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

Scandinavian Journal of Surgery
1 –9
© The Finnish Surgical Society 2018
Article reuse guidelines:
DOI: 10.1177/1457496918812218
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
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
Salvatore Giordano, M.D., PhD.
Department of Surgery
Satakunta Central Hospital
Sairaalantie 3
28500 Pori
812218SJS0010.1177/1457496918812218PRP might be more effective than HA for knee osteoarthritisJ. A. Annaniemi, et al.
Original Research Article
J. A. Annaniemi, et al.2
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.
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;
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.
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
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
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).
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).
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
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
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.
The author(s) declared no potential conflicts of interest with
respect to the research, authorship, and/or publication of
this article.
The author(s) received no financial support for the research,
authorship, and/or publication of this article.
S. Giordano
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Received: May 6, 2018
Accepted: September 25, 2018
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Full-text available
Objectives: This study aimed to describe patients treated for knee osteoarthritis between 2006 and 2013 in France and to compare the delay from diagnosis to total knee replacement between patients who received intra-articular hyaluronic acid injections and those who did not receive the injections. A second objective was to compare direct medical costs for ambulatory care between treatment groups. Materials and methods: Patients were selected from a representative sample of the real world administrative claims database using an algorithm developed by experts from the scientific committee of the study. Data were matched with the medico-administrative database for hospital care. A Cox proportional hazards model was stratified for the treatment group and adjusted for available socio-demographic and medical covariates to compare restricted mean survival times at different time points (1, 3, 5 and 7.5 years) between groups. Costs were expressed in 2013 euros. Results: A total of 14,782 patients were treated for knee osteoarthritis (67% women; mean age = 68 years). Among this population, 1,662 patients had total knee replacement (11.2%). At each time point, restricted mean survival time without total knee replacement was significantly higher (p-values<0.001) for hyaluronic acid group, from +51 to +217 days at 1 and 7.5 years, respectively. For the year preceding total knee replacement, the means for total direct medical costs were similar between groups, €744 vs €805 for treatment and control groups, respectively, (p-value = 0.104). Intra-articular injections accounted for less than 10% of the total costs. Conclusion: This is the first retrospective longitudinal study involving knee osteoarthritis patients using medico-administrative databases in France. The results support the effectiveness of hyaluronic acid injections in delaying total knee replacement and show that patients treated with hyaluronic acid have similar direct medical costs for ambulatory care compared to patients treated with corticosteroids only.
Full-text available
Background Quite a few randomized controlled trials (RCTs) investigating the efficacy of platelet-rich plasma (PRP) for treatment of knee osteoarthritis (OA) have been recently published. Therefore, an updated systematic review was performed to evaluate the temporal effect of PRP on knee pain and physical function. Methods Pubmed, Embase, Cochrane library, and Scopus were searched for human RCTs comparing the efficacy and/or safety of PRP infiltration with other intra-articular injections. A descriptive summary and quality assessment were performed for all the studies finally included for analysis. For studies reporting outcomes concerning Western Ontario and McMaster Universities Arthritis Index (WOMAC) or adverse events, a random-effects model was used for data synthesis. ResultsFourteen RCTs comprising 1423 participants were included. The control included saline placebo, HA, ozone, and corticosteroids. The follow-up ranged from 12 weeks to 12 months. Risk of bias assessment showed that 4 studies were considered as moderate risk of bias and 10 as high risk of bias. Compared with control, PRP injections significantly reduced WOMAC pain subscores at 3, 6, and 12 months follow-up (p = 0.02, 0.004, <0.001, respectively); PRP significantly improved WOMAC physical function subscores at 3, 6, and 12 months (p = 0.002, 0.01, <0.001, respectively); PRP also significantly improved total WOMAC scores at 3, 6 and 12 months (all p < 0.001); nonetheless, PRP did not significantly increased the risk of post-injection adverse events (RR, 1.40 [95% CI, 0.80 to 2.45], I2 = 59%, p = 0.24). Conclusions Intra-articular PRP injections probably are more efficacious in the treatment of knee OA in terms of pain relief and self-reported function improvement at 3, 6 and 12 months follow-up, compared with other injections, including saline placebo, HA, ozone, and corticosteroids. Review registrationPROSPERO CRD42016045410. Registered 8 August 2016.
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Background The growing prevalence of osteoarthritis (OA) and the medical costs associated with total knee replacement (TKR) surgery for end-stage OA motivate a search for agents that can delay OA progression. We test a hypothesis that hyaluronic acid (HA) injection is associated with delay of TKR in a dose-dependent manner. Methods and Findings We retrospectively evaluated records in an administrative claims database of similar to 79 million patients, to identify all patients with knee OA who received TKR during a 6-year period. Only patients with continuous plan enrollment from diagnosis until TKR were included, so that complete medical records were available. OA diagnosis was the index event and we evaluated time-to-TKR as a function of the number of HA injections. The database included 182,022 patients with knee OA who had TKR; 50,349 (27.7%) of these patients were classified as HA Users, receiving >= 1 courses of HA prior to TKR, while 131,673 patients (72.3%) were HA Non-users prior to TKR, receiving no HA. Cox proportional hazards modelling shows that TKR risk decreases as a function of the number of HA injection courses, if patient age, gender, and disease comorbidity are used as background covariates. Multiple HA injections are therefore associated with delay of TKR (all, P < 0.0001). Half of HA Non-users had a TKR by 114 days post-diagnosis of knee OA, whereas half of HA Users had a TKR by 484 days post-diagnosis (chi(2) = 19,769; p < 0.0001). Patients who received no HA had a mean time-to-TKR of 0.7 years; with one course of HA, the mean time to TKR was 1.4 years (chi(2) = 13,725; p < 0.0001); patients who received >= 5 courses delayed TKR by 3.6 years (chi(2) = 19,935; p < 0.0001). Conclusions HA injection in patients with knee OA is associated with a dose-dependent increase in time-to-TKR.
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The European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) published a treatment algorithm for the management of knee osteoarthritis (OA) in 2014, which provides practical guidance for the prioritization of interventions. Further analysis of real world data for OA provides additional evidence in support of pharmacological interventions, in terms of management of OA pain and function, avoidance of adverse events, disease-modifying effects and long-term outcomes, e.g. delay of total joint replacement surgery, and pharmacoeconomic factors such as reduction in healthcare resource utilization. This paper provides an updated assessment of the literature for selected interventions in OA, focusing on real-life data, with the aim of providing easy-to-follow advice on how to establish a treatment flow in patients with knee OA in primary care clinical practice, in support of the clinicians’ individualized assessment of the patient. In step 1, background maintenance therapy with symptomatic slow-acting drugs for osteoarthritis (SYSADOAs) is recommended, for which high-quality evidence is provided only for the prescription formulations of crystalline glucosamine sulfate and chondroitin sulfate. Paracetamol may be added for rescue analgesia only, due to limited efficacy and increasing safety signals. Topical non-steroidal anti-inflammatory drugs (NSAIDs) may provide additional symptomatic treatment with the same degree of efficacy as oral NSAIDs without the systemic safety concerns. Oral NSAIDs maintain a central role in step 2 advanced management of persistent symptoms. However, oral NSAIDs are highly heterogeneous in terms of gastrointestinal and cardiovascular safety profile, and patient stratification with careful treatment selection is advocated to maximize the risk:benefit ratio. Intra-articular hyaluronic acid as a next step provides sustained clinical benefit with effects lasting up to 6 months after a short-course of weekly injections. As a last step before surgery, the slow titration of sustained-release tramadol, a weak opioid, affords sustained analgesia with improved tolerability.
Background: The use of platelet-rich plasma (PRP) for the treatment of osteoarthritis (OA) has demonstrated mixed clinical outcomes in randomized controlled trials when compared with hyaluronic acid (HA), an accepted nonsurgical treatment for symptomatic OA. Biological analysis of PRP has demonstrated an anti-inflammatory effect on the intra-articular environment. Purpose: To compare the clinical and biological effects of an intra-articular injection of PRP with those of an intra-articular injection of HA in patients with mild to moderate knee OA. Study design: Randomized controlled trial; Level of evidence, 1. Methods: A total of 111 patients with symptomatic unilateral knee OA received a series of either leukocyte-poor PRP or HA injections under ultrasound guidance. Clinical data were collected before treatment and at 4 time points across a 1-year period. Synovial fluid was also collected for analysis of proinflammatory and anti-inflammatory markers before treatment and at 12 and 24 weeks after treatment. Several measures were used to assess results: (1) Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale; (2) International Knee Documentation Committee (IKDC) subjective knee evaluation, visual analog scale (VAS) for pain, and Lysholm knee score; and (3) difference in intra-articular biochemical marker concentrations. Results: There were 49 patients randomized to treatment with PRP and 50 randomized to treatment with HA. No difference was seen between the groups in the primary outcome measure (WOMAC pain score). In the secondary outcome measure, linear contrasts identified a significantly higher IKDC score in the PRP group compared with the HA group at 24 weeks (mean ± standard error [SE], 65.5 ± 3.6 vs 55.8 ± 3.8, respectively; P = .013) and at final follow-up (52 weeks) (57.6 ± 3.37 vs 46.6 ± 3.76, respectively; P = .003). Linear contrasts also identified a statistically lower VAS score in the PRP group versus the HA group at 24 weeks (mean ± SE, 34.6 ± 3.24 vs 48.6 ± 3.7, respectively; P = .0096) and 52 weeks (44 ± 4.6 vs 57.3 ± 3.8, respectively; P = .0039). An examination of fixed effects showed that patients with mild OA and a lower body mass index had a statistically significant improvement in outcomes. In the biochemical analysis, differences between groups approached significance for interleukin-1β (mean ± SE, 0.14 ± 0.05 pg/mL [PRP] vs 0.34 ± 0.16 pg/mL [HA]; P = .06) and tumor necrosis factor α (0.08 ± 0.01 pg/mL [PRP] vs 0.2 ± 0.18 pg/mL [HA]; P = .068) at 12-week follow-up. Conclusion: We found no difference between HA and PRP at any time point in the primary outcome measure: the patient-reported WOMAC pain score. Significant improvements were seen in other patient-reported outcome measures, with results favoring PRP over HA. Preceding a significant difference in subjective outcomes favoring PRP, there was a trend toward a decrease in 2 proinflammatory cytokines, which suggest that the anti-inflammatory properties of PRP may contribute to an improvement of symptoms. Registration: (Identifier: NCT02588872).
Objective: To describe the evolution of the use and reporting of propensity score (PS) analysis in observational studies assessing a surgical procedure. Background: Assessing surgery in randomized controlled trials raises several challenges. Observational studies with PS analysis are a robust alternative for comparative effectiveness research. Methods: In this methodological systematic review, we identified all PubMed reports of observational studies with PS analysis that evaluated a surgical procedure and described the evolution of their use over time. Then, we selected a sample of articles published from August 2013 to July 2014 and systematically appraised the quality of reporting and potential bias of the PS analysis used. Results: We selected 652 reports of observational studies with PS analysis. The publications increased over time, from 1 report in 1987 to 198 in 2013. Among the 129 reports assessed, 20% (n = 24) did not detail the covariates included in the PS and 77% (n = 100) did not report a justification for including these covariates in the PS. The rate of missing data for potential covariates was reported in 9% of articles. When a crossover by conversion was possible, only 14% of reports (n = 12) mentioned this issue. For matched analysis, 10% of articles reported all 4 key elements that allow for reproducibility of a PS-matched analysis (matching ratio, method to choose the nearest neighbors, replacement and method for statistical analysis). Conclusions: Observational studies with PS analysis in surgery are increasing in frequency, but specific methodological issues and weaknesses in reporting exist.
Purpose This study was performed to compare the efficacy of treatment in three groups of patients with knee osteoarthritis (OA) given an intra-articular injection of platelet-rich plasma (PRP), hyaluronic acid (HA) or ozone gas. Methods A total of 102 patients with mild–moderate and moderate knee OA who presented at the polyclinic with at least a 1-year history of knee pain and VAS score ≥4 were randomly separated into three groups. Group 1 (PRP group) received intra-articular injection of PRP × 2 doses, Group 2 (HA group) received a single dose of HA, and Group 3 (Ozone group) received ozone × four doses. Weight-bearing anteroposterior–lateral and Merchant’s radiographs of both knees were evaluated. WOMAC and VAS scores were applied to all patients on first presentation and at 1, 3, 6 and 12 months. Results At the end of the 1st month after injection, significant improvements were seen in all groups. In the 3rd month, the improvements in WOMAC and VAS scores were similar in Groups 1 and 2, while those in Group 3 were lower (p < 0.001). At the 6th month, while the clinical efficacies of PRP and HA were similar and continued, the clinical effect of ozone had disappeared (p < 0.001). At the end of the 12th month, PRP was determined to be both statistically and clinically superior to HA (p < 0.001). Conclusion In the treatment of mild–moderate knee OA, PRP was more successful than HA and ozone injections, as the application alone was sufficient to provide at least 12 months of pain-free daily living activities. Level of evidence Therapeutic study, Level I.
Background: Platelet-rich plasma (PRP) injections have become an intriguing treatment option for osteoarthritis (OA), particularly OA of the knee. Despite the plethora of PRP-related citations, there is a paucity of high-level evidence that is comparable, cohort specific, dose controlled, injection protocol controlled, and double-blinded. Purpose: To determine the safety and efficacy of leukocyte-poor PRP autologous conditioned plasma (ACP) for knee OA treatment through a feasibility trial regulated by the US Food and Drug Administration (FDA). Study design: Randomized controlled trial; Level of evidence, 1. Methods: In accordance with FDA protocol, patient selection was based on strict inclusion/exclusion criteria; 114 patients were screened, and 30 were ultimately included in the study. These patients were randomized to receive either ACP (n = 15) or saline placebo (n = 15) for a series of 3 weekly injections. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores served as the primary efficacy outcome measure. Patients were followed for 1 year. Results: No adverse events were reported for ACP administration. Furthermore, the results demonstrated no statistically significant difference in baseline WOMAC scores between the 2 groups. However, in the ACP group, WOMAC scores at 1 week were significantly decreased compared with baseline scores, and the scores for this group remained significantly lower throughout the study duration. At the study conclusion (12 months), subjects in the ACP group had improved their overall WOMAC scores by 78% from their baseline score, compared with 7% for the placebo group. Conclusion: ACP is safe and provides quantifiable benefits for pain relief and functional improvement with regard to knee OA. No adverse events were reported for ACP administration. After 1 year, WOMAC scores for the ACP subjects had improved by 78% from their baseline score, whereas scores for the placebo control group had improved by only 7%. Other joints affected with OA may also benefit from this treatment.