Research ArticleThe Effectiveness of Minimally Invasive Techniques in theTreatment of Patellar Tendinopathy: A Systematic Review andMeta-Analysis of Randomized Controlled Trials
M. P. Lopez-Royo,1,2 M. Ortiz-Lucas ,1 E. M. Gomez-Trullen,2 and P. Herrero1
1iPhysio Reaserch Group, Universidad San Jorge, Campus Universitario, Autov. A23, Km 299, Villanueva de Gallego,Zaragoza 50830, Spain2Universidad de Zaragoza, Facultad de Ciencias de la Salud, Dpto. de Fisiatrıa y Enfermerıa, C/Domingo Miral s/n,Zaragoza 50009, Spain
Correspondence should be addressed to M. Ortiz-Lucas; [email protected]
Received 8 June 2020; Revised 14 August 2020; Accepted 25 August 2020; Published 7 September 2020
-e aim was to determine the effectiveness of minimally invasive techniques (MIT) in patients with patellar tendinopathy.Database searches were performed for randomized controlled trials (RCTs) in electronic databases (WOS, Cochrane Central,SportDiscus, and Medline via PubMed and PEDro). -e inclusion criteria used were published in English or Spanish andinvolving adults with patellar tendinopathy (pain on the inferior pole of the patella for a minimum of 3 months), with at least onegroup receiving MIT. -e quality of the relevant RCTs was evaluated using the PEDro scale. -e primary outcome wasfunctionality using the VISA-p questionnaire. Secondary outcome was focused on pain. A total of 1164 studies were screened forpossible inclusion in our systematic review. Finally, 10 RCTs were included with a total of 326 individuals. Five RCTs wereincluded in the meta-analysis. -e quality assessment revealed that all the studies included were considered to possess highmethodological quality. All studies analyzing MIT such as platelet-rich plasma (PRP), dry needling, or skin-derived tenocyte-likecells, when combined with exercise, proved to be effective for patellar tendinopathy. Moreover, the PRP technique with dosesgreater than 4mL together and combined with an exercise program lasting over 6 weeks obtained better results in functionalityand pain than other treatments in the short term. However, in the long term, dry needling and skin-derived tenocyte-like cells aremore effective than PRP. Although the infiltration of drugs was effective at posttreatment, these improvements were notmaintained over time and may have secondary effects. Although there are no RCTs analyzing the effectiveness of MIT likepercutaneous needle electrolysis, there has been an increasing number of publications achieving excellent results in the last years.However, it is necessary to develop RCTs analyzing not only the effect but also comparing the effectiveness between different MITsuch as dry needling and percutaneous needle electrolysis.
1. Introduction
Patellar tendinopathy (PT) is a degenerative disease of thepatellar tendon, in which the patient complains of pain in theinferior pole of the patella. Also, a disturbed collagen dis-tribution, changes in vascularity and cellularity, increasedthickness of tendon, and incompletely healed tendonmicroruptures are common changes observed in patients withthis pathology [1–3]. -e major cause of this injury is overuse
during activities that involve jumping, running, and rapidchanges of direction, which are very common movements insports such a basketball and volleyball. Specifically, in non-professional athletes, the prevalence varies between 2.5% insoccer players and 14.4% in volleyball players. In contrast, inboth elite sports, 40–50% of professional athletes are affected[4–6]. -e diagnosis of PT is typically based on medicalhistory and clinical findings [7]. Imaging techniques such asColor Doppler sonography (CD) and magnetic resonance
HindawiEvidence-Based Complementary and Alternative MedicineVolume 2020, Article ID 8706283, 16 pageshttps://doi.org/10.1155/2020/8706283
imaging (MRI) are valuable tools to confirm the diagnosis andprovide guidance for treatment [8].
Conventional treatments such as eccentric exercise (EE)programs for the quadriceps tendon, as a part of standardtreatment, has demonstrated to have positive results, to thepoint that many authors have defended this technique as thegold standard for the treatment of tendinopathies [9–12]. Arecent systematic review reported that the best exercise forimproving knee function and reducing pain in the long termis based on EE and heavy slow resistance exercises (HSR)[13]. In addition, recent research has focused on minimallyinvasive techniques (MIT) using needles, with high expec-tations of success. -ese techniques seek a rapid regenera-tion of the injured tendon and the relief of chronic pain[4, 8, 14–16]. -eir effect is based on stimulating the cellularactivity and the production of collagen, as well as influencingthe biomechanics of tendons to obtain restructuration of thematrix.
It can be classified according to whether they injectany substances or not. Regarding techniques that do notinfiltrate any substances, good clinical results are beingreported with dry needling (DN) [17] and percutaneousneedle electrolysis (PNE) [4, 18–20], which adds the effectof the galvanic current to the mechanical effect of theneedle. PNE combined with EE programs offer excellentresults in terms of the clinical and functional improve-ment of the patellar tendon in the short-term and a rapidreturn to the previous level of activity [4, 18]. Concerningtechniques based on the infiltration of substances, it ispossible to differentiate between pharmacological ornonpharmacological agents. -e most used technique isplatelet-rich plasma (PRP) [21–23]. Literature reviewscarried out based on the application of the PRP techniqueon other tendons have concluded that there are no sig-nificant differences between PRP and DN or placebo atthe 6-months follow-up, although it seems that there maybe small differences depending on the injured tendon[24]. Moreover, some reviews and meta-analysis haveanalyzed the effect of PRP in PT versus other techniques,regardless of whether they are conservative or invasivetreatments, finding that PRP seems to be a more effectivetreatment in the long term than other treatments, such asextracorporeal shockwave therapy (ESWT) [15, 25, 26].However, when compared to other invasive treatmentssuch as cell therapy or DN, the results for PRP are worseregarding functionality in the long term, whereas theseother techniques have a promising future for this pa-thology [27, 28]. Most studies conclude that more studies,specifically for randomized controlled trials (RCTs), arenecessary to make accurate conclusions with scientificrigor, as most of the included studies reviewed are of lowscientific quality.
A variety of MIT are being used in clinics for thetreatment of PT, either used alone or as a complement toother conservative treatments. However, evidence-basedtherapies are limited, and there is no consensus regardingwhich of these is the most effective. -e variability of thetypes of studies, together with the low quality of the same,lead us to consider the need for a review and meta-
analysis of high-quality RCT on MIT for the treatment ofPT.
-us, our primary aim was to systematically review theeffectiveness of MIT for functionality and pain of the PT inhumans. Where possible, meta-analysis of outcome data onpain and function was performed.
2. Materials and Methods
A systematic review and meta-analysis were performedaccording to the Preferred Reporting Items for SystematicReview and Meta-Analysis (PRISMA) [29]. -e review wasregistered in the international PROSPERO database(CRD42015025801). -e software used to assemble all thepapers included in this review is EndNote X7 v17.0.1.
2.1. Data Sources and Searches. We conducted a systematicliterature search in Web of Science, Cochrane Central,SportDiscus, and Medline via PubMed and PEDro. -edatabase search was conducted by two reviewers (MPLR andEMGT) in January 2018 with the final search conducted inSeptember 2019, using the following search terms: patellarten∗, patellar ligament, jumper’s knee, chronic patellar ten∗,dry need∗, intratissue percutaneous electrolysis, acupunc-ture, electroacupuncture, mesotherapy, injection,injectable∗, puncture, and infiltrate∗. Search strategy forMedline is described in detail in Appendix 1.
Two independent reviewers (MPLR and EMGT)screened the titles and/or abstracts and full texts accordingto the stated inclusion criteria. Discrepancies were discussedat a consensus meeting, and the opinion of a third inde-pendent reviewer (MOL) was sought if agreement could notbe achieved. Reviewers were not blinded to informationregarding the authors, journal of origin, or outcomes foreach paper reviewed.
2.2. Study Selection. -e inclusion criteria were as follows:(a) RCT; (b) English or Spanish; (c) involving adults; (d)with a diagnosis of chronic patellar disease (minimum of 3months of pain in the inferior pole of the patella); and (e) atleast one group receiving MIT. We excluded articles inwhich the sample was under 18 years old, non-RCTs(quasiexperimental trials, case series, and observationalstudies), and those in which subjects had received a previoussurgical intervention.
In studies with more treatment groups in which patientsunderwent different procedures, each treatment group wasanalyzed independently according to the treatment appliedand always compared with the group receiving MIT.
2.3. Data Extraction. -e primary outcome evaluated wasfunctionality using the Victorian Institute of Sport Assess-ment of Patellar Questionnaire (VISA-p) [30]. Secondaryoutcome measures focused on pain.
A standardized electronic data extraction form wasdeveloped to obtain key information relevant to this review.Data extraction for each article was performed by two
2 Evidence-Based Complementary and Alternative Medicine
authors (MPLR and EMGT), with a third reviewer (MOL)solving potential discrepancies, and including the following:(1) sample characteristics (sample age and sample sex); (2)methodological characteristics (study design, number ofgroups, associated interventions, time of measurements, andassessment tools); (3) main results; and (4) conclusions.
Finally, ameta-analysis was performed grouping the RCTsaccording to the technique used. Means, standard deviation(SD), and sample sizes for pain and function were extractedfor each group at short-term and medium/long-term follow-up. When data were not extractable or expressed in otherform instead of mean and SD, a total of three attempts weremade contacting with the corresponding author to request theinformation by e-mail, and in case of not getting an answer ofthe study data, were not used for themeta-analysis. To analyzethe benefit of this treatment, studies without pre- andpostintervention data were excluded.
2.4. Risk of Bias Assessment. -e quality of the relevant RCTswas evaluated using the PEDro scale. Eleven PEDro criteriawere used to evaluate the quality of the retrieved studies. Eachsatisfied item (except for item 1, which, unlike other scaleitems, pertains to external validity) contributes one point tothe total PEDro score (range 0–10 points). Each criterion wasassessed with the alternatives ‘‘Yes’’ (1 point) or ‘‘No” (0points). Items 2–9 assess internal validity, and the last twoitems (10 and 11) reveal whether the statistical informationpresented in the study is enough to perform a correct in-terpretation of the outcomes. Articles fulfilling at least 6/10positive criteria were considered to be of “good quality,”studies with 4-5/10 positive criteria were considered to be“average quality,” and articles with less than 4 points wereconsidered “poor quality” [31]. Two reviewers (MPLR andEMGT) separately evaluated the quality of the studies usingthe PEDro scale, and when they could not reach agreement, athird independent reviewer was consulted.
2.5. Statistical Analysis. -e random effects model was usedfor all meta-analyses. -e VISA-p score and visual analogscale (VAS) mean differences and SD for each group (be-tween pre and posttreatment and between pretreatment andthe follow up) were collected for this purpose. Heterogeneitybetween studies was assessed using the Cochran’s Q test, andthe I2 index was used to quantify the amount of heteroge-neity, with a value greater than 50% indicating substantialheterogeneity [32, 33]. Additional intragroup meta-analysesof each treatment differences of means were performed toexplain the heterogeneity found. Also, subgroup analyseswere performed according to dose (≤ or >4mL), amount ofexercise (≤ or >6 weeks), and basal VISA-p score (< or ≥48).Prior to this, scatter plots of possible factors of heterogeneitywere drawn to detect suitable variables for subgroup analysesand their cut off values.
3. Results
3.1. Characteristics of Included Trials. A total of 1164 studieswere screened for possible inclusion in this systematic
review; 10 RCTs met our inclusion criteria and included inthe review (Figure 1).
All the articles included in the present review involved326 individuals, most of whom were athletes practicingvarious sports and aged between 18 and 55 years. Func-tionality with VISA-p was assessed in eight studies[8, 21, 23, 34–38], and pain was evaluated using a numericscale in all studies except one [38]. -e main features ofthese studies are summarized in Table 1. -e quality as-sessment revealed that all the studies included were con-sidered to be of high methodological quality (≥6 pointsabout 10) (Appendix 2).
4. Review
A heterogeneity of results was found after performing thesystematic review. On the one hand, MIT that do not in-filtrate any substances such as DN or PNE showed a highincrease of studies in the last years, although the studiespublished are still of low quality except for the one publishedby Dragoo et al. [21]. However, there was a protocol pub-lished by Lopez-Royo et al [41] analyzing the additionaleffects of both DN and PNE over EE whose results have notpublished yet, but that will increase the knowledge in thisfield. On the other hand, other therapies including the in-filtration of substances, such as PRP therapy, were associatedwith a significant improvement in functionality and pain atposttreatment [21, 34–37] and at follow-up measurements[21, 35–37] and a significant decrease in hypoechogenicityand tear size at 6 months [37] in patients with PT, with nosignificant differences between one or two PRP injections.
In the systematic review, we found studies comparingdifferent interventions, such as a study that compared PRPwith ESWT, showing that the effectiveness of two injectionsof PRP was superior for pain and functionality measure-ments at posttreatment and at follow-up and for pain only atfollow-up [35]. In other study, that compared PRP with DNtherapy, controversial results were observed, as, in the shortterm (3 months), PRP obtained better results on pain andfunctionality compared to DN, whereas at 6months, DNwasmore effective than PRP for functionality [21]. In this study,when comparing subjects at baseline, DN was more effectivethan PRP on levels of pain and function also at 6 months.Moreover, other RCTs have reported PRP as being less ef-fective than other therapies [34, 37], like the study com-paring PRP with tenocyte-like cell treatment at 6 months[37], with the latter showing improved effectiveness forfunctionality, pain, tendon thickness, hypoechogenicity, andtear size. In other recent study [34], comparing two differentgroups of leukocyte-poor PRP (LP-PRP) and leucocyte-richPRP (LR-PRP) versus saline injection, 58% of the patientsexperienced an improvement of the VISA-p score at post-treatment regardless of their assigned treatment group. Inthis study, no significant differences were found between thethree groups in the short term, failing to demonstrate anysignificant benefit of LP-PRP or LR-PRP over saline injec-tion. Eventually, the effectiveness of the autologous blood(AB) injections was studied in a recent RCT [38], showingthat both AB and saline groups experienced a significant
Evidence-Based Complementary and Alternative Medicine 3
improvement in symptoms, with nonsignificant statisticaldifferences between groups.
Regarding pharmacological treatments, several studies[8, 23, 38–40] applied different drug infiltrations protocols,including steroids and sclerosing agents. A study comparingsteroids with placebo showed an improvement at 6 monthsin the steroids group for pain measured with a numericrating scale and a decrease of tendon thickness, maintainingthis effect at 6 months [39]. Nevertheless, in a study com-paring corticosteroid injections (CI) with EE and HSRT, allgroups improved functionality, pain, and tendon thicknessand swelling, with significant differences in favor of the CIgroup when compared with the other two exercise groups inthe short term. However, these improvements were main-tained at 6 months for both exercise groups but not for thegroup receiving corticosteroids [23]. Polidocanol was ef-fective on functionality at 4 months posttreatment in onestudy [8]; however, no results were found in VAS mea-surements either in the short or long term [8, 40]. Fur-thermore, functional improvements were not maintained atlong-term [8]. In a subsequent study of the same group witha 44-months follow-up, more than one-third of the group
treated with polidocanol ended up in a surgical interventionbecause of the pain they suffered. Willberg et al. [40] in theirstudy showed that the group receiving arthroscopic treat-ment found better improvements in pain and satisfactioncompared to baseline as opposed to the cited polidocanolgroup at 6 weeks [40]; however, once again, the results werelost in the follow-up period (2, 6, and 12 months).
4.1. Meta-Analysis. -e only MIT with enough RCTs tocarry out a meta-analysis was PRP. For this reason, weincluded all articles with at least one group consisting of PRPinjection treatment. Finally, five RCTs were included in themeta-analysis (Figure 1).
For the meta-analysis, different cutoff points wereestablished. Regarding the dose of treatment received,three RCTs [21, 36, 37] applied doses equal to or greaterthan 4mL of PRP, and two RCTs [34,35] employed threedifferent injections, applying doses less than 4mL. -esesame subgroups were obtained when comparing theduration of EE performed by the subjects of the PRPgroup. When the dose was bigger than 4mL of PRP, aprogram of over 6 weeks of exercise was continued;
WOSn = 472
PubMedn = 332
SportDiscusn = 121
PEDron = 111
Cochranen = 128
Records identified throughdatabase searching
n = 1164
Duplicate studiesn = 340
Abstract and full-text excludedn = 757
Potentially relevant articlesn = 67
Studies included inthe systematic review
n = 10
Studies included inthe meta-analysis
n = 5
Articles excludedNo control group = 48No humans = 1No PT = 4No regenerative treatment = 4
Figure 1: PRISMA flow diagram. PT�patellar tendinopathy; WOS�Web of Science.
4 Evidence-Based Complementary and Alternative Medicine
Table 1: Study characteristics of the included trials.
Study (y) Participants(N, age, sex) Intervention Outcomes Results Conclusion
Dragoo et al.(2014) [21]
DN (n� 12,40 (SD 14)yrs, 100% M)
A nurse obtained 55mL ofperipheral blood that was
discarded.
Functionality: VISA-p, Tegner/Lysholm.
Pain: VAS.Others: SF-12.
Temporality: pre/post(12wks)/follow-up
(26wks).
DN: significantimprovement from
baseline on Lysholm at12wks and on VISA-p,Tegner, Lysholm, and
VAS at 26wks.PRP: significant
improvement frombaseline on VISA-p,Lysholm, and VAS at12wks and on VISA-pand VAS at 26wks.
DN vs. PRP: significantimprovement in PRP vs.
DN on VISA-p at12wks and DN vs. PRPon Lysholm at 26wks.
-e PRP group showed asignificant improvementcompared with the DNgroup at 12wks, but thedifference between groupswas not significant at
26wks.Lysholm scores were notsignificantly different
between groups at 12 wks,but the DN group hadimproved significantly
more than the PRP groupat 26wks.
3mL of 0.25% bupivacainewith 1 :100,000
epinephrine were theninjected subcutaneously
using a sterile technique toanesthetize. Subsequently,10 mechanical needle
insertions were performedin the area of thetendinopathy.
Standardized a 5-phaseprogram of EE during
12wks.
PRP (n� 9, 28(SD 8) yrs,89% M)
A nurse obtained 55mL ofperipheral blood, and it wasprocessed. -en, 3mL of0.25% bupivacaine with 1 :100,000 epinephrine wassubcutaneously injected
using a sterile technique toanesthetize. -is wasfollowed by 6mL
infiltration of leukocyte-rich PRP. Finally, 10mechanical needle
insertions were performedin the area of the
tendinopathy. Standardizeda 5-phase program of EE
during 12wks.
Clarke et al.(2010) [37]
Cells (n� 33);total sample:36 yrs (20–51)
Skin-biopsy: 4-mm skinsample. 1 infiltration ofisolated and amplified
cells + plasma.Standardized program ofincreased eccentric loadingand stretching exercises
during 6mo.
Functionality: VISA-p.
Others: US (tendonthickness,
hypoechogenicity,intrasubstance tears,and neovascularity).Temporality: pre/post(6 wks)/follow-up(3mo and 6mo).
Cells: significantimprovement frombaseline on VISA-p,tendon thickness,
hypoechogenicity andtear size at 6mo.PRP: significant
improvement frombaseline on VISA-p,hypoechogenicity, and
tear size at 6mo.Cells vs. PRP:significant
improvement in cells vs.PRP on VISA-p at 6mo.
Ultrasound-guidedinjection of autologousskin-derived tendon-likecells can be safely used at6mo to treat PT, with afaster treatment responseand significantly greaterimprovements in pain andfunction than with plasma
VISA-p, and SF-MPQ at1mo/3mo/1 yr.AB vs. saline: no
significant differences.
AB and saline groupsexperienced a significant
improvement insymptoms. However,when the results werecompared, there was nostatistical difference
between the 2 groups.
Saline (n� 11,39 yrs)
2mL of AB was extracted.2mL saline injection + EE
3mo
Evidence-Based Complementary and Alternative Medicine 7
however, when the dose was less than 4mL, the exerciseprogram lasted 6 weeks or less. Regarding the meanbaseline score of the VISA-p, the following subgroupswere defined: subjects with less than 48 points [21, 34]and subjects with more than 48 points [34–37].
4.2. Intergroup Differences. -ere was no difference be-tween groups in the case of the VISA-p after treatment orat follow-up (Figures 2(a) and 2(b)). However, in thosestudies where the dose was greater than 4mL and theduration of the exercise program was longer than 6 weeks,treatment with PRP was better than other therapies aftertreatment. Surprisingly, the opposite happened in thefollow-up (Figures 3(a) and 3(b)).
Concerning the effectiveness of treatment in themanagement of pain measured by VAS, PRP was superiorto other treatments in the case of doses greater than 4mLand exercise programs of more than 6 weeks durationafter treatment. In the follow-up, there were no differ-ences between groups in any of the situations (Figures 4(a)and 4(b)).
4.3. Intragroup Differences for the PRP Group. Concerningthe intragroup analysis of those patients treated with PRP,treatment was effective both after treatment and during thefollow-up, according to both measurement scales: the VISA-p (Figures 5(a) and 5(b)) and VAS (Figures 6(a) and 6(b)). Inthe case of pain, heterogeneous findings were found;however, the results of all studies suggest an improvementafter treatment.
5. Discussion
-e main finding of this study was that all studies analyzingMIT, such as PRP, DN, or cells, when combined with ex-ercise, were found to be effective for PTat posttreatment andfollow-up. -is systematic review has identified ten RCTsassessing the effectiveness of MIT in the treatment of PT. A
meta-analysis was conducted with five RCTs that includedPRP injection. It was not possible to perform meta-analysiswith otherMITdue to a lack of data for conducting statisticalanalysis. All studies selected in this review had a high-qualitylevel.
MITcan be divided into two different groups, dependingon whether they inject any substances or not. For the in-jection of substances, a differentiation can be made betweeninfiltrating pharmacological agents or nonpharmacologicalones. In our review, all injection therapies with pharma-cological agents (i.e., steroids, corticosteroids, and polido-canol) obtained good clinical effects in the short term, evenfor the decrease of the tendon diameter [8, 23, 40]; however,in the long term, results were poor [8]. -ese findings are inline with the conclusions of previous systematic reviews forthe treatment of other tendon disorders affecting other areasof the body [42,43]. Furthermore, the role of steroids in themanagement of tendinopathy is also controversial, sug-gesting the relapse of symptoms in the long term [43]. Also,steroid injections may produce undesirable side effects, suchas tendon rupture, as reported elsewhere [42, 44].
Concerning infiltration with nonpharmacological agentssuch as PRP, in this meta-analysis, as reported by severalRCTs [25, 26, 42, 45], PRP was found to be an effectivetechnique for PT treatment, and these effects were main-tained in the long term. Nonetheless, these studies concludethe need to perform further quality RCTs including placebotreatments to elucidate their true effects. Moreover, thisstudy has found that other MITsuch as tenocyte-like cells orDN may have better results in the long term for this pa-thology. Studies focusing on other tendinopathies, whichcompare PRP versus MIT that do not infiltrate substances,are available. In the case of the rotator cuff tendinopathy,PRP resulted in better results at 3 and 6months whencompared with DN [46]. Nonetheless, a single study com-paring PRP with DN in PT [21] showed better short-termresults in the case of PRP but the opposite at 6 months followup. -ese differences may be due to the comparison ofdifferent tendons and a different methodology, as the
Table 1: Continued.
Study (y) Participants(N, age, sex) Intervention Outcomes Results Conclusion
Scott et al.(2019) [34]
LP-PRP(n� 20, 33(SD 7.3) yrs)
52mL of venous blood wascollected. 2% hematocrit in
No significantdifference betweengroups in any time.
Combined with anexercise-based
rehabilitation program, asingle injection of LR-PRPor LP-PRP was no moreeffective than saline for the
improvement of PTsymptoms.
LR-PRP(n� 20, 32(SD 9.8)
52mL of venous blood wascollected. 15% haematocritin 3.5mL PRP+HSRT 3times/wk during 6wks.
Saline (n� 21,31 (SD 7.9)
3.5mL saline +HSRT 3times/wk during 6wks.
AB, autologous blood; Cells, prepared in laboratory (cells of collagen and plasma); CD, Color Doppler; CG, control group; CORT, peritendinous corti-costeroid injections; DN, dry needling; EE, eccentric decline squat training; ESWT, extracorporeal shock wave therapy; HSRT, heavy slow resistance training;IKDC, international knee documentation committee form; LP-PRP, leukocyte poor PRP; LR-PRP, leukocyte rich PRP; M, masculine; mo, months; MRI,magnetic resonance imaging;N, number; NRS, numeric rating scale; PRP, platelet-rich plasma; PT, patellar tendinopathy; RCT, randomized control trial; SF-12, Short Form–12; TG, treatment group; US, ultrasound; VAS, visual analog scale; VISA-p, Victorian Institute of Sport Assessment of Patellar; wks, weeks; yr,years.
8 Evidence-Based Complementary and Alternative Medicine
aforementioned studies differ in the number of injections(1–8) and dosage (6mL versus 3mL of PRP and 10 versus40–50 needle insertions for DN group) in the PTand rotatorcuff tendinopathy, respectively.
In line with the study by Dragoo et al. [21] and Clarkeet al. [37], in our meta-analysis according to the subgroupanalysis, we can affirm that in doses of less than 4mL of PRP,there is no difference between groups, and when the dose ismore than 4mL of PRP, in the long term, other treatmentsare more effective than PRP. One of such treatments is skin-derived tenocyte-like cells, which has proven to be effectivefor the recovery of other tendinopathies, such as lateral
epicondylitis [47]. -erefore, this appears to be a goodoption for the treatment of tendinopathies, although furtherstudies are required to demonstrate the effectiveness of thissame. According to some studies [16, 36, 45], it seems thatdifferent PRP preparations, timing, and frequency of in-jections should be considered in future studies as thesefactors could, at least in part, explain the differences in theeffectiveness of this technique. A recent meta-analysiscompared the application of one or two PRP injections,showing that two injections do not show better results than asingle injection [16]. In our meta-analysis, we have gonefurther and have tried to clarify not only the number of
D + L pooled WMD = –5.28993 (–13.3291, 2.74921)Heterogeneity chi-squared = 8.13 (d.f = 4) p = 0.087I-squared = 50.8%Test of WMD = 0: z = 1.29 p = 0.197
Weighted mean diff.–36.4829 0 36.4829
Study _ % weight Weighted mean diff. (95% CI)
–5.70 (–15.86, 4.46)Vetrano (2013) 24.4
–20.80 (–36.48, –5.12)Dragoo (2014) 15.9
–9.90 (–26.23, 6.43)Kaux (2015) 15.1
6.00 (–5.29, 17.29)Scoot (2019 LP) 22.4
–2.00 (–13.40, 9.40)Scoot (2019 LR) 22.2
–5.29 (–13.33, 2.75)Overall (95% CI)
(a)
D + L pooled WMD = 3.47839 (–6.14014, 13.0969)Heterogeneity chi-squared = 20.48 (d.f. = 5) p = 0.001I-squared = 75.6%Test of WMD = 0: z = 0.71 p = 0.478
Weighted mean diff.–27.7218 0 27.7218
Study _ % weight Weighted mean diff. (95% CI)
11.00 (2.51, 19.49)Clarke (2011) 19.4
–13.80 (–23.80, –3.80)Vetrano (2013) 18.3
9.70 (–8.32, 27.72)Dragoo (2014) 12.7
0.30 (–14.45, 15.05)Kaux (2015) 14.8
16.00 (4.71, 27.29)Scoot (2019 LP) 17.3
–1.00 (–12.04, 10.04)Scoot (2019 LR) 17.5
3.48 (–6.14, 13.10)Overall (95% CI)
(b)
Figure 2: Analysis VISA-p mean differences. (a) Analysis VISA-p prepost mean difference. (b) Analysis of VISA-p pre-follow-up meandifference.
Evidence-Based Complementary and Alternative Medicine 9
>4 mL ≤4 mL
D + L pooled WMD = –15.569 (–26.879, –4.259)I-squared = 0%Test of WMD: p = 0.007
D + L pooled WMD = –0.875 (–7.675, 5.925)I-squared = 14.1%Test of WMD: p = 0.801
Note: weights are from random effects analysis
.
.
Overall (I-squared = 50.8%, p = 0.087)
Kaux (2015)
Dragoo (2014)
Scoot (2019 LR)
Subtotal (I-squared = 14.1%, p = 0.312)
>4
Scoot (2019 LP)
Subtotal (I-squared = 0.0%, p = 0.345)
Vetrano (2013)
<4
StudyID
–5.29 (–13.33, 2.75)
–9.90 (–26.23, 6.43)
–20.80 (–36.48, –5.12)
–2.00 (–13.40, 9.40)
–0.88 (–7.68, 5.93)
6.00 (–5.29, 17.29)
–15.57 (–26.88, –4.26)
–5.70 (–15.86, 4.46)
WMD (95% CI)
100.00
15.11
15.87
22.20
69.02
22.39
30.98
24.43
%weight
–36.5 0 36.5
(a)
>4 mL ≤4 mLD + L pooled WMD = 8.534 (1.724, 15.344)I-squared = 0%Test of WMD: p = 0.014
D + L pooled WMD = 0.247 (–6.774, 17.268)I-squared = 86.7%Test of WMD: p = 0.977
Note: weights are from random effects analysis
.
.
Overall (I-squared = 75.6%, p = 0.001)
Vetrano (2013)
Clarke (2011)
<4
StudyID
Subtotal (I-squared = 0.0%, p = 0.464)
Scoot (2019 LP)
Scoot (2019 LR)
>4
Kaux (2015)
Dragoo (2014)
Subtotal (I-squared = 86.7%, p = 0.001)
3.48 (–6.14, 13.10)
–13.80 (–23.80, –3.80)
11.00 (2.51, 19.49)
8.53 (1.72, 15.34)
16.00 (4.71, 27.29)
–1.00 (–12.04, 10.04)
0.30 (–14.45, 15.05)
9.70 (–8.32, 27.72)
0.25 (–16.77, 17.27)
WMD (95% CI)
100.00
18.28
19.35
%weight
46.85
17.34
17.53
14.84
12.66
53.15
–27.7 0 27.7
(b)
Figure 3: Subgroup analysis VISA-pmean difference. (a) Subgroup analysis VISA-p prepost mean difference. (b) Subgroup analysis VISA-ppre-follow-up mean difference.
10 Evidence-Based Complementary and Alternative Medicine
>4 mL ≤4 mLD + L pooled WMD = 1.828 (0.670, 2.987)I-squared = 0%Test of WMD: p = 0.002
D + L pooled WMD = 0.344 (–1.035, 1.723)I-squared = 73.6%Test of WMD: p = 0.625
Note: weights are from random effects analysis
.
.
Overall (I-squared = 66.6%, p = 0.018)
Kaux (2015)
Scoot (2019 LR)
Subtotal (I-squared = 0.0%, p = 0.802)
>4
Vetrano (2013)
<4
Subtotal (I-squared = 73.6%, p = 0.023)
Dragoo (2014)
Scoot (2019 LP)
StudyID
0.87 (–0.19, 1.93)
2.00 (0.23, 3.77)
1.10 (–0.24, 2.44)
1.83 (0.67, 2.99)
1.00 (–0.08, 2.08)
0.34 (–1.03, 1.72)
1.70 (0.17, 3.23)
–1.10 (–2.37, 0.17)
WMD (95% CI)
100.00
16.49
20.56
35.13
23.12
64.87
18.64
21.20
%weight
–3.77 0 3.77
(a)
Note: weights are from random effects analysis
.
.
Overall (I-squared = 83.9%, p = 0.001)
Kaux (2015)
Scoot (2019 LR)
Subtotal (I-squared = 91.2%, p = 0.001)
>4
Vetrano (2013)
<4
Subtotal (I-squared = 82.6%, p = 0.003)
Dragoo (2014)
Scoot (2019 LP)
StudyID WMD (95% CI) %
weight
0.99 (–0.53, 2.50)
3.50 (1.94, 5.06)
1.10 (–0.24, 2.44)
1.60 (–2.12, 5.32)
1.80 (0.64, 2.96)
0.61 (–1.13, 2.34)
–0.30 (–1.86, 1.26)
–1.10 (–2.37, 0.17)
100.00
19.12
20.22
38.25
21.02
61.75
19.13
20.52
>4 mL–5.32 5.320
≤4 mLD + L pooled WMD = 1.600 (–2.124, 5.324)I-squared = 91.2%Test of WMD: p = 0.400
D + L pooled WMD = 0.609 (–1.126, 2.34)I-squared = 82.6%Test of WMD: p = 0.491
(b)
Figure 4: Subgroup analysis VAS mean difference. (a) Subgroup analysis VAS prepost mean difference. (b) Subgroup analysis VAS pre-follow-up mean difference.
Evidence-Based Complementary and Alternative Medicine 11
infiltrations but also what is the dose producing the vestresults. -us, our study provides novel and valuable in-formation regarding the PRP technique and what appears tobe the best dose.
In the most recent RCT (2019) [34], aimed at examiningthe differences between the concentration of leukocytesinjected in the PRP, a platelet-rich sample was comparedwith a platelet-poor sample and a final control group with a
saline solution. -is study revealed that there are no dif-ferences between the groups neither in the short nor in thelong term. Along these lines, Resteghini et al. [38] comparedthe effectiveness of AB versus saline and found no differ-ences between groups. Finally, this review is in line with aprevious study [21] that reported that PRP was not superiorto placebo or DN at a 6-month follow-up for tendinopathytreatment. -ese results may support the hypothesis by
Weighted mean diff.–41.2971 0 41.2971
Study _ % weightWeighted mean diff.(95% CI)
–20.90 (–29.82, –11.98)Vetrano (2013) 38.4
–25.40 (–41.30, –9.50)Dragoo (2014) 12.1
–13.90 (–31.94, 4.14)Kaux (2015) 9.4
–22.00 (–34.44, –9.56)Scoot (2019 LP) 19.7
–14.00 (–26.23, –1.77)Scoot (2019 LR) 20.4
–19.60 (–25.12, –14.07)Overall (95% CI)
D + L pooled WMD = –19.595 (–25.122, –14.068)Heterogeneity chi-squared = 1.92 (d.f = 4) p = 0.750I-squared = 0.00%Test of WMD = 0: z = 6.95 p ≤ 0.001
(a)
Study _ % weightWeighted mean diff.(95% CI)
D + L pooled WMD = –23.1575 (–29.9637, –16.3513)Heterogeneity chi-squared = 9.80 (d.f = 5) p = 0.081I-squared = 49.0%Test of WMD = 0: z = 6.67 p ≤ 0.001
Weighted mean diff.–44.3742 0 44.3742
–20.00 (–29.34, –10.66)Clarke (2011) 21.3
–31.40 (–39.64, –23.16)Vetrano (2013) 23.4
–26.80 (–44.37, –9.23)Dragoo (2014) 10.5
–25.10 (–42.12, –8.08)Kaux (2015) 11.0
–26.00 (–37.77, –14.23)Scoot (2019 LP) 17.2
–9.00 (–21.23, 3.23)Scoot (2019 LR) 16.5
–23.16 (–29.96, –16.35)Overall (95% CI)
(b)
Figure 5: Intragroup VISA-p mean difference in the PRP group. (a) Intragroup prepost VISA-p mean difference in the PRP group. (b)Intragroup pre-follow-up VISA-p mean difference in the PRP group.
12 Evidence-Based Complementary and Alternative Medicine
Vetrano [35] who proposed that needling on tissues withtendinopathy may provide cellular and humoral mediators,which promote the healing of tissues.
Although there are no RCTanalyzing the effectiveness ofMIT like PNE, there has been an increasing number ofpublications achieving excellent results in the last years[4, 18–20]. However, it is necessary to develop RCTs ana-lyzing not only the effect but also comparing the effec-tiveness between different MIT such as DN and PNE.
Fortunately, this review found two high quality protocolspublished that aim to compare the effects of PNE and DN inPT [41] and plantar heel pain [48], although results are notavailable yet.
-e studies previously mentioned in this review testingcell therapy, PRP, DN, and AB [21, 31, 34, 35, 37, 38] wereaccompanied by a standardized program of exercise duringtreatment, most of themwith EE which is until now, the goldstandard technique for the treatment of this injury.
Study _ % weightWeighted mean diff.(95% CI)
D + L pooled WMD = 2.61934 (1.65689, 3.58179)Heterogeneity chi-squared = 9.87 (d.f. = 4) p = 0.043I-squared = 59.5%Test of WMD = 0: z = 5.33 p ≤ 0.001
Weighted mean diff.–5.24613 0 5.24613
3.40 (2.36, 4.44)Vetrano (2013) 24.6
2.40 (0.95, 3.85)Dragoo (2014) 19.3
3.25 (1.25, 5.25)Kaux (2015) 13.9
3.20 (1.83, 4.57)Scoot (2019 LP) 20.3
1.00 (–0.24, 2.24)Scoot (2019 LR) 21.9
2.62 (1.66, 3.58)Overall (95% CI)
(a)
Study _ % weightWeighted mean diff.(95% CI)
D + L pooled WMD = 3.30942 (1.89387, 4.72498)Heterogeneity chi-squared = 26.24 (d.f. = 4) p ≤ 0.001I-squared = 84.8%Test of WMD = 0: z = 4.58 p ≤ 0.001
Weighted mean diff.–6.46839 0 6.46839
4.20 (3.13, 5.27)Vetrano (2013) 20.9
2.40 (1.01, 3.79)Dragoo (2014) 19.3
5.10 (3.73, 6.47)Kaux (2015) 19.4
3.80 (2.52, 5.08)Scoot (2019 LP) 19.9
1.10 (–0.02, 2.22)Scoot (2019 LR) 20.6
3.31 (1.89, 4.72)Overall (95% CI)
(b)
Figure 6: IntragroupVAS mean difference in the PRP group. (a) Intragroup prepost VAS mean difference in the PRP group. (b) Intragrouppre-follow-up VAS mean difference in the PRP group.
Evidence-Based Complementary and Alternative Medicine 13
However, several studies have shown that HSR is moreeffective than EE [23]. Further studies are necessary to re-define the gold standard of conservative treatment of thispathology. In the subgroup analysis of functionality and painin PRP treatment, RCTs which carried out EE programs over6 weeks showed greater improvements than those which hada duration of less than 6 weeks. Further research is needed toelucidate the ideal type and duration of exercise programsfor the different subtypes of patients with different levels offunctionality.
-e current systematic review and meta-analysis hadseveral limitations due to the inherent biases of the includedstudies. -us, caution should be taken when interpreting thefindings. First, there is a scarcity of RCTs concerning certainMIT that do not rely on the infiltration of substances (i.e.,DN or PNE). -is hinders the possibility of performing ameta-analysis with all the MIT. Second, a standardization oftreatment may be necessary (number of doses, frequency,and PRP amount).-ird, publication bias may be present, asonly English or Spanish language studies were included, andonly 5 databases were searched; however, in order to de-crease publication bias, a monthly update of the publishedpapers on databases were performance.
6. Conclusions
In conclusion, the most important finding of the presentstudy was that all studies analyzing MIT, such as PRP, DN,or cells, when combined with exercise, were found to beeffective for PT at posttreatment and follow-up. Moreover,the PRP technique with doses greater than 4mL togetherand combined with an exercise program lasting over 6 weeksobtained better results in functionality and pain compared toother treatments in the short-term. However, in the long-term, DN and skin-derived tenocyte-like cells are moreeffective than PRP. In addition, although the infiltration ofdrugs was effective at posttreatment, these improvementswere not maintained over time and could have secondaryeffects.
Abbreviations
AB: Autologous bloodCD: Color Doppler sonographyCI: Corticosteroid injectionsDN: Dry needlingEE: Eccentric exerciseESWT: Extracorporeal shockwave therapyHSR: Heavy slow resistance exercisesLP-PRP: Leukocyte-poor PRPLR-PRP: Leucocyte-rich PRPMIT: Minimally invasive techniquesMRI: Magnetic resonance imagingPNE: Percutaneous needle electrolysisPRISMA: Preferred Reporting Items for Systematic Review
and Meta-AnalysisPRP: Platelet-rich plasmaPT: Patellar tendinopathyRCT: Randomized controlled trial
SD: Standard deviationVAS: Visual analog scaleVISA-p: Victorian Institute of Sport Assessment of
Patellar QuestionnaireWOS: Web of Science.
Data Availability
-e data used to support the findings of this study are in-cluded within the supplementary information file.
Conflicts of Interest
-e authors declare that there are no conflicts of interestregarding the publication of this paper.
Supplementary Materials
Appendix 1: search strategy in databases. Appendix 2:methodological quality scores using the PEDro scale.(Supplementary Materials)
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