315

TH E JO U R NA L O F B O N E & JO I N T SU RG E RY J B J S . O RG
V O L U M E 98-A N U M B E R 4 F E B R UA R Y 17, 2 016
d

E V I D E N C E -B A S E D O R T H O PA E D I C S

Evidence-Based Orthopaedics

Platelet-Rich Plasma Injections Were Not Better Than Hyaluronic

Acid Injections for Knee Joint Degeneration
Filardo G, Di Matteo B, Di Martino A, Merli ML, Cenacchi A, Fornasari P, Marcacci M, Kon E. Platelet-rich plasma
intra-articular knee injections show no superiority versus viscosupplementation: a randomized controlled trial.
Am J Sports Med. 2015 Jul;43(7):1575-82.
Question: In patients with knee joint degeneration, how do injections of platelet-rich plasma
(PRP) compare with those of hyaluronic acid
(HA)?
Design: Randomized (unclear allocation concealment), blinded (patients and outcome
assessors), controlled trial with 12 months of
follow-up.
Setting: A specialized referral center for orthopaedics in Bologna, Italy.
Patients: 192 patients with chronic knee pain
lasting 4 months or swelling and imaging ndings
of cartilage degeneration indicating chondropathy
or osteoarthritis. Exclusion criteria were an age
,80 years, Kellgren-Lawrence score .3, major
axial deviation, focal chondral or osteochondral
lesion, concomitant knee lesion causing pain or
swelling, inammatory arthropathy, hematological or severe cardiovascular diseases, infection,
immunodepression, treatment with anticoagulants
or nonsteroidal anti-inammatory drugs, or decreased hemoglobin or platelet counts. 183 patients (mean age, 55 years; 61% men) completed
follow-up.

Intervention: Patients were allocated to 3

weekly intra-articular injections of PRP (n =
96) or HA (n = 96). PRP preparation involved harvesting 150 mL of peripheral venous
blood from each patient. 2 centrifugations
were performed to separate erythrocytes and
platelets to provide 20 mL of PRP, divided
into 4 5-mL units, with 1 unit sent to the
laboratory for quality testing. Before each
injection, the PRP was activated by adding
10% calcium chloride. Patients in both
groups were instructed to restrict use of
the leg for 24 hours after each injection
and to apply ice or other cold therapy to
relieve pain.
Main outcome measures: The primary outcome measure was the International Knee
Documentation Committee (IKDC) subjective
score (range, 0 to 100, with higher scores indicating better outcomes). Patients were also
assessed with the Knee injury and Osteoarthritis Outcome Score, EuroQol visual analog
scale, and Tegner score. Range of motion and
the transpatellar circumference of the knee
were also measured.

Main results: The study was powered to detect a

minimum clinically signicant difference of 6.7
points on the IKDC score. The PRP and HA groups
both demonstrated improvement in terms of
the IKDC score and did not differ at any follow-up
time point. The baseline scores were 52.4 and
49.6 and the 12-month scores were 66.2 and 64.2 in
the PRP and HA groups, respectively. PRP was
associated with more post-injection swelling and
pain, but the effects lasted only a few days and
required no medical intervention. The PRP and HA
groups did not differ in terms of any secondary
outcome measures.
Conclusion: In patients with knee joint degeneration, injections of PRP did not provide more
benet than injections of HA.
Source of funding: RICERCA FINALIZZATA 2009;
Italian Health Ministry; PRRU (Emilia-Romagna/
University of Bologna Project).
For correspondence: Dr. B. Di Matteo, Orthopaedic and
Traumatologic ClinicBiomechanics and Technology Innovation Laboratory, Rizzoli Orthopaedic Institute, 1/10
Via Di Barbiano, Bologna, 40136, Italy. E-mail address:
bernardo.dimatteo@gmail.com

Commentary
In this well-constructed trial, Filardo and colleagues compared the effect of
PRP injections with that of HA injections for the treatment of symptomatic
chondropathy of the knee. This is the largest study of its kind and was
adequately powered for the primary outcome measure (IKDC score). The
size of the study, combined with the rigorous methodology, gives the
ndings weight: there was no difference between the two groups, and
the improvement in both groups was, at best, modest. Given the enthusiasm with which PRP injections have been used, practitioners should take
note of this study.
The authors provide a comprehensive review of the available
literature and place their study in context. In seeking explanations for
the disparity between their ndings and those of studies that have
demonstrated ndings in favor of PRP injections, they highlight two issues.
One is that their study cohort was older and thus the effect of age cannot
be excluded. The other is that the PRP preparation in the current study
contained leukocytes. Preparations of PRP vary widely in terms of the
presence of leukocytes, activation of the platelets, and platelet concentra-

tions. Arguments based on in vitro studies can be made for and against
the inclusion of leukocytes. Nonetheless, the authors acknowledge that
leukocyte inclusion may be a reason for the absence of a favorable outcome
for PRP over HA.
The authors make no mention of physical therapy. It is unclear
whether the patients had physical therapy before or after the injections. The
inclusion criteria include pain or swelling. One could question the inclusion of patients with painless swelling, although it is unclear how many of
the participants were in this category.
Given the lack of difference between PRP and HA injections and the
modest clinical improvement following both, there is a place for appropriately sized and similarly well-constructed studies comparing each with
a placebo.

Julian Feller, MBBS

OrthoSport, Richmond, Victoria, Australia

Disclosure: The author indicated that no external funding was received for any aspect of this work. The Disclosure of Potential Conicts of Interest form is provided with the
online version of the article.

J Bone Joint Surg Am. 2016;98:315

http://dx.doi.org/10.2106/JBJS.15.01441