Platelet-Rich Plasma vs Hyaluronic Acid Injections for Knee Osteoarthritis: A Propensity-Score Analysis

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https://doi.org/10.1177/1457496918812218
Scandinavian Journal of Surgery
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© The Finnish Surgical Society 2018
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SCANDINAVIAN
JOURNAL OF SURGERY
SJS
PLATELET-RICH PLASMA VERSUS HYALURONIC ACID INJECTIONS
FOR KNEE OSTEOARTHRITIS: A PROPENSITY-SCORE ANALYSIS
J. A. Annaniemi1,2, J. Pere1, S. Giordano1,2,3
1 Department of Surgery, Welfare District of Forssa, Forssa, Finland
2 The University of Turku, Turku, Finland
3 Department of Surgery, Satakunta Central Hospital, Pori, Finland
ABSTRACT
Background and Aims: Intra-articular injections of viscosupplements have been an option
in the treatment of knee osteoarthritis. Platelet-rich plasma is an experimental treatment in
osteoarthritis. Previous studies have shown that platelet-rich plasma reduces osteoarthritis
symptoms in similar proportions as viscosupplements. The aim of this study was to
compare platelet-rich plasma versus viscosupplements in terms of symptoms’ relief and
time to arthroplasty.
Material and Methods: A total of 190 patients included in this retrospective study
received either intra-articular injections of platelet-rich plasma (94 patients) or hyaluronic
acid (86 patients) between January 2014 and October 2017. Western Ontario and McMaster
Universities Osteoarthritis Index, Visual Analogue Scale, and range of motion were
measured before injection, at 15 days, 6 months, 12 months, and at last follow-up. We
compared outcomes between these two groups using propensity score analysis for risk
adjustment in multivariate analysis and for one-to-one matching.
Results: Hyaluronic acid–treated patients experienced a higher arthroplasty rate (36.0%
vs 5.3%, p < 0.001), lower range of motion, worse Visual Analogue Scale and Western
Ontario and McMaster Universities Osteoarthritis Index scores, and increased risk of
any arthroplasty occurrence (log-rank < 0.001) than platelet-rich plasma patients. Cox
proportional hazards analysis revealed a tendency to decrease the risk of knee arthroplasty
for the patients treated by platelet-rich plasma (hazard ratio = 0.23, 95% confidence interval,
0.05–1.05, p = 0.058). When the treatment method was adjusted for propensity score in the
propensity score–matched pairs (n = 78), we found that platelet-rich plasma group still
showed significant improvement over the hyaluronic acid group in arthroplasty rate
(12.8% vs 41.0%, p = 0.010), Visual Analogue Scale and Western Ontario and McMaster
Correspondence:
Salvatore Giordano, M.D., PhD.
Department of Surgery
Satakunta Central Hospital
Sairaalantie 3
28500 Pori
Finland
Email: salvatore.giordano@gmail.com
812218SJS0010.1177/1457496918812218PRP might be more effective than HA for knee osteoarthritisJ. A. Annaniemi, et al.
research-article2018
Original Research Article

J. A. Annaniemi, et al.2
BACKGROUND AND AIMS
Knee osteoarthritis (OA) is the most common degen-
erative joint disease and a significant burden to the
society (1). It is a debilitating and progressive disease
that often leads to arthroplasty when non-operative
treatments fail (1). The incidence of OA is increasing
and studies predict that joint replacement surgery
demand will grow rapidly (2–4).
Non-operative treatments include non-steroidal
anti-inflammatory drugs (NSAIDs), weight loss, die-
tary supplements such as glucosamine and chondroitin
sulfate, topical agents, intra-articular injections of corti-
costeroids, and/or hyaluronic acid (HA) (5–8). The role
of glucosamine and chondroitin sulfate is still debated
(7, 8). None of these treatment options can modify the
natural course of the disease, but can instead alleviate
the symptoms (8). Intra-articular injections of corticos-
teroids and/or HA viscosupplementations are often the
last treatment options before arthroplasty.
Single intra-articular injection of HA is expensive
and did not diminish the inflammatory process in the
joint, causing sometimes adverse reactions (9–11).
Viscosupplementation seems to delay the need for
joint replacement surgery up to 3.6 years compared to
placebo, when multiple injections are given to patients,
and the arthroplasty survivorship is higher in up to
5-year follow-up (12, 13).
Intra-articular platelet-rich plasma (PRP) treatments
aim to balance the pro-inflammatory and catabolic state
in OA-affected joint toward anti-inflammatory and
anabolic state, which is thought to reduce patients’
symptoms (14–18). Effects of the intra-articular treat-
ments usually decline after 6–12 months, but a trend of
decline in pro-inflammatory cytokines has also been
observed, further reinforcing the anti-inflammatory
properties of PRP in OA symptoms’ alleviation (19, 20).
Both HA and PRP have demonstrated to provide
pain relief; however, there is no consensus whether one
of them provides better outcomes (19–22). In addition,
in the available studies, although some of them rand-
omized, the comorbidities, types of OA, and treatment
factors vary, which can affect the outcomes. Furthermore,
the length of follow-up is very heterogeneous
among the published studies, further complicating
interpretation of these data (14, 15, 20, 21). Thus, the
comparison of these two treatment modalities is diffi-
cult due to problems with forming comparable groups
and to avoid confounding factors (20).
To overcome these issues, we analyzed our long-
term results of knee injections using PRP and HA by
adjusting the baseline differences between the two
groups using propensity score analysis. We hypothe-
sized that patients treated with PRP would have less
arthroplasty operations and better outcome measure-
ment scores than patients treated with HA.
Thus, the aim of this study was to investigate and
compare the effects of PRP versus HA in the treatment
of mild to moderate knee OA, in terms of arthroplasty
avoidance and symptoms relief.
MATERIAL AND METHODS
We retrospectively evaluated all consecutive patients
who received knee injections of PRP or HA due to
knee OA between January 2014 and October 2017 at
the Welfare District of Forssa, Finland. The clinical
investigation for this study was conducted in accord-
ance with the ethical principles of the World Medical
Association Declaration of Helsinki. This study was
approved by the Institutional Review Board, and indi-
vidual informed consent was waived because the
source data were de-identified.
The outcomes of patients who received knee injec-
tions of PRP (experimental group) were compared
with those of patients who received HA due to knee
OA (control group). Patients with major systemic dis-
orders (hematological diseases, infections, immuno-
deficiency, active or fulminant rheumatoid disease),
major symptomatic hip arthrosis at the same side of
the knee, and pregnancy or possible pregnancy were
excluded from the study. Inclusion criteria were age
between 18 and 90 years, knee OA diagnosed by radio-
graphic imaging, pre-intervention pain Visual
Analogue Scale (VAS) of 30–100, and Kellgren–
Lawrence (KL) grade 1–3 OA. Patients who have
received any other kind of intra-articular injections or
oral medication other than paracetamol/NSAIDs
were excluded from this study.
Patients were followed up with physical examina-
tion, comprehensive of Western Ontario and McMaster
Universities Osteoarthritis Index (WOMAC) question-
naire, VAS, and range of motion (ROM) of the knee.
Universities Osteoarthritis Index scores, but not in the range of motion, during the mean
follow-up of 16.7 months.
Conclusion: Intra-articular injections of platelet-rich plasma associated with better
outcomes than hyaluronic acid in knee osteoarthritis. Platelet-rich plasma might prolong
the time to arthroplasty and provide a valid therapeutic option in selected patients with
knee osteoarthritis not responding to conventional treatments. Further larger studies are
needed to validate this promising treatment modality.
Key words: Platelet-rich plasma; viscosupplementation; hyaluronic acid; knee osteoarthritis; arthroplasty;
orthopedics

PRP might be more effective than HA for knee osteoarthritis 3
Data were meticulously collected both from a pro-
spectively maintained departmental database and
from the patients’ electronic medical records. Patients’
demographics, treatment modality, frequency, and
knee OA grades were analyzed, and clinical outcomes
were directly compared between the experimental
and control groups. Patients were assessed for their
symptoms before injections, at 15 days after treatment,
at 6 months, at 12 months, and/or at the last follow-
up. The primary outcome measure was the occurrence
of any knee arthroplasty at follow-up after intra-artic-
ular injections. Secondary outcome measures included
adverse events, VAS, WOMAC, and ROM of the knee.
The PRP group received three intra-articular injec-
tions at 10–14 days interval (defined as one treatment
term). Commercial Glo PRP kit (GloFinn Corporation,
Salo, Finland) was utilized in manufacturing of autol-
ogous PRP from patients’ whole blood. A specifically
trained nurse drew up to 10 mL of patients’ whole
blood in a syringe and the whole blood was centri-
fuged 5 min at 1200 r/min. Excess red blood cells
(RBCs) were removed between centrifugations. The
final product contained four to eight times higher
concentration of platelets compared to the whole
blood. One typical injection consisted of approxi-
mately 5 mL of PRP. Five patients received more than
one treatment term and, thus, more than three injec-
tions, while three patients received less than three
injections all together.
The HA group had received either single intra-artic-
ular injection or three injections at 1-week interval
(defined as one treatment term). A total of 33 patients in
the HA group received more than one treatment. HA
products utilized were high-viscosity and high-molec-
ular-weight products: Hylan G-F 20 (Synvisc One®,
Naarden, Netherlands, 6,000,000 Da, 48 mg/6 mL injec-
tion) or sodium hyaluronate (Arthrum75®, Chartres,
France, ⩾2,800,000 Da, 75 mg/3 mL injection). Five
patients received low-molecular-weight HA (Hyalgan®,
Abano Terme, Italy, 500,000–730,000 Da, 20 mg/2 mL
injection). The follow-up was calculated from the time
of the first injection until the last control.
STATISTICAL ANALYSIS
Continuous variables were reported as the mean ± stand-
ard deviation. Pearson’s chi-square test, Fisher’s exact
test, and the Mann–Whitney test or t-test were used for
univariate analysis, as appropriate.
Logistic regression with enter selection was per-
formed to calculate the likelihood of patients to be
included in either the PRP group or HA group. Hosmer–
Lemeshow’s test was used to assess the regression
model fit. Variables included in the regression model are
shown in Table 1. The calculated propensity score was
employed for one-to-one matching as well as to adjust
for other variables in estimating their impact on the
postoperative outcomes (23). One-to-one propensity
score matching between study groups was done using
the nearest neighbor method and a caliper of 0.2 of the
standard deviation of the logit of the propensity score
(24). Continuous outcomes were compared in the pro-
pensity score–matched (PSM) groups using paired t-test
or Wilcoxon signed-rank test as appropriate; differences
TABLE 1
Baseline characteristics of patients who underwent intra-articular injections of PRP or HA for knee OA.
Overall series Propensity score–matched pairs
PRP group HA group p-value* PRP group HA group p-value
n = 94 n = 86 n = 39 n = 39
Mean age (years)a57.4 ± 10.3 65.7 ± 9.2 <0.001 62.3 ± 8.9 61.9 ± 8.4 0.866
Females 60 (63.8%) 50 (58.1%) 0.448 15 (38.5%) 15 (38.5%) 1.000
Mean BMIa (kg/m2) 28.9 ± 4.5 29.7 ± 5.1 0.311 30.0 ± 5.5 29.4 ± 4.5 0.621
Obese (BMI > 30 kg/m2)a63 (67.0%) 39 (45.3%) 0.004 24 (61.5%) 22 (56.4%) 0.818
Comorbiditya31 (33.0%) 53 (61.6%) <0.001 18 (46.2%) 17 (43.6%) 1.000
Diabetesa6 (6.4%) 23 (26.7%) <0.001 5 (12.8%) 3 (7.7%) 0.711
Cardiac diseasea10 (10.6%) 16 (18.6%) 0.142 7 (17.9%) 7 (17.9%) 1.000
Smokersa16 (17.0%) 6 (6.2%) 0.043 3 (7.7%) 3 (7.7%) 1.000
Bilateral 12 (12.8%) 16 (18.6%) 0.309 6 (15.4%) 8 (20.5%) 0.769
Flexion degree 130.3 ± 19.4 129.5 ± 18.4 0.776 126.8 ± 18.2 126.4 ± 21.3 0.932
Extension degree 88.6 ± 3.1 88.1 ± 3.4 0.389 88.7 ± 3.0 88.1 ± 4.1 0.430
Osteoarthritis Grade
(Kellgren–Lawrence)
2.3 ± 0.6 2.4 ± 0.6 0.193 2.3 ± 0.7 2.4 ± 0.5 0.852
Grade 1 9 4 6 1
Grade 2 52 46 18 23
Grade 3 33 36 15 15
VAS pain score (0–100) 64.8 ± 17.4 69.3 ± 18.3 0.107 67.3 ± 16.8 69.7 ± 17.0 0.527
WOMAC overall 31.2 ± 13.0 36.7 ± 14.6 0.011 32.0 ± 12.4 34.0 ± 15.3 0.523
Follow-up (months) 16.9 ± 9.5 17.1 ± 7.3 0.860 16.7 ± 6.7 16.7 ± 9.2 1.000
BMI: body mass index; PRP: platelet-rich plasma; HA: hyaluronic acid; OA: osteoarthritis; VAS: Visual Analogue Scale; WOMAC: Western
Ontario and McMaster Universities Osteoarthritis Index.
aVariable included in regression model for estimation of the propensity score.
*Bold values are statistically significant.

J. A. Annaniemi, et al.4
in proportions were compared using the McNemar’s or
binominal test as appropriate.
Long-term outcome was assessed by Kaplan–
Meier’s methods in the overall series and in the pro-
pensity-matched pairs with the log-rank test and the
Cox proportional hazards method with log minus log
test. All p-values <0.05 were considered statistically
significant. All analyses were carried out using SPSS
statistical software (IBM SPSS Statistics, version 23,
Armonk, NY).
RESULTS
A total of 180 consecutive patients, treated for knee
OA between 2014 and 2017, were included into this
study. Of them, 94 patients (52%) received PRP injec-
tions while 86 (48%) received HA injections. Baseline
characteristics are outlined in Table 1, showing sig-
nificant difference in age, obesity prevalence, comor-
bidity, diabetes, and overall WOMAC score, which
were significantly higher among HA group. Mean
follow-up was similar in both groups and over
17 months. Similar adverse events occurred in both
groups, while the number of injections was signifi-
cantly higher among PRP group (PRP 3.2 ± 1.2 vs HA
1.7 ± 0.9, p < 0.001).
The HA patients experienced a more than four-
fold higher odds for arthroplasty rate (36.0% vs
5.3%) than the PRP patients (odds ratio (OR), 4.4;
95% confidence interval (CI), 1.9–10.1; p < 0.001,
Fig. 1 and Table 2). Cox proportional hazard model
including confounding factor identified by univari-
ate analysis revealed a tendency to decrease the risk
of knee arthroplasty for the patients treated by PRP
(hazard ratio (HR) = 0.23; 95% CI, 0.05–1.05; p = 0.058;
Fig. 2).
Among secondary outcomes, VAS pain score showed
a statistically significant difference favoring PRP group
at 6 months, at 1 year, and at last follow-up. Similarly,
WOMAC overall scores and ROM were significantly
better at all the treatment intervals among PRP patients
(Table 2, Figs 3). Kaplan–Meier curves showed a statis-
tically significant difference in risk of any arthroplasty
between the two groups (Fig. 1).
The propensity score yielded 39 matched pairs
without any differences in baseline characteristics
(Table 1). The number of injections was still signifi-
cantly higher among PRP group (3.1 ± 0.7 vs 2.0 ± 1.1,
p < 0.001), while the arthroplasty rate was signifi-
cantly higher among HA patients even when matched
through the propensity score (PRP 5 vs HA 16,
p = 0.010).
Furthermore, a statistically significant lower VAS
pain score was observed in PRP group at 6 months, at
12 months, and at last follow-up. Similarly, WOMAC
overall score showed a statistically significant differ-
ence at 6 months and at the last follow-up favoring
PRP over HA patients (Table 2, Fig. 4). In contrast, we
did not detect any statistically significant differences
in ROM (extension and flexion degree) at any
Fig. 1. Kaplan–Meier curves of any arthroplasty occurrence for patients who underwent intra-articular injections of PRP or HA for knee OA.

PRP might be more effective than HA for knee osteoarthritis 5
follow-up point in the PSM group (Table 2, Fig. 4).
Kaplan–Meier curves showed a statistically signifi-
cant difference in risk of any arthroplasty between the
two matched paired groups (Fig. 5).
DISCUSSION
In our study, PRP outperformed HA in both the overall
patient series and in the PSM series in symptom alle-
viation and in terms of avoiding the knee arthroplasty.
Our results are consistent with the current literature,
providing that PRP results in a statistically significant
improvement in major pain and functional outcome
measurements when compared to HA (15–22, 25–27).
To the best of our knowledge, this is the first study to
report differences on the risk of arthroplasty between
autologous PRP versus HA in knee OA, and the first
PSM study to compare PRP to HA.
There has been only one previous study about
arthroplasty delay involving PRP by Turajane et al.
(22) including 60 patients. They compared intra-artic-
ular injections of autologous activated peripheral
blood stem cells (AAPBSC) with PRP added growth
factors, and HA along with arthroscopic mesenchymal
stem cells versus the same combination without the
added growth factors versus only intra-articular HA.
They found that AAPBSC groups performed better
than HA alone; however, they concluded that further
research on the matter is required (22). Our study
demonstrated a statistically significant difference in
delaying knee arthroplasty favoring patients treated
with autologous knee intra-articular injections of PRP
versus high-molecular-weight HA.
There have been some reports indicating that PRP
may not be superior to HA (19, 28). Filardo etal. (28)
did not find any statistically significant differences
between PRP and HA groups in the International
Knee Documentation Committee (IKDC) subjective
score and VAS score (28). Cole etal. (19) found a sta-
tistically significant difference favoring PRP in IKDC
and VAS score at 24 and 52 weeks. However, no sta-
tistically significant differences between PRP and
HA in WOMAC pain score were found at any fol-
low-up point (19). Possible confounding factors in
the studies were use of frozen PRP surplus and sta-
tistically significant age difference between the
groups, different PRP protocols utilized, and statisti-
cally significant difference of body mass index (BMI)
between the groups (19, 28).
Randomized controlled trials (RCTs) showed that
multiple intra-articular PRP injections are statisti-
cally significantly more effective in early knee OA
than placebo, HA or single injections of PRP (14,
25–27). A meta-analysis of RCTs by Shen etal. (20)
concluded that PRP injections reduce knee pain and
improve WOMAC scores better than other intra-
articular injections (including HA, saline, corticos-
teroids, and ozone) up to 12 months (20). In our
TABLE 2
Outcomes of patients who underwent intra-articular injections of PRP or HA for knee OA.
Overall series Propensity score–matched pairs
PRP group HA group p-value* PRP group HA group p-value*
n = 94 n = 86 n = 39 n = 39
Adverse events 4 (4.3%) 4 (4.1%) 1.000 1 (2.6%) 2 (5.1%) 1.000
Number of injections 3.2 ± 1.2 1.7 ± 0.9 <0.001 3.1 ± 0.7 2.0 ± 1.1 <0.001
Flexion degree (15 days) 134.4 ± 16.2 131.0 ± 17.3 0.229 129.7 ± 17.3 129.4 ± 19.6 0.927
Extension degree (15 days) 89.1 ± 2.3 88.3 ± 3.3 0.074 89.1 ± 2.3 88.2 ± 4.0 0.231
VAS pain score (0–100) (15 days) 39.2 ± 20.9 38.8 ± 28.3 0.907 38.8 ± 19.8 37.0 ± 25.5 0.729
WOMAC overall (15 days) 20.1 ± 11.7 25.3 ± 16.6 0.021 21.2 ± 12.2 22.6 ± 14.6 0.658
Flexion degree (6 months) 137.8 ± 15.7 131.4 ± 19.12 0.020 131.6 ± 18.6 131.0 ± 18.6 0.896
Extension degree (6 months) 89.9 ± 3.6 88.8 ± 3.9 0.061 90.3 ± 5.2 88.5 ± 3.8 0.087
VAS pain score (0–100) (6 months) 18.9 ± 23.5 45.5 ± 31.5 <0.001 26.3 ± 26.6 45.0 ± 32.4 0.007
WOMAC overall (6 months) 10.7 ± 12.3 27.3 ± 18.3 <0.001 15.7 ± 14.3 24.7 ± 17.6 0.016
Flexion degree (12 months) 137.9 ± 14.8 132.4 ± 17.4 0.048 130.8 ± 16.6 131.9 ± 19.3 0.814
Extension degree (12 months) 89.2 ± 2.1 88.3 ± 2.8 0.033 89.0 ± 2.4 88.4 ± 3.0 0.385
VAS pain score (0–100) (12 months) 21.1 ± 25.1 47.1 ± 29.4 <0.001 27.6 ± 28.2 42.7 ± 29.6 0.043
WOMAC overall (12 months) 11.9 ± 14.2 29.2 ± 18.4 <0.001 17.3 ± 17.3 25.3 ± 17.9 0.077
Flexion degree (last follow-up) 137.8 ± 15.4 130.4 ± 18.8 0.006 131.7 ± 17.8 129.9 ± 20.4 0.681
Extension degree (last follow-up) 89.2 ± 2.3 88.2 ± 2.9 0.025 88.7 ± 2.7 88.5 ± 2.8 0.687
VAS pain score (0–100) (last follow-up) 21.4 ± 25.0 52.7 ± 28.9 <0.001 29.5 ± 28.6 54.5 ± 27.7 <0.001
WOMAC overall last follow-up) 12.8 ± 14.8 32.0 ± 19.7 <0.001 19.2 ± 17.5 30.2 ± 20.0 0.012
Any knee arthroplasty 5 (5.3%) 31 (36.0%) <0.001 5 (12.8%) 16 (41.0%) 0.010
Unicompartmental knee arthroplasty 2 (2.1%) 18 (20.9%) <0.001 2 (5.1%) 9 (23.1%) 0.047
Total knee arthroplasty 3 (3.2%) 13 (15.1%) 0.007 3 (3.8%) 7 (17.9%) 0.310
PRP: platelet-rich plasma; HA: hyaluronic acid; OA: osteoarthritis; VAS: Visual Analogue Scale; WOMAC: Western Ontario and McMaster
Universities Osteoarthritis Index.
*Bold values are statistically significant.

J. A. Annaniemi, et al.6
study, the VAS score showed similar results favor-
ing the PRP group at 6 months, 12 months, and last
follow-up, even after propensity score analysis. In
addition, our WOMAC outcomes corroborate Cerza
et al.’s study (14), which demonstrated superior
clinical outcomes for PRP against HA with WOMAC
Fig. 2. Cox proportional hazards estimates of knee arthroplasty according to intra-articular injections of HA or PRP for knee OA
(HR = 0.23, 95% CI, 0.05–1.05, p = 0.058).
Fig. 3. Mean values of range of motion, VAS, and WOMAC in the overall series of PRP and HA groups. ROM values expressed in extension
0 to 90 degrees and flexion 0 to 155 degrees. Columns with a statistically significant difference are marked with asterisk (*).

PRP might be more effective than HA for knee osteoarthritis 7
Fig. 4. Mean values of range of motion, VAS, and WOMAC in the propensity score–matched pairs of PRP and HA groups. ROM values
expressed in extension 0 to 90 degrees and flexion 0 to 155 degrees. Columns with a statistically significant difference are marked with
asterisk (*).
Fig. 5. Kaplan–Meier curves of any arthroplasty occurrence for patients who underwent intra-articular injections of PRP or HA for knee
OA after propensity score matching.

J. A. Annaniemi, et al.8
scores. Our results verified the ones of Shen etal.’s
(20) meta-analysis, but with a longer follow-up (20).
We did not find significant differences in ROM
between the groups and this is probably due to the
mild to moderate grade of OA in the study popula-
tions, as joint becomes truly rigid in the later stages of
OA. Adverse effects were meticulously documented in
our study, but we did not find serious adverse effects
in either of the groups. The adverse effects recorded
were mostly prolonged pain of the injection site (up to
5 days) or mild effusion post injection. Previous studies
found no serious adverse effects in treating patients
with intra-articular PRP injections (20, 25–28).
Strengths of this study are the reasonable number
of patients and relatively long follow-up. The propen-
sity-score matching also improves the reliability of the
study by reducing the demographic differences
between the groups. The multivariable regression
using propensity score analysis allowed the opportu-
nity to control for selection bias and confounding by
treatment indication. Particularly, this is important
when there is a relatively large number of confound-
ers compared with the number of outcomes (29). This
unique approach of using propensity scores permitted
us to consider not only the factors that affected out-
come but also the factors that contributed to selection
for the type of injection.
A limitation of this study is the retrospective view
point. A true randomization of the patients would fur-
ther reduce the possible bias concerning the patient
selection. The PRP group in the overall series were
younger, more obese, and smoked more often than
HA groups. However, the HA group were older, had
more comorbidity, and had greater initial WOMAC
overall score. The PRP group received significantly
more injections than the HA group, due to the treat-
ment protocol inherent to these two different meth-
ods, and we consider it irrelevant. In addition, due to
the lack of data, we have no information about the
amount of oral medications used for arthrosis,
although paracetamol and NSAIDs were mostly pre-
scribed. Nonetheless, patients who have received any
other kind of intra-articular injections or oral medica-
tion other than paracetamol/NSAIDs were excluded
from this study.
We lost over 50% of the total patients enrolled to
this study during the propensity score analysis. This is
probably due to the physician leaning toward HA,
rather than PRP, when treating heavily symptomatic
OA patients. HA has a longer history and it has been
successfully utilized before, which may lead to a bias
of continued use in uncertain situations such as heav-
ily symptomatic OA. Nevertheless, propensity score
analysis has its pitfalls and weaknesses due to its
methodology, as there might be some variables not
included in the propensity score which might have
affected the treatment selection and outcomes (29).
Reduction of symptoms and slowing the disease pro-
gression are the goals of treatment (30). A recent consen-
sus statement included HA as one method in achieving
the goals (30). In this view, PRP may prove to be a viable
alternative to HA when patients are not yet ready for
arthroplasty. A larger RCT study with longer follow-up
is required to determine the length of arthroplasty delay.
Moreover, defining the optimal PRP injection interval in
order to provide the maximum efficacy would be of
great interest. It is still unknown whether PRP is a dis-
ease-modifying treatment option in OA, as it is still a
progressive disease that will eventually ruin the affected
joint.
CONCLUSION
This study demonstrated that PRP intra-articular knee
injections compared to HA reduce the odds of knee
arthroplasty in mild to moderate knee OA patients. A
significant improvement in pain at 6 months and there-
after in the PRP group versus HA group was found.
Similarly, a statistically significant improvement was
also detected in WOMAC overall score at 6 months and
at the last follow-up. A trend toward improvement in
WOMAC overall was observed at 12 months. Our
results suggest that autologous PRP may be an effective
treatment for patients with mild to moderate knee OA.
The authors suggest that PRP may be used as an
alternative to high-molecular-weight HA in mild to
moderate graded symptomatic knee OA as it seems to
reduce the odds of early arthroplasty and alleviate
symptoms better than other injection therapies. In our
experience, three injections given at 2-week interval as
one treatment term may be optimal. Treatment terms
might be repeated when symptoms arise again or until
symptoms are not alleviated. Arthroplasty should be
considered when neither HA nor PRP reduce the
symptoms. Longer follow-up studies to further clarify
the role of PRP in arthroplasty delay are warranted.
DECLARATION OF CONFLICTING INTERESTS
The author(s) declared no potential conflicts of interest with
respect to the research, authorship, and/or publication of
this article.
FUNDING
The author(s) received no financial support for the research,
authorship, and/or publication of this article.
ORCID ID
S. Giordano https://orcid.org/0000-0001-5981-6870
REFERENCES
1. Cross M, Smith E, Hoy D etal: The global burden of hip and
knee osteoarthritis: Estimates from the global burden of disease
2010 study. Ann Rheum Dis 2014;73(7):1323–1330.
2. Patel A, Pavlou G, Mujica-Mota RE etal: The epidemiology of
revision total knee and hip arthroplasty in England and Wales:
A comparative analysis with projections for the United States.
A study using the National Joint Registry dataset. Bone Joint J
2015;97-B(8):1076–1081.
3. Kurtz S, Ong KL, Lau E etal: Projections of primary and revi-
sion hip and knee arthroplasty in the United States from 2005
to2030. J Bone Joint Surg Am 2007;89:780–785.
4. Mont MA, Issa K: Impact of the economic downturn on total
joint replacement demand in the United States: Updated projec-
tions to 2021. J Bone Joint Surg Am 2014;96(8):624–630.

PRP might be more effective than HA for knee osteoarthritis 9
5. Strand S, McIntyre LF, Beach WR etal: Safety and efficacy of US-
approved viscosupplements for knee osteoarthritis: A systematic
review and meta-analysis of randomized, saline-controlled trials.
J Pain Res 2015;8:217–228.
6. Riecke BF, Christensen R, Christensen P etal: Comparing two
low-energy diets for the treatment of knee osteoarthritis symp-
toms in obese patients: A pragmatic randomized clinical trial.
Osteoarthritis Cartilage 2010;18(6):746–754.
7. Nelson AE, Allen KD, Golightly YM etal: A systematic review
of recommendations and guidelines for the management of
osteoarthritis: The chronic osteoarthritis management initiative
of the U.S. Semin Arthritis Rheum 2014;43(6):701–712.
8. McAlindon TE, Bannuru RR, Sullivan MC etal: OARSI guide-
lines for the non-surgical management of knee osteoarthritis.
Osteoarthritis Cartilage 2014;22(6):890–891.
9. Chevalier X, Jerosch J, Goupille P et al: Single, intra-articular
treatment with 6 mL hylan G-F 20 in patients with sympto-
matic primary osteoarthritis of the knee: A randomised, mul-
ticentre, double-blind, placebo controlled trial. Ann Rheum Dis
2010;69(1):113–119.
10. Kirchner M, Marshall D: A double-blind randomized controlled
trial comparing alternate forms of high molecular weight hya-
luronan for the treatment of osteoarthritis of the knee. Osteoar-
thritis Cartilage 2006;14(2):154–162.
11. Petrella RJ, Petrella M: A prospective, randomized, double-
blind, placebo controlled study to evaluate the efficacy of
intraarticular hyaluronic acid for osteoarthritis of the knee. J
Rheumatol 2006;33(5):951–956.
12. Altman R, Lim S, Steen RG et al: Hyaluronic acid injections
are associated with delay of total knee replacement surgery in
patients with knee osteoarthritis: Evidence from a large U.S.
PLoS ONE 2015;10(12):e0145776.
13. Delbarre A, Amor B, Bardoulat I et al: Do intra-articular
hyaluronic acid injections delay total knee replacement in
patients with osteoarthritis—A Cox model analysis. PLoS ONE
2017;12(11):e0187227.
14. Cerza F, Carni S, Carcangiu A et al: Comparison between
hyaluronic acid and platelet-rich plasma, intra-articular infil-
tration in the treatment of gonarthrosis. Am J Sports Med
2012;40(12):2822–2827.
15. Filardo G, Kon E, Buda R etal: Platelet-rich plasma intra-artic-
ular knee injections for the treatment of degenerative cartilage
lesions and osteoarthritis. Knee Surg Sports Traumatol Arthrosc
2011;19(4):528–535.
16. Kon E, Buda R, Filardo G et al: Platelet-rich plasma: Intra-
articular knee injections produced favorable results on degen-
erative cartilage lesions. Knee Surg Sports Traumatol Arthrosc
2010;18(4):472–479.
17. Kon E, Mandelbaum B, Buda R et al: Platelet-rich plasma
intraarticular injection versus hyaluronic acid viscosupplemen-
tation as treatments for cartilage pathology: From early degen-
eration to osteoarthritis. Arthroscopy 2011;27:1490–1501.
18. Spakova T, Rosocha J, Lacko M et al: Treatment of knee
joint osteoarthritis with autologous platelet-rich plasma in
comparison with hyaluronic acid. Am J Phys Med Rehabil
2012;91(5):411–417.
19. Cole BJ, Karas V, Hussey K et al: Hyaluronic acid versus
platelet-rich plasma: A prospective, double-blind randomized
controlled trial comparing clinical outcomes and effects on
intra-articular biology for the treatment of knee osteoarthritis.
Am J Sports Med 2017;45(2):339–346.
20. Shen L, Yuan T, Chen S et al: The temporal effect of platelet-
rich plasma on pain and physical function in the treatment of
knee osteoarthritis: Systematic review and meta-analysis of ran-
domized controlled trials. J Orthop Surg Res 2017;12(1):16.
21. Duymus TM, Mutlu S, Dernek B etal: Choice of intra-articu-
lar injection in treatment of knee osteoarthritis: Platelet-rich
plasma, hyaluronic acid or ozone options. Knee Surg Sports
Traumatol Arthrosc 2017;25(2):485–492.
22. Turajane T, Chaveewanakorn U, Fongsarun W etal: Avoidance
of total knee arthroplasty in early osteoarthritis of the knee with
intra-articular implantation of autologous activated peripheral
blood stem cells versus hyaluronic acid: A randomized con-
trolled trial with differential effects of growth factor addition.
Stem Cells Int 2017;2017:8925132.
23. Austin PC: An introduction to propensity score methods for
reducing the effects of confounding in observational studies.
Multivariate Behav Res 2011;46(3):399–424.
24. Austin PC: Optimal caliper widths for propensity-score match-
ing when estimating differences in means and differences in pro-
portions in observational studies. Pharm Stat 2011;10(2):150–161.
25. Gormeli G, Gormeli CA, Ataoglu B etal: Multiple PRP injec-
tions are more effective than single injections and hyaluronic
acid in knees with early osteoarthritis: A randomized, double-
blind, placebo-controlled trial. Knee Surg Sports Traumatol
Arthrosc 2017;25(3):958–965.
26. Patel S, Dhillon MS, Aggarwal S etal: Treatment with platelet-
rich plasma is more effective than placebo for knee osteoarthri-
tis: A prospective, double-blind, randomized trial. Am J Sports
Med 2013;41(2):356–364.
27. Smith PA: Intra-articular autologous conditioned plasma
injections provide safe and efficacious treatment for knee
osteoarthritis: An FDA-sanctioned, randomized, double-
blind, placebo-controlled clinical trial. Am J Sports Med
2016;44(4):884–891.
28. Filardo G, DiMatteo B, DiMartino A etal: Platelet-rich plasma
intra-articular knee injections show no superiority versus visco-
supplementation: A randomized controlled trial. Am J Sports
Med 2015;43(7):1575–1582.
29. Lonjon G, Porcher R, Ergina P etal: Potential pitfalls of report-
ing and bias in observational studies with propensity score
analysis assessing a surgical procedure: A methodological sys-
tematic review. Ann Surg 2017;265(5):901–909.
30. Bruyére O, Cooper C, Pelletier JP et al: A consensus state-
ment on the European Society for Clinical and Economical
Aspects of Osteoporosis and Osteoarthritis (ESCEO) algorithm
for the management of knee osteoarthritis—From evidence-
based medicine to the real-life setting. Semin Arthritis Rheum
2016;45(4 Suppl):S3–11.
Received: May 6, 2018
Accepted: September 25, 2018