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Autologous Blood-Derived Products Compared With Corticosteroids for Treatment of Plantar Fasciopathy

A Systematic Review and Meta-Analysis

Chen, Yu-Jen, MD; Wu, Yi-Cheng, MD; Tu, Yu-Kang, PhD; Cheng, Ju-Wen, MD; Tsai, Wen-Chung, MD, PhD; Yu, Tung-Yang, MD

American Journal of Physical Medicine & Rehabilitation: May 2019 - Volume 98 - Issue 5 - p 343–352
doi: 10.1097/PHM.0000000000001070
Original Research Articles: CME Article . 2019 Series . Number 5
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Objective This review article evaluated the efficacy of autologous blood-derived products, including whole blood and platelet-rich plasma, in reducing pain and improving function compared with corticosteroids for plantar fasciopathy patients.

Design Literature comparing autologous blood-derived product and corticosteroids for the treatment of plantar fasciopathy was systematically reviewed. Twelve randomized controlled trials and four quasi-experimental studies were included. The visual analog scale pain score and American Orthopedic Foot and Ankle Society hindfoot score were evaluated at 1.5, 3, and 6 mos' follow-up. Subgroup analyses were performed concerning platelet-rich plasma preparation techniques, injection regiments, and study designs.

Results Corticosteroids were found to reduce pain more effectively than whole blood at 1.5 and 3 mos, but the effect disappeared at 6 mos. Platelet-rich plasma reduced pain more effectively at 6 mos' postinjection than corticosteroids. However, there was no significant difference in the American Orthopedic Foot and Ankle Society score between platelet-rich plasma and corticosteroids injections at any time point. In the subgroup analyses, pain was significantly reduced at 6 mos by self-prepared platelet-rich plasma, one-step separation platelet-rich plasma, platelet-rich plasma of more than 3 ml, and platelet-rich plasma without local analgesics.

Conclusions The results of this meta-analysis suggest that platelet-rich plasma may provide a long-term effect in relieving pain in plantar fasciopathy patients.

To Claim CME Credits Complete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCME

CME Objectives Upon completion of this article, the reader should be able to: (1) Compare the efficacy of whole blood (WB), platelet-rich plasma (PRP), and corticosteroid (CS) in short-term pain reduction in patients with plantar fasciopathy (PF); (2) Compare the efficacy of WB, PRP, and CS in long-term pain reduction in patients with PF; (3) Identify the potential complication of corticosteroid injection for plantar fasciopathy; and (4) Identify the components of whole blood that might influence the growth factors in healing process.

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Accreditation The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Association of Academic Physiatrists designates this Journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.

From the Department of Physical Medicine and Rehabilitation, Chang Gung Memorial Hospital, Linkou, Taoyuan City, Taiwan (Y-JC, Y-CW, J-WC, W-CT, T-YY); Institute of Epidemiology & Preventive Medicine, College of Public Health, National Taiwan University, Taipei City, Taiwan (Y-KT); College of Medicine, Chang Gung University, Taoyuan City, Taiwan (J-WC, W-CT, T-YY); and Graduate Institute of Clinical Medical Sciences, Chang Gung University, Taoyuan City, Taiwan (T-YY).

All correspondence should be addressed to: Tung-Yang Yu, MD, Department of Physical Medicine and Rehabilitation, Chang Gung Memorial Hospital, Linkou, 5, Fushing St, Kuei-Shan District, Taoyuan City 33305, Taiwan.

Y-JC and Y-CW contributed equally to this work.

Yu-Jen Chen is in training.

Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s Web site (www.ajpmr.com).

Plantar fasciopathy (PF) is a common cause of heel pain involving the plantar fascia and accounts for approximately one million patient visits in the United States.1 Because the disorder is likely to be degenerative rather than inflammatory in nature, “fasciopathy” may be more precise than the commonly used term, “plantar fasciitis.”2 Plantar fasciopathy is a self-limiting disease that usually resolves within 10 mos.3 Stretching exercises of the plantar fascia and calf muscles, heel silicon insoles, night splints, and extracorporeal shock wave therapy of the plantar fascia are among the noninterventional treatments.4 However, previous studies have shown that these treatments have diverse outcomes; approximately 10% of patients do not benefit from them at all and progress to chronic status.4

Corticosteroid (CS) injection into the plantar fascia results in rapid pain relief and is therefore commonly used to treat patients with PF.5 However, its effect is short, with an efficacy of between 4 and 12 wks.5 In addition, its potential complications, including heel pad atrophy and plantar fascia rupture, raise further concerns regarding this treatment method, limiting its use.6

Although the etiology of PF is not clear, it is considered to be multifactorial. One important factor may be myxoid degeneration with fragmentation and chronic inflammatory changes in the plantar fascia.7 This supports the proposed theory that the tensile load over the plantar fascia leads to recurrent microtrauma, resulting in a degenerative process at the origin of the plantar fascia over the medial tuberosity of the calcaneus.

Considering the degenerative nature of PF, autologous blood-derived products (ABPs), including whole blood (WB) and platelet-rich plasma (PRP), may be beneficial for PF patients. These products carry bioactive molecules to the lesion site and modulate processes such as inflammation, angiogenesis, cell migration, and metabolism.8

Whole blood is autologous blood that contains platelets, which can release platelet-derived growth factors to promote the healing process. However, the effect of these growth factors may be influenced by other blood cell types in WB, such as red blood cells and leukocytes.9 Platelet-rich plasma is autologous plasma with concentrated platelets centrifuged from autologous blood. It promotes the release of a variety of growth factors and enhances tissue healing.10 Although ABP has been shown to improve PF outcomes,11 the relative efficacy of PRP versus WB is controversial.

Platelet-rich plasma induces cellular anabolism and regeneration through cytokines, as well as growth factors that are involved in chemotaxis, cell proliferation and maturation, and modulation of inflammatory molecules, thus promoting wound healing.8 Different PRP preparation methods may affect the quality of PRP and concentration of blood components, thus influencing the treatment outcome. The initial separation technique divides the red blood cells, whereas the subsequent separation concentrates the platelets and other components. The platelet and leukocyte concentrations of the one-step separation procedure are generally lower than those in the two-step procedure,10 which may be beneficial.12 However, the optimal injected volume of PRP, efficacy of injecting local anesthetic with PRP, and platelet and leukocyte concentrations to treat PF remain uncertain. Moreover, the efficacy of commercial PRP preparation systems has not been compared with that of a self-prepared PRP preparation technique.

This meta-analysis aimed to compare the efficacy of ABP (including WB and PRP) to CS by comparing refractory PF-related pain relief and functional improvement at chronic stage.

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METHODS

Literature Selection

This systematic review and meta-analysis were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (see Checklist, Supplemental Digital Content 1, http://links.lww.com/PHM/A691).13 All analyses were based on previous studies; therefore, no ethical approval and informed consent were required. PubMed, Scopus, Cochrane Central Register of Controlled Trials, Cochrane database, Embase, and ClinicalTrial.gov were systematically searched to identify relevant articles up to June 26, 2018. The search strategy is listed in Appendix 1. The bibliographies of identified studies, meta-analyses, and reviews were also manually reviewed for additional references. The title and abstracts were screened, and the full text of potentially related articles was downloaded for further review. Randomized controlled trials (RCTs) and quasi-experimental studies that compared the efficacy of ABP and CS were included according to the following criteria: (1) population: patients diagnosed with PF who did not respond to noninterventional treatments, with a symptom duration of more than 2 mos, i.e., nonacute onset PF; (2) intervention: injection of WB or PRP into the plantar fascia; (3) comparison: injection of CS into the plantar fascia; and (4) outcome: visual analog scale (VAS) pain score or American Orthopedic Foot and Ankle Society (AOFAS) hindfoot score. The VAS pain score assigns pain intensity a value between 0 and 10. The AOFAS score includes the following three categories: pain (40 points), function (50 points), and alignment (10 points).14 Studies were excluded if the patients received a local ABP or CS injection within 1 mo, received oral steroid or nonsteroidal anti-inflammatory drugs within 1 wk, or had had previous surgical intervention in the heel or ankle or a previous calcaneal fracture. Studies were also excluded if the outcome data could not be extracted. The following key terms were used in different combinations: “heel pain,” “plantar fasciitis,” “plantar fasciosis,” “plantar fasciopathy,” “plantar fasc*,” “corticosteroid,” “steroid,” “whole blood,” “PRP,” “platelet-rich plasma,” “autologous blood,” and “injection.”

Two authors independently conducted the search, screened the titles and abstracts, evaluated eligibility, and identified articles. Discrepancies were solved through discussion and consensus. The following data were extracted: first author, year of publication, number of patients, patient characteristics, details of treatment regimens (including preparation method of PRP), outcome measures, and adverse events. If there were missing data or any query regarding the relevant article, the authors of this review contacted the authors via e-mail to obtain further information.

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Risk of Bias Assessment and Sensitivity Analysis

The quality of the included trials was independently appraised with the Jadad scale and Newcastle–Ottawa Scale by two authors. The Jadad scale15 was used to assess the likelihood of bias of the selected RCTs; the total score ranged between 0 and 5 points, and trials with scores of less than 3 were considered to have a lower methodologic quality. The Newcastle-Ottawa Scale,16 which includes aspects of selection, comparability, and outcome, was used for quasi-experimental studies; the maximum score was 9 points, and total scores of less than 4 points were considered to indicate a low-quality study. A sensitivity analysis was conducted to determine the representativeness of the actual effect. Discrepancies between authors were solved through discussion and consensus.

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Data Synthesis and Analysis

To evaluate pain reduction and improvement in foot function in patients with PF, the standardized mean differences (SMDs) with 95% confidence interval (CI) of the VAS pain score and AOFAS hindfoot score between the baseline and posttreatment were calculated, and the outcome pooled. Random-effect models were used for the meta-analyses because of the variations of patient characteristics and details of treatment regimens. I2 and Cochran's Q test were used to evaluate heterogeneity. A P value ≤0.1 was considered statistically significant. Heterogeneity was considered low, moderate, high, and very high when the I2 value was less than 25%, between 25% and 50%, between 50% and 75%, and more than 75%, respectively. A subgroup analysis was performed based on: (1) the steps of PRP separation (one-step vs. two-step separation); (2) the types of PRP preparation systems (commercial PRP kit vs. self-prepared PRP); (3) activators versus nonactivators of PRP; (4) volume of the injected PRP; (5) PRP with versus without anesthetics; and (6) study design (RCTs vs. quasi-experimental studies). The small study bias was assessed using a funnel plot and Egger's test. All statistical analyses were conducted using the statistical software package Stata (Version 15; College Station, TX). Two-sided P values <0.05 were considered to indicate statistical significance.

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RESULTS

Literature Search

A total of 296 studies were identified in the initial search. After evaluation of the titles and abstracts, 20 full-text articles were assessed for eligibility. After a review of the full-text articles, 16 studies were included in the meta-analysis.17–32Figure 1 illustrates the literature search and reasons for exclusion.

FIGURE 1

FIGURE 1

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Features of Included Studies

The characteristics of the included studies are summarized in Table 1. These studies were published between 2006 and 2018. Five of the eligible studies, all of which were RCTs, compared WB and CS. Eleven of the eligible studies, including seven RCTs and four quasi-experimental studies, compared PRP and CS. In studies with more than two arms,17,19,20,29 data from the PRP, WB, and CS groups were extracted. None of the included studies reported significant adverse events after injection.

TABLE 1

TABLE 1

The studies had between 24 and 61 participants, with 214 patients for WB versus CS, and 506 patients for PRP versus CS. Platelet-rich plasma, WB, and CS were injected as a single dose in all studies. The mean age of the patients ranged between 30 and 55 yrs. The length of follow-up ranged between 2 wks and 12 mos.

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Risk of Bias Assessment

The Jadad scale was used to assess the risk of bias in RCTs, whereas Newcastle–Ottawa Scale was applied to evaluate quasi-experimental studies. The total score of the quality assessment is shown in Table 1, and the scores of each domain are in Appendices 2 and 3 (Supplemental Digital Content 2 and 3, http://links.lww.com/PHM/A692, http://links.lww.com/PHM/A693). Based on the obtained scores, seven RCTs and four quasi-experimental studies were found to be of good quality.

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Outcomes Data

Visual Analog Scale Pain Scores

Autologous Blood-Derived Product Versus CS

No significant difference was found between ABP and CS groups at 1.5, 3, or 6 mos (SMD = 0.09, 95% CI = −0.37 to 0.55, I2 = 87.3%; SMD = −0.08, 95% CI = −0.59 to 0.42, I2 = 88%; and SMD = −0.38, 95% CI = −0.89 to 0.13, I2 = 87.6%, respectively) (Fig. 2A).

FIGURE 2

FIGURE 2

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White Blood Versus CS

The VAS pain score significantly improved in the CS group relative to the WB group at 1.5 and 3 mos (SMD = 0.69, 95% CI = 0.40 to 0.98, I2 = 0%; and SMD = 0.56, 95% CI = 0.22 to 0.89, I2 = 0%); however, no difference was apparent at 6 mos (SMD = 0.31, 95% CI = −0.06 to 0.69, I2 = 42.7%) (Fig. 2B).

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Platelet-Rich Plasma Versus CS

The VAS pain score significantly improved in the PRP group relative to the CS group at 6 mos (SMD = −0.83, 95% CI = −1.51 to −0.15, I2 = 88.3%); however, no difference was apparent at 1.5 and 3 mos (SMD = −0.19, 95% CI = −0.79 to 0.41, I2 = 89%; and SMD = −0.29, 95% CI = −0.91 to 0.33, I2 = 89%) (Fig. 2C).

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American Orthopedic Foot and Ankle Society

Autologous Blood-Derived Product Versus CS

No significant difference was found between the ABP and CS groups at 1.5, 3, or 6 mos (SMD = −0.21, 95% CI = −0.84 to 0.42, I2 = 79.3%; SMD = −0.08, 95% CI = −1.01 to 0.84, I2 = 92.2%; and SMD = −0.29, 95% CI = −0.86 to 0.27, I2 = 74.3%, respectively) (Fig. 3A).

FIGURE 3

FIGURE 3

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White Blood Versus CS

White blood versus CS was not analyzed as only one study17 used the AOFAS score to compare the efficacy of WB and CS.

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Platelet-Rich Plasma Versus CS

No significant difference was found between the PRP and CS groups at 1.5, 3, or 6 mos (SMD = −0.21, 95% CI = −0.84 to 0.42, I2 = 79.3%; SMD = −0.08, 95% CI = −1.01 to 0.84, I2 = 92.2%; and SMD = −0.48, 95% CI = −1.08 to 0.13, I2 = 74.2%, respectively) (Fig. 3B).

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Sensitivity Analysis

Sensitivity analysis revealed that one study had obvious variance. However, removing this study from the analysis did not dramatically alter the pooled result for pain reduction due to PRP compared with CS at 6 mos (Appendix 4, Supplemental Digital Content 4, http://links.lww.com/PHM/A694).

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Subgroup Analysis

A subgroup analysis was performed for reductions in the VAS pain score at 6 mos. Results of the subgroup analysis found that PRP led to greater pain reduction than CS at 6 mos for self-prepared PRP, one-step separation PRP (Table 2),23,25,26,29 larger volume of injected PRP (≥3 ml), PRP without local anesthetic, and RCT study design (Fig. 4). Another subgroup analysis was performed to determine whether activators influence pain reduction between the PRP and CS groups at 6 mos; no significant difference was identified. The injected WB were all venous blood without further preparation, and all studies that compared WB and CS were RCTs. Therefore, no subgroup analysis was performed for the comparison between WB and CS.

TABLE 2

TABLE 2

FIGURE 4

FIGURE 4

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Small Study Bias

Small study bias refers to the larger treatment effects from smaller studies, which is necessary for smaller studies to be statistically significant.33 Appendices 5 and 6 (Supplemental Digital Content 5 and 6, http://links.lww.com/PHM/A695, http://links.lww.com/PHM/A696) demonstrate the funnel plots and Egger's test of the VAS pain scores at different time points to investigate small study bias. Asymmetry was observed in the funnel plot of PRP versus CS, based on the effect sizes of improvement in the VAS pain scores. Asymmetric funnel plots may indicate potential small study bias. In Egger's test, small study bias was identified for the PRP versus CS groups at 6 mos' postinjection (P = 0.046). No small study bias was found in the PRP versus CS groups at 1.5 (P = 0.999) and 3 mos' (P = 0.870) postinjection.

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DISCUSSION

This meta-analysis compared the efficacy of ABP versus CS to treat patients with PF. Although not achieving statistical difference, a trend favoring ABP over CS for relieving pain was noted within 1.5 to 6 mos' postinjection. In addition, because the ABP used in the literature contains two major blood products, i.e., PRP and WB, the differences between the products were further analyzed. Corticosteroid provided greater pain reduction than WB within 1.5 and at 3 mos. Notably, the superiority of CS to WB disappeared at 6 mos. Compared with CS, PRP is significantly more effective in reducing pain at 6 mos' postinjection. However, there was no difference in the AOFAS functional scores between CS and PRP at 1.5, 3, or 6 mos. Compared with CS, self-prepared PRP, one-step separated PRP, injected PRP volume of more than 3 ml, and PRP without local analgesics significantly reduced pain at 6 mos. This effect was stronger in RCTs than quasi-experimental studies.

Platelet-rich plasma has been used widely in patients with soft tissue injuries. It is beneficial as platelets that are activated by thrombin-release cytokines to enhance tendon proliferation.34 Furthermore, the growth factors present in PRP, such as transforming growth factor beta, vascular endothelial growth factor, and platelet-derived growth factor, stimulate tissue regeneration from mesenchymal cells, thus promoting cell replication and differentiation.8 Several meta-analyses have compared the efficacy of ABP and CS in PF treatment.11,35 Hsiao et al.11 performed a meta-analysis that comprised three RCTs and three quasi-experimental studies comparing ABP with CS, and they concluded that ABP provided better pain relief than CS at 3 and 6 mos, while PRP appeared to increase the efficacy of treatment. Another meta-analysis35 indicated that PRP was associated with better improvements in pain and functional scores than CS at 3 mos, whereas no difference was noted at 1, 6, and 12 mos' follow-up. However, the previously mentioned meta-analyses had inconsistent results. The inconsistency regarding the effect of PRP may be due to insufficiency of the included literature, lack of functional evaluation, and absence of a separate comparison for PRP and WB. Jain et al.26 reported that PRP tended to lead to greater pain reduction than CS at 6 mos and patients who were administered PRP showed significantly better VAS and AOFAS scores until 12 mos' postinjection, compared with those who were given CS, implying the late-onset and long-term effect of PRP in relieving pain and improving function in patients with PF. To clarify the efficacy of ABP (including WB and PRP) in patients with PF, ABP and CS were compared; WB and CS, as well as PRP and CS, were further compared separately in terms of pain relief and functional improvement. Although WB and PRP are commonly categorized as ABPs, the results of this study revealed that WB and PRP possess different effects in the treatment of PF. Therefore, WB and PRP should be discussed separately.

While the VAS pain score may indicate the treatment efficacy, functional aspects such as gait and motion are also crucial to improve quality of life. The AOFAS hindfoot score measures function, alignment, and pain and has been shown to be associated with quality of life.14 Therefore, it has been widely used to evaluate the functional outcome of the foot. A previous meta-analysis35 suggested that PRP injection was associated with better AOFAS score than CS at midterm follow-up, although no difference was found between the groups at short- and long-term follow-up. Notably, only one high-quality study was included in a long-term follow-up analysis. The current study demonstrated that there was no difference in the AOFAS hindfoot score for ABP versus CS and PRP versus CS at 1.5, 3, and 6 mos. There are two possible reasons for this result: (1) the included studies were subject to high heterogeneity, even with a random-effect model, and (2) one study36 demonstrated that there was significantly better AOFAS scores among patients who received PRP at 6 mos' follow-up than those who received CS. However, it provided only the mean and range values of the AOFAS score, which are insufficient for analysis. On the other hand, only one study17 used the AOFAS score to compare the efficacy of WB and CS; it found no significant difference between the groups. A further study to evaluate functional improvement in different subdomains may clarify the effect of PRP in patients with PF. Because of limitations of the relevant literature, further studies should evaluate whether there are differences in WB and PRP compared with CS in terms of functional improvement of the foot.

Different preparation techniques may influence the components of PRP and therefore influence the efficacy of treatment. The subgroup analysis of this study revealed that one-step separation PRP was significantly superior to CS for pain relief at 6 mos, whereas no significant difference was found between two-step separation PRP and CS. Although none of the studies provided data regarding the leukocyte counts of PRP, one-step separation PRP preparation systems mostly yield leukocyte-poor PRP (LP-PRP)10; our results may therefore indicate that LP-PRP provides significantly greater pain reduction than CS. Leukocytes release high levels of toxic reactive oxygen substances that may be detrimental to the surrounding tissue, increase catabolic cytokine concentrations, and possibly decrease growth factor levels.10,37 One recent study revealed that leukocyte-rich PRP had a detrimental effect on rabbit tendon stem cells and was associated with increased apoptosis.37 Yan et al.12 also found that LP-PRP had a better effect on tendon healing than leukocyte-rich PRP because of its anabolic effects. However, these findings concerning the effect of leukocyte concentration in PRP for PF treatment require further investigation, with quantification of the actual leukocyte count of PRP.

Differences in PRP composition may also result from discrepancies between self-preparation and commercial kit techniques. This study demonstrated that patients treated with self-prepared PRP had greater pain reduction than those treated with CS at 6 mos' postinjection. However, substantial heterogeneity was noted and limited the value of this finding. In addition, different PRP preparation techniques and compositions were not analyzed in most studies. Because PRP composition was found to have an effect on outcomes, further research is certainly warranted.

The volume of injected PRP and whether local analgesics were co-administered may affect the treatment efficacy. Our study revealed that patients with PF who were injected with more than 3 ml of PRP had greater pain reduction at 6 mos' postinjection. The effect of PRP on tissue healing is associated with platelet count and concentration of growth factors.38 Therefore, a higher volume of PRP may improve tissue healing and thus lead to better pain relief. In addition, PRP injection without local analgesics is associated with better efficacy in pain reduction at 6 mos. Although analgesics may reduce pain transiently, a previous study has shown that analgesics such as lidocaine and bupivacaine attenuate tenocyte proliferation and cell viability.39 Our study also suggests that PRP injection without local analgesics is associated with better long-term pain relief in PF.

The design of the studies may have also influenced the outcome. Quasi-experimental designs do not randomly assign patients and have less internal validation, giving them less standing to posit causal relationships. In contrast, RCTs render the groups comparable and are regarded as the criterion standard to evaluate the efficacy of interventions.40 Therefore, subgroup analysis was conducted to determine whether PRP and CS are significantly different in both RCTs and quasi-experimental studies. Theoretically, quasi-experimental studies are more likely to have statistically significant results because of potentially higher risks and confounded causal inference than RCTs. However, this study revealed that there was a significant reduction in pain in patients who participated in RCTs. The result further strengthens the finding that PRP provides better pain relief than CS at 6 mos in patients with refractory PF. Another possible reason is that all the RCT-designed studies examined had more than 3 ml of PRP injected without local analgesics, factors that have been shown to be associated with better pain relief. Notably, a greater pain difference was identified in the CS group at 6 mos in one study,30 which may have caused a marked effect size.

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Strengths and Limitations

This study has several limitations. First, the included studies had substantial heterogeneity in terms of injection regimens (PRP preparation, CS dosage, and WB volume), length of follow-up period, and patient characteristics (age, duration of symptoms, and body mass index). A meta-regression may be beneficial, but it was not performed because of a limited number of studies. However, the statistical significance of our results indicates that they have a possible clinical value. A further study with long-term follow-up is required to investigate the effect of different PRP regimens and components. Second, four of the 16 included studies were quasi-experimental in nature, a design that is of lower quality than RCT and may thus limit the current study findings. Third, PRP subgroup analyses of the leukocyte count and mean platelet concentration were not performed because of incomplete data. Fourth, an analysis of each AOFAS score domain was not performed, also because of incomplete data. Fifth, comparison between WB and CS using the AOFAS hindfoot score was not performed because of the limited number of studies. Sixth, in this study, we did not directly compare WB with PRP, because only one previous study had made this comparison.41 Significant improvement in pain, function, and plantar fascia thickness were demonstrated in both groups at 1 or 3 mos, although between-group differences were not apparent.41

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CONCLUSIONS

This meta-analysis demonstrated that CS provided greater pain reduction than WB at 1.5 and 3 mos' postinjection, whereas the effect was diminished at 6 mos. Platelet-rich plasma was significantly more effective in reducing pain at 6 mos' postinjection. The subgroup analysis indicated that self-prepared PRP, PRP of more than 3 ml, PRP without local analgesics, and one-step separation PRP are associated with greater pain reduction at 6 mos of follow-up than other factors. In addition, RCTs demonstrated a greater effect than quasi-experimental studies. The results of this meta-analysis suggest that PRP may provide a long-term, beneficial effect in relieving pain in patients with PF.

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REFERENCES

1. Riddle DL, Schappert SM: Volume of ambulatory care visits and patterns of care for patients diagnosed with plantar fasciitis: a national study of medical doctors. Foot Ankle Int 2004;25:303–10
2. Rompe JD: Plantar fasciopathy. Sports Med Arthrosc Rev 2009;17:100–4
3. Davis PF, Severud E, Baxter DE: Painful heel syndrome: results of nonoperative treatment. Foot Ankle Int 1994;15:531–5
4. Franceschi F, Papalia R, Franceschetti E, et al: Platelet-rich plasma injections for chronic plantar fasciopathy: a systematic review. Br Med Bull 2014;112:83–95
5. Ang TW: The effectiveness of corticosteroid injection in the treatment of plantar fasciitis. Singapore Med J 2015;56:423–32
6. Kim C, Cashdollar MR, Mendicino RW, et al: Incidence of plantar fascia ruptures following corticosteroid injection. Foot Ankle Spec 2010;3:335–7
7. Lemont H, Ammirati KM, Usen N: Plantar fasciitis: a degenerative process (fasciosis) without inflammation. J Am Podiatr Med Assoc 2003;93:234–7
8. Vannini F, Di Matteo B, Filardo G, et al: Platelet-rich plasma for foot and ankle pathologies: a systematic review. Foot Ankle Surg 2014;20:2–9
9. Kampa RJ, Connell DA: Treatment of tendinopathy: is there a role for autologous whole blood and platelet rich plasma injection? Int J Clin Pract 2010;64:1813–23
10. Perez AG, Lana JF, Rodrigues AA, et al: Relevant aspects of centrifugation step in the preparation of platelet-rich plasma. ISRN Hematol 2014;2014:176060
11. Hsiao MY, Hung CY, Chang KV, et al: Comparative effectiveness of autologous blood-derived products, shock-wave therapy and corticosteroids for treatment of plantar fasciitis: a network meta-analysis. Rheumatology (Oxford) 2015;54:1735–43
12. Yan R, Gu Y, Ran J, et al: Intratendon delivery of leukocyte-poor platelet-rich plasma improves healing compared with leukocyte-rich platelet-rich plasma in a rabbit Achilles tendinopathy model. Am J Sports Med 2017;45:1909–20
13. Moher D, Liberati A, Tetzlaff J, et al: Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Int J Surg 2010;8:336–41
14. Ibrahim T, Beiri A, Azzabi M, et al: Reliability and validity of the subjective component of the American Orthopaedic Foot and Ankle Society clinical rating scales. J Foot Ankle Surg 2007;46:65–74
15. Jadad AR, Moore RA, Carroll D, et al: Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials 1996;17:1–12
16. Wells GA, Shea B, O'Connell D: The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses [Internet] 2014. Available at: http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp. Accessed November 17, 2018
17. Kiter E, Celikbas E, Akkaya S, et al: Comparison of injection modalities in the treatment of plantar heel pain: a randomized controlled trial. J Am Podiatr Med Assoc 2006;96:293–6
18. Lee TG, Ahmad TS: Intralesional autologous blood injection compared to corticosteroid injection for treatment of chronic plantar fasciitis. A prospective, randomized controlled trial. Foot Ankle Int 2007;28:984–90
19. Kalaci A, Çakici H, Hapa O, et al: Treatment of plantar fasciitis using four different local injection modalities. J Am Podiatr Med Assoc 2009;99:108–13
20. Karimzadeh A, Raeissadat SA, Erfani Fam S, et al: Autologous whole blood versus corticosteroid local injection in treatment of plantar fasciitis: a randomized, controlled multicenter clinical trial. Clin Rheumatol 2017;36:661–9
21. Omar AS, Ibrahim ME, Ahmed AS, et al: Local injection of autologous platelet rich plasma and corticosteroid in treatment of lateral epicondylitis and plantar fasciitis: Randomized clinical trial. Egyptian Rheumatol 2012;34:43–9
22. Aksahin E, Dogruyol D, Yuksel HY, et al: The comparison of the effect of corticosteroids and platelet-rich plasma (PRP) for the treatment of plantar fasciitis. Arch Orthop Trauma Surg 2012;132:781–5
23. Tiwari M, Bhargava R: Platelet rich plasma therapy: a comparative effective therapy with promising results in plantar fasciitis. J Clin Orthop Trauma 2013;4:31–5
24. Shetty VD, Dhillon M, Hegde C, et al: A study to compare the efficacy of corticosteroid therapy with platelet-rich plasma therapy in recalcitrant plantar fasciitis: a preliminary report. Foot Ankle Surg 2014;20:10–3
25. Say F, Gurler D, Inkaya E, et al: Comparison of platelet-rich plasma and steroid injection in the treatment of plantar fasciitis. Acta Orthop Traumatol Turc 2014;48:667–72
26. Jain K, Murphy PN, Clough TM: Platelet rich plasma versus corticosteroid injection for plantar fasciitis: A comparative study. Foot (Edinb) 2015;25:235–7
27. Sherpy NA, Hammad MA, Hagrass HA, et al: Local injection of autologous platelet rich plasma compared to corticosteroid treatment of chronic plantar fasciitis patients: a clinical and ultrasonographic follow-up study. Egyptian Rheumatol 2016;38:247–52
28. Acosta-Olivo C, Elizondo-Rodriguez J, Lopez-Cavazos R, et al: Plantar fasciitis. A comparison of treatment with intralesional steroids versus platelet-rich plasma (PRP). A randomized, blinded study. J Am Podiatr Med Assoc 2017;107:490–6
29. Mahindra P, Yamin M, Selhi HS, et al: Chronic plantar fasciitis: effect of platelet-rich plasma, corticosteroid, and placebo. Orthopedics 2016;39:e285–9
30. Vahdatpour B, Kianimehr L, Moradi A, et al: Beneficial effects of platelet-rich plasma on improvement of pain severity and physical disability in patients with plantar fasciitis: a randomized trial. Adv Biomed Res 2016;5:179
31. Yesiltas F, Aydogan U, Parlak A, et al: The comparison of intralesionary steroid injection and autologous venous blood injection in patients with plantar fasciitis. Acta Medica Mediterranea 2015;31:711
32. Jain SK, Suprashant K, Kumar S, et al: Comparison of plantar fasciitis injected with platelet-rich plasma vs corticosteroids. Foot Ankle Int 2018;39:780–6
33. Sterne JA, Gavaghan D, Egger M: Publication and related bias in meta-analysis: power of statistical tests and prevalence in the literature. J Clin Epidemiol 2000;53:1119–29
34. Anitua E, Andia I, Sanchez M, et al: Autologous preparations rich in growth factors promote proliferation and induce VEGF and HGF production by human tendon cells in culture. J Orthop Res 2005;23:281–6
35. Singh P, Madanipour S, Bhamra JS, et al: A systematic review and meta-analysis of platelet-rich plasma versus corticosteroid injections for plantar fasciopathy. Int Orthop 2017;41:1169–81
36. Monto RR: Platelet-rich plasma efficacy versus corticosteroid injection treatment for chronic severe plantar fasciitis. Foot Ankle Int 2014;35:313–8
37. Zhang L, Chen S, Chang P, et al: Harmful effects of leukocyte-rich platelet-rich plasma on rabbit tendon stem cells in vitro. Am J Sports Med 2016;44:1941–51
38. Lubkowska A, Dolegowska B, Banfi G: Growth factor content in PRP and their applicability in medicine. J Biol Regul Homeost Agents 2012;26(2 suppl 1):3s–22
39. Carofino B, Chowaniec DM, McCarthy MB, et al: Corticosteroids and local anesthetics decrease positive effects of platelet-rich plasma: an in vitro study on human tendon cells. Art Ther 2012;28:711–9
40. Stang A: Randomized controlled trials-an indispensible part of clinical research. Dtsch Arztebl Int 2011;108:661–2
41. Vahdatpour B, Kianimehr L, Ahrar MH: Autologous platelet-rich plasma compared with whole blood for the treatment of chronic plantar fasciitis; a comparative clinical trial. Adv Biomed Res 2016;5:84
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APPENDIX 1

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Keywords:

Autologous Blood; Corticosteroid; Pain Relief; Plantar Fasciopathy; Platelet Rich Plasma; Whole Blood

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