The objective of this study is to systematically review available evidence from published articles to assess the effectiveness and relevant factors of PRP treatment in managing PF. The assessment also would encompass safety, side effect, and complications of this mode of treatment.
The searches were performed in the PubMed (2000–2015), Google Scholar (2000–2015), and Scopus (2000–2015) using a series of keywords, terms, and subject headings made from Pub-Med's medical subject headings (MeSH). The search of MeSH included: PF, plantar fasciopathy, heel pain, PRP, and PRP.
Selected articles were limited to human studies, publications in English-language and all kind of studies, including clinical trial, case series, and case report. This study did not proceed with meta-analysis thus no specific statistical test was done. Inclusion criteria for target population comprised subjects that were diagnosed to have suffered from PF and received PRP treatment. Studies should have clear details of clinical assessments which might be any of the following methods, i.e., evaluation of pain using visual analog scale (VAS), evaluation of function using Roles–Maudsley (RM) scores, evaluation with American Orthopaedic Foot and Ankle Society (AOFAS) scale and ultrasonography evaluation.
Studies were excluded if the patients in the study received local steroid injection within 6 months, have previous surgery of the foot, previous fracture to calcaneus or having other associated diseases of lower limb (vascular insufficiency, Diabetic, neuropathy, and ankle joint disorder). Furthermore, studies with insufficient follow-up during the study were excluded.
Titles and abstracts of all the studies were reviewed by two reviewers to identify relevant studies. Any disagreement for inclusion or exclusion if an article was fixed by discussion with the third reviewer. Two reviewers extracted the data from eligible studies independently. These data were included author, year of publication, study design, sample size, and details of intervention in study and control group, finding of studies, mean age of patients, assessment method, duration of follow-up, any reported complication, duration of symptoms in patient at the beginning of the study, amount of blood collected for PRP, method of PRP preparation, details of PRP injection, method of confirmation/diagnosis for PF before recruiting participants and usage of ultrasound guidance for injection.
JADAD score was used for the quality assessment of randomized controlled trials (RCTs) and Newcastle–Ottawa Scale (NOS) was used for nonrandomized studies. Studies achieving, at least, JADAD score of three or NOS of seven were considered to bequalify (good) to be included in this systematic review.
A total of 1126 articles were retrieved using different keywords (Google Scholar: 1012, PubMed: 21, Scopus: 93). By reviewing the titles and abstracts, only 102 articles were eligible to be reviewed based on their relevance to the aim of this systematic review. Finally, 12 articles were met all inclusion and exclusion criteria to be reviewed in this study.,,,,,,,,,,, These were four RCTs, seven prospective cohort and one retrospective cohort studies. The rest of articles were excluded in view of non-English language, letter to editor, review articles, incomplete RCT, and protocol [Figure 1]. [Table 1],[Table 2],[Table 3] show details of the selected articles.
Both male and female patients were recruited in these 12 studies. Sample size of the twelve studies ranged from 14 to 60 with a total of 455 patients. The majority of patients have unilateral PF. However, a total of 22 patients from three studies have had bilateral PF. The duration of symptoms (PF) in patients at the beginning of interventions was from 3 to 24 months. Different assessments, including AOFAS, RM scores, visual analog scores (VAS), postinjection foot and ankle outcome scores, foot function index, and 12-item short form health survey (SF-12) were used to measure the outcome of treatments. Only three out of nine studies have used ultrasound guidance for injection of PRP. Seven studies have had a single injection of PRP while the other two studies have done more than one-time injection.
Blood collected for PRP preparation was ranged from 10 ml to 52 ml. Three studies used double spin centrifugation for PRP preparation and the rest of studies used single spin. Eight out of 12 studies used different commercial systems for the PRP preparation and the other four studies have used normal centrifuge. The injected volume of PRP was between 2 ml and 5 ml. Follow-up for monitoring the improvement or any complications of PRP or steroid was done from 2 weeks up to 24 months.
PRP has shown promise in the treatment of various musculoskeletal conditions including chronic lateral epicondylitis, osteoarthritis, muscle strain, ligament sprain, cartilage damage, fractures, and tendon injury and has been approved by the International Olympic Committee in the treatment of soft tissue injuries and tendon disorders., 27, ,,, Furthermore, PRP might be considered as an alternative treatment for plantar fascia. The steps from preparation to injection are equally crucial when we are assessing the effectiveness of PRP in the treatment of PF. In all the selected studies, PRP injection has been done directly into the plantar fascia. However four of these studies have used ultrasound guidance during injection.,,, It is arguable that ultrasound guidance may promise a more accurate placement of PRP and injection without ultrasound guidance may be considered as a shortcoming of a study. Nevertheless, no advantage of ultrasound guidance over direct palpation guidance was reported by Kane et al. during steroid injection for PF.
The technique of injection may also indirectly affect the outcome of this study, for example, peppering or direct single injection. In peppering technique, the needle was placed into the target tissue and withdrawn slowly while maintaining the tip of the needle within the tissue. The needle was then angulated and reinserted to make another puncture onto the fascia at different sites. Peppering on the plantar fascia could possibly stimulate the release of endogenous growth factors that help in regeneration. Kalaci et al. reported a superior effect in his study when peppering technique was used as compared to single direct injection.
The main purpose of blood centrifugation is to concentrate the growth factors within the platelet. Some investigators believe that the action of growth factors is dose-dependent. This means that only at certain concentration can it generate new cells growth. No data had been published to date to indicate the quantity of growth factors required to stimulate the healing process. However, there were studies which showed clinical efficacy could be expected when there is minimal 4- to 6-fold increase in platelet concentration from the whole blood baseline., Thus, platelet concentration appears as an important factor in ensuring cell regeneration. Despite having achieved the desired concentration, the amount or volume of PRP may also play an important role in determining the effectiveness. Kumar et al. found that three of his patients who had bilateral plantar fasciitis injections at the same setting failed to improve. The explanation for this can be attributed to the small amount of PRP that was injected into each heel (only 1.5 ml to each heel). During the subsequent injections to these three patients, improvement was noted after injection of 3 ml of PRP into each heel. This strongly suggested that tissue regeneration may take place only with adequate volume of PRP.
Diagnosis of PF is commonly made base on clinical examination and observations. It is, therefore, crucial to have a precise and accurate diagnosis. A wrong diagnosis could possibly be an important factor affecting the outcome of the effectiveness of PRP in the management of PF. This is because diseases respond differently according to their underlying pathophysiology. As in the prospective study done by Kumar et al., one patient with tarsal tunnel syndrome only showed improvement after surgical decompression. Therefore in resistant cases, it is important to exclude other conditions which sign and symptoms might resemble PF, such as tarsal tunnel syndrome and stress fractures. Further investigations may be necessary for us to arrive at correct diagnosis, such as magnetic resonance imaging scan or nerve conduction study.
The efficacy of PRP treatment should also take into account the onset of effect and the duration for the patient to remain symptoms free. Most patients would prefer something that offer instant pain relief with no recurrence of symptoms. In most of the studies, the improvement was observed during the first 3 months after injection. Significant improvement was also noted when the patient was followed up till 12 months postinjection. The onset of action after PRP injection also greatly depends on the degree of degeneration as the organ or tissue is in demand for longer recovery time for a complete regeneration. The coupled home therapy after the injection may affect the outcome of the effectiveness of PRP. Those patients who reported relief of pain and other improvement, believed on direct effect of PRP injection, although all patients were also recommended to remain under conventional treatment, including gel heel cups and stretching exercises.
Steroid injection has been a popular mode of treatment when conservative management failed. However, corticosteroid injection is effective only in the short-term and only to a limited degree.,, There is also close association with a higher rate of relapse and recurrence. Moreover direct pain relief after injection results in a tendency to overuse the affected foot., Besides, it also carries the risk of tendon rupture as mentioned earlier. There were few studies that compare the results of steroid and PRP injections in other chronic tendon disorder apart from PF.,, Peerbooms et al. found a positive effect of PRP injection for lateral epicondylitis. This was the first comparison of PRP with corticosteroid injection in patient with lateral epicondylitis. The results indicated that a single injection of PRP decreased pain and improves function better than a corticosteroid injection.
As direct injection onto a degenerative area of the plantar fascia, should not arise any adverse side effect or complication then theoretically PRP injection also should not have any side effect. As expected, none of the above studies reported any complication from PRP injection. In fact to date, study of PRP injection for musculoskeletal conditions has not revealed any serious adverse , events. PRP should thus be deemed as a safe procedure in treating PF.
PF is a common cause of foot complaints resulting from degeneration of planter fascia. Treatment that stimulates tissue regeneration should be deemed as a better alternative for conservative managements. All the selected and reviewed studies showed significant improvement with no evidence of side effect or complications when PRP was used in treating PF. This suggests that PRP could be an effective mode of treatment for PF with promised safety. It helps in stimulation of new cell growth and thus should be regarded as a suitable modality in treating a degenerative disease. Studies also showed the superiority of PRP when compared with steroid injection.
One of the limitations of these studies include the sample sizes which were frequently small, Absence of placebo, diagnosis of PF, and duration of follow-up might appear to be another limiting factors in the process of assessing the efficacy of PRP. Besides, when selecting a preparation system, many factors must be taken into account, such as volume of autologous blood drawn, centrifuge rate/time, leukocyte concentration, delivery method, activating agent, final PRP volume and final platelet and growth-factor concentration. Due to differences in PRP characteristics, reported evidence for the clinical effectiveness of PRP cannot be generalized to all of these systems. Furthermore, variation of hematologic parameters between patients may also affect the final PRP preparation. Controversies regarding the optimal quantity of platelets and growth factors required for muscle and tendon healing still persist. PRP's effectiveness is demonstrated with less concentrated preparations.
All authors contributed equally to this work. SKC developed the concept of the work, conducting the literature search, writing the first draft and approval of the final version of the manuscript. FA contributed in the conception of the study, literature search and drafting, revising and approving the manuscript. TSR contributed in, conducting the study, drafting and revising the draft, approval of the final version of the manuscript. All the authors agreed for all aspects of the work.
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