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C OPYRIGHT 2016 BY T HE J OURNAL OF B ONE AND J OINT S URGERY, I NCORPORATED

Hyaluronic Acid Injections for Treatment of

Advanced Osteoarthritis of the Knee
Utilization and Cost in a National Population Sample
Jack W. Weick, BS, Harpreet S. Bawa, MD, and Douglas R. Dirschl, MD

Investigation performed at the Department of Orthopaedic Surgery and Rehabilitation Medicine,

Division of Biological Sciences, University of Chicago, Chicago, Illinois

Background: The prevalence of knee osteoarthritis is increasing in the aging U.S. population. The efcacy and cost-
effectiveness of the use of hyaluronic acid (HA) injections for the treatment of knee osteoarthritis are debated. In this
study, we assessed the utilization and costs of HA injections in the 12 months preceding total knee arthroplasty (TKA) and
evaluated the usage of HA injections in end-stage knee osteoarthritis management in relation to other treatments.
Methods: MarketScan Commercial Claims and Encounters and Medicare Supplemental and Coordination of Benets
databases (Truven Health Analytics) were reviewed to identify patients who underwent TKA from 2005 to 2012. The
utilization of patient-specic osteoarthritis-related health care (including medications, corticosteroid injections, HA in-
jections, imaging, and ofce visits) and payment information were analyzed for the 12 months preceding TKA.
Results: A total of 244,059 patients met the inclusion criteria. Of those, 35,935 (14.7%) had 1 HA injection in the 12
months preceding TKA. HA injections were responsible for 16.4% of all knee osteoarthritis-related payments, trailing only
imaging studies (18.2%), and HA injections accounted for 25.2% of treatment-specic payments, a rate that was higher
than that of any other treatment. Patients receiving HA injections were signicantly more likely to receive additional knee
osteoarthritis-related treatments compared with patients who did not receive HA injections.
Conclusions: Despite numerous studies questioning the efcacy and cost-effectiveness of HA injections for osteoar-
thritis of the knee, HA injections are still utilized for a substantial percentage of patients. Given the paucity of data
supporting the effectiveness of HA injections and the current cost-conscious health-care climate, decreasing their use
among patients with end-stage knee osteoarthritis may represent a substantial cost reduction that likely does not
adversely impact the quality of care.

Peer review: This article was reviewed by the Editor-in-Chief and one Deputy Editor, and it underwent blinded review by two or more outside experts. It was also reviewed
by an expert in methodology and statistics. The Deputy Editor reviewed each revision of the article, and it underwent a nal review by the Editor-in-Chief prior to publication.
Final corrections and clarications occurred during one or more exchanges between the author(s) and copyeditors.

T
he prevalence of osteoarthritis is increasing in the aging
U.S. population; recent estimates indicate that approx-
imately 46 million people in the U.S. have symptomatic
osteoarthritis1. Osteoarthritis of the knee impairs quality of life
and is the primary clinical indication for total knee arthro-
plasty (TKA)2. In 2013, more than 732,000 primary TKAs were
performed in the U.S., and the annual number continues to
rise3,4. The increasing number of TKAs can be attributed to
the safety and cost-effectiveness of the procedure in the set-
ting of a growing elderly population and the higher prevalence
of obesity 5,6.
Treatment guidelines for knee osteoarthritis suggest at
least 6 months of nonoperative treatment prior to considering
a TKA7. The specic nonsurgical treatments recommended by
various sources have changed over time7-9. The goal of intra-
articular injection of hyaluronic acid (HA) is to improve the
lubrication of the knee joint by enhancing the viscoelastic
properties of the synovial uid10. It also has been suggested that
HA may have anti-inammatory and analgesic properties11.
Despite these theoretical benets, the efcacy of treatment with
HA injections has been called into question. A number of meta-
analyses, the earliest from more than a decade ago, have suggested

Disclosure: No external funding was received for this investigation. The Disclosure of Potential Conicts of Interest forms are provided with the online
version of the article.

J Bone Joint Surg Am. 2016;98:1429-35 d http://dx.doi.org/10.2106/JBJS.15.01358


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TABLE I Patient Demographics
HA Group Non-HA Group P Value
No. of patients 35,935 208,124
Mean age (yr) 64.7 64.9 0.002
Female 64.5% 60.7% <0.001
Mean CCI score 0.060 0.043 <0.001
Commercial 56.9% 55.5% <0.001
insurance
that HA injections may not be effective and may actually be
associated with a greater risk of adverse events12-14. The 2008
guidelines of the American Academy of Orthopaedic Surgeons
(AAOS) for the nonoperative treatment of osteoarthritis of the
knee stated that the evidence for the use of HA injections was
inconclusive8. Updated AAOS guidelines in 2013 included a
strong recommendation against the use of HA8. In contrast, a
position statement by the American College of Rheumatology
supported the use of HA injections in the management of knee
osteoarthritis in patients who cannot tolerate nonsteroidal anti-
inammatory drugs (NSAIDs)15. Despite these contradictory
recommendations, the costly injections continue to be admin-
istered in large numbers. In 2012, Medicare paid $207 million
for HA preparations alone16. Furthermore, each HA injection
generates an additional charge for its administration, thereby
raising the cost and making administration lucrative for pro-
viders. The high costs to the health-care system of HA injections
despite the paucity of supporting evidence for their clinical ef-
fectiveness warrants further investigation into their use.
Population-level data would be helpful to better charac-
terize the magnitude of HA use and its role in end-stage knee
osteoarthritis; to our knowledge, such data have not been pre-
viously published. The purpose of the current study was to
examine a national sample of patients to assess the utilization
of, and payments for, the use of HA injections in the treatment
of end-stage knee osteoarthritis, which was dened as the 12
months prior to TKA. Additionally, we sought to compare the
use of HA injections with that of other osteoarthritis treatments,
such as corticosteroid injections, prescription narcotic and non-
narcotic analgesic medications, and physical therapy, in this
patient population.
Materials and Methods
Data Source
T his was a retrospective cohort study conducted using the MarketScan Com-
mercial Claims and Encounters (commercial insurance) and Medicare
Supplemental and Coordination of Benets (Medicare with supplemental com-
mercial insurance) databases (Truven Health Analytics). The databases provide
de-identied, integrated, person-specic claims data for approximately 17 to
51 million individuals per year. The commercial insurance database includes
health-care claims information for individuals with insurance through a com-
mercial provider or a self-insuring employer under fee-for-service, fully capi-
tated, or partially capitated health plans. The database for Medicare with
supplemental commercial insurance includes claims information for indi-
viduals with both Medicare and commercial employer-sponsored coverage.
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Patients are included in the Medicare database only if they have supplemental
commercial insurance in addition to Medicare. All claims reect the coor-
dination of benets between the commercial insurer and Medicare such that
all payments made by either entity are captured within the database. The age
distribution in the database is representative of the overall Medicare popu-
lation. International Classication of Diseases, Ninth Revision (ICD-9) di-
agnosis codes and Current Procedural Terminology (CPT)-4 codes can be
identied in individual claims. The data include claims made from both inpatient
and outpatient clinical encounters as well as claims for prescription medica-
tions. Information regarding durable medical equipment and certain injections
can also be identied using Healthcare Common Procedure Coding System
(HCPCS) codes. National Drug Codes (NDCs) are utilized to organize pre-
scription medication claims. The NDCs specify both the type and dosage of
the prescribed medication.
Study Sample
The databases were reviewed for subjects with a CPT-4 code for TKA (CPT-4 =
27447) from 2005 to 2012. Because TKA is the nal common pathway for
patients with end-stage osteoarthritis of the knee, identifying TKA patients and
assessing their treatment history is a valid method of examining the manage-
ment of end-stage knee osteoarthritis. To be included in the study cohort, these
TKA subjects were required to have prescription medication information in-
cluded in the database, continuous enrollment in the database for at least 12
months prior to TKA, and an associated diagnosis of osteoarthritis of the
lower leg. Patient-specic knee osteoarthritis-related health-care informa-
tion was gathered for the 12 months prior to TKA. Data collected included
the utilization of, and payment information for, HA injections, analgesic med-
ications, corticosteroid injections, imaging of the knee, non-TKA knee pro-
cedures (arthroscopies and unicondylar knee arthroplasties), durable medical
equipment relating to the knee (including canes, crutches, wheelchairs, walkers,
knee braces, cold therapy, and continuous passive motion devices), outpatient
ofce evaluations, and physical and occupational therapy. Prescription analgesic
medications were divided into narcotic analgesics or non-narcotic analgesics
on the basis of NDC. Specic NDC, CPT-4, ICD-9, and HCPCS codes are
provided in the Appendix.
Charlson comorbidity index (CCI) scores were calculated for each
17
subject using ICD-9 codes for comorbidities, as previously described . Mean
age, percentage of female patients, CCI scores, and geographic region were
compared between patients who received an HA injection in the 12 months
prior to TKA (the HA group) and those who did not receive an HA injection
(the non-HA group). Chi-square tests were performed for categorical variables
and Student t tests were performed for continuous variables. All statistical
analyses were performed with SAS software (version 9.3; SAS Institute).
Utilization Analysis
All HA injection claims were recovered. We then performed descriptive sta-
tistical analysis of the HA group and calculated the mean number of injections
per patient. Variations exist in how HA injections are administered. Some
guidelines recommend 1 injection per week for 3 weeks, whereas others
18
recommend once-weekly injections for 5 weeks . The number of HA injec-
tion claims per year in the study period was calculated; these data were ex-
pressed as claims per 100,000 TKAs per year to control for variations in the
numbers of TKAs performed each year.
Payment Analysis
Payment analysis was performed using payment information for each claim
supplied by the databases. For individuals with Medicare with supplemental
commercial coverage, all payments made for each individual claim by both the
supplemental commercial insurance and Medicare were captured in this anal-
ysis. All payments were adjusted to 2012 U.S. dollars using the Medical Con-
sumer Price Index.
Payments included were specic to knee osteoarthritis-related health
care. For example, if an osteoarthritis-related procedure occurred while the
patient was admitted as an inpatient, only the osteoarthritis-related claims
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Association of HA Utilization with Other Knee Osteoarthritis-

TABLE II Odds of Receiving Other Knee Osteoarthritis-Related Related Health Care
Care Among Those Receiving HA Injection in the
12 Months Prior to TKA* Further analysis was conducted to assess the use of osteoarthritis-related
treatment modalities in the HA and non-HA groups. The groups were analyzed
OR 95% CI separately to evaluate utilization of other forms of knee osteoarthritis treat-
ment, specically, corticosteroid injections, prescription narcotic and non-
Corticosteroid injection 4.172 4.073-4.274 narcotic analgesic medications, and physical therapy. Multivariate logistic
Narcotic analgesics 2.178 2.128-2.230 regression analysis was performed to compare the prevalence of these inter-
ventions in the study period in the HA group compared with the non-HA
Non-narcotic analgesics 2.545 2.467-2.582 group. The model controlled for the effects of age, sex, insurance status, CCI
Physical therapy 2.231 2.172-2.292 score, and region.

*Odds ratios are relative to those who did not receive an HA injection. Results
Multivariate logistic regression analysis adjusted for the effects of Population Characteristics
age, sex, insurance status, CCI score, and region.

A total of 244,059 subjects met the inclusion criteria; 55.7%

payments were included; other hospital fees with ICD-9 and CPT-4 codes
unrelated to osteoarthritis were excluded. Payment information related to HA
and corticosteroid injections included payments for the administration of the
injection as well as for the medication. Payments associated with HA injections
were compared with those associated with other forms of knee osteoarthritis-
related health care to assess the role the injections played in the overall cost of
care received in the 12 months prior to TKA.
were covered under commercial insurance and 44.3%, under
Medicare with a commercial supplement (Fig. 1). Overall, 61.2%
of the study population was female, and 38.8% was male. A total
of 35,935 patients (14.7% of the study population) had 1 claim
for HA injection in the 12 months preceding TKA. A signicantly
greater percentage of the HA group (64.5%) was female com-
pared with the non-HA group (60.7%) (p < 0.001). Signicant
differences between the groups were also demonstrated for age,

Fig. 1
Study sample selection from the MarketScan databases, 2005 to 2012.
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Fig. 2
Total hyaluronic acid injection claims per 100,000 TKA patients for each year during the study period.

insurance status, and CCI score (Table I); however, these dif-
ferences did not appear to be clinically important.
HA Injection Utilization
Among the 14.7% of the study population who received 1 HA
injection in the 12 months preceding TKA, the mean number
of injections received was 3.6. Between 2004 and 2012, the
number of HA injections per 100,000 patients in the study pop-
ulation ranged from a low of 24,030 in 2004 to a high of 30,914
in 2008 (Fig. 2).
HA Payment Analysis
Total payments associated with HA injections in the study
cohort amounted to $40,547,881 over the study period. The
mean payment per individual HA injection was $310, and the
mean total payment for HA injections per patient receiving an
HA injection (all HA injections for a patient) was $1,128. HA
injections accounted for 16.4% of all knee osteoarthritis-related
health-care payments in the study population. HA injections
ranked as the second highest knee osteoarthritis-related health-
care expenditure, behind only imaging (knee radiography and
magnetic resonance imaging [MRI]), which accounted for
18.2% of payments (Fig. 3-A). Outpatient ofce evaluations and
prescription non-narcotic analgesic medications accounted for
16.0% and 14.9% of payments, respectively. Corticosteroid in-
jections and non-TKA knee procedures represented 11.9% and
11.6% of payments. Next were prescription narcotic analgesic
medications, durable medical equipment, and physical and oc-
cupational therapy, at 6.3%, 2.9%, and 2.0% of payments,
respectively.

Fig. 3-A
Percentage of total payments by type of knee osteoarthritis (OA)-related health care received, including evaluative services. PT = physical therapy,
and OT = occupational therapy.
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Fig. 3-B
Percentage of total payments by type of knee osteoarthritis (OA)-related palliative treatment received. PT = physical therapy.
When focusing on payments specic to treating knee os-
teoarthritis (excluding ofce visits and imaging, which are eval-
uative expenses), HA injections emerged as the largest expenditure,
accounting for 25.2% of payments (Fig. 3-B). Prescription non-
narcotic analgesic medications (22.9%) and corticosteroid in-
jections (18.2%) ranked as second and third, respectively.
Multivariate Analysis to Characterize the Role of HA in
Patient Care
Multivariate logistic regression analysis controlling for the ef-
fects of age, sex, insurance status, CCI score, and region showed
that patients in the HA group demonstrated an increased like-
lihood of also having received other knee osteoarthritis-related
care (Table II). Patients in the HA group were 4.2 times more
likely to have also received 1 corticosteroid injection in the study
period than those in the non-HA group (odds ratio [OR] = 4.172;
95% condence interval [CI] = 4.073 to 4.274). Patients in the
HA group were also 2.2 times more likely to have received
1 prescription for a narcotic analgesic medication (OR = 2.178;
95% CI = 2.128 to 2.230), 2.5 times more likely to have received
1 prescription for a non-narcotic analgesic medication (OR =
2.545; 95% CI = 2.467 to 2.582), and 2.2 times more likely to
have had physical therapy (OR = 2.231; 95% CI = 2.172 to 2.292).
Discussion
D espite the paucity of data supporting the efcacy of HA
injections, they are still widely administered, as demon-
strated by the rate in the present study, in which 14.7% of pa-
tients received HA injections within the 12 months preceding
TKA. Patients treated with HA injection received an average of
3.6 injections during this time period. This may be due to ex-
isting guidelines, which recommend 3 to 5 weekly injections in
a single treatment course18. We found that HA injections were
more likely to be administered in the 12 months preceding TKA
to patients who are female (64.5% of the HA group compared
with 60.7% of the non-HA group; p < 0.001), who are younger
H YA L U R O N I C A C I D I N J E C T I O N S FOR T R E AT M E N T OF A D VA N C E D
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(mean age of 64.7 years compared 64.9 years; p = 0.002), and
who have more comorbid conditions (mean CCI score of 0.060
compared with 0.043; p < 0.001) (Table I). Although the dif-
ferences noted in age and CCI score were signicant, the small
difference in absolute values observed is likely of little clinical
importance.
Patients who received an HA injection were signicantly
more likely to receive additional knee osteoarthritis-related
treatments, being over 4 times more likely to receive a corti-
costeroid injection (OR = 4.172), and approximately twice as
likely to be prescribed narcotic analgesic medication (OR =
2.178), non-narcotic analgesic medication (OR = 2.545), or
physical therapy (OR = 2.231) compared with the non-HA
group (Table II). These results indicate that patients receiv-
ing HA injections prior to TKA are, generally speaking, high
utilizers of treatments directed at osteoarthritis of the knee
compared with patients not receiving HA injections. It also
indicates that HA treatments, rather than replacing other knee
osteoarthritis-related treatments, appear to be used in addition
to other forms of treatment. Whether this is because of these
patients having more advanced disease, because of a lack of
effectiveness of HA injections, or because these patients have
better access to care cannot be determined from this study and
warrants investigation.
Although this study does not permit an assessment of the
effectiveness of HA injections, the study data indicate that HA
injections are still highly utilized, despite the ndings of prior
studies questioning their effectiveness as well as clinical guide-
lines published by the AAOS discouraging their use. As shown in
Figure 2, the rate of utilization of HA injection remained rela-
tively stable during the study period. The high utilization of HA
injection also results in substantial health-care costs. HA injec-
tions represented 16.4% of all knee osteoarthritis-related health-
care payments in this patient population, second only to imaging
studies (18.2%). When evaluative expenses were excluded and
the analysis was focused specically on treatment expenses, HA
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injections emerged as the single largest expense in the study
population, accounting for 25% of payments. Furthermore,
intra-articular corticosteroid injections, which are an estab-
lished treatment modality for symptomatic knee osteoarthritis,
only represented 11.9% of total payments and 18.2% of treatment-
specic payments. Additionally, physical therapy, an effective,
relatively low-cost option, appeared to be underutilized (only
15.1% of the patients had a claim for physical therapy in the
12 months prior to TKA) and accounted for only a small frac-
tion of the osteoarthritis-related health-care cost (1.8% of
treatment-specic payments). These results highlight that,
despite the controversy surrounding the efcacy of HA injec-
tions, they continue to constitute a substantial portion of pay-
ments in the treatment of end-stage knee osteoarthritis and are
more costly than all other currently utilized treatment mo-
dalities. While it is possible that HA injections could be ben-
ecial for a certain subset of patients with specic phenotypes,
we are unaware of any studies that have been able to success-
fully identify such an individual prole. A decrease in the use of
HA injections in end-stage knee osteoarthritis could reduce the
overall health-care cost burden, potentially without causing an
adverse effect on outcomes.
The study utilized Truven Health Analytics MarketScan
Commercial Claims and Encounters and Medicare Supplemental
and Coordination of Benets databases, which allow for large
sample sizes but also have inherent limitations. Although the
databases are likely a representative sample of the overall popu-
lation, they do not include patients without insurance or on
Medicaid, or claims that may have been led under a different
system, such as Veterans Affairs. Additionally, claims information
in the databases does not designate the laterality of the injections
or of the eventual TKA. It is possible that treatments under study
were designated for the knee contralateral to the knee of interest,
or, in the case of analgesic prescriptions, for diseases other than
osteoarthritis of the knee. However, this is unlikely to have had a
major impact on our ndings given that the study included
244,059 patients and only 3% of the study population had a
subsequent TKA claim in the 6 months following the index TKA.
Therefore, it is reasonable to assume that the osteoarthritis-
related expenses evaluated pertained mostly to the joint that was
eventually replaced. The databases only contain claims infor-
mation and do not include any knee function or pain scores; as
such, we cannot comment on the patient-related outcomes of
HA injection but merely on the utilization of other modalities in
addition to HA injection. The study design did not permit the
determination of who prescribed the HA injections or other
treatments (e.g., the primary care physician or an orthopaedic
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Appendix
A table showing the codes and drug information used in
the identication of knee osteoarthritis-related health care
is available with the online version of this article as a data sup-
plement at jbjs.org. n
Jack W. Weick, BS1
Harpreet S. Bawa, MD1
Douglas R. Dirschl, MD1
1Pritzker School of Medicine (J.W.W.) and Department of Orthopaedic
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