„„ Knee

Intra-­articular corticosteroid
S. R. W. Wijn,
M. M. Rovers,
T. G. van Tienen,
G. Hannink
From Radboud
Institute for Health
Sciences, Radboud
University Medical
Center, Nijmegen, The
Netherlands
injections increase the risk of requiring
knee arthroplasty
a multicentre longitudinal observational study using
data from the Osteoarthritis Initiative
Aims
Recent studies have suggested that corticosteroid injections into the knee may harm the
joint resulting in cartilage loss and possibly accelerating the progression of osteoarthritis
(OA). The aim of this study was to assess whether patients with, or at risk of developing,
symptomatic osteoarthritis of the knee who receive intra-­articular corticosteroid injections
have an increased risk of requiring arthroplasty.
Methods
We used data from the Osteoarthritis Initiative (OAI), a multicentre observational cohort
study that followed 4,796 patients with, or at risk of developing, osteoarthritis of the knee
on an annual basis with follow-­up available up to nine years. Increased risk for symptomat-
ic OA was defined as frequent knee symptoms (pain, aching, or stiffness) without radiolog-
ical evidence of OA and two or more risk factors, while OA was defined by the presence of
both femoral osteophytes and frequent symptoms in one or both knees. Missing data were
imputed with multiple imputations using chained equations. Time-­dependent propensity
score matching was performed to match patients at the time of receving their first injec-
tion with controls. The effect of corticosteroid injections on the rate of subsequent (total
and partial) knee arthroplasty was estimated using Cox proportional-­hazards survival
analyses.

Results
After removing patients lost to follow-­up, 3,822 patients remained in the study. A total of
249 (31.3%) of the 796 patients who received corticosteroid injections, and 152 (5.0%) of
the 3,026 who did not, had knee arthroplasty. In the matched cohort, Cox proportional-­
hazards regression resulted in a hazard ratio of 1.57 (95% confidence interval (CI) 1.37 to
1.81; p < 0.001) and each injection increased the absolute risk of arthroplasty by 9.4% at
nine years’ follow-­up compared with those who did not receive injections.

Conclusion
Corticosteroid injections seem to be associated with an increased risk of knee arthroplasty
in patients with, or at risk of developing, symptomatic OA of the knee. These findings sug-
gest that a conservative approach regarding the treatment of these patients with cortico-
steroid injections should be recommended.

Cite this article: Bone Joint J 2020;102-B(5):586–592.

Correspondence should be Introduction of pain, although the effect is often temporary.2,3

sent to S. R. W. Wijn; email:
​Stan.​Wijn@​radboudumc.​nl
© 2020 The British Editorial
Society of Bone & Joint Surgery
doi:10.1302/0301-620X.102B5.
BJJ-2019-1376.R1 $2.00
Bone Joint J
2020;102-B(5):586–592.
The routine treatment of patients with osteo-
arthritis (OA) of the knee currently includes a
combination of physiotherapy, analgesia, and
surgery where necessary.1 Intra-­articular cortico-
steroid injections may be used for the management
The safety of recurrent corticosteroid injections,
however, remains unknown. Studies dealing with
the long-­ term complications of intra-­ articular
injections have reported contradictory findings.4-6
It thus remains unclear whether these injections

586 The Bone & Joint Journal

 Intra-­articular corticosteroid injections increase the risk of requiring knee arthroplasty
can be safely used in these patients. Corticosteroids have a time-
and dose-­dependent effect on articular cartilage. High doses,
frequent injections, or both, such as > 3 mg per injection or a
cumulative dose of 18 to 24 mg, have been shown to be associ-
ated with gross cartilage damage and chondrocyte toxicity. Low
doses, such as < 2 mg to 3 mg per injection or a cumulative dose
of 8 to 12 mg, have been shown to increase cell growth and
recovery from cartilage damage.7 Two randomized controlled
trials have investigated the long-­term effect of intra-­articular
injections on articular cartilage. Raynauld et al5 reported no
long-­term harmful effects of corticosteroid injections on the
anatomical structure of the knee when injections were repeated
every three months for two years. McAlindon et al,4 however,
reported that the same pattern of repeated injections resulted in
loss of cartilage volume without a long-­term effect on knee pain
after two years, compared with saline injections. The adverse
effect on cartilage volume was, however, small and possibly
not clinically relevant. Others have indicated that corticosteroid
injections are mainly used for acute symptoms and that repeated
injections at three-­monthly intervals do not reflect routine clin-
ical practice, reducing the generalizability of the findings.8
More recently, Zeng et al6 studied the effects of intra-­articular
corticosteroid injections on the radiological Kellgren and
Lawrence (KL) grade of OA9 and the width of the joint space in
patients with grade 2 or 3 OA. They concluded that injections
increase the risk of worsening the grade of OA and joint space
narrowing by three-­fold compared with patients who did not
receive injections. Although the radiological assessment of the
progression of OA using the KL grade or joint space narrowing
can be valuable, radiological features of OA do not always
correlate with symptoms and vice versa.10 Knee pain is ulti-
mately the indication for arthroplasty. The aim of this study was
to assess whether patients with, or at risk of developing, symp-
tomatic OA of the knee and have corticosteroid injections have
an increased risk of undergoing (total or partial) arthroplasty.
Methods
Study design. This study used data from the Osteoarthritis
Initiative (OAI) database which is available for public access
at https://​data-​archive.​nimh.​nih.​gov/​oai/. It is a multicentre,
longitudinal cohort study which included patients with, or at
risk of developing, symptomatic OA of the knee. Patients were
enrolled between February 2004 and May 2006 in four centres
and were followed up for nine years. The present study was
conducted and reported according to STROBE guidelines.11
Patients. The patients in the OAI cohort were divid-
ed into a progression cohort and an incidence cohort. The
progression cohort consisted of patients with symptomatic
OA of the knee, defined as having tibial-­femoral osteophytes
(OARSI (Osteoarthritis Research Society International) atlas
grade 1 to 3;12 definite osteophytes and mild to severe joint
space narrowing) at baseline and pain, aching, or stiffness on
most days of the month during the previous year. The inci-
dence cohort consisted of patients without symptomatic OA of
the knee (OARSI atlas grade 0;12 no osteophytes or joint space
narrowing), but with an increased risk of developing sympto-
matic OA in one or both knees. The increased risk was defined
as either frequent symptoms without radiological evidence of
VOL. 102-B, No. 5, May 2020
587
OA, the presence of osteophytes in one or both knees but not
in combination with frequent symptoms in the same knee, or at
least two additional risk factors for OA (knee symptoms in the
previous 12 months, obesity, a history of injury to the knee or
of knee surgery, family history of OA-­related arthroplasty of
the knee, Heberden’s nodes, repetitive daily flexion of the knee,
and age between 70 and 79 years).
The other inclusion criteria were patients aged between 45
and 79 years, living in the USA. Exclusion criteria included
inflammatory arthritis, contraindications to 3-­Tesla MRI,
and bilateral end-­stage OA of the knee. The OAI protocol is
available at http://​data-​archive.​nimh.​nih.​gov/​binaries/​content/​
documents/​ndacms/​resources/​oai/​oai-​study-​protocol/​oai-​study-​
protocol/​ndacms%​3Aresource. The cohort consisted of 4,674
patients, with a progression cohort of 1,390 (30%) and an
incidence cohort of 3,284 (70%). At the final follow-­up, 2,938
completed nine years of follow-­up, 844 had sporadic missing
follow-­up visits, and 852 were lost to follow-­up with structural
missing data (more than half of follow-­up was missing) due to
patient withdrawal and/or consent not having been obtained at
the time of extension of the study after the initial 48 months of
follow-­up. The latter were excluded from the analyses. After
removing patients lost to follow-­up, 3,822 patients remained
with a mean age of 61 years (45 to 79) at baseline and 2,233
(58%) were female.
Variables. At the baseline and annual follow-­up visits, between
one and nine years, a large set of variables were collected,
from which we extracted the following details at each visit:
age, sex, physical activity, body mass index (BMI), education
(categorized in ‘less than high school graduate’, ‘high school
graduate’, ‘some college’, ‘college graduate’, ‘some graduate
school’, ‘graduate degree’), occupational activities, access to
health care, health insurance cover, treatment centre, family
history of knee arthroplasty surgery, clinical variables (medi-
cation use, history of knee surgery, knee symptoms, number of
hyaluronic acid injections, radiological signs of OA (according
to the KL grading scale of the knee and hand), quality of life
measurements (12-­Item Short Form Survey (SF-12),13 func-
tional scores (Knee injury and Osteoarthritis Outcome Score
(KOOS),14 and Western Ontario and McMasters Osteoarthritis
index (WOMAC).15
Whether the patients had received an intra-­articular injection
or undergone (total or partial) arthroplasty was recorded at each
visit. For those who had received bilateral injections, the first
knee that was treated was selected for inclusion. For all other
patients, the left or right knee was selected randomly.
Statistical analysis. Because of the annual follow-­up visits,
the exact time of both the injections and arthroplasty were un-
known, so this was approximated by taking a random day of the
year (by random sampling a value between one and 365) indi-
cating the day between the follow-­up visit at which the injection
or arthroplasty was reported and the preceding visit.
Patient characteristics at baseline had a small percentage
of missing values (< 1%). The KOOS Function in Sport and
Recreation (KOOS FSR) subdomain that had 944 (25%)
missing values. All missing values (as described in Table I)
were imputed using multivariate imputation by chained equa-
tions creating ten independent imputed datasets. We performed
588 S. R. W. Wijn, M. M. Rovers, T. G. van Tienen, G. Hannink

Table I. Characteristics of patients in the overall cohort and the propensity matched datasets at time of the first intra-­articular corticosteroid
injection.
Characteristic Missing at Entire cohort at baseline (n = 3,822) Matched cohort at time of first injection*
baseline, n (%) (n = 1,366)
Treated (n = 796) Control (n = 3,026) SMD Treated (n = 683) Control (n = 683) SMD
Mean age (SD) 0 (0) 62.4 (8.9) 60.9 (9.1) 0.00 68.4 (9.6) 68.4 (9.8) 0.00
Gender, female, % 0 (0) 63.4 57.1 0.11 62.7 62.1 0.01
Mean BMI, kg/m2 (SD) 71 (1.9) 29.8 (4.8) 28.3 (4.7) 0.00 29.7 (4.8) 29.7 (5.3) 0.00
Mean physical activity (PASE)† (SD) 0 (0) 159.9 (83.8) 164.7 (82.2) 0.00 141.2 (75.2) 141.9 (81.2) 0.00
Health care access and health 0 (0) 97.7 96.6 0.06 98.8 98.6 0.01
insurance coverage, %
Education (> college graduate),‡ % 0 (0) 56.0 62.9 -0.11 56.3 57.1 -0.01
Family history of knee arthroplasty 58 (1.5) 16.3 14.6 0.04 15.8 15.8 0.00
surgery, %
Occupational activities, % 0 (0) 72.4 72.4 0.00 72.6 72.2 0.01
Medication use, % 0 (0) 69.8 51.1 0.32 87.3 88.5 -0.03
Hand OA at baseline, % 0 (0) 23.8 21.1 0.05 23.7 23.9 0.00
History of knee surgery at 0 (0) 21.8 12.1 0.21 21.2 20.8 0.01
baseline, %
Knee symptoms at baseline, % 15 (1.0) 64.0 43.6 0.34 62.2 61.3 0.02
Radiological OA at baseline,§ % 25 (1.0) 53.0 38.5 0.24 52.0 51.8 0.00
Mean KOOS Knee related QoL§ 0 (0) 57.7 (22.3) 68.9 (20.9) 0.00 50.5 (20.3) 50.5 (22.5) 0.00
(SD)
Mean KOOS Knee symptoms§ (SD) 0 (0) 79.2 (18.2) 87.9 (13.9) 0.00 71.7 (18.8) 71.8 (20.1) 0.00
Mean KOOS Pain§¶ (SD) 0 (0) 76.0 (19.8) 86.4 (16.1) 0.00 66.7 (19.4) 66.7 (22.1) 0.00
Mean KOOS FSR§¶ (SD) 944 (24.7) 58.2 (27.0) 73.5 (24.8) 0.00 49.4 (26.5) 49.0 (27.3) 0.00
Mean WOMAC stiffness§, ** (SD) 0 (0) 2.2 (1.8) 1.4 (1.5) 0.05 2.6 (1.8) 2.6 (1.9) 0.00
Mean WOMAC pain§, †† (SD) 0 (0) 3.9 (3.8) 2.1 (3.0) 0.00 5.7 (4.0) 5.6 (4.4) 0.00
Mean WOMAC disability§, ‡‡ (SD) 0 (0) 11.5 (12.7) 6.9 (10.2) 0.00 16.9 (12.6) 17.1 (14.2) 0.00
Mean SF-12 Physical scale (SD) 0 (0) 46.5 (9.4) 50.1 (8.4) 0.00 42.2 (9.9) 42.2 (10.3) 0.00
Mean SF-12 Mental scale (SD) 0 (0) 53.8 (8.5) 53.7 (7.7) 0.00 54.1 (9.0) 54.0 (9.2) 0.00
*Time-­dependent propensity score matching resulted in 1,366 matched patients.
†0 to 400.
‡Education is categorized in ‘less than high school graduate’, ‘high school graduate’, ‘some college’, ‘college graduate’, ‘some graduate school’,
and ‘graduate degree’.
§Knee-­specific variable available for both left and right knee. Standardized mean difference < 0.1 is considered appropriate balance.18
¶0 to 100.
**0 to 8.
††0 to 20.
‡‡0 to 68.
BMI, body mass index; FSR, function in sport and recreation; IAC, intra-­articular corticosteroid; KOOS; Knee injury and Osteoarthritis Outcome
Score; OA, osteoarthritis; QoL, quality of life; SF-12, 12-­Item Short Form Survey; SMD, standardized mean difference; WOMAC, Western Ontario
and McMasters Osteoarthritis index.

time-­dependent propensity score matching (tdPSM) to match
patients at the time of their first injection with available
controls at any given timepoint using a 1:1 matching algorithm
and nearest neighbour matching with a caliper of 0.05.16 The
propensity score was defined as the probability of receiving
intra-­articular injections based on patient characteristics (age,
sex, BMI, physical activity, health care access, treatment centre,
education, family history with OA, occupation), clinical vari-
ables (medication use, grade of knee and hand OA at baseline,
knee symptoms at baseline), quality of life (SF-12 subscales),
and functional scores (KOOS and WOMAC). Covariate
balance was assessed by calculating standardized mean differ-
ences (SMDs) between patients and controls. Patients with a
balance < 0.10 SMD were assumed to have appropriate balance
and were visually inspected using balance plots.17 Balance was
assessed for every annual follow-­up visit for all imputed data-
sets. The overall balance of all visits and the imputation sets
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combined was evaluated by calculating the average standard-
ized absolute mean difference (ASAMD).18
The effect of intra-­articular injections on the risk of under-
going (total or partial) arthroplasty was estimated using Cox
proportional hazards survival analyses with cumulative injec-
tions as a time-­dependent covariate and time to (total or partial)
arthroplasty as the dependent variable. The Cox proportional
hazards survival analyses were performed for each imputation
dataset and the estimates were pooled using Rubin’s Rule.19
Statistical significance was set at p < 0.05.
In order to assess the clinical relevance of the estimated
effect, the increase in absolute risk per injection was derived
from the Cox proportional hazard model.20 All analyses were
performed in R (version 3.5.2, The R Foundation for Statistical
Computing, Vienna, Austria), using packages ‘mice’, ‘MatchIt’,
and ‘cobalt’. As a sensitivity analysis, the effect of injections on
the risk of arthroplasty was also estimated in the unmatched
The Bone & Joint Journal
 Intra-­articular corticosteroid injections increase the risk of requiring knee arthroplasty 589

Fig. 1

Flowchart showing patient selection. Of the 796 patients who received intra-­articular corticosteroid (IAC) injections, 683 were matched at their first
injection with 683 controls. The dotted line represents 113 patients treated with injections who would receive treatment later during follow-­up but
were matched as controls. KAS, knee arthroplasty surgery; tdPSM, time-­dependent propensity score matching.

cohort. The progression and incidence cohorts were analyzed
separately to detect potential differences between them.
Results
At follow-­up of nine years, 796 (20.8%) had received one or
more intra-­articular injection(s). The mean number of injec-
tions was (1.55 (1 to 8)) while 401 (10.5%) underwent (total
or partial) arthroplasty. Of those who received injections, 249
(31.3%) underwent arthroplasty, and of the 3,026 patients who
did not receive injections, 152 (5.0%) underwent arthroplasty
(Figure 1). The baseline characteristics are shown in Table I.
Additionally, 288 patients received a hyaluronic acid injection.
Time-­dependent propensity score matching resulted in 1,366
matched patients in total for every imputed dataset; 683 patients
at the time of their first injection were matched to 683 control
patients at different time points that were at risk of receiving
injections. Because the annual follow-­up visits were matched
sequentially, 113 treated patients (of the 796) were matched
as controls before they received their first injection. Some
controls had multiple time points matched to two different
treated patients. Thus, at one-­ year follow-­up, two treated
patients received their first injection and were matched to a
single control at four- and eight-­year follow-­up resulting in 23
double matches. In total, 1,343 unique patients were matched
(Figure 1). At every time point, most characteristics were well
VOL. 102-B, No. 5, May 2020
balanced with SMDs < 0.10 (Figure 2). The overall covariate
balance was appropriate with an ASAMD of 0.072 (SD 0.005).
The hazard ratio (HR) for arthroplasty was estimated to be
1.57 (95% confidence interval (CI) 1.37 to 1.81; p < 0.001) for
each cumulative injection. Each injection increased the absolute
risk of arthroplasty by 9.4% at nine years’ follow-­up compared
with patients who did not receive injections. Sensitivity analysis
of the unmatched cohort showed a HR of 2.15 (95% CI 1.96 to
2.38; p < 0.001) for each cumulative injection. The pooled HRs
of the incidence and progression sub-­cohorts were 1.78 (95%
CI 1.42 to 2.23; p < 0.001) and 1.41 (95% CI 1.19 to 1.67; p <
0.001), respectively (Figure 3).
Discussion
We found that intra-­ articular corticosteroid injections
seemed to be associated with an increased risk of (total or
partial) arthroplasty of the knee in patients with, or at risk of
developing, symptomatic OA of the knee. The HR was 1.57
(95% CI 1.37 to 1.81) for each subsequent injection. The results
suggest that by nine years of follow-­up, each injection increased
the absolute risk of requiring arthroplasty by 9.4% compared
with similar patients who did not receive injections. This is in
line with previous studies showing that intra-­articular corti-
costeroid injections have a detrimental effect on the articular
590 S. R. W. Wijn, M. M. Rovers, T. G. van Tienen, G. Hannink

Fig. 2

Covariate balance at each timepoint before and after propensity score matching, pooled for the imputation sets. The dark grey lines indicate the
standardized mean difference between the intervention and control groups before matching. The light grey lines indicate the standardized mean
difference between the intervention and control groups after matching. Dotted vertical lines represent -0.10 and 0.10 standardized mean difference;
a standardized mean difference between these lines indicates good balance between patients who received intra-­articular corticosteroid (IAC)
injections and those who did not. BMI, body mass index; FSR, function in sport and recreation; KOOS; Knee injury and Osteoarthritis Outcome
Score; OA, osteoarthritis; QoL, quality of life; SF-12, 12-­Item Short Form Survey; WOMAC, Western Ontario and McMasters Osteoarthritis index.

cartilage of the knee, possibly accelerating the progression of
OA.4,6,7
Zeng et al6 studied the association between intra-­articular
injections and KL grade and joint space narrowing using OAI
data and reported a HR of 3.02 (95% CI 2.19 to 4.16) and 4.67
(95% CI 2.92 to 7.47) for deteriorating grade of OA and 2.93
(95% CI 2.13 to 4.02) and 3.26 (95% CI 1.78 to 5.96) for joint
space narrowing for initial and continuous intra-­articular injec-
tions, respectively, which is higher compared with our results.
This difference can be explained by differences in population,
treatment, outcome, and duration of follow-­up. Zeng et al only
included patients with a KL score of 2 or 3 with a maximum
follow-­up of four years, did not estimate the risk per cumulative
injection, and used the progression of radiological OA as the
outcome of interest.
Our results may be explained by several independent
or combined hypothetical reasons. Corticosteroids induce
chondrocyte toxicity and gross cartilage loss and inflamma-
tion.7 Loss of cartilage can increase symptoms, increasing the
probability that patient and physician will opt for arthroplasty.
Local anaesthetic agents, such as bupivacaine or lidocaine,
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which are injected with corticosteroids, have been shown to be
chondrotoxic, especially in an already inflamed or damaged
knee, contributing to cartilage loss.21 Secondly, although we
adjusted for several patient characteristics such as education,
occupation, health care access, and health insurance cover,
patients who received injections may be more likely to receive
treatment because they experience pain differently, lowering
their threshold to seek attention.22,23 Consequently, they may
be more likely to undergo arthroplasty than patients who have
similar levels of pain and function. Thirdly, the reduction of pain
might increase the range of movement of the knee, provoking
peak stress and increasing the strain on the joint. This may lead
to increased degradation of cartilage.
The strength of our study is the large number of patients,
who were followed for nine years in an observational setting
using data from the OAI. This database was developed to docu-
ment the natural history of OA of the knee across a wide range
of patients with different grades of OA and characteristics,
using regular follow-­up and standardized questionnaires. This
enabled us to analyze and compare patient characteristics, clin-
ical variables, and standardized quality of life and functional
The Bone & Joint Journal
 Intra-­articular corticosteroid injections increase the risk of requiring knee arthroplasty
Fig. 3
Hazard ratios with 95% confidence intervals. Values > 1 indicate that
intra-­articular corticosteroid (IAC) injections had an increased risk of
arthroplasty compared with those who did not receive injections. The
results are shown for the primary analysis, the unmatched cohort, the
incidence cohort, and the progression cohort. KAS, knee arthroplasty
surgery.
scores, both at baseline and at the time of treatment. Those
who received injections had, in general, higher pain scores
and lower functional scores compared with those who did not
receive injections. We used tdPSM to create matches of patients
at the time of their first injection, instead of regular propensity
score matching that achieves a covariate balance at baseline.16,24
This resulted in comparable patients at the time of treatment,
eliminating changes that occurred between their inclusion at the
start of the study and their first injection. Thus, a patient who
reported their first injection at the fifth follow-­up visit might
have a lower functional score compared with a control whose
function was similar at baseline.
Some potential limitations should be highlighted. Time-­
dependent propensity score matching was used to account for
bias, but there remains a risk of residual confounding due to vari-
ables which were either not measured or not included. However,
the relationship between injections and arthroplasty appears to
be robust. The sensitivity analyses that were performed showed
similar effects. Treatment regimens for intra-­articular injec-
tions and arthroplasty might have changed during the study
period, which might reduce the generalizability of the findings.
We noticed a small increase in the rate of injections and arthro-
plasty with the passage of time during the study period of nine
years. However, this could also be due to the increasing age of
the cohort and progression of OA. A proportion of the patients
who were treated with injections also received hyaluronic acid
injections into the knee; of the 288 patients that received a hyal-
uronic acid injection, 218 (76%) also received corticosteroid
injections. We analyzed the effect of hyaluronic acid on our
results by including it once as a covariate in the propensity score
model and once as a variable in the Cox proportional hazard
VOL. 102-B, No. 5, May 2020
591
model. In both cases, hyaluronic acid did not alter the effect found
in our analysis. A portion of the OAI had incomplete follow-­up
of patients who received an injection, therefore we excluded
852 patients from the analysis. This was essential because the
missing values were, in those with incomplete follow-­up, struc-
tural and could not be assumed to be missing at random. In
order to check if the analysis had an impact on the results, we
additionally performed a last observation carried forward impu-
tation as sensitivity analysis to impute the subsequent missing
values. This method showed a similar result compared with our
analysis. Lastly, we used arthroplasty as the ultimate endpoint of
OA progression. Ideally, in order to assess the association between
intra-­articular injections and arthroplasty, radiological evidence
of cartilage deterioration such as KL grade or cartilage volume
should be included in the matching algorithm to improve the
balance between the two groups. Unfortunately, the OAI did not
routinely acquire MRIs and radiographs annually, and if available,
a large portion were missing. Nevertheless, we do not expect that
the inclusion of radiological evidence would change our conclu-
sions, as we included a wide range of variables relating to the
progression of disease such as pain, and functional and quality
of life scores in our model to account for potential imbalances
between the two groups.
In conclusion, intra-­articular corticosteroid injections seem to
be associated with an increased risk of knee arthroplasty, for each
cumulative injection in patients with, or at risk of developing,
symptomatic OA of the knee. These findings suggest that a conser-
vative approach to injections of corticosteroids into the knee joint
to treat symptoms related to OA should be recommended.
Take home message
-- Corticosteroid injections seem to be associated with an
increased risk of knee arthroplasty in patients with, or at risk
of developing, symptomatic osteoarthritis of the knee.
-- These results suggest that a conservative approach regarding the
treatment of these patients with corticosteroid injections should be
recommended.
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References
1. McAlindon TE, Bannuru RR, Sullivan MC, et  al. OARSI guidelines for
the non-­ surgical management of knee osteoarthritis. Osteoarthritis Cartilage.
2014;22(3):363–388.
2. He W-­W, Kuang M-­J, Zhao J, et al. Efficacy and safety of intraarticular hyaluronic
acid and corticosteroid for knee osteoarthritis: a meta-­ analysis. Int J Surg.
2017;39:95–103.
3. Liu S-­H, Dubé CE, Eaton CB, et  al. Longterm effectiveness of intraarticular
injections on patient-­ reported symptoms in knee osteoarthritis. J Rheumatol.
2018;45(9):1316–1324.
4. McAlindon TE, LaValley MP, Harvey WF, et  al. Effect of intra-­ articular
triamcinolone vs saline on knee cartilage volume and pain in patients with knee
osteoarthritis: a randomized clinical trial. JAMA. 2017;317(19):1967–1975.
5. Raynauld J-­P, Buckland-­Wright C, Ward R, et al. Safety and efficacy of long-­
term intraarticular steroid injections in osteoarthritis of the knee: a randomized,
double-­blind, placebo-­controlled trial. Arthritis Rheum. 2003;48(2):370–377.
6. Zeng C, Lane NE, Hunter DJ, et  al. Intra-­ Articular corticosteroids and the
risk of knee osteoarthritis progression: results from the osteoarthritis initiative.
Osteoarthritis Cartilage. 2019;27(6):855–862.
592 S. R. W. Wijn, M. M. Rovers, T. G. van Tienen, G. Hannink
7. Wernecke C, Braun HJ, Dragoo JL. The effect of intra-­articular corticosteroids on
articular cartilage. Orthop J Sports Med. 2015;3(5):232596711558116.
8. Maloney WJ, Jevsevar DS, Shea KG. Long-­Term intra-­articular steroid injections
and knee cartilage. JAMA. 2017;318(12):1184–1185.
9. Kellgren JH, Lawrence JS. Radiological assessment of osteo-­arthrosis. Ann
Rheum Dis. 1957;16(4):494–502.
10. Guermazi A, Niu J, Hayashi D, et al. Prevalence of abnormalities in knees detected
by MRI in adults without knee osteoarthritis: population based observational study
(Framingham osteoarthritis study). BMJ. 2012;345:e5339.
11. von Elm E, Altman DG, Egger M, et  al. The strengthening the reporting of
observational studies in epidemiology (STROBE) statement: guidelines for reporting
observational studies. Int J Surg. 2014;12(12):1495–1499.
12. Altman R, Hochberg M, Murphy W, Wolfe F, Lequesne M. Atlas of individual
radiographic features in osteoarthritis. Osteoarthritis and Cartilage. 1995;3(A):3–70.
13. Ware J, Kosinski M, Keller SD. A 12-­Item short-­form health survey: construction of
scales and preliminary tests of reliability and validity. Med Care. 1996;34(3):220–233.
14. Roos EM, Roos HP, Lohmander LS, Ekdahl C, Beynnon BD. Knee Injury and
Osteoarthritis Outcome Score (KOOS)--development of a self-­administered outcome
measure. J Orthop Sports Phys Ther. 1998;28(2):88–96.
15. Bellamy N, Buchanan WW, Goldsmith CH, Campbell J, Stitt LW. Validation
study of WOMAC: a health status instrument for measuring clinically important patient
relevant outcomes to antirheumatic drug therapy in patients with osteoarthritis of the
hip or knee. J Rheumatol. 1988;15(12):1833–1840.
16. Lu B. Propensity score matching with time-­ dependent covariates. Biometrics.
2005;61(3):721–728.
17. Austin PC. An introduction to propensity score methods for reducing the effects of
confounding in observational studies. Multivariate Behav Res. 2011;46(3):399–424.
18. Girman CJ, Gokhale M, Kou TD, et al. Assessing the impact of propensity score
estimation and implementation on covariate balance and confounding control within
and across important subgroups in comparative effectiveness research. Med Care.
2014;52(3):280–287.
19. Rubin DB. Multiple Imputation for Nonresponse in Surveys. New York: Wiley, 2004.
20. Austin PC. Absolute risk reductions and numbers needed to treat can be obtained
from adjusted survival models for time-­ to-­
event outcomes. J Clin Epidemiol.
2010;63(1):46–55.
21. Kreuz PC, Steinwachs M, Angele P. Single-­Dose local anesthetics exhibit a
type-, dose-, and time-­dependent chondrotoxic effect on chondrocytes and cartilage:
a systematic review of the current literature. Knee Surg Sports Traumatol Arthrosc.
2018;26(3):819–830.
22. Rosemann T, Laux G, Szecsenyi J, Wensing M, Grol R. Pain and osteoarthritis in
primary care: factors associated with pain perception in a sample of 1,021 patients.
Pain Med. 2008;9(7):903–910.
23. Langley P, Müller-­Schwefe G, Nicolaou A, et al. The societal impact of pain in
the European Union: health-­related quality of life and healthcare resource utilization.
J Med Econ. 2010;13(3):571–581.
24. Groenwold RHH, Hak E, Hoes AW. Quantitative assessment of unobserved
confounding is mandatory in nonrandomized intervention studies. J Clin Epidemiol.
2009;62(1):22–28.
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Author information:
S. R. W. Wijn, MSc, PhD candidate, Evidence-­Based Surgery
G. Hannink, PhD, Senior scientist, Evidence-­Based Surgery
Department of Operating Rooms, Radboud Institute for Health Sciences,
Radboud University Medical Center, Nijmegen, the Netherlands.
M. M. Rovers, PhD, Professor, Evidence-­Based Surgery, Department
of Operating Rooms, Radboud Institute for Health Sciences, Radboud
University Medical Center, Nijmegen, the Netherlands; Radboud University
Medical Center, Radboud Institute for Health Sciences, Department of
Health Evidence, Nijmegen, the Netherlands.
T. G. van Tienen, MD PhD, Orthopaedic Surgeon, Laurentius Hospital,
Roermond, The Netherlands; Chief Medical Officer, ATRO Medical BV,
Department of Orthopedics, Radboud Institute for Health Sciences,
Radboud University Medical Center, Nijmegen, the Netherlands.
Author contributions:
S. R. W. Wijn: Conceived the study, Collected, validated, and analyzed the
data, Drafted and gave final approval of the manuscript.
M. M. Rovers: Conceived the study, Drafted and gave final approval of the
manuscript.
T. G. van Tienen: Conceived the study, Drafted and gave final approval of
the manuscript.
G. Hannink: Conceived the study, Collected, validated, and analyzed the
data, Drafted and gave final approval of the manuscript.
Funding statement:
Junior Research project (2018) grant provided by the Radboud Institute
for Health Sciences, Radboud University Medical Centre, Nijmegen, The
Netherlands. The funding source had no role in the design or conduct of
the study; collection, analysis, or interpretation of the data; or writing of
the report.
No benefits in any form have been received or will be received from a
commercial party related directly or indirectly to the subject of this article.
Acknowledgements:
The OAI is a public-­private partnership composed of five contracts (N01-­
AR-2 to 2258; N01-­AR-2 to 2259; 01-­AR-2 to 2260; N01-­AR-2 to 2261;
N01-­AR-2 to 2262) funded by the National Institutes of Health, a branch
of the Department of Health and Human Services, and conducted by the
OAI Study Investigators. Private funding partners include Merck Research
Laboratories; Novartis Pharmaceuticals Corporation, GlaxoSmithKline; and
Pfizer, Inc. Private sector funding for the OAI is managed by the Founda-
tion for the National Institutes of Health. This manuscript was prepared
using an OAI public use data set and does not necessarily reflect the
opinions or views of the OAI investigators, the NIH, or the private funding
partners.
Ethical review statement:
This study did not require ethical approval.
This article was primary edited by P. Walmsley and first proof edited by J.
Scott.
The Bone & Joint Journal