and implant placement in the posterior edentulous maxilla with or without using PRP as an adjunctive material to the bone graft. Data were extracted independently by two reviewers. The Cochrane tool was used for assessing the quality of included studies. Metaanalysis was performed for the included RCTs. Results: Nine RCTs were identified, four of which were included in the study. Three of these trials were judged to be at unclear risk of bias and one was at low risk of bias. The meta-analysis revealed no difference between the PRP versus non-PRP groups regarding implant failure and complication rate. Conclusion: The meta-analysis revealed no statistically significant difference regarding implant failure and complication rate of implants placed in the atrophic posterior maxilla with sinus floor augmentation with or without PRP as an adjunctive material to the bone graft. This finding should be interpreted with great caution given the serious numerical limitations of the included studies. (Quintessence Int 2018;49:139–146; doi: 10.3290/j.qi.a39616)

Dental implants are now commonly used in the rehabilitation of totally and partially edentulous patients and are reported to offer favorable treatment outcomes. One of the most complex cases that may face the oral implantologist is an atrophic posterior maxillary ridge, which results from bone resorption together with maxillary sinus pneumatization, leading to insufficient bone volume to support dental implants. Consequently, the maxillary sinus elevation surgical procedure is used to increase alveolar bone height by the formation of new bone in the lower portion of the maxillary sinus.4

Several materials with osteoconductive properties (autologous bone, allografts, alloplasts, and xenografts) have been suggested as bone substitutes for maxillary sinus augmentation, with successful results.5-7 Nonetheless, none of the previously mentioned materials meet all requirements to achieve a successful osseointegrated implant.

The rate of achievable bone regeneration is considered a decisive factor in the success of implant dentistry, and the use of biologic mediators with osteoinductive properties has been proposed to reduce the consolidation of the osteoconductive materials and accelerate the formation of newly formed bone.8,9 Platelet-rich plasma (PRP) has been proposed as an adjunct to osteoconductive materials. As yet, the results of several studies regarding the effectiveness of PRP are controversial. Some studies have reported positive effects,9,10 while other studies have shown limited effects in relation to the efficacy of PRP in bone formation.11,12

Benefits of the adjunctive use of PRP may be derived from its role in enhancing the rate of osseointegration, and it may therefore decrease the failure rate of dental implants. Nevertheless, more robust evidence is needed to assess the effectiveness of PRP as an adjunctive material in the sinus elevation technique, in terms of implant failure and complication rate. The aim of this systematic review was to answer the following question: In patients requiring implant placement with sinus augmentation, does the adjunctive use of PRP with bone graft have a positive effect in terms of implant failure and complication rate when compared to only bone graft? 

Review Method

This systematic review was conducted in accordance with the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines.13 Inclusion criteria were as follows:

• Study design: all randomized controlled trials (RCTs), including parallel group and split-mouth designs

• Participants: any subject with atrophic posterior maxillary ridge receiving dental implants together with sinus augmentation

• Control: maxillary sinus elevation with bone graft only

• Intervention: maxillary sinus elevation with bone graft and PRP

• Outcome measures:

   - Implant failures: defined as implant mobility and removal of stable implants dictated by progressive marginal
     bone loss or infection
   - Complications at treated sites (eg, sinusitis, infection, hemorrhage).

Exclusion criteria were:

• Non-randomized trials, retrospective studies, caseseries, and case reports

• Studies not reporting implant failure, and/or complications.

Fig 1 Flow diagram showing the details of the data search, identification, and selection process.

Information sources

Electronic databases (PubMed and the Cochrane Library) were searched to identify randomized controlled trials without time restrictions, comparing patients requiring sinus elevation and implant placement in the posterior edentulous maxilla with or without using PRP as an adjunctive material to the bone graft. In addition, a manual search of the following implant-related journals was performed: Clinical Implant Dentistry and Related Research, Clinical Oral Implants Research, European Journal of Oral Implantology, Implant Dentistry, Journal of Clinical Periodontology, Journal of Dental Research, Journal of Oral and Maxillofacial Implants, Journal of Periodontology, The International Journal of Periodontics and Restorative Dentistry, and Quintessence International. Moreover, online databases providing information about clinical trials in progress were checked (clinicaltrials.gov; www.centerwatch.com/clinicaltrials; www.clinicalconnection.com). The last performed search was on 6 September 2017. The search did not include gray literature databases.

Search strategy

Two reviewers (RIBA and AYA) independently performed the search. Combinations of controlled terms 

(MeSH) and key words were used whenever possible. The search terms used for MEDLINE (PubMed) and Cochrane databases are summarized in Appendix 1.

The full search results from all databases were pooled after removal of duplicates. Two reviewers (RIBA and AYA) performed a thorough title and abstract screening independently. The inclusion of articles for the full-text analyses was performed only after a mutual agreement between the two reviewers. Any disagreements were resolved by discussion and consensus with the third author (AK).

Data extraction was performed after mutual agreement on the final list of included publications. Data were extracted independently by the two reviewers (RIBA and AYA) who were reciprocally blinded to each other’s extraction. The following information was extracted: name of the author(s), publication year, study design, intervention type, observation period, number of patients, number of placed and failed implants, and complication events at the patient level. 

Quality assessment (risk of bias)

The assessment of the risk of bias of the included trials was done independently by two reviewers (RIBA and AYA) using the Cochrane collaboration’s tool.14 Six specific domains were rated, namely sequence generation, allocation concealment, blinding, incomplete outcome data, selective outcome reporting, and other bias. Each of these criteria was rated as “low risk of bias,” “high risk of bias,” or “unclear risk of bias.” The validity of each RCT was summarized as “low risk of bias” if all domains were at low risk of bias, “unclear risk of bias” if there was unclear risk of bias of at least one domain, and “high risk of bias” if at least one domain was scored as being at a high risk of bias. Disagreements were resolved by discussion. Where resolution was not possible, a third review author was consulted.

Statistical analysis

For dichotomous outcomes, the effect estimate of an intervention was expressed as risk differences (RDs) together with 95% confidence intervals (CIs). The statistical unit was the patient and not the implants. If the included articles had any missing relevant information, the corresponding authors were contacted by email. In case of no responses, reminder emails were sent. 

Data synthesis and assessment of heterogeneity

All statistical tests were performed using RevMan software version 5.3 (AYA).15 The significance of any variations in the estimates of the treatment effects from the different trials was assessed by means of Cochran’s test for heterogeneity, and heterogeneity was considered significant if P value < .1. Heterogeneity between the 

studies was assessed using the I-squared statistic (I2-statistic), which describes the variation percentage due to heterogeneity rather than chance.16 I2 over 50% was considered as moderate to high heterogeneity.

Meta-analysis was undertaken where studies of simi- lar comparisons reported the same outcome measures. Risk differences (RD) for the implant failure and complications events were calculated and compared between the two studied interventions. CIs were set at 95% (95% CI).

Weighted means across the studies were calculated using a fixed-effects model. Where statistically significant (P < .1) heterogeneity was detected, a random-effects model was used to assess the significance of treatment effects. 

Assessment of reporting biases

Publication bias was not assessed because just four studies were included in this systematic review. If fewer than 10 studies are included, the statistical examination of publication bias is not useful because of the lack of power of statistical tests to detect this bias.

Results

The electronic search yielded a total of 1,385 articles (PubMed, 1,179; The Cochrane Library, 206). The inter-investigator agreement for the data extraction was consid- ered very good (κ = .85). One more relevant article was identified from the reference crosschecks. Of the nine potentially eligible RCTs,12,17-24 four trials12,19,22,24 fulfilled the inclusion criteria and were subsequently analyzed in this systematic review (Fig 1). Details of all included studies are summarized in Table 1. Five trials17,18,20,21,23 were excluded because two21,23 were not RCTs, and three trials17,18,20 had outcome measures not related to the implant, as summarized in Table 2.

Characteristics of included studies

All of the included trials were split-mouth RCTs, and compared the effect of the adjunctive use of PRP and 

bone graft in sinus augmentation procedures with implant placement placed in posterior atrophic maxilla versus bone graft only without PRP.

One trial was conducted in The Netherlands,12 one in Germany,22 one in Spain,24 and one in Turkey.19 All trials were conducted in university dental clinics.

The follow-up period ranged from 1 year to 2 years. A prior calculation for the sample size was not undertaken in any of the included studies.

The outcomes were reported for studies comparing PRP versus non-PRP as follows:

implant failures: four trials reported this outcome.

complications: four RCTs reported complications. The outcomes were reported for studies comparing early versus delayed loading, as described below. 

Quality assessment

The final risk of bias assessment of the included trials is summarized in Figs 2 and 3. For each trial, the level of bias was assessed as low, unclear, or high. Three of the included four trials were judged to be at unclear risk of bias and one was at low risk of bias. 

Fig 2 Risk of bias summary: review authors’ judgments about each risk of bias item for each included study (+, low risk of bias; ?, unclear risk of bias).
Fig 3 isk of bias graph: review authors’ judgments about each risk of bias item presented as percentages across all included studies. 

Meta-analysis

Meta-analysis was performed for studies with similar comparisons and similar outcome measures. The comparisons, number of studies, and participants are summarized in Figs 4 and 5.

Fig 4 Forest plot of comparison: PRP versus no PRP, outcome implant failure.
Fig 5 Forest plot of comparison: PRP versus no PRP, outcome complications.

PRP versus non-PRP (implant failure)

The meta-analysis of four trials that compared the adjunc- tive use of PRP with bone graft during sinus floor elevation and then implant placement in atrophic posterior maxillary ridge versus the use of only bone graft regarding implant failures showed a non-statistically significant difference between the two interventions. (I2 = 0%, P = 1.00, RD = 0.0001, 95% CI −0.07 to 0.07) (Fig 4).

PRP versus non-PRP (complications)

The meta-analysis of four trials that compared the adjunctive use of PRP with bone graft during sinus floor augmentation and then implant placement in atrophic posterior maxillary ridge versus the use of only bone graft regarding complications showed a non-statistically significant difference between the two interventions. (I2 = 0%, P = 1.00; RD = 0.0001, 95% CI −0.06 to 0.06) (Fig 5).

Discussion

This review provides a meta-analysis of the RCTs associated with the posed research question. Although the employed format is regarded as the highest level of contemporary scientific evidence today,25 the pooled results are limited in number. This meta-analysis of four RCTs includes a total of 106 patients (212 sinus elevation procedures performed and 604 implants placed). The pooled data of the selected four RCTs revealed no significant RD between PRP versus non-PRP groups in regard to implant failure and complication rate.

An explanation for the lack of difference between the PRP- and non-PRP groups might be that the majority of the bony regeneration takes place within the first month of healing. This would be in line with the mode of action of platelet growth factors. Degranulation and release of growth factors occur within 3 to 5 days, and the growth factor activity may end in as soon as 7 to 10 days.26,27 Moreover, Raghoebar et al12 clarified that the PRP may have a beneficial effect on bone healing in critical size defects and defects with compromised vascularization because of its effect as a local regulator of bone regeneration, while it has no adjuvant value in smaller defects like in sinus floor elevation surgery.

A previously published systematic review conducted by Bae and Myung28 in 2011 include non-randomized trials, therefore potentially biased conclusions were reached. Herein, a more robust approach was sought regarding the effect of the adjunctive use of PRP with bone graft during sinus lift elevation including only RCTs, given their acknowledged place in the scientific hierarchy of reported evidence.

Nonetheless, various limitations should be considered when interpreting the results of this systematic review. First, numerous confounding factors may have affected reported long-term outcomes. For example, the investigators placed implants of different brands and surface treatment, which may also directly impact related outcome considerations. The follow-up periods varied from 12 months to 2 years. A longer follow-up period might lead to an increase in failure rate, especially if it extends beyond functional loading, because other prosthetic factors can influence implant failure from that point onward. This might have led to an underestimation of actual failures in some studies, and limits the ability to draw any conclusion beyond this period. Long-term follow-up studies are awaited. These confounding factors as well as others should be taken into consideration in future clinical trials. Second, three of the included RCTs were considered to have an unclear risk of bias, and most of the studies had inadequate methods of the allocation concealment. Finally, the limited number of included studies demands cau- tion in interpretation of the results and the conclusions that can be drawn from the limited number of reports on the topic. 

Conclusion

The meta-analysis revealed non-statistically significant differences regarding implant failure and the complica tion rate of implants placed in the atrophic posterior maxilla with or without PRP as an adjunctive material to the bone graft. This finding should be interpreted with great caution given the serious numerical limitations of the included studies. Moreover, three of the analyzed RCTs were considered to have unclear risk of bias. Larger, well-conducted RCTs are recommended that include a wide range of functional, prosthodontic, and patient-oriented outcomes with a longer follow-up period. 

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Authors

Rasha Imam Bayoumy Abdalla PhD Student, Department of Prosthodontics, Faculty of Oral and Dental Medicine, Cairo University, Cairo, Egypt; and Assistant Lecturer of Prosthodontics, Prosthodontic Department, College of Dental Surgery, MUST University,Cairo, Egypt.

Ahmed Yaseen Alqutaibi Lecturer in Prosthodontics, Faculty of Oral and Dental Medicine, Ibb University, Ibb, Yemen; and Lecturer, Prosthodontics Department, Faculty of Dentistry, Ahram Canadian University, Cairo, Egypt.

Amal Kaddah Professor, Department of Prosthodontics, Faculty of Oral and Dental Medicine, Cairo University, Cairo, Egypt.

Correspondence: Dr Ahmed Yaseen Alqutaibi, 10 Alishreef, Almanial, Cairo, Egypt. Email: AM01012002@gmail.com