Increasing Indications of Treatment with
Vitamin D, The Magic Hormone of Present Time
Picarelli G1,5*, Di Munno O2,5, Tarantino U3,5, Iolascon G4,5 and Migliore A1,5
1Fatebenefratelli Unit of Rheumatology, San Pietro Fatebenefratelli Hospital, Italy
2Rheumatology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Italy
3Department of Orthopaedics, University of Rome Tor Vergata, Italy
4Department of Medical and Surgical Specialties and Dentistry, University of Campania “Luigi Vanvitelli”, Italy
5SI GUIDA member
Submission: July 03, 2019;Published: July 17, 2019
*Corresponding author: Giovanna Picarelli, Operative Unit of Rheumatology, San Pietro Fatebene fratelli Hospital, Italy
How to cite this article: Picarelli G, Di Munno O, Tarantino U, Iolascon G, Migliore A. Does the Post-Operative Infectious Risk increase in Patients Previously Treated with Intra-Articular Injections?. Ortho & Rheum Open Access J 2019; 14(3): 555889.. DOI: 10.19080/OROAJ.2019.14.555889
Background: several systematic reviews have been conducted to study the relation between intra-articular injections and the associated risk of post-operative infection following arthroplasty. Despite the large use of intra-articular corticosteroids and hyaluronic acid injections in fact, there are no guidelines regarding the safety and timing of intra-articular drug administration related to the subsequent arthroplasty.
Questions/Purposes: the purpose of this study is to conduct a narrative review to report literature data about intra-articular corticosteroid or viscosupplementation and the risk for infection after arthroplasty.
Patients and Methods: full-length English articles up to August 2018 were included and identified through a literature research on PubMed using predefined text words related to the topic.
Results: 12 studies were analysed: patients had hip or knee steroid intra-articular injections before undergoing arthroplasty surgery. Eight of the studies were performed in patients with total hip arthroplasty and the other four were in patients with total knee arthroplasty. In each study we analysed the average time from injection to replacement and the types of steroids injected. Steroid injection had no significant effect on either deep or superficial infection rates of subsequent arthroplasty and only two of the analysed studies reported a significant increase in the incidence of deep infection in hip or knee replacement surgery following steroid injections.
Conclusion: This review reports that intra-articular steroid injections have no effect on deep infection rates of subsequent joint arthroplasty, suggesting that such practice is justifiable. Studies investigating the infectious risk of viscosupplementation prior to surgery are desirable.
Osteoarthritis (OA) is a leading cause of pain and disability worldwide. OA affects 240 million people globally and is becoming an increasing problem with the rates of total knee and hip arthroplasty rising globally. Intra-articular corticosteroid and viscosupplementation injections have become a widespread therapy in conservative management in the treatment of OA. Specifically, injections can be helpful in clinical practice for patients with initial or moderate OA and when end stage OA patients are not willing or able to undergo an arthroplasty in the short term. Regarding viscosupplementation, there is a lack of agreement between national and international guidelines on the use of intra-articular hyaluronic acid for medical management of symptomatic OA. However, results from randomized controlled
trials and meta-analysis indicate that viscosupplementation
offers the best benefit / risk ratio among various pharmacologic treatments to improve knee OA pain [1–5].
While different medical organizations, including the American Academy of Orthopaedic Surgeons , the American College of Rheumatology , the European League Against Rheumatism , and thle European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis , endorse corticosteroid injection for the handling of knee pain associated with OA, concerns exist about the timing of injections before undergoing a subsequent arthroplasty and a potential association with prosthetic joint infection in the peri-operative period [10–14]. Joint sepsis is considered the most serious complication of intra-articular corticosteroid injections. Research in literature has estimated that the risk of developing an infected joint following intra-articular corticosteroid injections is low, approximately
4.6 per 100,000 .
Periprosthetic joint infection is a devastating complication
following knee or hip replacement leading to a significant
increase in morbidity. A recent meta-analysis estimates the
rate of surgical site infection to be 2.5% and the rate of deep
periprosthetic joint infection to be 0.9% after arthroplasty .
Furthermore, it is important to identify the right sequence
of conservative and surgical treatments for OA patients since it
is also relevant from an economic point of view considering the
high costs of the revisions.
Therefore, there is a debate about whether steroid injections
increase the risk of post-operative infection following total
knee arthroplasty [17–19]. Despite the widespread use of
intra-articular corticosteroids and hyaluronic acid injections
worldwide, there are currently no guidelines regarding safety
and timing of intra-articular drug administration related to the
subsequent arthroplasty. The purpose of this study is to conduct
a narrative review to report literature data about intra-articular
corticosteroid or viscosupplementation and the risk for infection
Articles included in this narrative review were identified
through a literature research on PubMed using predefined text
words related to the operation (i.e. “total hip replacement”
or “total knee replacement” or “hip arthroplasty” or “knee
arthroplasty”), injection (e.g., “intra-articular” or “steroid” or
“viscosupplementation”), infection (e.g., “infectious risk”) and a
combination of these keywords. The search strategy was limited
to studies conducted in humans, publications in English language
and full-length articles published until August 2018.
Ten retrospective studies and 2 control cases were analysed
(Table 1). The sample size ranged from 32 to 352 for patients
and from 32 to 224 for control group, for a total number of 972
patients in the control group and 1213 in the experimental
group. Patients had hip and knee steroid intra-articular
injections before undergoing arthroplasty surgery. Eight of the
studies were performed in patients with total hip arthroplasty
and the other four were in patients with total knee arthroplasty.
The average time from injection to replacement was between 0.5
and 50 months. We also extracted information, at least where
available, about the types of steroid injected.
Joshy et al.  conducted a retrospective matched
case control study. He compared a group of 32 patients who
underwent knee arthroplasty complicated by infection with
a control group of 32 patients with a past knee arthroplasty,
selected from a database, who did not develop infection. An
intra-articular steroid injection was performed in each group.
The mean time between last steroid injection and arthroplasty
was 46 months (range 12–121 months) in the infection group
and 33 months (range 8–56 months) in the non-infected group.
The results of the study showed no significant differences
between the numbers of patients who received an intra-articular
steroid injection in both groups. The authors concluded that
steroid injection, performed before arthroplasty, was not a risk
factor for post-operative infection. The small sample size of this
study does not have much impact on the results.
Another retrospective case control study , with similar
findings to those of Joshy et al.  compared 40 patients who
developed post-operative infection within 6 months following
total knee arthroplasty or who had revision surgery with 352
patients who underwent knee arthroplasty with no infection or
wound healing problems. Patients completed a questionnaire
asking if they had received knee infiltration before undergoing
arthroplasty. The groups of non-responsive patients or deceased
patients were removed and 28 infected cases and 219 patients
who did not develop infection were selected. For all patients who
received injections, the mean time of the last injection before
arthroplasty was 16 months (range 1 month to 45 years). In
the control group, it was determined that 32% of patients had
received a steroid injection prior to surgery, compared with
39% in the infected group. The results demonstrated that prior
steroid injection was not associated with a higher risk of postoperative
To identify infected wounds, a follow-up of only 6 months was
considered, thus excluding patients who developed infections
later. Besides, risk factors such as smoking and diabetes mellitus,
were self-reported by questionnaire. Even the execution of the
steroid infiltration before knee arthroplasty was identified
only through the questionnaire. Desai et al.  reported the
outcome of 440 total knee arthroplasties with a 1 year follow-up.
90 knees in 80 patients were identified from hospital records as
having had intra-articular steroid injections before undergoing
total knee arthroplasty. A control group, where the patients were
matched for age, sex and year of operation of 180 knees in 170
patients and did not undergo steroid injections, was used.
The results demonstrated that no cases of deep infection
occurred in both groups. Two cases of superficial infection were
found in the study group and five cases in the control group. For
the two infected cases in the study group, steroid injections were
given 18 months prior to surgery. Furthermore, 45 knees in the
study group received an injection within the 12 months prior to
surgery. It is difficult to identify significant differences between
treatment and control groups due to the low infection rate
reported in this study. However, it was observed that 60 out of
90 knees received steroid injections in the operating room under
strict sterile conditions, which possibly contributed to the low
infection rate in the study group. But this method of performing
steroid injections is not common. Therefore, the findings of this
study illustrated that giving a steroid injection before surgery is
not a risk factor for infection and should not be extrapolated in
the centres where aseptic techniques are less severe.
Chitre  analysed in retrospective all patients who had
had steroid injection followed by hip arthroplasty over a 5-year
period, with no case of deep joint sepsis reported. The average
interval between injection and surgery was 18 months (range 4
to 50 months). Sankar et al.  also reviewed retrospectively
40 patients who had undergone hip arthroplasty after a steroid
hip injection with an average interval from injection to joint
replacement of 6.2 months. All patients during follow up did
not develop deep infection. Meermans, et al.  evaluated 175
patients who underwent intra-articular steroid hip injections
within one year before total hip arthroplasty to a control group.
The authors reported no difference in superficial or deep
infection between groups at average 71-month follow-ups.
Sreekumar, et al.  compared 68 patients who had injections
at an average of 14 months prior to total hip arthroplasty
with a control group of 136 patients who underwent total hip
arthroplasty and found no difference in post-operative infection.
Only a few studies showed that steroid injections prior to
total knee arthroplasty may be associated with an increased
incidence of post-operative infection. Papavasiliou et al. 
showed a statistically higher deep infection rate in knee
arthroplasty that had had a steroid injection prior to surgery
as compared to those who were not given the injection. Three
deep infections in the patients with previous steroid injection
occurred whereas none developed in the control group. Deep
infection, occurring within one year of surgery, was defined
on the basis of certain characteristics (i.e. purulent drainage
from the depths of the incision, microbiological culture from
aseptically aspirated fluid, or pus cells present on microscopy,
an abscess, local pain plus tenderness and patient temperature
above 38 °C).
The time from the last injection to surgery for the three
infected cases was eight, ten and eleven months respectively.
The timing of injections for those patients who did not develop
infection was not evaluated.
This study proved to be weak because no relationship
between the number, dosage and timing of injections and risk of
post-operative infection was established. Finally, these findings
are not correlated to the general population because subjects
with common risk factors such as diabetes mellitus, smoking
and inflammatory arthritis were not included. It would have
been more useful to include those risk factors to ensure that the control group was matched accordingly. Kaspar et al. 
conducted a retrospective, matched, cohort study about infective
complications after total hip arthroplasty, in 40 patients who
had received an injection and 40 who had not. In the injection
group there were five revisions, four of which were due to deep
infection. There were no infections in the control group. Despite
the moderate size of the study, complications in the injection
group were very high with 30% having some form of sepsis
of the hip, a rate which was four times higher than that of the
Similarly to Kaspar, McIntosh  retrospectively compared
224 patients who underwent total hip arthroplasty implanted
within 1 year of steroid injection with 224 patients in the control
group. The authors reported hazard ratios of 3 for deep infection
and 1.5 for superficial infection in patients who underwent total
hip arthroplasty within one year of steroid injection. It should
be kept in mind that certain sub-populations may be at risk
of infection regardless of the injection, for example, very old
patients and/or in multidrug therapy, diabetics, or patients in
therapy with immunosuppressants. In these cases, routine preoperative
precautions should take place including identification
and optimization of recognized risk factors for post-operative
infection, such as anemia, diabetes mellitus, smoking withdrawal,
reduction or withdrawal of immunosuppressants. Besides, the
different studies have used different types of steroids at different
dosages with results that are not always comparable. The length
of time that steroids remain active in the knee or in the hip is
debatable. It has been hypothesised that steroid crystals do not
fully dissolve into the joint but remain within the knee or the
hip, and at the time of the surgery, the steroid crystals might
be released. Furthermore, low-grade deep infection is often
diagnosed after one year post surgery and therefore studies
evaluating post-operative infection rates with a follow-up of only
one year or less may underestimate the true infection rates.
The evaluation of the infectious risk of intra-articular steroid
injections before arthroplasty was evaluated in several reviews
while there is currently no data regarding the infectious risk
of viscosupplementation, for hip and knee, on the subsequent
surgery. Although numerous clinical trials have assessed the
safety and efficacy of hyaluronic acid for the management of
knee and hip OA, cumulative evidence leads to inconsistent
interpretations. The most important finding of this review is that
intra-articular steroid injection had no statistically significant
effect on deep infection rates of subsequent joint arthroplasty,
suggesting that such practice is justifiable. However, caution
should be used before giving an intra-articular steroid injection.
It is difficult to determine what is the best time from injection
to subsequent surgery and there is no certain correlation with
timing, dosage or frequency of injections. We may suggest, as
a precautionary measure and while awaiting further study,
avoiding the use of intra-articular steroids injected in the hip or
in the knee for at least 3 months before surgery. Considering the
lack of data, it is essential that good communication regarding the
previous steroid treatment exists among general practitioners,
rheumatologists and orthopedic surgeons when arthroplasty
surgery is considered.
Several systematic reviews have been conducted to study
the relationship between intra-articular corticosteroid and the
increased risk for infection after arthroplasty. The pooled results
of these reviews are still controversial and could not provide
strong evidence; for this reason, we conducted a narrative review
to report recent and updated literature data. Concerning the risk
of infection, 12 studies looking at hip and knee arthroplasties
were analyzed. These showed that steroid injection had no
significant effect on either deep or superficial infection rates
of subsequent arthroplasty. This narrative review suggests
that intra-articular steroid injections prior to arthroplasty do
not increase infection rates after surgery, however, further
studies (i.e. high quality, prospective, multi centre RCTs) are still
required to verify the safety of steroid injections given prior to
the surgery. Furthermore, studies investigating the infectious
risk of viscosupplementation prior to surgery are desirable.
Jevsevar DS, Brown GA, Jones DL, Matzkin EG, Manner PA, et al. (2013) The American Academy of Orthopaedic Surgeons Evidence-Based Guideline on: Treatment of Osteoarthritis of the Knee, 2nd The Journal of Bone and Joint Surgery. American Volume 95: 1885–1886.