Research Article
Analysis of the Cost and Efficacy of Intra-Articular
Knee Injections
Sean Pirkle, MD
Henry Seidel, BS
Sarah Bhattacharjee, BS
Lewis L. Shi, MD
Michael J. Lee, MD
Jason A. Strelzow, MD
From the Department of Orthopaedics and
Sports Medicine, University of Washington,
Seattle, WA (Pirkle); the Pritzker School of
Medicine, University of Chicago, Chicago, IL
(Seidel, Bhattacharjee); and the Department of
Orthopaedic Surgery and Rehabilitative
Medicine, University of Chicago Medicine,
Chicago, IL (Shi, Lee, and Strelzow).
Correspondence to Dr. Pirkle: scpirkle@uw.edu
Shi has been a paid consultant for Depuy
Synthes. Lee has been a paid consultant for
Depuy Synthes, Stryker Spine, and Globus
Medical.
JAAOS Glob Res Rev 2022;6: e21.00203
DOI: 10.5435/JAAOSGlobal-D-21-00203
Copyright 2022 The Authors. Published by
Wolters Kluwer Health, Inc. on behalf of the
American Academy of Orthopaedic Surgeons.
This is an open access article distributed under
the Creative Commons Attribution License 4.0
(CCBY), which permits unrestricted use,
distribution, and reproduction in any medium,
provided the original work is properly cited.
Journal of the AAOS Global Research & Reviews ®
ABSTRACT
Introduction: Intra-articular joint injections have been used with the
goal of providing patients with symptomatic relief. Recently, however,
the efficacy of corticosteroid (CS) and hyaluronic acid (HA) injections in
the management of knee osteoarthritis (OA) is questionable. In this
analysis, we investigated the costs associated with injections by
assessing overall use, conversion and average time to total knee
arthroplasty (TKA), and reimbursement.
Methods: Patients aged 50 to 70 years with a knee-related diagnosis
of pain, effusion, or OA were identified in the Humana insurance
national data set. Patients who received intra-articular injections were
stratified by the type and number of injection(s) received. The
subsequent rates of TKA were compared with Kaplan-Meier curves for
patients who underwent CS injections, HA injections, and a
benchmarking cohort of patients with OA and no history of knee
injections in the medical record. Average time to TKA was determined
from index diagnosis, and total cost was compared using Wilcoxon
rank sum analyses.
Results: A total of 778,686 patients were identified. Of these, 637,112
had no knee injection history, while 124,129 received CS and 17,445
received HA injections. The 10-year conversion to TKA was highest in
HA cohort (31.6%), followed by the CS cohort (24.0%) and the
noninjection cohort (7.3%) (P , 0.001). Time to TKA increased with
number of injections for both injection types. For patients who
underwent TKA, median cost was greater in HA ($16,687) and CS
($15,563) cohorts relative to noninjection cohort ($14,733) (P , 0.001).
Discussion: Compared with the noninjection cohort, both HA and CS
cohorts experienced increased costs and increased time to TKA.
However, while the cost incurred in HA cohort was greater than that in
CS cohort, no appreciable benefit was demonstrated for conversion or
time to TKA. Therefore, if intra-articular knee injections are indicated for
the nonsurgical management of knee OA, the results of this study
support CS over HA.
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February 2022, Vol 6, No 2 © American Academy of Orthopaedic Surgeons
Intra-Articular Knee Injections
K
nee osteoarthritis (OA) is one of the most fre-
quently encountered orthopaedic conditions,
affecting more than 9.3 million adults and
accounting for more than $27 billion in annual healthcare
expenditures in the United States alone.1,2 Although OA is
known to be caused by wear and tear on knee joint
cartilage,3 current treatment modalities target different
aspects of the condition and follow a tiered approach.4-6
Medical management often begins with acetaminophen
and nonsteroidal anti-inflammatory drugs to address
inflammatory mediators, while physical therapy im-
proves outcomes for symptomatic pain and stiffness.7 As
the condition severity worsens, affected joints may be
managed with intra-articular injections or operative
management with total knee arthroplasty (TKA).8
The efficacy of joint injections, however, presents a
contentious topic. While corticosteroid (CS) injections
have been repeatedly found to offer rapid onset pain re-
lief, they have not demonstrated long-term effects.9
Although they are the most widely used intra-articular
therapy for OA,10 reviews on CS injections have
reported pain relief duration spans as short as 1 week11
and up to 6 weeks,12 while effects past that window
remain under debate.4,12 CS injections may paradoxi-
cally induce cartilage damage over time and increase the
risk of OA progression.13 Similarly, the outcomes of
hyaluronic acid (HA) injections are contested, with the
long-term efficacy of this treatment modality unproven.
Comparatively, the pain relief provided by HA seems
enduring than that by CS injections, with several studies
suggesting HA outperforms CS beyond 8 weeks from
treatment.14 HA is also designed to restore and protect
the physiologic environment of the joint capsule, which,
in principle, is a positive effect on function.15 However,
perceived benefits are weighed against a higher price
point and the context of industry-backed studies with a
preponderance for many of the positive findings cur-
rently published in peer-reviewed journals.16
Notwithstanding injection type, outcomes studies
published in the orthopaedic literature primarily focus on
short-term pain scales to compare injection types.4,9,11,12,14
Because the injections themselves are designed with the
goal of symptomatic relief in avoidance of escalated care
in the form of joint replacement, using TKA as the
foundation of a clinical analysis is justified if not war-
ranted. With this study, we sought to investigate the
trends related to the proportion of patients with OA
Shi or an immediate family member serves as a paid consultant to Depuy Synthes. Lee or an immediate family member serves as a paid consultant to
Depuy Synthes. None of the following authors or any immediate family member has received anything of value from or has stock or stock options held
in a commercial company or institution related directly or indirectly to the subject of this article: Pirkle, Seidel, Bhattacharjee, Shi, Lee, and Strelzow.
2
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Journal of the AAOS Global Research & Reviews ®
receiving injections and to report the number of CS and
HA injections received by patients and the efficacy of
intra-articular joint injections regarding rate and time to
TKA. Moreover, we aimed to examine the reimburse-
ment related to various treatments for knee OA and the
associated costs in all patients treated with intra-
articular joint injections and perform a subanalysis of
those who specifically went on to receive TKA.
Methods
Database
This study was conducted within PearlDiver, a national
administrative claims database with more than 25 mil-
lion patients. Records span from the years 2008 to 2018.
With medical, prescription, and laboratory data, records
are searchable through physician billing codes, including
Current Procedural Terminology (CPT) and Interna-
tional Classification of Disease, 9th and 10th revision
(ICD-9 and ICD-10) codes.
Patient Selection
All patients who underwent an intra-articular knee
injection were identified by CPT-20610. Because large
joint injections may not be specific to the knee, a knee-
related diagnosis code for knee pain, effusion, or OA was
required to be present on the same day as the injection
procedure. Patients were then stratified by the type of
injection administered based on Healthcare Common
Procedure Coding System J codes for either CS or HA
injections. Laterality of the injection and the injection
type were confirmed with CPT modifiers, and the num-
ber of injections administered within patients’ record
was determined using count codes with each instance of
an injection counted as a single injection; a series of
shots was counted as multiple shots in this study and
not a single event. Patients lacking laterality modifiers or
patients who received both injection types (CS and HA)
were excluded. Any patient with a history of platelet-
rich plasma injection into the knee joint was excluded as
well. A comparator group was defined by patients with
the knee-related diagnosis codes for knee pain, effusion,
or OA who had no history of intra-articular knee in-
jections at any point in their disease course. Finally, all
patients were restricted to those between the ages of 50
and 70 years at the time of their first injection or knee-
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February 2022, Vol 6, No 2 © American Academy of Orthopaedic Surgeons

related diagnosis. The selected age range was chosen
because it represents a time when patients are generally
optimal candidates for both joint injection and TKA.
Because patients in PearlDiver are accessible through
deidentified insurance records, data may not be reported
secondary to a change of insurance, loss to follow-up, or
death, for instance. To minimize the effect of reporting
bias, when indicated, patients were excluded from further
study when they were found to no longer have active re-
cords in the data set, with active records defined as unin-
terrupted enrollment with the insurance carrier.
Outcome Measures
The rate of ipsilateral TKA and the average time to TKA
from the date of indexed knee-related diagnosis was as-
sessed for all patients. Patients were further stratified by type
of injection and number of injections administered. A cost
comparison was performed to determine any differences in
reimbursement between injection cohorts and control sub-
jects. Reimbursement data included all hospital and/or
clinic visits, imaging, physical therapy, and prescription
medication filled, provided the knee-related diagnosis was
coded as either the primary or secondary problem in the
patient record. The terms cost, payment, and reimburse-
ment are used interchangeably and represent the actual
amount paid by the insurer. The median reimbursement for
the continuum of care received from initial knee-related
diagnosis was first assessed for all patients in this study.
Subsequently, a calculation of the median reimbursement
for those who converted to TKA was conducted and strat-
ified by treatment wing (noninjection, CS, and HA). For
patients who were managed nonsurgically, cost collection
stopped at the end of the study period; for patients treated
surgically, tracking was halted the day after surgery.
Statistical Analysis
All nominal variables were compared using chi-square
tests. Conversion to TKA was evaluated for the injection
cohorts and the noninjection group using Kaplan-Meier
survival curves with log-rank tests. Statistical signifi-
cance was set to P , 0.05. For nonnormally distributed
data such as reimbursement, Wilcox rank-sum tests
were used to compare cohorts with median, first quartile
(Q1), and third quartile (Q3) used as descriptive sta-
tistics to minimize skew by outlying individuals.
Results
Rate of Intra-articular Injections
A total of 778,686 patients matched the inclusion criteria.
Statistical differences in age, sex, race, and Elixhauser
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Journal of the AAOS Global Research & Reviews ® February 2022, Vol 6, No 2
Sean Pirkle, MD, et al
Research Article
Comorbidity Index existed between the three treatment
arms, with demographic information presented in Table
1. Among these patients, 637,112 did not have a history
of intra-articular knee injections, while 141,574 received
at least one intra-articular knee injection (86.7% CS
versus 13.3% HA).
Of the patients receiving CS injections, most (65.0%)
were administered only one injection with fewer receiving
2 (21.6%), 3 (5.9%), 4 (3.5%), and 51 (4.0%) injections
(Table 2). Of the patients receiving HA injections, 25.6%
were administered only one injection, with a compara-
tively larger proportion receiving multiple injections (2
(16.8%), 3 (25.0%), 4 (7.1%), and 51 (25.5%)). In both
injection cohorts, the gross number of injections was not
found to be associated with conversion to TKA.
Comparison of CS and HA Injections
When directly comparing the two injection cohorts
regarding the rate of TKA, CS injections were found to
significantly outperform HA. After 1 year of knee-related
diagnosis, 4.4% of patients treated with CS injections
had undergone TKA. For patients active at 10 years
follow-up, 24.0% had undergone TKA. The rates were
5.1% and 31.6% at 1 and 10 years for patients treated
with HA injections, respectively (Figure 1; P , 0.001).
For patients who did not receive an injection, 7.3% had
undergone TKA by 10 years after diagnosis.
When investigating average time to TKA for the subset
of patients receiving injections who ultimately converted
to TKA, one CS injection was associated with an average
time to TKA of 615.6 days; one HA injection was
associated with a time to TKA of 671.2 days. Among
patients receiving more than one injection, CS was
associated with greater time to TKA relative to HA, with
approximately 143.1 days gained with each additional
injection and nearly double that of HA (average of
72.1 days gained per additional injection). For the non-
injection group, the average time to TKA was observed to
be 342.4 days from knee-related diagnosis. A compari-
son regarding time to TKA is fully depicted in Figure 2.
Cost Analysis
In our analysis of cost, the median reimbursement for the
care received for knee-related diagnoses without intra-
articular injection administration was $178 (Table 3).
The median cost was relatively higher in patients
receiving intra-articular joint injections (CS: median cost
$601 in patients receiving one injection and $1610 for
five or more; HA: median cost $1554 in patients
receiving one injection and $2752 for five or more).
With an increasing number of injections received,
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© American Academy of Orthopaedic Surgeons
Intra-Articular Knee Injections

Table 1. Baseline Characteristics of Patient Cohort

Patient Group
Noninjection CS HA
N = 637,112 N = 124,129 N = 17,445 P-Value
Characteristic
Age
50-54 96,761 (15.2) 15,112 (12.2) 1,967 (11.3) ,0.001
55-59 117,359 (18.4) 20,842 (16.8) 2,912 (16.7) ,0.001
60-64 128,501(20.2) 27,762 (22.4) 3,620 (20.8) ,0.001
65-69 294,491(46.2) 60,413 (48.7) 8,946 (51.3) ,0.001
Sex
Female 382,330 (60.0) 79,709 (64.2) 11,021 (63.2) ,0.001
Male 254,782 (40.0) 44,420 (35.8) 6,424 (36.8)
Race
Asian 3,369 (0.5) 411 (0.3) 64 (0.4) ,0.001
Black 78,441 (12.3) 13,152 (10.6) 1,521 (8.7) ,0.001
Hispanic 7,980 (1.3) 1,071 (0.9) 130 (0.7) ,0.001
Native 1,077 (0.2) 164 (0.1) 31 (0.2) 0.012
White 331,129 (52.0) 67,868 (54.7) 9,982 (57.2) ,0.001
Unknown 215,116 (33.8) 41,463 (33.4) 5,717 (32.8) 0.002
ECI 5.83 6 4.44 6.09 6 4.40 5.78 6 4.27 ,0.001

ANOVA = analysis of variance, CS = corticosteroid, ECI = Elixhauser comorbidity index

Groups were compared using Chi-square analyses for categorical variables and ANOVA for linear variables.
P is significant at , 0.05.

whether CS or HA, the associated costs rose sequen-
tially. For patients requiring TKA for the treatment of
their knee-related diagnosis, the median cost was sig-
nificantly greater in HA patients ($16,688) relative to
CS ($15,563; P , 0.001) and the noninjection group
($14,733; P , 0.001) (Figure 3).
Discussion
TKA offers profound benefits to patients in both pain
alleviation and functional outcomes.17,18 However, for
some patients with knee OA, TKA may not be a viable
treatment, and even among surgical candidates, many
may seek to delay or avoid surgery altogether. A number
of reasons for this have been cited, with the most fre-
quently reported including concerns over interference
with work and life-events and perception of surgery-
related pain.19,20 For the latter group, intra-articular
injections are a common strategy for providing
symptomatic relief while potentially postponing the
need for TKA because roughly 30% of TKA patients
receive knee injections before their procedure.21-26
Despite their popularity, the use of injections to pre-
vent disease progression has been driven more so by
dogma than contemporary evidence-based literature
because neither CS nor HA injections have been consis-
tently shown to prevent conversion to or delay TKA. In
fact, in the 2013 guidelines for the nonsurgical treatment
of osteoarthritis, the AAOS issued a strong recommen-
dation against the use of HA injections,27 finding that the
current literature was unable to demonstrate a clinically
effective response to HA injections.6 In addition, the
guidelines could not recommend for or against the use of
CS injections due to conflicting evidence.28 Because of
this ambiguity, in this study we sought to define the
clinical utility of intra-articular injections and compare
which injection type carries the most value, if any at all.
In this study, 18.2% of patients with knee-related diag-
noses underwent intra-articular injection. Although some-
what lower than rates reported in the literature, to isolate the
effect of each type of injection, we excluded individuals
fitting criteria for both treatment groups (and any platelet-
rich plasma injection) and, consequently, effectively low-
ered the proportion of patients receiving injections. Of those

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Journal of the AAOS Global Research & Reviews ® February 2022, Vol 6, No 2 © American Academy of Orthopaedic Surgeons
 Sean Pirkle, MD, et al

Research Article
Table 2. Rate of TKA Stratified by Number of Injections Received
Patient Group N Total N TKA Rate of TKA
Noninjection 637,112 20,140 0.0316
CS
1 injection 80,664 6,906 0.0856
2 injections 26,826 2,161 0.0806
3 injections 7,322 790 0.1079
4 injections 4,377 347 0.0793
51 injections 4,940 344 0.0696
HA
1 injection 4,463 636 0.1425
2 injections 2,929 273 0.0932
3 injections 4,353 625 0.1436
4 injections 1,243 117 0.0941
51 injections 4,457 349 0.0783

CS = corticosteroid, HA = Hyaluronic acid, TKA = total knee arthroplasty

Noninjection represents patients who did not receive intra-articular knee injection throughout the study period.

included in either the CS or HA injection group, CS in- received, hypothesized to be an indicator of severity of knee
jections alone were far more common than HA injections joint pathology, did not correlate with an increased likeli-
alone. Of interest, an increasing number of joint injections hood of conversion to TKA in either injection cohort. The

Figure 1

Graph showing Kaplan-Meier survival curve of rate of total knee arthroplasty in patients with a diagnosis of knee osteoarthritis, pain, or
effusion. Noninjection represents patients who did not receive intra-articular knee injection throughout duration of study period;
Corticosteroid represents patients receiving one or more intra-articular corticosteroid injections before total knee arthroplasty (TKA).
Hyaluronic acid (HA) represents patients receiving one or more intra-articular hyaluronic acid injections before total knee arthroplasty.
P , 0.001, log-rank analysis.

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Journal of the AAOS Global Research & Reviews ® February 2022, Vol 6, No 2 © American Academy of Orthopaedic Surgeons
Intra-Articular Knee Injections

Figure 2

Graph showing average time to total knee arthroplasty (TKA) stratified by number of injections received and injection contents.
Noninjection represents patients who did not receive intra-articular knee injection throughout the study period.

authors conjecture this is possibly due to an overrepresen- Overall, for patients receiving one injection who ulti-
tation of patients who may not be surgical candidates and mately went on to TKA, both groups (CS, 615.6 days;
were thus more likely to receive strictly intra-articular in- HA, 671.2 days) experienced greater time from diagnosis
jections as definitive management of their OA. to TKA compared with noninjection group (342.4 days).

Table 3. Total Cost of Care for Patients Diagnosed With Knee Osteoarthritis, Pain, Effusion Stratified by Treatment
Received, and Number of Injections (if Applicable)

All Patients TKA Patients

N Q1 Median Q3 N Q1 Median Q3
Noninjection 637112 71 178 611 20,140 13,205 14,773 17,854
CS
1 injection 80,664 260 601 2194 6,906 13,728 15,408 19,141
2 injections 26,826 387 834 2,945 2,161 13,879 15,617 19,484
3 injections 7,322 564 1225 4,518 790 14,112 16,080 21,450
4 injections 4,377 621 1,250 3,782 347 14,026 16,076 20,639
51 injections 4,940 848 1,610 4,226 344 13,973 16,418 22,278
HA
1 injection 4,463 824 1,554 5,085 636 14,390 15,978 19,603
2 injections 2,929 932 1,733 4,140 273 14,161 16,624 21,758
3 injections 4,353 947 1,661 4,777 625 14,657 16,533 21,360
4 injections 1,243 1,326 2,270 4,935 117 15,125 17,557 22,791
51 injections 4,457 1,612 2,753 5,834 349 15,371 17,498 23,541

CS = corticosteroid, HA = hyaluronic acid, Q1: first quartile; Q3: third quartile, TKA = total knee arthroplasty
All patients represent all patients matching inclusion criteria, regardless of treatment outcome. TKA patients represent a subset of total cohort
who required TKA after initial treatment with or without intra-articular joint injection. All prices are reported in US dollars (USD).

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Figure 3
Graph showing total cost of care for patients diagnosed with knee osteoarthritis, pain, and effusion who required total knee arthroplasty
(TKA) after initial treatment, stratified by treatment received. All prices are reported in US dollars (USD). Q1 = first quartile, Q3 = third
quartile. P , 0.001, Wilcoxon rank-sum test.
Therefore, we assume that the differences in the total
number of days would suggest a delaying effect from the
injection on the time to TKA. For each subsequent
injection after the first, HA was found to offer less benefit
when compared with CS (average 1 143.1 days from
diagnosis to TKA for the CS cohort and 172.1 days for
the HA cohort). Of note, HA injections are often mar-
keted to consumers in bundled packs (e.g., three and
five). The number of patients observed receiving HA
injections was consistent with this practice because most
patients received one, three, or five injections total, with
fewer receiving two or four injections. Although both
groups were noted to have better outcomes relative to
patients who did not receive injections regarding time
from knee-related diagnosis to TKA, in contrast to
industry claims,9,16 these data suggest decreasing mar-
ginal returns with increasing number of HA injections.
These bundled packs are not specifically coded for
billing purposes, so it cannot be confirmed at what stage
of a bundled pack patients may be at or whether they are
participating in a bundled treatment therapy at all, nor
can the subjective experience of symptoms at time of HA
injection be as specific as that of CS. Accordingly, the
utility of comparing multiple HA injections with mul-
tiple CS injections is restricted by the bundled method of
delivery.
When directly comparing conversion to TKA in CS
group with that in HA group over the course of the 10-
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Journal of the AAOS Global Research & Reviews ®
Sean Pirkle, MD, et al
Research Article
year follow up, CS (24.0% at 10 years) cohort was found
to outperform HA cohort (31.6% at 10 years), although
both cohorts were observed to fare worse than their
noninjection counterpart (7.3% at 10 years). Further-
more, CS was found to be significantly more cost effective
relative to HA. Although both injection modalities may
initially result in lower costs for patients, over time, the
utilization of injections for OA accrue increased down-
stream healthcare expenses in comparison with patients
who elect to initially undergo TKA.29 The differences in
cost observed in this study are similar to those in pre-
vious studies, which found the average cost of CS in-
jections to be $437 in 20132 compared with $900 per
HA injection in 2013.30 Although HA was more
expensive compared with CS, we did not observe a
clinical benefit in this analysis.
Limitations
With this study, we analyzed the records of nearly
800,000 knee OA patients and investigated the man-
agement strategies for their OA, the rate of conversion to
TKA, and the reimbursement data linked to outcomes as
measured by primary joint replacement. However, as
with any large database study, we are limited by a
number of factors. First, the accuracy of the data ana-
lyzed is dependent on physician billing codes from
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February 2022, Vol 6, No 2 © American Academy of Orthopaedic Surgeons
Intra-Articular Knee Injections
numerous providers and care settings. Second, by ana-
lyzing patients who only received either CS or HA in-
jections, we cannot comment on the potential effects of
receiving both types of injections. In addition, some
degree of controversy exists regarding the specific
molecular structure of the HA injected and its variable
effect on disease progression,31,32 details that are not
specified in the patient record. Because of this, all HA
types are therefore treated as a single group. The issue of
differences exists in baseline OA because our analysis
begins at the first instance of a diagnosis code for knee
OA, which may differ in severity between patients and
cannot be confirmed with radiographic evidence. By
aggregating thousands of OA patients in each of our
cohorts and excluding patients with contralateral dis-
ease or multiple injection types received, we have at-
tempted to minimize the degree of heterogeneity. Of
course, when comparing patients who received in-
jections to those who did not, it is likely the case that
patients receiving injections are at different stages along
the management paradigm for their disease and there-
fore have requested or been advised to undergo these
treatment options. The survival curves plotting con-
version to TKA reflect this assumption. Thus, although
our rate of conversion in patients who did not undergo
injections is consistent with published studies using
similar methodologies,33 the noninjection cohort is
primarily useful as a benchmarking group for providing
context to the rates observed in the injection cohorts,
rather than as a control group.
Conclusion
In conclusion, we recommend counseling patients that
neither CS nor HA injections were particularly successful
in staving off eventual conversion to TKA. However, for
patients seeking nonsurgical treatment, intra-articular
joint injections—particularly CS injections over HA—
may offer a short-term cost-effective option in the
management of knee OA.
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