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MUSCULOSKELETAL REHABILITATION (NA SEGAL, SECTION EDITOR)

PRP: review of the current evidence for musculoskeletal

conditions

Gerard A. Malanga •Michael Goldin

Published online: 25 January 2014

Springer Science + Business Media New York 2014

Abstract Injection of platelet-rich plasma (PRP) is an

evolving treatment option for various musculoskeletal

injuries. There is basic scientific evidence that suggests that

the various growth factors present in PRP can help to

augment the body’s natural healing. There are also clinical

studies suggesting efficacy for several conditions, particu-

larly tendinopathy and osteoarthritis. This article reviews

the definition and first uses of PRP, the basic scientific

rationale for its use, and the basic science and evidence for

its use in the treatment of tendon, joint, ligament, and

muscle injuries. There are varying levels of evidence for

and against the use of PRP for these types of injuries, and

this article reviews studies that support as well as studies

that refute the use of this new treatment. There are several

studies that have assessed the basic science supportive of

PRP treatments, as well as the clinical efficacy of this

treatment in vivo. While the current evidence is mixed,

several recent studies have demonstrated therapeutic ben-

efit in the treatment of various tendinopathies and degen-

erative joint diseases of the knee. There are several factors

that need to be addressed to elucidate whether PRP is truly

effective. These include fully defining the PRP mixture

(e.g. concentration, growth factor levels, presence of white

cells and red cells, etc.), determining the optimal prepara-

tion and delivery of the PRP graft, calculating the

appropriate number of injections for each specific patho-

logic process, and defining optimal post-procedure

rehabilitation.

Keywords PRP Tendinopathy Treatment Arthritis 

Growth factors

Introduction

Platelet-rich plasma (PRP) has evolved as a treatment

option for a variety of orthopedic conditions over the past

decade. PRP treatments have historically been used in

cardiac and dental procedures in humans. Since these ini-

tial uses, it has been used in a variety of musculoskeletal

conditions in humans over the past 10 years. Initial studies

were directed at treatment of chronic, refractory tendin-

opathy, in particular chronic tennis elbow pain. Over the

past decade, its use has been expanded to treating a variety

of other musculoskeletal conditions including ligament

injuries, muscle tears, and osteoarthritis.

In this article, we will review the current evidence

regarding PRP for musculoskeletal injuries. We will first

review the basic science of PRP and the rationale for its use

in tendinopathy and other musculoskeletal conditions. This

review will primarily focus on the evidence specifically for

non-invasive management of pathologic processes involv-

ing tendons, joints, ligaments, and fibro-cartilaginous

structures.

Definition

PRP has been defined as a volume of autologous plasma

that has a platelet concentration above baseline [1]. The

G. A. Malanga M. Goldin

New Jersey Sports Medicine, LLC, New Jersey Regenerative

Institute, New Brunswick, NJ, USA

G. A. Malanga (&)M. Goldin

Department of Physical Medicine and Rehabilitation, Rutgers

University-New Jersey Medical School, New Brunswick, NJ,

USA

e-mail: gerardmalanga@gmail.com

123

Curr Phys Med Rehabil Rep (2014) 2:1–15

DOI 10.1007/s40141-013-0039-5

process of concentrating the platelets necessitates two sets

of centrifugation, one after the other. The first spin (a hard

spin) separates the red blood cells from the plasma, the

latter of which contains platelets, white blood cells, and

clotting factors [1]. The second spin (a soft spin) finely

separates the platelets and white blood cells, together with

a few red blood cells [1]. In 2003, Weibrich et al. [2] felt

that the optimum platelet concentration in PRP to have a

positive effect on bone regeneration was around 1 million

platelets/microliter (ll), and above that, there was an

inhibitory effect on healing. However, several recent arti-

cles have produced different conclusions about ideal

platelet count and challenged these initial theories. Giusti

et al. found the optimal platelet concentration for angio-

genesis was 1.5 million/ll (5–79baseline). Lower levels

produced less angiogenesis, and inhibition was not noted

until levels reached 2–3 million/ll (109baseline) [3].

Finally, Kevy documented that the ideal platelet concen-

tration is 1.5 million/ll (5–79baseline) and could be as

high as 3 million/ll (109base-line). Kevy and Jacobson

[4] also noted that current commercially available PRP

devices could not attain levels higher than 109baseline

levels.

First uses

In 1987, Ferrari et al. [5] used autologous PRP and red

blood cell concentrates as an autologous transfusion for

support of cardiac surgery patients in 15 operations. No

homologous blood products were required. In 1990, Del-

Rossi et al. [6] showed that in patients undergoing heart

operations on cardiopulmonary bypass, PRP-infused

patients required 65 % less banked blood products com-

pared to patients not receiving this infusion. In 1998, Marx

et al. [7] assessed PRP and its effect on increasing the rate

of bone graft maturity of dental implants compared to a

control group. This study demonstrated that an average

concentration of 338 % of baseline platelet count resulted

in greater trabecular bone density relative to bone grafts

that were not augmented with PRP [7].

Rationale for use of PRP

Platelets have several components that may help to aug-

ment healing. Dense granules within the platelets have

compounds that influence cell migration, cell proliferation,

and vascular tone [8]. They contain several types of

granules, each with different components and various roles

in platelet activities. These granules include dense gran-

ules, alpha granules, lysosomal granules, etc. Alpha gran-

ules have several proteins with various functions including

platelet-derived growth factors (PDGF) such as PDGFaa,

PDGFbb, and PDGFab; TGFb1 and TGFb2; vascular

endothelial growth factor (VEGF), transforming growth

factor beta (TGFB), insulin-like growth factor (IGF), vas-

cular endothelial growth factor (VEGF), basic fibroblast

growth factor (BFGF), and epithelial growth factor (EGF).

The functional groupings of these proteins include adhe-

sive proteins, clotting factors, fibrinolytic factors, prote-

ases, growth factors, cytokines, basic proteins, anti-

microbial proteins, and membrane glycoproteins [8].

PDGF and epidermal growth factors are present in ten-

dons during the tendon healing process [9]. TGFbhas been

shown to increase type I and type III collagen production in

tendon sheath cells, epitenon cells, and endotenon cells [10].

Marui et al. [11] showed that TGFb-1 increased collagen and

non-collagen protein synthesis in the medial collateral liga-

ment and anterior cruciate ligament fibroblasts in a dose-

dependent manner. Koch et al. [12] studied TGFb-1 in mice,

finding that the release of this growth factor from platelets

and macrophages may actually increase inflammation and

slow wound closure. In the early stages of inflammation,

matrix metalloproteinases activate TGFb-1 from macro-

phages, which acts as a chemoattractant for neutrophils [11]

and, later on in the process, promotes tissue repair [13].

In contrast, in a study using a mouse model, TGFb-3

was found to progressively decrease during the onset of

osteoarthritis [14]. However, TGFb-3 was found to be

strongly expressed in chondrocyte clusters just prior to

osteophyte formation [12]. In a human model, Verdier

et al. [15] demonstrated that TGFb-1 had decreased

expression in degraded cartilage. However, in osteophytes,

there was a marked increase in expression of TGFb-1 and

TGFb-3. This research suggests that these growth factors

have different functions depending on the stage of degen-

eration of the joint. Marui et al. [11] also showed that

BFGF administration was not associated with an increase

in collagen or non-collagen protein synthesis.

VEGF has been shown to be increased by day 7 after

acute tendon injury, and new vessel length and density has

been shown to peak at 17 days after acute injury [16].

Daily injections of epidermal growth factor have been

shown to increase the extent and organization of granula-

tion tissue [17]. IGF has been shown to increase the syn-

thesis of proteoglycan, collagen, and non-collagen proteins

[18]. Phornphutkul et al. [19] showed that IGF-1 promotes

chondrocyte proliferation and differentiation.

PRP duration of effect

Prior literature has suggested that once platelets are acti-

vated by clotting, 70 % of the stored growth factors are

released after 10 min, and almost all stored growth factors

2 Curr Phys Med Rehabil Rep (2014) 2:1–15

123

are released within 1 h of injection [1]. The platelets can

then synthesize and secrete growth factors for about

8 days, until the platelets die [1].

Various factors should be weighed when considering the

use of PRP and when reviewing prior research of PRP.

These include platelet concentration, leukocyte count, pH

of the injected substance, use of activators, the total number

of injections given, and the method of delivery and the type

of post-procedure rehabilitation protocol [20]. In particular,

the post-procedure rehabilitation has ranged from activities

as tolerated to full immobilization. A suggested post-reha-

bilitation program was present in the paper based on the

known healing patterns of most tissues with progressive

loading of the tissues through the various phases following

PRP procedures. This generally allows for full activities at

the 6–8 week time-frame following injection [20].

The components of PRP have also been examined to

assess if certain compositions have a better healing profile.

Dragoo et al. [21] showed that leukocyte-rich PRP had a

greater inflammatory response relative to leukocyte-poor

PRP at post-injection day 5, but there was no difference at

day 14. McCarrel et al. [22] demonstrated that leukocyte-

reduced PRP had decreased levels of tumor necrosis factor

alpha and interleukin 1 beta relative to standard PRP, high-

concentration PRP, and concentrated-leukocyte PRP.

Evidence regarding use of PRP for tendinopathy

Basic science

De Mos et al. [23] showed that both platelet-rich clot releasate

(PRCR) and platelet-poor clot releasate (PPCR) increased

tenocyte cell number and collagen production in vitro. In this

study, PRP was ‘‘activated’’ by placing calcium chloride into

the PRP concentrate to induce the platelets to clot and to

release their growth factors. Some limitations of this study are

that the tendons were from young donors, and the fact that this

experiment was performed in vitro and, therefore, may not be

applicable in vivo. Additionally, this PRCR was not autolo-

gous, but rather the PRCR was from a different donor source

than the tendons. Wang et al. [24] demonstrated that PRCR

can promote human tenocyte proliferation and promote col-

lagen synthesis. Bosch et al. [25] performed a study in which

they surgically created lesions in the superficial digital flexor

tendons of horses. They then used a commercially available

PRP system, Biomet, to create 3 ml of therapeutic injectate.

Ultrasound guidance was used to place either the PRP or the

control in the lesion. They demonstrated that there was sta-

tistically significant improvement in collagen, glycosamino-

glycan, and DNA content in the PRP-treated tendons relative

to the controls. In addition, the repair tissue showed higher

strength failure and better collagen organization relative to

the control tendons. One of the limitations of this study was

that the lesion was created artificially by acutely inducing

mechanical damage. This differs from the more clinically

relevant incidence in humans in which repetitive overuse

injury is primarily the etiology for tendon damage [25].

Zhang and Wang [26] showed that PRCR promotes the dif-

ferentiation of tendon stem cells into active tenocytes. This

experiment was performed in vitro, and used PRP that was

activated with calcium chloride to form the PRCR. These

tenocytes had increased collagen production relative to con-

trol cells treated only with autologous serum. Furthermore,

this showed that PRCR did not induce cells to turn into ‘‘non-

tenocytes’’. This was significant, because it demonstrated that

PRCR would not change tendon cells into non-tendon cells,

potentially exacerbating a tendinopathy. Strengths of this

study included that autologous serum was used on the tendon

stem cells. Limitations of this study include that healthy

tendon stem cells from young rabbits were used, and this may

not be applicable to subjects with older tendons. Additionally,

these experiments were performed in vitro; therefore, the

tendons were not subjected to the mechanical loading that

occurs in vivo [26]. Platelet concentrate was found to

improve Achilles tendon repair callus strength for 3 weeks

after surgical transection in an experimental rat model. This

experiment used heterologous PRCR activated by thrombin.

The PRCR was obtained from one group of rats and was

injected into different rats with surgically induced lesions;

thus, it was not autologous PRCR. Limitations of this study

include the possibility that the measured force that caused

failure of the un-operated tendons may have been underesti-

mated due to the design of the mechanical testing apparatus

[27]. Sadoghi et al. [28] studied whether rotator cuff fibro-

blasts isolated from human subjects would have dose-

dependent increased proliferation when exposed to PRP.

They showed that a concentration of platelets five times that

of plasma had an effect on increasing human rotator cuff

fibroblast proliferation, specifically, increasing the DNA to

glycosaminoglycan ratio (the latter being one of the markers

for tendon degeneration). The onefold and five-fold concen-

trations of PRP had improved DNA to glycosaminoglycan

ratios relative to the ten-fold concentration of PRP. The

limitations of this study include the older age of the patients

(61 years or older), which may have limited both the amount

of growth factors present in the PRP and the regenerative

response of (older) rotator cuff fibroblasts.

Evidence regarding use of PRP for meniscus/cartilage

Ishida et al. [29] demonstrated that PRP had regenerative

effects on meniscal cells in vitro. The PRP was prepared by

doing serial centrifugations at 4 C. Once the PRP was

obtained, it was thawed and then stored at -80 C until ready

for use. Furthermore, in vivo PRP combined with a hydrogel

Curr Phys Med Rehabil Rep (2014) 2:1–15 3

123

had beneficial healing effects on surgically induced meniscal

lesions in a rabbit model. Limitations of this study include

that the lesions were surgically induced, and may therefore

not have similar results in primarily degenerative lesions

[29]. Surgically induced osteochondral defects were treated

in a rabbit model. A polylactic-glycolic acid scaffold was

impregnated with PRP and a thrombin/calcium chloride

solution to activate the PRP. This was then surgically

implanted in the osteochondral defect. Activated PRP-

impregnated polylactic glycolic acid improved osteochon-

dral healing relative to a control group in a rabbit model. This

study included the limitation that the osteochondral defect

was surgically induced, and a traumatic or degenerative

lesion may have a different response to this treatment [30].

Van Buul et al. [31] performed a laboratory study in which

they examined whether PRP releasate (PRPr) could decrease

the effect of interleukin-1 on osteoarthritic chondrocytes.

The PRPr was formed by serial centrifugation of whole blood

from healthy donors, and then activated with calcium chlo-

ride. PRPr decreased multiple inflammatory effects of IL-1

beta on human osteoarthritic chondrocytes in this in vitro

study. Limitations of this study include that the PRPr was not

autologous, and it is questionable whether these in vitro

effects would occur in vivo. Akeda et al. [32] used PRPr

activated with a thrombin/calcium chloride solution to

examine effects on porcine chondrocytes in vitro. This PRPr

administration to chondrocytes resulted in a statistically

significant increase in collagen synthesis and chondrocyte

DNA relative to chondrocytes treated with platelet-poor

plasma releasate or fetal bovine serum. Additionally, the

chondrocyte cells remained phenotypically stable in the

presence of the PRP. Limitations of this study included the

fact that the chondrocytes were pooled from multiple pigs,

and therefore it was not purely autologous PRPr [32].

Evidence regarding use of PRP for muscle injury

In a mouse model, experimentally induced contusion to the

gastrocnemius muscle was treated with a series of three

injections of either autologous conditioned serum (ACS) or

a series of three injections of saline [33]. Histological

evaluation revealed that there was increased myofiber

diameter regeneration and increased satellite cell activation

in the ACS group compared to the control group [33].

Evidence regarding use of PRP for tendinopathy

Lateral elbow/common extensor origin

Mishra and Pavelko [34] examined a cohort of 20 patients

with chronic lateral epicondylosis that had been refractory

to a standardized physical therapy protocol and who had

significant and persistent pain for an average of 15 months.

These patients were all considering surgical treatment.

Fifteen patients were given a single PRP injection, and five

were given a single bupivacaine injection. The PRP in-

jectate was produced by serial centrifugation of autologous

whole blood. No activating agent was used, and the PRP

was buffered to physiologic pH using 8.4 % sodium

bicarbonate solution. The tendon was anesthetized with

0.5 ml of bupivacaine with epinephrine. The outcome

measures that they used were a 100-mm visual analog pain

score (0, no pain; 100, worst pain possible) and a modified

Mayo elbow score (best score, 100). At the 8-week follow-

up, the PRP patients had 60 % improvement in symptoms,

and the bupivacaine group had 16 % improvement in their

symptoms. Three of the five control subjects withdrew or

sought other treatments after 8 weeks. At 6 months’ fol-

low-up, the PRP cohort noted 81 % improvement in the

visual analog pain scores. At final follow-up (an average of

25.6 months), the PRP patients reported 93 % pain

reduction. The limitations of this study include the lack of a

randomized control group, and the small number of

patients. The tendon also had a small amount of bupiva-

caine injected, which can theoretically decrease the effi-

cacy of PRP [35]. It is also important to note that 140

patients were initially evaluated, and only 15 % were

enrolled in the study. This may be viewed as one of the

strengths of this study, as PRP was reserved as a treatment

only for patients with severe tendinopathy that did not

improve with either time or more conservative measures.

Additional strengths include that all patients had also

completed a standardized stretching and strengthening

protocol prior to the injections, and after the injections all

subjects were again given a standardized 4-week stretching

and strengthening program [34].

Peerbooms et al. [36] compared PRP injections to cor-

ticosteroid injections in patients with greater than 6 months

of pain from lateral epicondylitis. One hundred patients

were randomized to receive either a PRP injection or a

corticosteroid injection into the extensor tendon of the

symptomatic elbow. The PRP preparation method involved

serial centrifugations, buffering with sodium bicarbonate

8.4 %, and adding 0.5 % bupivacaine with epinephrine to

the injectate. Success was defined as 25 % improvement in

either VAS score or DASH (Disabilities of the arm,

shoulder, and hand) score, without a re-intervention after

1 year. Using the VAS score, 49 % of the corticosteroid

group and 73 % of the PRP group were successful. Using

the DASH score, 51 % of the corticosteroid group and

73 % of the PRP group were successful. There were sev-

eral strengths of this study. It was double-blind, random-

ized, and controlled. Patients were excluded if they had a

steroid injection into the tendon within the past 6 months.

The subjects were given a graded post-procedure

4 Curr Phys Med Rehabil Rep (2014) 2:1–15

123

rehabilitation including 2 weeks of stretching followed by

2 weeks of eccentric strengthening. The primary outcome

measure, DASH, was a validated upper limb functional

score. Limitations of this study include that the PRP was

combined with a local anesthetic, which may inhibit some

of the beneficial effects of the PRP [35]. Additionally, prior

to the procedure, subjects had been treated with cast

immobilization, a steroid injection, or physiotherapy. All of

the subjects had not definitively undergone a course of

physical therapy and were deemed to have symptoms

recalcitrant to this [36]. This cohort of patients was also

examined at a 2-year follow-up to assess efficacy of the

intervention [37•]. At the 2-year follow-up, with success

defined as 25 % improvement in either VAS score or

DASH score without a re-intervention after 2 years, 65 %

of the PRP group and 35 % of the corticosteroid group had

successful outcomes [37•].

In a prospective, double-blind, randomized trial, 150

patients were randomized to receive either two PRP

injections or two autologous blood injections (ABIs) [38].

Successful outcome was defined as a 25-point improve-

ment on the Patient-Rated Tennis Elbow Evaluation

(PRTEE), which they reported was comparable to other

studies. The authors reported that PRTEE is a well vali-

dated 0–100 composite scale measuring pain and physical

function. At the 6-month follow-up, there was a 66 %

success rate in the PRP group and a 72 % success rate in

the ABI group, with no statistically significant difference

between the two groups [34]. Strengths of this study

include that all the patients had already failed a course of

physical therapy including stretching and eccentric

strengthening. They also had a single practitioner who had

15 years of experience and had performed 20,000 ultra-

sound guided injections perform all the injections. Limi-

tations of this study include that the tendon was bathed in

bupivacaine in both treatment groups, as this can poten-

tially decrease the therapeutic effect [35]. Also, the per-

forming physician was not blinded to the procedure.

Additionally, this study introduces the experiment as

comparing an ABI to a ‘‘moderate yield PRP’’ which they

describe as ‘‘essentially plasma with erythrocytes and

leukocytes removed’’. However, in the methods section,

they describe obtaining the plasma by doing a single cen-

trifugation and then obtaining 1.5 ml from ‘‘the buffy coat

layer’’. In the introduction, they had described the buffy

coat as ‘‘leukocyte-rich, high yield PRP.‘‘ Therefore, one of

these descriptions is inaccurate. Another randomized con-

trolled trial evaluated 28 patients who received either a

single injection of PRP or a single injection of ABI. The

PRP was obtained by performing a single centrifugation of

the whole blood and then the platelet-rich portion was

aspirated. In the analysis of the PRP, they described it as

leukocyte-containing PRP due to histologic analysis

showing leukocytes. Follow-up VAS scores were taken at

6 weeks, 3 months, and 6 months. Changes in VAS scores

and Liverpool elbow scores were used as outcome mea-

sures. They report that the Liverpool elbow score evaluates

range of motion, daily activities, and ulnar nerve function.

There was improvement in both groups at all follow-up

assessments. The only statistically significant difference

between the two groups was a larger reduction in pain

score in the PRP group compared to the ABI group at

6 weeks’ follow-up. They did not report any clinically

significant differences in the two groups [39]. Strengths of

this study include that each subject was given a stretching

and eccentric strengthening exercise program one week

after the injection. Limitations of this study include that it

was single-blind, and the patients were aware which

treatment they were receiving. They also explain that the

Liverpool elbow score evaluates elbow range of motion as

well as the ulnar nerve, which is not usually affected in this

condition. They explain that these two components may

hide clinically significant differences.

Krogh et al. [40•] performed a randomized controlled

trial on 60 patients comparing the effects of a blinded

injection of PRP, saline, or glucocorticoid. The primary

outcome measure was a change in pain using the PRTEE

questionnaire at 3 months post-procedure. For pain

assessment, the PRTEE validated for lateral epicondylitis

was applied. The PRP was processed by performing a

single centrifugation cycle on whole blood, and then the

PRP was aspirated. It was then buffered with 8.4 % sodium

bicarbonate solution. They found that pain reduction was

observed in all three groups, and there was no statistically

significant difference between the groups at a 3-month

follow-up [40•]. They also measured the following sec-

ondary outcomes: ultrasonographic changes in tendon

thickness and color Doppler activity. They reported that

glucocorticoid was more effective than PRP and saline in

both reducing color Doppler activity as well as reducing

tendon thickness. Limitations of this study include that a

local anesthetic was used in the peritendon, and this may

have decreased the therapeutic effect of the PRP [35]. The

authors describe that the initial primary outcome measure

was going to be the PRTEE at 12 months post-procedure.

However, there was significant drop-out during the study in

all 3 groups, and therefore, the primary outcome was

changed to 3 months post-procedure. They also explained

that 60 % of the subjects in the glucocorticoid group were

not naı

¨ve to steroid injection treatment. It was possible that

patients initially treated with glucocorticoid to good effect

would not have been referred for further treatment; there-

fore, it was not surprising that these subjects failed to have

a successful result the second time they were treated with a

steroid injection. Strengths of this study include that all

participants were given a standard stretching and

Curr Phys Med Rehabil Rep (2014) 2:1–15 5

123

strengthening protocol after the procedure [40•]. A careful

review of this study demonstrates the rapid early effects of

corticosteroid injection over the first 6 weeks following

injection, followed by a progressive decline in efficacy.

This contrasts with the slow improvement slope of the PRP

group. At the 3-month mark, the graphical representation

of the responses demonstrates the PRP group continuing a

downward slope of improvement that intersects the

upward, decreasing benefit of the corticosteroid injection.

This pattern (rapid benefit with regression over time) is a

common finding in reviewing the literature on corticoste-

roid injections for tendinopathy [41].

Achilles tendon

In 2010, de Vos et al. [42] published a double-blind, ran-

domized, placebo-controlled trial that was performed on a

group of 54 patients. They used the Victorian Institute of

Sports Assessment-Achilles (VISA-A) as a primary out-

come measure. The authors reported that this is a validated

questionnaire specifically designed for evaluating out-

comes in Achilles tendinopathy. Achilles tendinopathy was

treated with eccentric strengthening exercises and either a

PRP injection or a saline injection. The PRP was prepared

by performing a single centrifugation, and then the injec-

tate was buffered with 8.4 % sodium bicarbonate. This

study showed improvement in both groups, but there was

not a statistically significant difference between the saline

group and the PRP group [42]. Strengths of this study

include the design being double-blinded, randomized, and

controlled. Additionally, all subjects were given a standard

post-procedure rehabilitation protocol. The same physician

performed all the injections. A significant limitation of this

study was their exclusion criteria. They specifically

excluded any patient who had previously completed a

heavy load eccentric exercise program. Therefore, this

injection was performed on patients naı

¨ve to eccentric

strengthening exercises. This goes against a common rec-

ommendation that PRP treatment be performed in tendin-

opathy cases that are recalcitrant to an eccentric

strengthening protocol. In their conclusion, the authors

recommend that PRP treatment not be used in chronic mid-

portion Achilles tendinopathy. In line with their experi-

mental design, it may be more accurate to not recommend

PRP treatment in Achilles chronic mid-portion tendinopa-

thy in patients that are naı

¨ve to eccentric strengthening

exercises. Ultrasonographic tendon evaluation of the same

group of subjects showed no statistically significant dif-

ferences in tendon structure or neovascularization in the

PRP group compared to the saline injection group [43].

One-year follow-up of the same group of subjects did not

show statistically significant differences in VISA-A score

or ultrasonographic appearance of the PRP group compared

to the saline injection group [44•]. It is also noteworthy that

significant improvement occurred in both groups in this

study, and therefore, what lead to those improvements (the

needling itself, the injectate, and/or the eccentric exercise

program) is not clear from this study.

Patellar tendon

In a cohort study of 20 male athletes with a mean history of

20.7 months of patellar tendon pain, a series of 3 PRP

injections to treat patellar tendinopathy was performed to

assess the efficacy of this treatment for this condition [45].

They described that the primary purpose of the study was

to explore PRP for the treatment of chronic patellar tend-

inosis, and to specifically assess adverse events of subjects

before and after treatment. The secondary purpose was to

measure the results of the treatment. The blood went

through two serial centrifugations, and then the PRP was

aspirated. Before each injection, the PRP was mixed with

calcium chloride to activate the platelets. After the first

injection, the patients were allowed to use non-steroidal

anti-inflammatory drugs (NSAIDS) for somewhere

between 24 h up until the second injection. The exact

amount of time for which NSAIDS were permitted was not

clear in the paper. After the second injection, stretching and

mild activities were suggested. After the third injection,

participants were encouraged to begin a strengthening

program. After 1 month they were advised to return to

activities as tolerated. The outcome measures used were

Tegner, EQ-VAS, and SF-36. The mean clinically signifi-

cant difference was set at 15 points. At 6 months’ follow-

up, all parameters of the SF-36 demonstrated both statis-

tically and clinically significant improvement. The EQ-

VAS was also reported to demonstrate statistically signif-

icant improvement. The Tegner score assessment was

described to show a statistically significant improvement in

the patients. They further report that most of the men

returned to the sport with a lower score than their score

prior to their injury. However, the score of most of these

men was not statistically significantly different than their

score prior to their injuries. The strength of this study as

reported was that they did achieve their purpose, which was

to evaluate the safety of their protocol. There were several

limitations to this study. They described the purpose as

primarily looking for adverse events, and therefore the

results of the treatment were only a secondary purpose.

This was a cohort study, and therefore no control group

was present. They allowed the patients to use NSAIDS for

an inexact period of time for pain control between the first

and second injections, which could have inhibited some of

the therapeutic effect. The patients had tried a variety of

6 Curr Phys Med Rehabil Rep (2014) 2:1–15

123

treatments prior to these injections, but none of these prior

treatments was common to all the participants. This pro-

tocol also involved a series of three PRP injections. These

injections can be several hundred dollars each, and the cost

of three injections may be prohibitive to a large portion of

patients [45].

Filardo et al. [46] performed a cohort control study in

order to assess the therapeutic effect of three PRP injec-

tions in patients with chronic tendinopathy. They compared

a group of 15 patients who received a series of 3 PRP

injections for patellar tendinopathy to a group of 16

patients treated primarily with physical therapy. The blood

was put through two serial centrifugations, and then the

PRP was aspirated. The PRP was mixed with calcium

chloride prior to injection in order to activate the platelets.

They reported that Tegner, EQ-VAS, and pain scale were

used as outcome measures. The authors did not specifically

explain how they chose to use these particular outcome

measures. At 6-month follow-up, there was not a difference

in EQ-VAS or pain scale between the two groups. The

authors did report that the PRP group did achieve a greater

improvement in sport activity level relative to the control

group. This study had several limitations. The control

group had not had a course of physical therapy prior to

their intervention; thus, the two groups had a different pre-

intervention treatment regimen. Furthermore, the study was

neither blinded nor randomized [46].

De Almeida et al. [47] discussed that sports injuries

have heterogeneity of lesions, which makes it difficult to

compare efficacy of treatments in prospective randomized

trials. They also reviewed basic science literature that

showed PRP improved the mechanical properties of a

rabbit’s patellar tendon after resection of its central portion

[48]. Therefore, they used the patellar tendon harvest site

as an experimental model to assess the effect of PRP on

patellar tendon healing in humans in a prospective, ran-

domized, evaluator-blinded study. The primary outcome

was magnetic resonance imaging (MRI) assessment of

patellar tendon harvest site healing. Secondary outcomes

were functional and clinical evaluations of ACL recon-

struction with a patellar tendon graft to examine whether

adding PRP to the harvest site affects the clinical and

functional outcomes of the procedure. PRP was obtained

by using a cell separator with a specific kit for platelet

apheresis in the operating room simultaneously with ACL

reconstruction. Calcium chloride was added to one of the

vials of PRP to activate the platelets. With regards to the

primary outcome, PRP treatment to the patellar tendon

harvest site for ACL graft harvesting showed a smaller

tendon gap at 6 months relative to a control group [47]. On

the Tegner questionnaire, both groups had worse results.

When comparing the questionnaire scores of the two

groups, there was no statistically significant difference.

Notably in this study, due to the method of obtaining PRP,

30–50 ml of PRP was obtained for each patient. There

were several strengths of this study. A single surgeon

performed all the procedures. There was a standard defect

in the central portion of the patellar tendon, therefore the

authors could compare patellar tendon harvest site healing

after a standardized and well-established procedure. A

single musculoskeletal trained radiologist performed all the

blinded MRI evaluations. All subjects followed the same

rehabilitation protocol. Limitations of this study included

that post-procedure analgesic medications included keto-

profen, and this may have blunted the therapeutic efficacy

of the PRP [35]. Additionally, the surgeon performing the

procedures was not blinded to the two treatment groups.

A randomized controlled trial of 46 athletes compared

the treatment of patellar tendinopathy with either 2 PRP

injections or 3 sessions of focused extra-corporeal shock

wave (ECSW) therapy [49•]. The PRP was obtained by

performing a single centrifugation of whole blood, and the

PRP was then collected and stored until ready for injection.

The outcome measures were the Victorian Institute of

Sports Assessment–Patella (VISA-P) questionnaire, the

pain visual analog scale (VAS) during five single-legged

squats on the affected knee, and a modified Blazina scale.

The authors report VISA-P is the only published clinical

scale validated for patellar tendinopathy. Using the VISA-P

scale, there was statistically significant improvement in the

PRP group relative to the ECSW group at 6 months (PRP—

I86.7 [SD =14.2], ECSW—73.7 [19.9], P=0.014) and at

12 months (PRP—91.3 [SD =9.9], ECSW—77.6 [19.9],

P=0.026) [49•]. At 6- and 12-month follow-ups, there was

a greater improvement in VAS scores after 5 single-legged

squats in the PRP group compared to the ECSW group. At a

12-month follow-up, there was also a greater improvement

in the modified Blazina scale in the PRP group relative to

the ECSW group. Strengths of this study include that the

same physician performed all the procedures. They also

avoided the use of anesthetics in both treatment groups.

Limitations of this study include that the patients were not

blinded to the intervention, and it was not placebo-con-

trolled. It is possible that awareness of the treatment

modality may have had some effect on the patients’ per-

ception of their response to the treatment.

In the multi-center, retrospective study by Mautner et al.

[50], the patellar tendon was found to be the most difficult to

treat, with greater than 50 % or more improvement noted in

only 59 % of patients treated for chronic patellar tendinopathy.

Rotator cuff tendinopathy

Bergeson et al. [51] performed an observational cohort

study on 16 patients with at-risk arthroscopic rotator cuff

Curr Phys Med Rehabil Rep (2014) 2:1–15 7

123

repairs to determine the effect of platelet-rich fibrin matrix

(PRFM) augmentation on healing rates and functional

outcome scores. They used an algorithm to determine

patients with a rotator cuff tear that was at risk for a re-tear.

They used a retrospective control group of 21 patients that

had been operated on by the same group of surgeons per-

forming the PRP-augmented repair. The PRFM was cre-

ated by performing serial centrifugations on autologous

whole blood. The second centrifugation was done with

calcium chloride added, in order to initiate the fibrin clot-

ting cascade. Several functional outcome scales were used

to assess functional improvement in the two groups. These

included the American Shoulder and Elbow Surgeons

system (ASES), the Constant system, the University of

California at Los Angeles (UCLA) system, the Western

Ontario Rotator Cuff Index (WORC), and Single Assess-

ment Numeric Evaluation (SANE). There was no statisti-

cally detectable difference between the PRFM group and

the retrospective control group with respect to postopera-

tive functional scores. MRIs were also performed at 1 year

post-surgery in all patients except three. The percentage of

re-tears in the PRFM group was 56 %, and in the historical

control group was 38 %. This difference reached statistical

significance (P=0.024). Weaknesses of this study include

no randomization and the inherent selection bias due to the

use of an historical control group. There was heterogeneity

of repair technique, which may have also influenced the

results. The mean follow-up time for the PRFM group

functional scores was 13 months, and the mean follow-up

time for the historical control group functional scores was

27 months, which also may have introduced bias.

Rodeo et al. [52] performed a randomized trial on 79

patients undergoing surgical repair of full-thickness rotator

cuff tears. Forty patients received the experimental treat-

ment, which was surgical repair augmented with PRFM,

and 39 patients received surgical repair without augmen-

tation. The primary outcome measure was ultrasonographic

evidence of postoperative tendon healing at 6 and

12 weeks. Secondary outcomes included standardized

shoulder outcome scales and strength measurements. The

standard postoperative rehabilitation regimen was pre-

scribed in all patients. The authors report that the PRFM

was made intra-operatively by obtaining peripheral venous

blood at the start of the case. They report that they used a

second centrifugation and added calcium chloride during

this step in order to activate the fibrin-clotting cascade. At

6 weeks, 30 of 36 (83 %) rotator cuff tendons were intact

in the control group, and 28 of 34 (82.4 %) rotator cuff

tendons were intact in the PRFM group (P=0.913). At

12 weeks, 25 of 31 (80.6 %) rotator cuff tendons were

intact in the control group, compared with 24 of 36

(66.7 %) in the PRFM group (P=0.198). Strengths of this

study included that the evaluating sonographer was blinded

to which treatment each patient received. Weaknesses of

this study include that the surgeons performing the proce-

dure were not blinded to which patients were receiving the

PRFM augmentation. The follow-up points were also rel-

atively soon after the surgery.

In a prospective cohort study, 42 patients had arthro-

scopic repair of full-thickness rotator cuff tears, either with

or without PRP to augment the surgery [53]. The patients

made the decision whether or not they wanted to have PRP

used. The PRP was obtained by using a plateletpheresis

system with a leukoreduction set. In order to form a gel,

calcium gluconate was added to the PRP. After the medial

row of sutures were threaded, the PRP gel was applied. The

outcome assessments included pain, ROM, strength, and

functional scores and overall satisfaction at periodic

intervals up to 16 months. Several functional scales were

used: American Shoulder and Elbow Surgeons system, the

Constant system, the University of California at Los

Angeles (UCLA) system, the Disabilities of the Arm,

Shoulder and Hand (DASH) system, the Simple Shoulder

test, and the SPADI. The majority of functional scores

showed no significant difference at any of the follow-up

time periods, with the exception of the 3-month follow-up.

At this point, the ASES score, the Constant score, and the

SPADI score showed increased functional improvement in

the control group. Additionally, the authors commented

that the PRP group had a lower re-tear rate—26.7 %

compared to 41.2 %; however, they report that this was not

statistically significant. Strengths of this study include the

standardization of the PRP gel. The authors report that they

focused on two factors to obtain meaningful results—

standardization of PRP production and the reproducible

application of PRP. They obtained this by using a plate-

letpheresis system instead of a desktop system. They also

used a gel because they felt that an injection might be

diluted or washed out during an arthroscopic procedure due

to the nature of the procedure. All subjects had the same

postoperative protocol—shoulders were immobilized for

4–6 weeks using an abduction brace. They gradually pro-

gressed to short arc range of motion, then passive range of

motion and then active assisted range of motion. Patients

returned to sports after 6–9 months according to individual

recovery. The weaknesses of this study include lack of

randomization, a larger proportion of large and massive

tears in the PRP group, and an arbitrary volume, concen-

tration, and activation level for the PRP.

Kesikburun et al. [54•] performed a randomized con-

trolled trial on 40 patients with rotator cuff tendinosis or

partial thickness rotator cuff tears. The patients received

either a single PRP injection or a single saline injection.

The PRP was obtained by performing a single centrifuga-

tion on whole blood, and then separating out the PRP. The

primary outcome measure was the Western Ontario Rotator

8 Curr Phys Med Rehabil Rep (2014) 2:1–15

123

Cuff Index (WORC). The authors reported the WORC is a

valid and reliable disease-specific, quality of life self-

assessment measurement tool for rotator cuff disease. The

authors attempted to detect a clinically relevant difference

of 17 % in the WORC score between the 2 groups. This

study demonstrated no statistically significant differences

in the WORC score between the two treatment groups in

follow-ups at weeks 3, 6, 12, and 24, or at one year [54•].

Strengths of this study include that it was double-blinded,

and the clinician performing the injection, the patient, and

the evaluator were blinded as to which injection the patient

received. A single clinician performed all the injections.

All patients underwent the same post-procedure rehabili-

tation protocol. The patients were told to avoid NSAIDS

after the procedure. Limitations of this study include that

the rotator cuff was anesthetized with lidocaine prior to

either injection, which may decrease the therapeutic effect

of the PRP [35].

Rha et al. [55•] performed a prospective randomized,

double-blind, controlled study in 39 patients with rotator

cuff tendinosis or partial-thickness tears. They compared

the effects of two serial PRP injections that were performed

4 weeks apart to two serial dry needling procedures per-

formed 4 weeks apart. The PRP was obtained by perform-

ing two serial centrifugations on autologous whole blood.

SPADI was the main outcome measurement. Follow-up

evaluations were performed at several intervals up to

6 months after the second injection. Acetaminophen and

hydrocodone were used for post-procedure pain control.

After the second injection, they found that at 2-week fol-

low-up, at 3-month follow-up, and at 6-month follow-up,

the PRP treated group had statistically detectable

improvement relative to the dry needling group, using the

SPADI [48]. They did not specifically address the clinical

significance of the statistically detectable improvement in

the overall SPADI score. However, they did also perform a

separate analysis of the total pain score subset of SPADI

score between the two groups, and the total disability score

subset of SPADI score between the two groups. The authors

note that there was no statistically detectable difference

between the two groups at any time point when comparing

the total pain score subset and total disability score subset.

Strengths of the study include that the patients were blinded

as to which treatment they received. Weaknesses of this

study include that the physician performing the procedure

was not blinded as to which injectate he was using. Due to

this fact, the study was not technically double-blind,

because this presents the possibility of bias from the pro-

ceduralist, which may have affected the outcomes. There

was also a 25 % drop-out rate in this study by the end of the

6-month follow-up period, which may bias the results. The

authors do not describe a specific standardized rehabilita-

tion protocol for all subjects in the methods section.

Multi-tendon tendinopathy studies

In a retrospective cross-sectional survey, Mautner et al.

[50] assessed the results of 325 patients who received

ultrasound-guided PRP injections for tendinopathy that was

refractory to conventional management. Only 180 patients

that were contacted answered the survey. The primary

outcome measurement was the perceived improvement in

symptoms at least 6 months after the PRP injection(s). This

perception was quantified using the following Likert scale:

‘‘Not at all,’’ ‘‘Slightly,’’ ‘‘Moderately,’’ ‘‘Mostly,’’ and

‘‘Completely’’. The primary outcome measurement

(improvement in symptoms) was analyzed by calculating a

global average for all tendons, average improvement for

each of the most commonly treated tendon groups, and

average improvement according to the number of injec-

tions received. Secondary outcome measurements were the

following: perceived change in VAS before and after the

procedure (from 0 for no pain to 10 for worst pain),

functional pain after the procedure using the Nirschl Pain

Phase Scale for overuse injuries, and overall satisfaction

with the PRP procedure (quantified with the following

Likert scale: ’’Completely Dissatisfied,‘‘ ’’Mostly Dissat-

isfied,‘‘ ’’Somewhat Dissatisfied,‘‘ ’’No Difference,‘‘

’’Somewhat Satisfied,‘‘ ’’Mostly Satisfied,‘‘ and ’’Com-

pletely Satisfied‘‘). 82 % of patients that responded at

1 year or greater post-procedure recorded a moderate-to-

complete resolution of symptoms (C50 % improvement).

The three most common tendons treated were the insertion

of the common extensor tendon at the lateral epicondyle,

the Achilles, and the patellar tendons. 93 % of patients who

received a lateral epicondyle injection, 100 % of patients

who received an Achilles injection, and 59 % of patients

who received a patellar tendon injection reported moderate

to complete resolution of symptoms (C50 % improve-

ment). Over 80 % of patients that received an injection in

the rotator cuff, hamstring, gluteus medius or the common

flexor tendon at the medial epicondyle reported C50 %

improvement. 60 % of patients received only one injection;

30 % received two injections, and 10 % received three or

more injections. There was an average reduction in VAS of

74 % noted. Strengths of this study include that it repre-

sents the largest database of patients treated with PRP for

tendinopathy that has been published at the time of its

publication. Weaknesses of this study include that all the

patients had not uniformly attempted and failed an eccen-

tric strengthening therapeutic exercise program prior to

having the PRP procedure performed. Rather, the authors

state that the inclusion criteria was a diagnosis of tendin-

opathy for [6 months that had not resolved with conven-

tional treatments, including oral medications,

physiotherapeutic modalities, and eccentric exercises

(those that involve slow, controlled lengthening of the

Curr Phys Med Rehabil Rep (2014) 2:1–15 9

123

muscle/tendon unit), among others. This is further accen-

tuated by the fact that the authors document that the

patients must have completed a rehabilitation program that

included eccentric exercises no earlier than 4 weeks after

the procedure. This description makes it difficult to deter-

mine what portion of improvement was from the PRP

injection versus from the eccentric exercise rehabilitation

that they completed after the injection. This is especially

true given that they had not necessarily completed an

eccentric exercise program prior to the PRP injection,

based on the inclusion criteria described. Only 55 % of the

patients that were contacted responded to the survey, which

introduces selection bias as a possible confounder. The

study collected retrospective data, which results in recall

bias, does not control for confounding factors, and limits

the type of questions that can be asked.

In a two-part study, Finoff et al. examined 41 subjects

who first received a single ultrasound-guided percutaneous

needle tenotomy and PRP injection. In the second part of

the study, a diagnostic musculoskeletal ultrasound exami-

nation was performed on the tendon that was treated with

PRP [56]. The PRP used for the first part of the study was

obtained by processing autologous whole blood in one of

two different types of platelet concentrating devices. The

PRP was buffered with 8.4 % sodium bicarbonate prior to

being injected into the tendinopathic lesion. After the

injection, all patients were given the same progressive step-

wise rehabilitation protocol. The outcomes of primary

interest included clinical outcomes (pain severity [includ-

ing average, worst, and best], functional limitations, and

satisfaction) and tendon morphology (thickness, length of

tendinopathy, echotexture, and extent of neovasculariza-

tion). They report that a 3-point or greater improvement in

pain or function was considered clinically significant,

because a Cochrane review suggested that the placebo

effect on pain was approximately 24 mm (24 %) on a

100-mm VAS for pain [57].

They found that the mean time to maximum improve-

ment was 4 months. The mean functional improvement

was 68 %, and the mean ‘‘worst-pain’’ improvement was

58 %. There was an 84 % improvement in echotexture, and

83 % of the patients were satisfied with their outcome [56].

Strengths of the study include that all subjects completed

the standardized post-procedure rehabilitation protocol.

Strict inclusion and exclusion criteria were used when

selecting patients for the procedure, which reduced the

heterogeneity of the patient population. Only two providers

performed the procedures, thus reducing interoperator

variability of the procedure. Weaknesses of this study

include that all the patients had not definitively performed

an eccentric strengthening protocol, but rather eccentric

strengthening was reported to be performed ‘‘where

applicable’’. 2 ml of 1 % lidocaine was used to anesthetize

the tendon prior to the tenotomy and PRP injection, which

may have blunted the therapeutic effect [35]. There was not

a control group. It was also a retrospective study, which

can be subject to a variety of biases.

Evidence regarding use of PRP for ligament injuries

Anterior cruciate ligament (ACL)

There is little research regarding the role of PRP for most

ligament injuries, including the ACL. Murray et al. [58]

showed that placement of a collagen-PRP scaffold in a

central ACL defect in pigs, at the time of surgical repair,

was able to promote ACL healing both histologically and

biomechanically at a 4-week follow-up.

In a Level 1 study Silva, KSSTA 2009 noted that PRP

did not accelerate healing of autologous HS ACL recon-

struction as assessed by MRI [59].

In a Level III, case–control study of anterior cruciate

ligament reconstruction, there was noted improved liga-

mentization of tendon grafts treated with an endogenous

preparation rich in growth factors [60].

Ulnar collateral injury of the elbow

In a prospective cohort study, 34 athletes with MRI-con-

firmed partial tears of the ulnar collateral ligament were

treated with a single PRP injection under ultrasound

guidance [61]. The investigators found that 30 of 34 ath-

letes (88 %) had returned to the same level of play without

any complaints with an average follow-up of 70 weeks.

The average time to return to play was 12 weeks (range

10–15 weeks). The average KJOC score improved from 46

to 93 (P\0.0001). The average DASH score improved

from 21 to 1 (P\0.0001). DASH questionnaire improved

from 69 to 3 (P\0.0001). Medial elbow joint space

opening with valgus stress decreased from 28 to 20 mm at

final follow-up (P\0.0001). The difference in medial

elbow joint space opening (stressed vs. non-stressed)

decreased from 7 to 2.5 mm at final follow-up

(P\0.0001). One player had persistent UCL insufficiency

and required ligament reconstruction 31 weeks after

injection [61].

Evidence regarding use of PRP for joint and cartilage

damage

Knee joint

In an uncontrolled, prospective preliminary study, 14

patients with primary or secondary knee OA received intra-

10 Curr Phys Med Rehabil Rep (2014) 2:1–15

123

articular PRP injections at 4-week intervals for three total

injections [62]. Several outcome measures were used,

including the Brittberg–Peterson Visual Analog Pain,

Activities, and Expectations Score, which included a

10-mm VAS with resting, walking and with the knee in a

bent position; and the five subscale Knee Injury and

Osteoarthritis Outcome Score. The Brittberg–Peterson

scale showed statistically significant overall improvement

with respect to resting pain, moving pain, and bent knee

pain (P\0.05). At one-year follow-up, eight of the

patients indicated that they achieved their individual goal

with the injection; three patients indicated the pain was the

same, and two patients indicated the knee pain had

worsened.

A cohort of 100 patients with degenerative knee carti-

lage lesions received a series of 3 PRP injections admin-

istered at 21-day intervals [63]. The outcome measures

used were the International Knee Documentation Com-

mittee (IKDC) and EuroQol VAS (EQ VAS). There was a

statistically significant improvement in both outcome

measures from baseline to 6-month and baseline to

12-month follow-up (P\0.0005). The results significantly

worsened from 6 to 12 months, although the results at

12 months were still significantly higher with respect to

baseline (P\0.0005). There was a statistically significant

improvement in the IKDC score at 6-month follow-up.

Poorer outcomes were associated with older age, more

severe grade of osteoarthritis, and higher body mass index.

In a prospective cohort study, twenty patients with early

knee osteoarthritis received a single PRP injection [64].

Fifteen of the patients had clinical assessments at baseline,

1 week, and 1, 3, 6 and 12 months. They also had MRIs at

1 year. VAS scores and Western Ontario McMaster Uni-

versities Arthritis Index (WOMAC) scores were used as

outcome measures. There was a statistically significant

56.2 % (P\0.001) reduction in mean baseline VAS pain

scores at 6 months, and a 58.9 % reduction in mean VAS

pain scores (P=0.001) at 1 year [55]. The overall scores

also improved significantly at 6 months by 45.1 %

(P=0.003) and at 12 months by 56.2 % (P=0.002).

In a prospective cohort study, 65 patients with knee OA

were treated with a single PRP intra-articular knee injec-

tion [65]. VAS and IKDC scores were used as outcome

measures. Overall, the average VAS score improved from

7.4 before the procedure to 5.0, 4.5, and 4.2 for 1, 3, and

6 months after procedure, respectively. However, the

clinical symptoms tended to deteriorate to 4.7 and 5.0 for

9 months and 1 year, respectively. On average, patients

reported relapse of knee pain at an average of 8.8 months

after the procedure. The mean IKDC score changed from

54.1 before the procedure to 53.9 at 1 month post-proce-

dure, 61.6 at 6 months post-procedure, and 50.3 at 1 year

post-procedure. There was a shortened time to the re-onset

of pain according to KL grade (P=0.037). If PFJ

degeneration occurred, the pain returned at 7.9 months on

average; if FPJ was not present, pain returned at an average

of 10.2 months, and this was reported to be statistically

significant (P=0.038). There was also the suggestion that

at greater age, the clinical effect was attenuated.

Gobbi et al. [66] examined a 50-patient case series (25

patients with a prior operative intervention for a cartilage

lesion and 25 patients with surgically naı

¨ve knees) who

were given two intra-articular knee PRP injections to treat

knee OA. The primary outcome measure was the IKDC.

All patients showed significant improvement in all scores

at 6 and 12 months (P\0.01) and returned to previous

activities, including recreational sports.

In a prospective comparative study, 150 patients were

divided to receive either 3 autologous PRP injections, 3

high molecular weight HA (HWHA) injections, or 3 low

molecular weight HA injections (LWHA) [67]. All injec-

tions were given at 2-week intervals. IKDC and EQ VAS

scales were used for outcome measures. A statistically

significant improvement in all clinical scores from baseline

evaluation to the 2- and 6-month follow-up evaluations was

observed in all treatment groups. There was a higher

number of satisfied patients in the PRP group (82 % in PRP

group, 64 % in LWHA group and 66 % in the HWHA

group; P=0.04). The analysis at the 6-month follow-up,

the primary outcome of the study, showed better IKDC

results in the PRP group compared with the LW HA group

(P=0.003), as well as compared with patients treated

with HW HA (P=0.005). EQ VAS also showed greater

improvement in the PRP group compared to the other two

groups (PRP vs. LWHA, P=0.001; PRP vs. HWHA,

P=0.002). There were overall worst results in patients

aged over 50 years: at 6 months of follow-up, IKDC

evaluation showed lower scores in older patients in the

PRP group (P=0.004), as well as in the LW HA group

(P=0.003) and HW HA group (P=0.003). More severe

degeneration was also associated with worse outcomes in

all three groups.

Spakova

´et al. [68] performed a prospective cohort/

control study in which 120 patients received either three

PRP intra-articular knee injections or three hyaluronic acid

(HA) injections [68]. Outcome measures included the

Western Ontario and McMaster Universities Osteoarthritis

Index (WOMAC) and the 11-point pain intensity numeric

rating scale (NRS). At 3- and 6-month follow-ups, the PRP

group showed statistically significant improvement com-

pared to the HA group in both outcome measures

(P\0.01 in both outcome measures). In the PRP group,

the mean score of the WOMAC improved from 38.76

(SD =16.50) at baseline to 14.35 (SD =14.18) at

3-month follow-up and to 18.85 (SD =14.09) at 6-month

follow-up. The mean score of the 11-point pain intensity

Curr Phys Med Rehabil Rep (2014) 2:1–15 11

123

NRS was 5.27 (SD =1.87) at baseline, 2.06 (SD =2.02)

at 3-month follow-up, and 2.69 (SD =1.86) at 6-month

follow-up. In the HA group, the WOMAC improved from

43.21 (SD =13.70) to 26.17 (SD =17.47) at 3-month

follow-up and to 30.90 (SD =16.57) at 6-month follow

up. The mean score of the NRS was 6.02 (SD =1.77) at

baseline, 3.98 (SD =2.27) at 3-month follow-up, and 4.3

(SD =2.07) at 6-month follow-up.

In an observational retrospective cohort/control study,

Sa

´nchez et al. [69] examined 30 patients who received 3

weekly injections of an autologous preparation rich in

growth factors, and 30 patients received 3 weekly injec-

tions of HA. WOMAC was measured at baseline and at

5-week follow-up. The observed success rates by week 5

for the pain subscale reached 33.4 % for the autologous

preparations rich in growth factors (PRGF) group and 10 %

for the hyaluronan group (P=0.004).

A randomized controlled trial of 120 patients compared

two groups who received either 4 weekly PRP injections or 4

weekly HA injections [70•]. The WOMAC score was the

primary outcome measure. At week 24, the PRP group had

continuous improvement, whereas the subjects treated with

HA showed a sharp worsening. The mean WOMAC score was

36.5 in the ACP group (range 5–76; SD =617.9) and 65.1 in

the HA group (range 41–82; SD =610.6) (P\0.001). The

PRP group also had better functional scores at 4 and 12 weeks

follow-up compared to the HA group (P\0.001 and

P\0.001, respectively). A statistically significant difference

between grade III gonarthrosis treated with ACP and that

treated with HA was observed at week 12 as well as at week

24, with a noticeable improvement that was greater in the

patients treated with ACP (P\0.001). Other than the his-

torical use of viscosupplement injections in a series of 3

weekly injections, the rationale for performing PRP injections

in either 3 or 4 weekly injections is not substantiated by basic

science or clinical practice.

Hip joint

Sa

´nchez et al. [71] examined 40 patients with severe uni-

lateral hip OA who each received a series of 3 intra-articular

hip PRP injections. The primary end point was meaningful

pain relief, which was described as a reduction in pain

intensity of at least 30 % from baseline levels as evaluated

by the WOMAC subscale at 6 months post-treatment. There

was a significant reduction in the WOMAC pain scores over

the 6 to 7-week (W=438 P=0.00047) and 6-month

periods (W=516, P=0.00607).

Ankle joint

Mei-Dan et al. [72] assessed the efficacy of using PRP for

non-invasive management of osteochondral lesions (OCL)

of the talardome. They performed a randomized controlled

trial on 30 OCLs. The patients were randomized to receive

three consecutive injections of either HA or PRP. The

follow-up points were at 4, 12, and 28 weeks. The primary

outcome measures were VAS scale and Ankle Hindfoot

Scale (AHFS). Both groups were reported to have signifi-

cant improvement at all follow-up points compared to

baseline. The AHFS score improved from 66 and 68 to 78

and 92 in groups 1 and 2, respectively, from baseline to

week 28 (P\0.0001), favoring PRP (P\0.05). Mean

VAS scores (1 =asymptomatic, 10 =severe symptoms)

decreased for pain (group 1: 5.6 to 3.1; group 2 :4.1 to 0.9),

stiffness (group 1: 5.1 to 2.9; group 2: 5.0 to 0.8), and

function (group 1: 5.8 to 3.5; group 2: 4.7 to 0.8) from

baseline to week 28 (P\0.0001), favoring PRP (P\0.05

for stiffness, P\0.01 for function, P\0.05 for pain).

Subjective global function scores, reported on a scale from

0 to 100 (with 100 representing healthy, preinjury function)

improved from 56 and 58 at baseline to 73 and 91 by week

28 for groups 1 and 2, respectively (P\0.01 in favor of

PRP). The authors concluded that the group receiving the

PRP treatment had a significantly greater improvement

compared to the group receiving the HA treatment.

Muscle injury

At the Second World Congress on Regenerative Medicine

in 2005, a poster was presented describing the treatment of

20 professional athletes with muscle injury [73]. Based on

the severity of the injury, the athletes were treated with 1–3

injections of PRGF. Swelling and pain were reduced, and

functional capabilities were fully restored in half the

expected recovery time. Ultrasonographic images showed

full regenerated muscle tissue after treatment, and fibrosis

did not appear in any of the treated cases. This differs from

the normal pattern of muscle recovery following a muscle

strain, which generally includes disruption of the normal

architecture of the muscle fibers followed by muscle

regeneration; this is often associated with muscle fibrosis.

Depending on the severity of the injury, recovery can take

as long as 4–6 weeks, with return to sport participation

taking even longer.

Conclusions

There is evolving evidence for the efficacy of PRP for a

variety of musculoskeletal conditions. The best studies

have been performed in chronic tendinopathy, with positive

results noted for chronic lateral epicondylosis. There has

been mixed evidence in other tendons, in particular the

Achilles tendon, where in a randomized, controlled study

PRP was found to be no better than a saline injection. PRP

12 Curr Phys Med Rehabil Rep (2014) 2:1–15

123

does not appear to provide additive benefit in conjunction

with rotator cuff repair. There is good and increasing evi-

dence for the efficacy of PRP (in reducing pain and

improving daily function) in osteoarthritis of the knee and

limited but increasing evidence for other joints. PRP

injections appear to have superior efficacy to HA injec-

tions. PRP use appears to be effective in the treatment of

partial tears of ulnar collateral injury of the elbow in

baseball pitchers, but this is based on a single study. Its

efficacy for other ligament injuries and muscle tears has not

been proven. There are various factors that must be

addressed when considering the use of PRP, and when

reviewing prior research of PRP, which include platelet

concentration, leukocyte count, pH of the injected sub-

stance, use of activators, the total number of injections

given, the method of delivery, and perhaps most impor-

tantly, the type of post-procedure rehabilitation protocol.

Compliance with Ethics Guidelines

Conflict of Interest G. A. Malanga declares no conflicts of interest.

M. Goldin declares no conflicts of interest.

Human and Animal Rights and Informed Consent This article

does not contain any studies with human or animal subjects

performed by any of the authors.

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