Original Research

Comparison of Autologous Conditioned PlasmaInjection, Extracorporeal Shockwave Therapy,and Conventional Treatment for Plantar Fasciitis:A Randomized TrialKelvin Tai Loon Chew, MBBCH, MSpMed, Darren Leong, MBBS, Cindy Y. Lin, MD,Kay Kiat Lim, MBBS, MMed, Benedict Tan, MBBS, MSpMed

K.T.L.C. Changi Sports Medicine Centre,Changi General Hospital, SingaporeDisclosure: nothing to disclose

D.L. Changi Sports Medicine Centre, ChangiGeneral Hospital, SingaporeDisclosure: nothing to disclose

C.Y.L. Changi Sports Medicine Centre, ChangiGeneral Hospital, Singapore 529889. Addresscorrespondence to: C.Y.L.; e-mail: cindy.-lin@post.harvard.eduDisclosure: nothing to disclose

K.K.L. Department of Orthopedic Surgery,Changi General Hospital (affiliation of K.K.L.when study was performed), Singapore; Syn-ergy Orthopedic Group, SingaporeDisclosure: nothing to disclose

B.T. Changi Sports Medicine Centre, ChangiGeneral Hospital, SingaporeDisclosures outside this publication: boardmembership, Singapore Sports Council; pay-

Objectives: To evaluate the efficacy of autologous conditioned plasma (ACP) comparedwith extracorporeal shockwave (ESWT) and conventional treatments for plantar fasciitis.Design: Randomized trial.Setting: Sports medicine center in a tertiary care hospital.Patients: Fifty-four subjects (age range, 29-71 years) with unilateral chronic plantarfasciitis with more than 4 months of symptoms.Methods: Subjects randomized to 3 groups: 19 to ACP and conventional treatment (ACPgroup), 19 to ESWT and conventional treatment (ESWT group), and 16 to conventionaltreatment alone. Conventional treatment included stretching exercises and orthotics ifindicated.Main Outcome Measurements: Outcomes were pain-Visual Analog Scale (VAS),American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot scale, andultrasound plantar fascia thickness assessed at baseline before treatment and at 1 month,3 months, and 6 months after treatment.Results: VAS, AOFAS ankle-hindfoot scale, and plantar fascia thickness improved in allgroups. Significant VAS pain score improvements in the ACP group compared withconventional treatment at month 1 (P ¼ .037) and for the ESWT group compared withconventional treatment at months 1, 3, and 6 (P ¼ .017, P ¼ .022, and P ¼ .042).The AOFAS ankle-hindfoot scale score improved in the ACP group at months 3 and 6(P ¼ .004 and P ¼ .013) and, for the ESWT group, at months 1 and 3 (P ¼ .011 and P ¼.003) compared with conventional treatment. Significant improvements in plantar fasciathickness were seen in the ACP group at months 1 and 3 compared with conventionaltreatments (P ¼ .015 and P ¼ .014) and at months 3 and 6 compared with the ESWTgroup (P ¼ .019 and P ¼ .027). No adverse events reported.Conclusions: Treatment of plantar fasciitis with ACP or ESWT plus conventionaltreatments resulted in improved pain and functional outcomes compared with conven-tional treatment alone. There was no significant difference between ACP and ESWT interms of VAS and AOFAS ankle-hindfoot scale improvements, although the ACP groupdemonstrated greater reductions in plantar fascia thickness.

PM R 2013;5:1035-1043

ment for lectures (money to institution), Yong Siew Toh Conservatory; royalties, Fight theFat (author) and Run for Your Life! (author/editor); travel/accommodations/meeting ex-penses (money to institution), 2012 FIMSAnnual Congress

The study was funded by the SingaporeNational Medical Research Committee grant.

Peer reviewers and all others who controlcontent have no relevant financial relation-ships to disclose.

Submitted for publication December 9, 2012;accepted August 5, 2013.

INTRODUCTION

Plantar fasciitis is a common cause of heel pain associated with mild-to-severe activity lim-itations in athletes and the general population. In the United States, there were an estimated 1million outpatient visits per year for plantar fasciitis between 1995-2000 [1]. The condition isan enthesopathy at the plantar fascia attachment to the medial plantar tuberosity of thecalcaneus. Risk factors for plantar fasciitis include obesity, excessive foot pronation, running,decreased ankle dorsiflexion range, and prolonged standing [2,3]. Current treatmentapproaches are based on addressing identified anatomic and biomechanical abnormalities

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1036 Chew et al ACP, ESWT, AND CONVENTIONAL TREATMENT FOR PLANTAR FASCIITIS

and on providing pain relief. Conventional noninvasivetreatment options include plantar fascia, gastrocnemius, andsoleus stretching; customized orthotics; night splints; extra-corporeal shock wave therapy (ESWT); and pain medications[4,5]. Generally, plantar fasciitis is a self-limited condition.However, approximately 10% of patients with plantar fasciitisdo not respond to conventional treatments [6]. Invasivestrategies, for example, corticosteroid injections, and percu-taneous, endoscopic, or open fasciotomy have been used inrefractory cases with varying results [7-10].

The efficacy of blood-derived growth factors, includingautologous conditioned plasma (ACP), autologous condi-tioned serum (ACS), and platelet-rich plasma (PRP) inhealing ligaments, tendons, muscles, and cartilage injurieshave been investigated in several studies [11-15]. PRP, ACP,or ACS are platelet-rich preparations derived by drawingperipheral venous blood from the patient and centrifuging itto separate the red blood cells and platelets. The plateletconcentrate is then aspirated from the platelet-rich layer ofthe centrifuged plasma and is used for injection [11]. Forcases of plantar fasciitis refractory to conventional treat-ments, these autologous preparations have been suggested asan alternative management strategy [7,9,16]. Few studieshave examined the efficacy of ACP for the treatment ofplantar fasciitis. A case series of PRP for plantar fasciitisfound that, at 1 year, 7 of the 9 patients had complete painresolution. All 9 patients had ultrasound evidence ofimprovement, including reduced thickness of the medialplantar fascial band and increased signal intensity of thefascial bands [16]. Another study compared the efficacy ofPRP with corticosteroid injection for plantar fasciitis andfound no significant difference in outcomes between thegroups at 3-week and 6-month follow-ups [7].

The aim of this randomized trial was to investigate theefficacy of ACP for plantar fasciitis compared with that ofESWT and conventional treatments, including physiotherapystretching exercises and orthotics if indicated. The primaryoutcome measures were pain, function as measured by theAmerican Orthopaedic Foot and Ankle Society (AOFAS)ankle-hindfoot scale, and changes in plantar fascia thicknessseen on ultrasound. To our knowledge, this is the first pub-lished study to compare ESWT with ACP injection andconventional treatments for plantar fasciitis. Our hypothesiswas that ACP would be more effective than ESWT and con-ventional treatments in relieving pain, improving function,and reducing plantar fascia thickness on ultrasound inchronic plantar fasciitis over 6 months of follow up.

METHODS

The study design was a randomized trial that evaluatedthe efficacy of 3 different treatment groups. Fifty-fourpatients with unilateral plantar fasciitis were recruited at asingle sports medicine center in a public tertiary carehospital. Inclusion criteria were clinically diagnosed

unilateral chronic plantar fasciitis defined as the following: atleast 4 months of plantar heel pain, point of maximaltenderness on clinical examination over the medial tubercleof the calcaneus, and sonographic features of plantar fasciitis.Increased thickness of the plantar fascia and hypoechoicfascia are recognized as the sonographic findings of plantarfasciitis [17]. As in prior studies, a plantar fascia thicknessof more than 4 mm at baseline was taken as abnormal[18,19]. All the subjects had a radiograph of the symptom-atic foot before inclusion in the study. Potential subjects witharthritis, fractures, or tumors of the foot or ankle, rheuma-toid arthritis, generalized polyarthritis, seronegativearthropathy, diabetes mellitus, neurologic impairments,lower extremity nerve entrapment, vascular abnormalities,prior operative treatment of the foot, or current pregnancywere excluded. Subjects also were excluded if they hadreceived corticosteroid or other injections for plantar fasciitisduring the 4 months before study entry. Subjects were notexcluded if they had tried stretching exercises, physio-therapy, or orthoses before study enrollment. The study wasinstitutional review board approved, and all the subjectsgave written informed consent. The subjects were random-ized to the 3 groups at the time of enrollment by drawing afolded sealed paper with a corresponding group numberfrom a sealed box.

The 3 groups were (1) ACP injection and conventionaltreatment (ACP group), (2) ESWT and conventional treat-ment (ESWT group), and (3) conventional treatment alone.All subjects in all 3 treatment groups received conventionaltreatments, which included 1-2 physical therapy sessions tolearn an independent daily home exercise program,including (1) standing lunge stretch of the gastrocnemiusand soleus performed with the knee bent and the kneestraight and the palms of the hands pressed against a wall,and (2) seated plantar fascia stretch by pulling the toes backwith their fingers while seated and with the affected legcrossed over the other thigh [5,6,20]. The subjects received1-2 physical therapy sessions only, because the goal was tobecome independent in the stretching exercises. The subjectswere instructed to perform the stretches 3 times a day,3 times for each stretch, and to hold each stretch for 30seconds at a time. In addition, all the subjects in all thetreatment groups identified by the physician as havingbiomechanical foot abnormalities that contributed to theirsymptoms also were referred to podiatry for orthotics eval-uation. All the subjects in all 3 treatment groups wereadvised that they could continue pain medications on an as-needed basis only. No new pain medications were prescribedon study entry.

The subjects randomized to the ACP group had 10 mLof peripheral blood drawn and centrifuged at 1500 rpm for 5minutes by using the Arthrex ACP Double Syringe System(Arthrex Inc, Naples, FL). No buffer or preservativewas added, per manufacturer’s protocol. By using steriletechnique, 3 mL of ACP were extracted and subsequently

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injected with a 23-gauge, 1.5-inch needle at a single peri-fascial target at the site of plantar fascia thickening andtenderness at the medial calcaneal tubercle. The injectionwas performed under continuous ultrasound guidance by asingle sports medicine physician (K.T.C.) for all cases. Thisphysician did not perform any of the follow-up outcomemeasure assessments. No tenotomy or fasciotomy was per-formed. No local anaesthetic was administered. The patientswere instructed that they could resume their usual dailyactivities as tolerated after the procedure.

The subjects in the ESWT group received 2 sessions ofESWT 1 week apart using the Dornier EPOS Ultra ESWTMachine (The ESWT Co, Piqua, OH) delivered under ul-trasound guidance to the painful and thickened region of theplantar fascia at the medial calcaneal tubercle. The patientwas positioned prone on the examination table with the feethanging comfortably over the end of the table.

The ESWT protocol was as follows: ultrasound gel wasplaced on a water cushion and the ultrasound transducer.The water cushion and ultrasound transducer were posi-tioned so that the plantar fascia origin at the calcaneum wasvisible. The cross hair, which indicates the position of theshock wave focus, was positioned over the thickened andpainful region of the plantar fascia [21]. Continuous ultra-sound guidance was used to ensure accurate placement ofthe shock wave focus in the symptomatic region of theplantar fascia and to prevent the shock wave from contactingbone. Each treatment involved 2000 shockwaves with en-ergy levels progressing gradually from 0.02 mJ/mm3 to 0.42mJ/mm3. The total treatment duration was 10 minutes. Nolocal anaesthetic was administered. The patients wereinstructed that they could resume their usual daily activitiesas tolerated after the procedure.

The subjects were assessed at baseline (before treatment),1 month, 3 months, and 6 months after treatment. For theACP group, the 1-, 3-, and 6-month time points wereassessed after injection. For the ESWT group, the 1-, 3-, and6-month time points were assessed after completion of thesecond ESWT treatment. The Visual Analog Scale (VAS) of0-10 points was used as a self-report of pain at eachassessment time point. The American Orthopaedic Foot andAnkle Society (AOFAS) ankle-hindfoot scale was used toobjectively evaluate functional outcomes [22]. The AOFASankle-hindfoot scale is graded as excellent (91-100 points),good (81-90 points), fair (71-80 points), and poor (<70points) [23]. The AOFAS ankle-hindfoot scale was selectedas a measure because it evaluates pain, function, and align-ment, and it has been used in multiple prior clinical out-comes studies of plantar fasciitis treatments [4,24].Ultrasonography of the symptomatic plantar fascia wasperformed to manually measure the point of maximalproximal thickness at the medial calcaneal tubercle insertionsite [17]. Comparison of pre- and postintervention changesin plantar fascia thickness on ultrasound has been validatedas an objective measure to assess treatment efficacy for

plantar fasciitis [25]. Two sports medicine physicians (D.L.,Chung Sien Ng), each with more than 5 years of experiencewith musculoskeletal ultrasound, assessed the patients forthe 3 outcome measures. They also were blinded to eachsubject’s treatment group at initial and follow-up assess-ments. For each subject, the same assessor performed boththe initial and follow-up examination assessments. To ensureblinding, these assessors were not the same physicians whoperformed the ACP injection or ESWT treatment.

Statistical Analysis

The analysis endpoints were changes in VAS pain score,AOFAS ankle-hindfoot scale score, and plantar fasciathickness at 1-, 3-, and 6-month follow-up. SPSS softwarewas used for statistical analysis (SPSS Inc, Chicago, IL).Nonparametric statistical tests were used to compare thedifferences among the 3 treatment arms in terms of eachanalysis endpoint: Kruskal-Wallis test for the global test ofno difference among 3 groups and the Mann-Whitney U testfor pairwise comparison. To guard against inflated type Ierror rate due to multiple group comparison, pairwisecomparison was interpreted only if the global test of nodifference among the 3 groups was rejected. The dropoutrate at the 6-month final visit was compared among thegroups. Differences in the distribution of binary variableswere tested by the Mehta-Patel extension of the Fisher exacttest [26]. A P value <.05 was taken as statistical significance.

RESULTS

Of the approximately 100 subjects asked to participate in thestudy, 54 subjects gave informed consent to be included inthe study. Nineteen were randomized to the ACP group, 19 tothe ESWT group, and 16 to the conventional treatmentgroup. Nine subjects were unable to complete timely follow-up by 6 months, at which point, the number of subjectsassessed was 15 in the ACP group, 17 in the ESWT group,and 13 in the conventional treatment group. A Fisher exacttest showed that there were no significant differences in thedropout rates in the 3 groups at 6 months (P ¼ .506). Thedemographic characteristics of the 54 subjects are shown inTable 1. The 3 groups were comparable in age, gender, painduration before study enrollment, and left- and right-sidedistribution of plantar fasciitis. The conventional treatmentgroup had a better AOFAS ankle-hindfoot scale score at initialevaluation before treatment (P ¼ .03). At baseline, the VASpain score was lower in the conventional treatment groupand the ultrasound plantar fascia thickness was higher inthe ACP group, although not reaching statistical significance(P ¼ .606). The ESWT group had a slightly higher medianbody mass index and pain duration before study participationthan the ACP and conventional treatment groups; however,neither demographic characteristic demonstrated a statisticallysignificant difference among the 3 groups (P ¼ .606 and

Table 1. Patient demographic characteristics at enrollment*

Characteristics ACP (n [ 19) ESWT (n [ 19) Conventional Treatment (n [ 16) P Value

Age, y 46 (38-51) 45 (37-53) 47.5 (41-53) .833Men:women 10:9 11:8 8:8 .891Left:right side 8:11 8:11 10:6 .391Pain duration, mo 12 (7-24) 18 (7-24) 10.5 (6-16) .213BMI, kg/m2 23.4 (21.9-27.7) 25.3 (23.1-27.2) 24.7 (22.6-27.4) .606AOFAS ankle-hindfoot scale 65 (49-72) 62 (52-69) 72 (71-75) .030y

VAS pain score 7 (5-8) 7 (6-8) 6 (5-8) .606Plantar fascia thickness, mm 6.4 (5-7) 5.4 (5-6) 5.55 (5-7) .126

ACP ¼ autologous conditioned plasma; ESWT ¼ extracorporeal shockwave; BMI ¼ body mass index; AOFAS ¼ American Orthopaedic Foot and Ankle Society;VAS ¼ Visual Analog Scale.*For a binary endpoint, the count and the proportion is reported; for a continuous endpoint, the median and interquartile range is reported.yP < .05, statistical significance.

1038 Chew et al ACP, ESWT, AND CONVENTIONAL TREATMENT FOR PLANTAR FASCIITIS

P ¼ .213, respectively). No major adverse events, includinghematoma, deep vein thrombosis, nerve injury, or infection,were reported in any of the subjects during the treatment andfollow-up period for ESWT and ACP. All the patients toler-ated the procedures well, with no complications.

VAS Pain Score

Reductions in VAS pain scores were seen in all the treatmentgroups from baseline to the 6-month follow-up. The medianand range values of the VAS pain scores at all assessmenttime points are shown in Table 2. The VAS pain scoremedian change from baseline to all follow-up assessmenttime points are shown in Table 3 and Figure 1. At 1-month

Table 2. Median and range of VAS pain scores, AOFAS ankle-hindfoot scale scores, and plantar fascia thickness (mm) at allassessment time points

Time Point ACP ESWTConventionalTreatment

VAS pain scoresPreintervention 7 (4-10) 7 (5-8.5) 6 (3-8)1 mo 4 (1-10) 5 (0-7) 5 (3-8)3 mo 4 (0-8) 4 (0-7) 4 (1-9)6 mo 2 (0-6) 3 (0-8) 3 (0-7)

AOFAS ankle-hindfoot scalescoresPreintervention 65 (38-77) 62 (44-79) 72 (51-77)1 mo 75 (35-84) 73 (52-92) 75 (55-82)3 mo 86 (67-100) 85 (72-100) 80 (53-90)6 mo 90 (77-100) 90 (72-100) 87 (73-100)

Plantar fasciathickness, mmPreintervention 6.4 (4.6-7.9) 5.4 (4.4-8.1) 5.6 (4.8-8.0)1 mo 5.4 (4.0-6.9) 5.4 (3.8-7.9) 5.6 (5.1-7.6)3 mo 5.3 (3.4-6.9) 5.1 (3.2-6.8) 5.4 (4.4-6.6)6 mo 4.8 (3.5-6.0) 4.9 (3.6-7.0) 4.8 (3.3-6.7)

VAS ¼ Visual Analog Scale; AOFAS ¼ American Orthopaedic Foot and AnkleSociety; ACP ¼ autologous conditioned plasma; ESWT ¼ extracorporealshockwave.

follow-up, all 3 groups demonstrated significant improve-ment in the VAS pain score compared with baseline(P¼ .036). The median change in VAS pain score in the ACPand ESWT groups was a more than 1 point reduction at allassessment time points compared with the conventionaltreatment group. The ESWT group demonstrated significantimprovements in VAS pain scores at all assessment timepoints compared with the conventional treatment group. TheACP group demonstrated significant improvements at onlythe month 1 evaluation compared with the conventionaltreatment group (P ¼ .037). There was no statistically sig-nificant difference in VAS pain score improvements betweenthe ACP and ESWT groups at 1, 3, and 6 months (P ¼ .575,P ¼ .947, and P ¼ .791, respectively).

AOFAS Ankle-Hindfoot Scale Score

Improvements in AOFAS ankle-hindfoot scale scores wereseen in all the treatment groups from baseline to the6-month follow-up. The median and range values of theAOFAS ankle-hindfoot scale scores at all assessment timepoints are shown in Table 2. The AOFAS ankle-hindfootscale score median changes from baseline to all follow-upassessment time points are shown in Table 4 and Figure 2.All 3 groups demonstrated significant improvements inAOFAS ankle-hindfoot scale scores from the baseline tomonth 1 (P ¼ .045) and month 3 (P ¼ .004) follow-up. Thebaseline median AOFAS ankle-hindfoot scale scores inthe conventional treatment group were significantly higherthan that of the ESWT and ACP groups (P ¼ .024). The ACPgroup demonstrated a median improvement of 36 pointsin AOFAS ankle-hindfoot scale score, 28 points in the ESWTgroup, and 15.5 points in the conventional treatment groupoverall at 6 months. At all follow-up assessment time points,the conventional treatment group had the lowest medianchange in AOFAS ankle-hindfoot scale scores. The ACPgroup demonstrated significant improvements at the 3- and6-month evaluation (P ¼ .004 and P ¼ .013, respectively)compared with the conventional treatment group, whereasthe ESWT group showed greater improvements at the 1- and

Table 3. Median change and interquartile range in VAS pain scores at all assessment time points

ChangeFrom

Baseliney ACP ESWTConventionalTreatment

P Value

Global

ACP vsConventionalTreatment

ESWT vsConventionalTreatment

ACP vsESWT

1 mo �2.0 (�3.0 to �1.0) �2.0 (�3.8 to �1.0) �0.75 (�2.0 to 1.0) .036z .037z .017z .5753 mo �3.0 (�5.0 to �1.5) �3.25 (�4.5 to �2.0) �1.0 (�3.0 to 0.5) .053 .053 .022z .9476 mo �5.0 (�6.5 to �3.0) �5.5 (�6.5 to �4.0) �3.0 (�4.0 to �2.0) .090 .080 .042z .791

VAS ¼ Visual Analog Scale; ACP ¼ autologous conditioned plasma; ESWT ¼ extracorporeal shockwave.yScores at 1, 3, and 6 mo minus score at baseline.zP < .05, statistical significance.

PM&R Vol. 5, Iss. 12, 2013 1039

3-month evaluations (P ¼ .011 and P ¼ .003, respectively)compared with the conventional treatment group. Therewas no significant difference in median AOFAS ankle-hindfoot scale score improvements between ACP and ESWTgroups at all follow-up assessment time points.

Plantar Fascia Thickness

All the groups demonstrated improvements in plantar fasciathickness from baseline to the end of the evaluation period.The median and range of the plantar fascia thickness atall assessment time points are shown in Table 2. The medianchanges in ultrasound plantar fascia thickness at all follow-up assessment time points are shown in Table 5 andFigure 3. All 3 groups demonstrated a significant decreasein plantar fascia thickness at the month 1 (P ¼ .042) andmonth 3 (P ¼ .02) compared with baseline. The median

Figure 1. Median and range of Visual Analog Scale painscores in autologous conditioned plasma, extracorporealshockwave, and conventional treatment groups at all assess-ment time points.

ultrasound plantar fascia thickness improvement in the ACPgroup at the 6-month follow-up was 1.3 mm compared withthe ESWT and conventional treatment groups, which bothshowed improvements of 0.6 mm at 6 months. At the 1-and 3-month follow-ups, there were statistically significantdifferences in plantar fascia thickness in all groups (P ¼ .042and P ¼ .020, respectively). Significant improvements wereseen in the ACP group at 1 month and 3 months comparedwith the conventional treatment group (P ¼ .015 and P ¼.014, respectively). There was no significant difference in themedian plantar fascia thickness change at the 6-monthfollow-up compared with baseline in all 3 groups. There alsowas no significant difference between the absolute plantarfascia thickness measurements at the 6-month follow-upamong all 3 groups.

The ACP group demonstrated significant improvementsin plantar fascia thickness at the 3- and 6-month follow-upscompared with the ESWT group (P ¼ .019 and P ¼ .027,respectively). No significant difference was seen between theESWT and conventional treatment groups at all follow-upassessment time points for the median change in plantarfascia thickness (P ¼ .908, P ¼ .575, P ¼ .934, correspondsto 1-, 3-, 6-month follow-ups respectively).

DISCUSSION

Previous studies of biologic treatments for the plantar fasciahave involved injections of autologous whole blood and ofPRP [7-9]. This is the first study to our knowledge thatevaluated the effectiveness of ACP for treating chronicplantar fasciitis compared with ESWT and conventionaltreatments. The reason for the comparison with ESWT inthis study was to evaluate the effectiveness of ACP in painrelief because ESWT has been reported to provide good painrelief for chronic plantar fasciitis [27,28]. The mechanism ofpain relief with ESWT is thought to be due to a release ofenzymes that affect nociceptors [24]. ESWT can be consid-ered as a treatment option after conventional treatments havefailed.

There has been an increasingly prevalent use of autolo-gous blood-derived growth factor rich preparations in

Table 4. Median change and interquartile range in AOFAS ankle-hindfoot scale scores at all assessment time points

Change FromBaseliney ACP ESWT

ConventionalTreatment

P Value

Global

ACP vsConventionalTreatment

ESWT vsConventionalTreatment

ACP vsESWT

1 mo 10.0 (0.0-26.0) 14.5 (4.0-23.0) 0.5 (0.0-7.5) .045z .062z .011z .7493 mo 15.0 (12.0-36.0) 21.0 (13.0- 30.0) 5.0 (3.0-13.0) .004z .004z .003z .9866 mo 36.0 (18.0-40.0) 28.0 (10.0- 41.0) 15.5 (8.5-23.0) .061 .013z .187 .419

AOFAS ¼ American Orthopaedic Foot and Ankle Society; ACP ¼ autologous conditioned plasma; ESWT ¼ extracorporeal shockwave.yScores at 1, 3 and 6 months minus score at baseline.zP < .05, statistical significance.

1040 Chew et al ACP, ESWT, AND CONVENTIONAL TREATMENT FOR PLANTAR FASCIITIS

musculoskeletal disorders [7,12,13,15]. Growth factors suchas insulin-like growth factor-1, basic fibroblast growth factor,platelet-derived growth factor, epidermal growth factor,vascular endothelial growth factor, and transforming growthfactor-B1 are a diverse group of polypeptides that regulategrowth and tissue development [29-31]. It is believed thatthese cellular and humeral mediators provide conditionsfavorable for tissue healing [11,29,32]. Animal models havedemonstrated upregulation in temporal expression of growthfactors and their receptors during the healing process intendons [33,34], whereas healing has also been shown to takeplace in response to local injection of growth factors [31,35].

Our study found that ACP and ESWT were comparablein terms of pain relief. ACP and ESWT resulted in greatermedian improvements in functional AOFAS ankle-hindfootscale scores than in the conventional treatment group. Our

Figure 2. Median and range of the American OrthopaedicFoot and Ankle Society ankle-hindfoot scale score in autolo-gous conditioned plasma, extracorporeal shockwave, andconventional treatment groups at all assessment time points.

study demonstrated a more than 1 point median reductionin VAS pain scores in the ACP and ESWT groupscompared with conventional treatment, which was bothstatistically and clinically significant. Results of priorstudies indicated that the minimally important clinicalimprovement in VAS scores for foot pain is 9 mm on a100-mm VAS scale, which corresponds to a 0.9 pointimprovement on the 10-point VAS scale [36]. ACP treat-ment resulted in greater decreases in ultrasound plantarfascia thickness than ESWT but not when ACPwas compared with the conventional treatment group atthe 6-month follow-up. The ACP treatment groupdisplayed better objective improvements, with an overallmedian decrease of ultrasound plantar fascia thicknessby 1.3 mm at the 6-month follow-up. Changes in plantarfascia thickness more than 0.6 mm are considered changesin thickness not due to measurement error [37]. Changesin plantar fascia thickness are a valid objective measure-ment of assessing the effectiveness of plantar fasciatreatments [25].

No adverse events, such as fever, infection, hematoma,deep vein thrombosis, were reported among the studysubjects. The risks associated with ACP injections are lowbecause the preparations are derived from the patient’s ownblood; thus there is negligible risk of exogenous bloodborneinfections [29,38]. The harvesting procedure is simpleand fast, which allows for treatment to be administered in anoutpatient clinic setting.

Limitations

The study’s small sample size, which was limited by thetime frame and funding, may have resulted in positive ornegative effects being underdetected. Future larger trialsthat evaluate ACP for treatment of plantar fasciitis areneeded. At baseline, the median AOFAS ankle-hindfootscale scores were higher in the conventional treatmentgroup. This may partly explain why this score did notimprove as much for the conventional treatment group.

The subjects were unblinded to the treatments theyreceived, which may have biased their response. The sub-jects who received ACP or ESWT may have perceived their

Table 5. Median change and interquartile range of plantar fascia thickness (mm) at all assessment time points

ChangeFrom

Baseliney ACP ESWTConventionalTreatment

P Value

Global

ACP vsConventionalTreatment

ESWT vsConventionalTreatment

ACP vsESWT

1 mo �0.9 (�1.2 to �0.1) 0.2 (�1.0 to 0.7) 0.0 (�0.5 to 0.2) .042z .015z .908 .0563 mo �1.2 (�1.6 to �0.9) �0.3 (�1.1 to 0.0) �0.7 (�1.0 to �0.1) .020z .014z .575 .019z

6 mo �1.3 (�1.8 to �1.1) �0.6 (�1.2 to �0.1) �0.6 (�1.3 to �1.0) .068 .080 .934 .027z

ACP ¼ autologous conditioned plasma; ESWT ¼ extracorporeal shockwave.yScores at 1, 3, and 6 mo minus score at baseline.zP < .05, statistical significance.

PM&R Vol. 5, Iss. 12, 2013 1041

treatment as more “high tech” and a more effective treatmentmodality than conventional treatments because ACPinvolved an injection and ESWT was performed using amachine. Future studies, including the use of placebocontrolled injections compared with ACP, are warranted toisolate the treatment effect of the injectate alone for plantarfasciitis. The subjects did not keep a compliance log for theirstretching exercises or orthotic use; thus, it is unknown ifcompliance was comparable among the groups. If theconventional treatment group did not perform the stretchingexercises, then it is possible that this group represents thenatural history of plantar fasciitis. The subjects also didnot keep a pain medication use or an activity log. The singleassessor who performed ultrasound measurements of plantar

Figure 3. Median and range of plantar fascia thickness (mm)in autologous conditioned plasma, extracorporeal shockwave,and conventional treatment groups at all assessment timepoints.

fascia thickness manually measured the plantar fasciathickness once at each assessment time point. The interob-server reliability of the ultrasound measurement could havebeen increased if multiple measurements were averaged [25].

Future studies that compare the relative efficaciesof different preparations of ACP, PRP, and whole blood in-jections are needed to better understand the optimal con-centration of platelets and appropriate relative concentrationof platelets to leukocytes. The ACP from Arthex ACP overallhas concentrated platelets (�1.99) and diminished leuko-cytes (�0.13) compared with venous blood. ACP alsohas less catabolic cytokines than the Biomet GPS III MiniPlatelet Concentrate System (Biomet Biologics, Warsaw, IN)for PRP [39]. Platelets increase anabolic signaling, whereasleukocytes increase catabolic or inflammatory signalingmolecules that may degrade normal tissue matrix [39].The ACP from the Arthrex ACP system has been reportedto have a mean platelet concentration of 361,000/mL,whereas, in venous blood, the mean platelet concentration is183,000/mL [39].

Because our study investigated the use of a singleinjection only, future trials that investigate the optimalnumber of ACP injections are needed. Longer-term follow-up outcome studies to 1 year and beyond that examineoutcomes are also needed to determine the duration oftreatment effect. There is substantial variability in the in-jection techniques for platelet-rich preparations. Forplantar fasciitis, no single injection technique, whetherperifascial, intrafascial, peppering, layering, or percuta-neous tenotomy, and with or without ultrasound guidance,has been identified as the most effective [7,16,40]. In ourstudy, a perifascial approach under ultrasound guidancewas selected so that we could best isolate the treatmenteffect of ACP alone. We did not perform tenotomy orpeppering, as was performed in the studies by Ragab andOthman [40] and the Barrett and Erredge [16], because themicrotrauma to the fascia from the needling technique it-self has been postulated to mediate healing [41].We alsodid not perform a posterior tibial and sural nerve anes-thetic block before the injection, as was performed in thestudy by Barrett and Erredge [16]. Further studies that

1042 Chew et al ACP, ESWT, AND CONVENTIONAL TREATMENT FOR PLANTAR FASCIITIS

compare different injection techniques for platelet-richinjections to the plantar fascia are needed to determinewhether there is an optimal technique.

CONCLUSION

Treatment of plantar fasciitis with either ACP or ESWTresulted in modestly improved pain and functional scoreimprovements compared with conventional treatmentsalone over a 6-month follow-up period. Although therewere no significant differences between ACP and ESWT interms of VAS pain scores and AOFAS ankle-hindfoot scalefunctional score improvements, ACP demonstrated greaterobjective improvements in terms of plantar fascia thicknessreduction. ACP and ESWT are treatments that may beconsidered in patients with plantar fasciitis who have notresponded to conventional treatments.

ACKNOWLEDGMENTS

We would like to thank Dr. Chung Sien Ng for his assistancewith the study.

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CME QuestionIn this study, Autologous Conditioned Plasma injection for plantar fasciitis

a. extracorporeal Shockwave Therapyb. conventional treatmentc. corticosteroid injectiond. dry needling

Answer online at me.aapmr.org

40. Ragab EM, Othman AM. Platelets rich plasma for treatment ofchronic plantar fasciitis. Arch Orthop Trauma Surg 2012;132:1065-1070.

41. Finnoff JT, Fowler SP, Lai JK, et al. Treatment of chronic tendinopathywith ultrasound-guided needle tenotomy and platelet-rich plasma in-jection. PM R 2011;3:900-911.

This CME activity is designated for 1.0 AMA PRA Category 1 Credit� andcan be completed online at me.aapmr.org. Log on to www.me.aapmr.org,go to Lifelong Learning (CME) and select Journal-based CME from thedrop down menu. This activity is FREE to AAPM&R members and $25 fornon-members.

was found to be superior to: