Platelet-Rich Plasma Efficacy Versus Corticosteroid Injection Treatment for Chronic Severe Plantar Fasciitis

Abstract

519778FAIXXX10.1177/1071100713519778Foot & Ankle InternationalMonto 

research-article2013 

Article 

Platelet-Rich Plasma Efficacy Versus  Corticosteroid Injection Treatment for  Chronic Severe Plantar Fasciitis 

Raymond Rocco Monto, MD1 

Abstract 

Foot & Ankle International® 

2014, Vol. 35(4) 313–318 

© The Author(s) 2014 

Reprints and permissions: 

sagepub.com/journalsPermissions.nav DOI: 10.1177/1071100713519778 fai.sagepub.com 

Background: Chronic plantar fasciitis is a common orthopedic condition that can prove difficult to successfully treat. In  this study, autologous platelet-rich plasma (PRP), a concentrated bioactive blood component rich in cytokines and growth  factors, was compared to traditional cortisone injection in the treatment of chronic cases of plantar fasciitis resistant to  traditional nonoperative management. 

Methods: Forty patients (23 females and 17 males) with unilateral chronic plantar fasciitis that did not respond to a  minimum of 4 months of standardized traditional nonoperative treatment modalities were prospectively randomized and  treated with either a single ultrasound guided injection of 3 cc PRP or 40 mg DepoMedrol cortisone. American Orthopedic  Foot and Ankle Society (AOFAS) hindfoot scoring was completed for all patients immediately prior to PRP or cortisone  injection (pretreatment = time 0) and at 3, 6, 12, and 24 months following injection treatment. Baseline pretreatment  radiographs and MRI studies were obtained in all cases to confirm the diagnosis of plantar fasciitis. 

Results: The cortisone group had a pretreatment average AOFAS score of 52, which initially improved to 81 at 3 months  posttreatment but decreased to 74 at 6 months, then dropped to near baseline levels of 58 at 12 months, and continued  to decline to a final score of 56 at 24 months. In contrast, the PRP group started with an average pretreatment AOFAS  score of 37, which increased to 95 at 3 months, remained elevated at 94 at 6 and 12 months, and had a final score of 92  at 24 months. 

Conclusions: PRP was more effective and durable than cortisone injection for the treatment of chronic recalcitrant cases  of plantar fasciitis. 

Level of Evidence: Level I, prospective randomized comparative series. 

Keywords: platelet-rich plasma, PRP, cortisone injection, plantar fasciitis, heel pain

Chronic plantar fasciitis is a common orthopedic problem  that affects 10% of the population.44,45,50 It can be difficult  to treat in severe cases and represents an extensive annual  economic burden with direct costs to third party payers in  the United States estimated at up to $376 million in 2007.56 

The pathophysiology remains poorly understood, but  appears similar to Achilles tendinopathy with microscopic  degenerative injury and local disruption of the collagen  matrix and microtears rather than a failed healing response.5 

The presence of erratic blood flow with zones of hypovas cularization and hypervascularization also plays a role in  the disease process.25,29 Clinical findings of chronic plantar  fasciitis include local tenderness and associated stiffness  due to soft tissue tightness and contracture with common  patient complaints of morning pain and heel discomfort  with initiation of ambulation.57 

A myriad of nonoperative and operative approaches  have been utilized without uniform or reproducible suc cess. Nonoperative approaches include rest, heel cups,  

stretching, orthotics, immobilization, nonsteroidal and  steroidal anti-inflammatory medication, and physical ther apy.57 Cortisone usage, autologous blood injection, and  extracorporeal shock wave therapy have also been used  with variable success.1,6,13,27,30,58 Because traditional non operative management of chronic plantar fasciitis still  fails in 10% to 15% of patients, numerous surgical treat ments have been explored including, open, endoscopic  and percutaneous fascial release with varying clinical out comes.8,24,57 Concerns regarding increased stresses on the  ligaments and bones of the midfoot and forefoot resulting  from surgical release of the plantar fascia persist. MRI and  

1Nantucket Cottage Hospital Partners Healthcare System, Nantucket,  MA, USA 

Corresponding Author: 

Raymond Rocco Monto, MD, Nantucket Cottage Hospital, 57 Prospect  St, Ste 122, Nantucket, MA 02554, USA.  

Email: drmonto@hotmail.com 

314 Foot & Ankle International 35(4) ultrasound techniques have proven useful in assessing the response of plantar fascial injuries to various operative and nonoperative approaches in an objective, quantifiable, comparable, and reproducible manner.41,46,57 

Recently, platelet-rich plasma (PRP) has been proposed as a potential treatment for chronic plantar fasciitis. PRP is a bioactive component of whole blood with concentrations of platelets above baseline values.9,22,32,60 

Platelets play a critical role in the normal injury repair cycle of the body as well as modulating intercellular communication.3,9,22 The platelets secrete a wide variety of cytokines and growth factors that act as chemo-attractants for reparative cells.2,3,9,14 These agents include platelet derived growth factor (PDGF), transforming growth factor-beta 1 (TGFB-1), fibroblast growth factor (FBGF), vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), insulin-like growth factor (IGF), hepatocyte growth factor (HGF), and connective tissue growth factor (CGF). These growth factors modulate neovascularization and angiogenesis, promote mitogenesis, boost local collagen production, and provide anti-inflammatory effects by blocking cylco-oxygenase-2 (COX-2) enzyme production.2,3,7,9,14,15,18,34,36,53 

The different cellular sizes and densities among platelets, red blood cells, and white blood cells allow their isolation through centrifugation.22 By mechanically concentrating the level of platelets to levels 7 to 10 times baseline by simple centrifugation of whole blood, correspondingly high levels of these growth factors are   obtained.14,22,34,37 Levels of PDGF in PRP can range have  

been measured as high as 25× baseline value, while EGF,  TGF-beta, and VEGF levels can rise to 10× baseline  depending on the system used.2,14,17,22 These findings  have led to the use of PRP as a vector to deliver growth  factors to local muscle and tendon injury and repair zones  to induce and accelerate healing.2,3,9,14,18,19,23,36,38,51-53,55,59 PRP was first used in dental, maxillofacial, and plastic  surgery in the early 1990s and more recently to promote  anastomotic healing in coronary bypass surgery.22,32 

Recently, PRP has shown promise in the treatment of vari ous 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 ten don disorders.2,4,10-12,14-16,20,21,26,37,39,40,42,43,47-49,54 

Methods 

Forty patients with chronic unilateral plantar fasciitis who  had failed extensive traditional nonoperative management  were randomized into 2 groups for prospective treatment  and evaluation. Group 1 was treated with a single ultra 

sound guided (General Electric LOGIC Book XP) injection  

Figure 1. (a) Plain radiograph of calcaneus with typical adaptive  spur formation. (b) T2-weighted MRI image demonstrating  typical findings of plantar fasciitis with plantar fascial thickening,  tearing, spur formation, and reactive bone edema.

of 40 mg DepoMedrol cortisone (Pharmacia & Upjohn Co,  New York, NY), and group 2 was treated with a single ultra sound guided injection of autologous PRP. For the purposes  of this study, chronic refractory plantar fasciitis was defined  as those patients who had experienced at least 4 months of  heel pain despite a standardized trial of traditional nonop erative treatment including rest, physical therapy (minimum  6 weeks), silicone heel lifts (minimum 4 weeks), CAM  walker bracing or cast immobilization (minimum 4 weeks),  night splinting (minimum 4 weeks), and nonsteroidal medi cation. All patients were screened with plain radiographs  and MRI to confirm the diagnosis of plantar fasciitis  (Figures 1a and 1b). 

All patients gave informed consent and the study was  approved by an institutional review board. The PRP prepa ration system used in this study was the Accelerate Sport  Platelet Concentration System (Exactech, Inc, Gainesville,  FL). In this study a 27 cc venous blood sample was obtained  from the patient and mixed with 3 cc of anticoagulant citrate  

Monto 315

Figure 3. Graph demonstrating the clinical superiority of PRP  

versus cortisone for severe chronic Achilles tendinosis over a  

2-year period (P = .001, 95% CI).

Figure 2. Single-entry-point ultrasound-guided needle  

placement technique. 

dextrose solution formula A (ACD-A) to prevent clotting of  the sample. This sample was then centrifuged at 2400 rpm  for 12 minutes using a soft spin (zero braking) technique to  minimize mechanical damage to the platelets. A 3 cc PRP  unbuffered and unactivated isolate was then obtained from  the “buffy coat” of the centrifuged blood sample. With the  patient lying in a supine (Figure 2) position, the injury zone  was prepped in both groups using 2% chlorhexadine gluco nate/70% isopropyl alcohol and then a local anesthetic field  block was performed by the same individual in all cases  using a 23 gauge needle with a total of 6 cc of 0.5%  Marcaine (bupivicaine; Hospira, Lake Forest, IL). The  block was placed medially with 2 cc of 0.5% Marcaine  injected into the skin, 2 cc into the fascial tissue, and 2 cc  into the periosteum of the medial calcaneal tubercle.  Following injection with either PRP or DepoMedrol into  the injury site, patients were placed into a cam walker  brace for 2 weeks and allowed to return to activities as tol erated along with a daily home eccentric exercise (Swedish  heel drop program) and calf/arch stretching regimen.  Nonsteroidal anti-inflammatory use was not permitted dur 

ing the first 2 weeks after treatment and was discouraged  throughout the entire study period. No other treatment  modalities were used during the study. Interval AOFAS  hindfoot scoring data and physical examinations were com 

pleted by an investigator blinded to the treatment modality  immediately prior to injection, then repeated at 3, 6, 12, and  24 months after treatment. 

Statistical Analysis 

All data analysis was completed using a pre-established  plan with categorical values being compared using a  Pearson chi-square test. Pretreatment continuous variables  

were compared using the Student t test. The AOFAS scores  were compared with an analysis of variance with the  repeated measurements test. The level of clinical signifi cance was set at P = .05 with a confidence interval of 95%  for all tests. 

Results 

The cortisone group included 9 males and 11 females with  an average age of 59 (range, 24 to 74) years. Symptoms  averaged 5.4 (range, 4 to 24) months in duration prior to  treatment. The cortisone group had a pretreatment average  AOFAS score of 52 (range, 24 to 60), which initially  improved to 81 (range, 56 to 90) at 3 months posttreatment,  but decreased to 74 (range, 54 to 87) at 6 months, returned  to near baseline levels of 58 (range, 45 to 77) at 12 months  posttreatment, and had a final 24 posttreatment score of 56  (range, 30 to 75). The PRP group had 8 males and 12  females with an average age of 51 (range, 21 to 67) years.  They averaged 5.7 (range, 4 to 26) months of symptoms  prior to treatment. 

In contrast to the cortisone group results, the PRP group  started with an average pretreatment AOFAS score of 37  (range, 30 to 56), which increased to 95 (range, 88 to 100)  at 3 months, remained elevated at 94 (range, 87 to 100) at  6 months, was 94 at 12 months (range, 86 to 100), and had  a final 24-month posttreatment score of 92 (range, 77 to  100) (Figure 3). The difference between the posttreatment  AOFAS scoring results of the cortisone and PRP groups  was clinically significant (P = .001, 95% CI) at 3-, 6-, 12-,  and 24-month follow-up evaluations. The duration of symp toms prior to injection treatment did not have any clinically  significant impact on the results in either group. 

Although some variance was seen among height, weight,  and body mass index (BMI) among the groups, the differ ences did not reach statistical significance. The male  

316 Foot & Ankle International 35(4)  

patients in the PRP group averaged 182.6 cm in height  (range, 175.3-190.5) and 98.6 kg in weight (range, 77.1- 127.0) and had an average BMI of 29.5 kg/m3 (range, 25.1- 36.9). The male patients in the cortisone group averaged  182.9 cm in height (range, 157.5-200.6) and 89.9 kg in  weight (range, 73.0-115.7) and had an average BMI of  27.87 kg/m3 (range 23.0-29.9). The female patients in the  PRP group averaged 170.5 cm in height (range, 152.4- 195.6) and 70.8 kg in weight (range, 72.6-108.9) and had an  average BMI of 29.2 kg/m3 (range, 25.1-34.0). The female  patients in the cortisone group averaged 165.5 cm in height  (range, 160.0-170.2) and 70.4 kg in weight (range, 68.0- 95.3) and had an average BMI of 30.6 kg/m3 (range  23.5-35.0). 

Discussion 

The successful use of PRP formulations to treat chronic ten dinopathies led to its application in treating severe cases of  plantar fasciitis.1,28,31,41 Lopez-Gavito et al surveyed a small  group of patients with a minimum of 12 months of severe  chronic plantar fasciitis and/or Achilles tendinosis and  noted AOFAS hindfoot score improvement from 39 to 97  by a month and average Visual Analogue Scale (VAS) pain  scores dropping from 9 to 2 after PRP treatment.28 No con trol group was provided in this investigation. In another  small, nonblinded preliminary study without a control  group, Martinelli et al used 3 weekly injections for chronic  plantar fasciitis and noted average VAS scores decreased  from 7.1 to 2.1 after 12 months with excellent final results  

in 9 patients, good results in 4, and poor in 1.31 Ragab and Othman followed a group of 25 patients with  chronic plantar fasciitis treated with PRP without a con trol group for an average of 10.3 months and documented  VAS score improvement from 9.1 to 1.6.41 Prior to treat ment 72% of their patients noted severe activity limita tions, while 28% were moderately limited, but after PRP  treatment 92% had little or no noticeable limitations.  Ultrasonography demonstrated decreased plantar fascial  thickening after PRP treatment but no control group was  provided in that study. 

In the only controlled study other than ours comparing  PRP and cortisone treatment of chronic plantar fasciitis,  Akashin et al prospectively examined 60 patients who had  failed 3 months of conservative care.1 The patients were  treated in 2 nonrandomized consecutive groups of 30 with  either 40 mg methylprednisolone or 3 cc of PRP and then  followed for 6 month months posttreatment. Mean VAS  scores improved from 6.2 to 3.2 in the steroid group and  7.33 to 3.93 in the PRP group after 6 months. 

In our single-blinded, prospective, randomized, longi tudinal case series, the use of local PRP injection proved  more successfully than cortisone injection in the long term management of severe chronic plantar fasciitis in  

cases where prolonged traditional nonoperative treatment  had failed. The likely mechanism of this effect is the  release of growth factors and chemoattractants from the  highly concentrated platelets in the plantar fascial injury  zone.6,9,22,37,38,59 These platelet nests may act as rally points  for the local recruitment of macrophages and fibroblasts to  gradually repair the damaged collagen of the tendon fol lowing platelet activation. This can lead to modulation of  angiogenesis and local blood flow to assist correction of a  failed healing response.15,25 Collagen processing is  improved with the in-migration of fibroblasts.17,39 The  finding that the majority of improvement seen in our  patients occurred in the first month following the PRP  injection suggests an early anti-inflammatory effect pos sibly due to the inhibition of cyclo-oxygenase-2 (COX-2)  enzymes by the cytokines in PRP.22,53 The long-term  excellent durability of clinical success in the PRP group in  this 2-year study may be the result of improved collagen  upregulation and neovascularization. 

In contrast to the encouraging results demonstrated in the  PRP group in this study, the cortisone group long-term results  were disappointing. Although initial results at 3 months  postinjection were encouraging, subsequent clinical scoring  at 6, 12, and 24 months quickly degraded. With the number  of subjects available in this study, no significant difference  was noted between the pretreatment and posttreatment results  in the cortisone group after 12 and 24 months. 

The strengths of this study are its randomized and pro spective longitudinal nature, the long length of follow-up,  and its high subject retention rate. The single-blinded nature  of the study is not as optimal as a double blinded study,  however, and this is the primary flaw of the study. 

Since similar injection techniques were used in both  groups, it is unlikely that the long-term clinical success of  PRP treatment over cortisone in this study was due to any  mechanical effects as described in dry needling or brise 

ment procedures.22 There was difference in the volume of  injection between the study groups with 9 cc in the PRP  group (3 cc PRP + 6 cc block) and 7 cc in the DepoMedrol  group (1 cc DepoMedrol + 6 cc block), but the impact of  this on the study results is uncertain. 

The accelerated healing and recovery seen in the use  of PRP in plantar fasciitis has also been seen in studies  focusing on utilizing PRP to augment Achilles reconstruc tion for full thickness tears.4,18,48 The enhancing effects of  PRP injection have also been demonstrated when used for  chronic tennis elbow and patellar tendonitis management and  following acute muscle injury.9,22,23,26,36-38,52,53,55 Early encour aging results have also been reported in the use of PRP aug mentation for rotator cuff reconstruction, flexor tendon, and  anterior cruciate ligament repair.2,16,17,19,21,25,29,39,40,42,43,54,59 Future research will focus on optimization of the growth  factor concentration in PRP, the effects of white blood cells,  and the systemic results of PRP treatment.33,35,60,61

Monto 317 

Despite the long-term success of PRP in treating these  cases of chronic severe plantar fasciitis, the fundamental  treatment paradigm of rest, ice, eccentric exercise, activity  modification, and selective immobilization is still success 

ful in the majority of patients with mild to moderate dis ease and should not be abandoned. The PRP system used  in this study added approximately $300 per case. Based on  the findings in this report, cortisone injection can be  expected to provide only temporary relief from the symp toms of plantar fasciitis and is unlikely to improve long 

term clinical results in the treatment of this condition. In conclusion, this is the first study to demonstrate that  platelet rich plasma can provide successful longer term  treatment of severe chronic plantar fasciitis in patients who  have failed to respond to traditional nonoperative manage ment techniques. The use of PRP in these difficult situa tions seems far more efficacious than the traditional  treatment of cortisone injection and appears safer than sur gical alternatives. 

Declaration of Conflicting Interests 

The author declared the following potential conflicts of interest  with respect to the research, authorship, and/or publication of this  article: The author is a consultant for Exactech, Inc, Gainesville, FL. 

Funding 

The author received no financial support for the research, author ship, and/or publication of this article. 

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  34. Zavadil D, Satterlee C, Costigan J, et al. Autologous platelet  gel and platelet-poor plasma reduce pain with total shoulder  arthroplasty. JECT. 2007;39:177-182.

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