http://informahealthcare.

com/psm
ISSN: 0091-3847 (print)

Phys Sportsmed, 2015; Early Online: 1–5

DOI: 10.1080/00913847.2015.1017440

REVIEW

Current concepts on the use of corticosteroid injections

for knee osteoarthritis
Tsun Yee Law 1, Chau Nguyen1, Rachel M. Frank2, Samuel Rosas1 and Frank McCormick3
1
Holy Cross Orthopedic Institute, Fort Lauderdale, FL, USA, 2Rush University Medical Center, Chicago, IL, USA, and 3LESS Institute, Miami, FL, USA
The Physician and Sportsmedicine Downloaded from informahealthcare.com by Kainan University on 04/28/15

Abstract Keywords
Intraarticular corticosteroid injections are commonly used by the primary care providers and Corticosteroids, intraarticular, knee, osteoar-
orthopedic surgeons to treat knee pain associated with osteoarthritis (OA). There is a spectrum of thritis, injection
options for treating knee OA, ranging from ice therapy to partial or total knee replacement sur-
gery. In mid-range treatment spectrum are different kinds of injections, with the most widely History
used being corticosteroid and hyaluronic acid. In addition, there are different types of corticoste-
Received 23 October 2014
roids used and also commonly mixed with different local anesthetics. The purpose of this paper
Accepted 6 February 2015
is address current concepts on the use of corticosteroid steroid therapy for the treatment of
Published online 23 February 2015
knee OA.

Introduction the increased amounts of arachidonic acid found in bone mar-

For personal use only.

row fat is the possible starting point of the bone growth by

Currently, there are 51.8 million adults diagnosed with
arthritis, amounting to 22% of the active adult population [1].
Knee osteoarthritis (OA) is one of the leading causes of
disability in United States and worldwide [2]. There is a
spectrum of options for treating knee OA, ranging from ice
therapy to partial or total knee replacement surgery. In
mid-range treatment spectrum are different kinds of
injections, with the most widely used being corticosteroid
and hyaluronic acid (HA). The purpose of this paper is
address current concepts on the use of corticosteroid therapy
for the treatment of knee OA.
Mechanism of action of glucocorticoids in OA
The complete mitigation of the inflammatory cascade in OA
is not completely understood; however there is some litera-
ture to explain how cortisone reduces inflammation. Gluco-
corticoids reduce the proinflammatory effects of arachidonic
acid by acting directly on nuclear steroid receptors which
alter the synthesis of mRNA and proteins leading to changes
in T-cell and B-cell functions, decreases in the levels of cyto-
kines and enzymes, and inhibition of phospholipase A2 [3].
OA has a number of effects on the juxta-articular bone such
as bone remodeling, subchondral bone sclerosis, subchondral
cysts, and increased osteoblastic and osteoclastic activities
[4]. Increased levels of cytokines, in general, have been
found in subchondral OA bone, specifically IL-6 and TNF-a
have been implicated in bone formation as well as inflamma-
tion of the synovium [4]. Further, it has been suggested that
acting as a positive feedback mechanism [4]. The amount of
TNF-a and IL-6 will diminish over a short period of time
since the proinflammatory effects of arachidonic acid will no
longer be expressed due to the repression process induced
by steroids [4,5].
Effectiveness of intraarticular steroid injections
Intraarticular (IA) corticosteroid therapy may provide short-
term pain relief in patients with knee OA, with low risk of
adverse effects [6-8]. A systematic review of IA steroid injec-
tions for knee OA concluded that the beneficial effect of
treatment commenced 1 week after injection and could last
for 3–4 weeks [8,9]. A separate meta-analysis corroborated
these results, noting short-term benefits of up to 2 weeks after
injection and also reporting some longer-term benefit of up to
16 to 24 weeks [2].
A Cochrane systematic review conducted by Bellamy et al.
further evaluated the efficacy of IA corticosteroids in the treat-
ment of knee OA [6]. The review included results of 28 trials
comparing IA corticosteroid to IA placebo. In brief, IA corti-
costeroids were shown to be more effective than placebo in
pain reduction and patient global self-assessment at 1 and at
2–3 weeks post-injection [6]. Beyond 4–24 weeks post-injec-
tion, there were no significant changes in efficacy of IA corti-
costeroid [6]. The authors concluded that the beneficial effects
of IA corticosteroid appear rapid but may be of short duration
(1–3 weeks) [6]. An additional systematic review by

Correspondence: Tsun Yee Law, MD, Holy Cross Hospital, Orthopedic Research Institute, 5597 N. Dixie Highway, Fort Lauderdale, FL 33334, USA.
E-mail: tsun.s.law@gmail.com

2015 Informa UK Ltd.
 2 T. Y. Law et al.
Hepper et al. also determined that the duration of effect may
be short and only consistently lasts for 1 week [10].
Potential side effects of cortisone injections
A general concern expressed among the medical research
community is whether long-term use of IA steroids would
cause any deleterious effects on joints or tissues [11-15]. One
study attempted to addressed these concerns by comparing
clinical and radiographic outcomes in a group of 68 patients
treated with repeated IA knee injections of triamcinolone
acetonide 40 mg (Kenalog) with a control group of 34 patients
receiving saline injection into the knee; both IA steroid and
saline injections were given every 3 months over the course
The Physician and Sportsmedicine Downloaded from informahealthcare.com by Kainan University on 04/28/15
of 2 years [14]. The authors demonstrated no differences in
joint space width between the two groups at both 1 and
2 years of treatment. There was a greater improvement in
range of motion and pain control in the corticosteroid group
compared to the saline group at the end of the first year.
Further, there was a significant improvement in knee pain
and stiffness in the corticosteroid group over the 2 years;
these results were not demonstrated in the control group. This
trial provides some evidence for the long-term effectiveness
and safety of IA corticosteroid injections, with no accelera-
tion of the progression of OA noted in the treatment group.
While complications of IA corticosteroid treatment are
For personal use only.
infrequent, the most commonly reported unwanted side
effects include atrophy of the skin at the injection site, facial
flush, and post-injection flare (soreness and inflammation
following the injection) [12]. The facial flush is more
commonly seen ~ 16 hours after IA injection of triamcino-
lone and it lasts on average 36 hours [16]. The post-injection
steroid flare is thought to be due to injecting the crystalline
nature of deposteroids which causes a crystal-induced synovi-
tis [17]. This typically will occur within the first 24–36 hours
post-injection and is usually self-limited [18].
Systemic side effects such as infection, increased blood
glucose, hypercortisolism, and others are rarely seen,
although careful planning and precautions such as utilizing
gloves should be taken to avoid them. However, there is
some evidence in the literature that shows an acute 2- to
3-day rise in blood glucose in patients with diabetes after a
single IA corticosteroid injection of methylprednisolone or
betamethasone in the knee [19]. While there is only a limited
amount of literature regarding dose and systemic effects, it
has been suggested that a dose > 40 mg has no added benefit
and therefore limiting the dose accordingly will lower the
risk of systemic side effects [20].
Preclinical studies suggest certain corticosteroids and asso-
ciated anesthetics can be harmful to the viability of cartilage-
producing cells known as chondrocytes [9,21,22]. Tendon
rupture, predominantly the Achilles tendon, is another serious
possible adverse effect of IA corticosteroid use that the litera-
ture does not currently adequately address but is a possible
concern [23]. Although the clinical evidence to support these
findings is limited, clinicians must carefully determine the type
of steroid and dosage to be used for each individual patient.
The risk of immunosuppression caused by a steroid-induced
decrease in inflammatory response is not to be taken lightly.
Phys Sportsmed, 2015; Early Online:1–5
For that reason, multiple studies have reported the incidence of
arthroplasty infection after the use of IA steroid injections.
Only one study by the Mayo Clinic demonstrated a greater risk
of infections on joints treated previously with this type of
injection. There is no specific consensus on how long arthro-
plasty must be delayed to avoid this risk and therefore some
clinicians use 2 months in order to avoid this unnecessary yet
highly morbid risk [24]. A small amount of other side effects
that have been reported include stoppage of lactation and tran-
sient menstrual disorder, thought to occur due to a decrease in
estradiol. Other side effects may occur but are dependent on
site of injection. For example, 12% of patients reported having
ear, nose, and throat problems after a single epidural steroid
injection – most were described as a transient change in voice
[24]. Tachon’s Syndrome is a transient vagal response to IA or
periarticular steroid injection that causes great anxiety to
patients, but it is extremely rare – 1 event per 8000 injections.
It consists of any of the following: diaphoresis, chest pain,
hypotension, shortness of breath, and abdominal pain [24].
Ideal dosing schedule for IA corticosteroid shots
The American College of Rheumatology advices physicians
to only perform an IA steroid injection after 3 months from
the previous injection. The safety of undergoing multiple
corticosteroid injections in the knee joint over time has been
well established in a clinical setting [25,26]. Most clinicians
agree that for weight-bearing joints (such as the knee), a
period of at least 8 to 12 weeks between corticosteroid injec-
tions is optimal [27]. Large doses which may occur with
repeated dosing can cause more harm to the cartilage than
benefit [3]. This corresponds with the empirical 3-month rule
that is a common paradigm followed by many healthcare
professionals.
IA injection accuracy
The clinician normally uses anatomic landmarks when per-
forming an IA steroid injection. In the knee, this means pal-
pating the patella and patellar tendon to determine the best
access point to the joint. Depending on the condition of the
skin and clinician preference, several options exist for the
technical approach to knee IA corticosteroid injection [28].
Some of the more common injection sites include the supero-
lateral portal, anteromedial portal, anterolateral portal, and
mid-lateral portal. Importantly, injections placed via the
superolateral or mid-lateral portal should be performed with
the patient’s knee extended, while injections into the antero-
medial and anterolateral portals should be performed with the
knee flexed to ~ 60 to 90 [28]. The medial or lateral joint
space can be used. The least commonly used and accurate is
the infrapatellar bent knee approach [27].
The American College of Radiology advises that when
performing musculoskeletal procedures, ultrasound should be
used [29,30]. This, of course, is difficult in some settings as
personnel may not be trained or an ultrasound device may
not be available. While both methods are accepted, several
authors have reported that a large number of anatomical-
guided injections are inaccurately placed. One randomized
 DOI: 10.1080/00913847.2015.1017440 Current concepts of corticosteroid injections for knee osteoarthritis
controlled study demonstrated that one-third of all anatomi-
cally guided injections to 184 patients were inaccurate; these
injections were done at the elbow, wrist, ankle, shoulder, and
knee with the accuracy of a trainee using US guidance being
greater than a seasoned rheumatologist using anatomical
guidance [31]. Other studies and evidence-based summaries
show that US-guided injections are more accurate, ranging
from 69% to 100% compared to 39% to 100% anatomically
guided injections. This same study reports the finding of
increased clinical improvement with ultrasound-guided injec-
tion – 52% versus 23% in patients without US-guided injec-
tion. In a large randomized controlled trial, Sibbit et al. found
that US-guided IA injections, decreased 8% of the cost per
responder per year which amounted to US$7. The same
The Physician and Sportsmedicine Downloaded from informahealthcare.com by Kainan University on 04/28/15
authors also reported that US-guided IA injection, decreased
outpatient treatment costs by 33%, US$64 per responder per
year and also improved patient-recorded clinical outcomes
and cost-effectiveness [30,32,33].
A study comparing these three injection sites in 126 knees
suggests that injections using ultrasound were more accurate
in the mid-lateral and superolateral portal (95% p < 0.05 and
100% p < 0.05, respectively) compared to medial portals
which were only 75% accurate [14]. Many factors affect the
accuracy of a single injection and therefore we advise clini-
cians to perform the method that they are most comfortable
with and to use ultrasound when possible.
For personal use only.
Efficacy of different corticosteroid medications available
A variety of corticosteroids are available such as betametha-
sone (Celestone), dexamethasone (Decadron) LA, triamcino-
lone acetonide (Kenalog), and methylprednisolone acetate
(Depo-Medrol) [28]. The agent of choice depends on the con-
dition being treated, the joint being injected, and overall the
preference of the clinician. The more commonly used IA
steroids used in the United States include triamcinolone
acetonide (Kenalog) and methylprednisolone acetate (Depo-
Medrol) [34]. The typical dosage of both triamcinolone and
methylprednisolone acetate is 40 mg in large joints such as
the knee and hip, with lower doses used in the hands or feet
[35]. The recommended interval between injections is at least
3 months [35]. Table 1 lists the commonly used IA cortico-
steroid injections. A critical literature review with up-to-date
findings provides a summary of commonly used corticoste-
roids and their dosing [35]. The solubility and duration of
action differs in each corticosteroid, and typically, the lower
the solubility, the longer is the duration [3]. Therefore, careful
Table 1. Commonly used corticosteroids.
Steroid Common Common Approximate
concentration equivalent duration of
(mg per ml) dosea (mg) action (days)
Methylprednisolone acetate 40 or 80 40 8
Triamcinolone acetonide 10 or 40 40 14
Triamcinolone hexacetonide 20 40 21
Dexamethasone acetate 8 8 8
Dexamethasone sodium 4 8 6 efficacy of HA injections, especially when compared to corti-
Note: Steroid agents listed in order of prevalence of use.
a
Dose equivalent to 40 mg of methylprednisolone acetate or triamcino-
lone acetonide (the most commonly used intraarticular steroid).
3
analysis of steroid pharmacokinetics should be considered in
each treatment plan.
What is the purpose in combining IA corticosteroids
with local anesthetic agents?
Local anesthetics such as lidocaine and bupivacaine are
commonly used to provide rapid pain relief until the cortico-
steroid of choice begins to take effect [36]. Corticosteroids
can often take 24 hours before the patient begins to experi-
ence relief while local anesthetics have a much shorter onset
of action: lidocaine: ~ 1–2 minutes and bupivacaine: ~ 30
minutes. However, due to the limited duration of action of
the local anesthetics, ranging from ~ 1 hour for lidocaine to
~ 8 hours for bupivacaine, the patient may experience a tran-
sient return of joint pain as the local anesthetic wears off,
before the onset of the effects of the corticosteroid. If local
anesthetic is used in combination with the corticosteroid, then
the patient should be counseled as to the potential of a
transient recurrence of pain in the first 1–2 days following
injection. To further decrease the discomfort received by the
patient, many clinicians also employ a topical vapocoolant on
the skin prior to the injection [28].
Of note, there is some evidence for caution regarding
chondrotoxicity when combining local anesthetic with corti-
costeroids. One in vitro study found that 88 mg of 1%
lidocaine or 22 mg of 0.25% bupivacaine combined with
betamethasone sodium phosphate, betamethasone acetate,
methylprednisolone acetate, or triamcinolone acetate injected
into a bioreactor simulating normal joint fluid with chondro-
cyte culture cell wells results in a pronounced chondrotoxic
effect [37]. However, for single IA injections administered
with at least 3-month intervals between injections, the
chondrotoxicity is limited, and combination injections remain
widely used by clinicians.
What are the contraindications to IA corticosteroid use?
Based upon a review of the best available evidence, the
contraindications to IA injection are all relative. Certainly,
allergies to the injection preparation products and/or injection
agents are contraindications to injection. Other contraindica-
tions include active superficial skin/soft tissue infection
(cellulitis), suspected IA infection, unstable coagulopathy,
anticoagulant therapy, uncontrolled diabetes mellitus, and bro-
ken skin at the injection site [27,38,39]. Patients who are on
anticoagulant therapy should be approached with caution, and
certain precautions following injection such as placement of a
pressure dressing, as well as pre-injection precautions, such as
obtaining prothrombin time laboratory values, can be helpful.
What are the alternatives to corticosteroids?
IA injection of HA, also known as viscosupplementation, has
been an extremely popular treatment option for knee OA. The
costeroid injections, has become a topic of controversy within
the orthopedic community. In 2006, a Cochrane review of
76 clinical trials determined that HA is effective for the
 4 T. Y. Law et al.
treatment of knee OA and has a prolonged effect when com-
pared with IA corticosteroids [40]. Further, a recent study
comparing IA injection of HA efficacy to nonsteroidal anti-
inflammatory drugs (NSAIDs) concluded that IA injection of
HA is equal to NSAIDs being continuously used for 5 weeks
and has a better safety profile when considering side
effects [41].
Recently, a systematic review and meta-analysis assessing
the outcomes of IA corticosteroids versus HA injections was
conducted, in which seven clinical trials analyzing 610 knees
were described. The authors concluded that by week 4 follow-
ing therapy, corticosteroids are relatively more effective for
pain than HA, but that after 2 months, HA has greater effi-
cacy [11]. This suggests that HA may be beneficial for long-
The Physician and Sportsmedicine Downloaded from informahealthcare.com by Kainan University on 04/28/15
term management of OA.
In 2013, the American Academy of Orthopaedic Surgeons
updated their clinical practice guidelines for the treatment of
OA, and specifically noted that HA is no longer recom-
mended as a modality for treating symptomatic OA. The
authors noted that while several of the 14 studies included in
their review demonstrated the effectiveness of HA, the overall
combined results of all studies did not meet minimum
clinically important improvement thresholds. This same
workgroup did, however, recommend the use of IA cortico-
steroids for short-term pain relief of symptomatic OA. Cer-
tainly, further research into the efficacy of both treatment
For personal use only.
options is warranted. One of the biggest downsides to HA
injections involves cost, and this should be taken into consid-
eration if recommending HA therapy. In addition, several HA
treatment regimens require serial injections over the series of
3–5 weeks, which may affect patient compliance and
cooperation.
Conclusion
IA corticosteroid injections have been shown to be safe and
effective in treating the painful symptoms of OA of the knees.
It may not be effective for all patients and the duration of
effect can also be short although rapid in onset. This makes
corticosteroid injections viable in the short term but may limit
its ability to be used as a single long-term treatment option.
Alternative options such as HA can be considered when IA
corticosteroid injections fail to provide adequate pain relief.
Recommendations
Upon reviewing the literature it is clear that IA corticosteroids
are effective but may not have an immediate onset of pain
relief. Therefore, it may be beneficial to combine the cortico-
steroid of choice with a local anesthetic to offer the patient
rapid pain relief. Although short-acting lidocaine is used for
diagnostic purposes, a long-acting bupivacaine to prevent the
flare and dilute the lidocaine (to prevent chondrotoxicity in
large joints) is recommended. In addition, whenever possible
the use of an ultrasound would enhance the accuracy of injec-
tions. Although the literature is not conclusive on treatment
frequency, it is generally recommended to keep the injections
limited to once every 3 months but can be earlier if symptoms
warrant.
Phys Sportsmed, 2015; Early Online:1–5
Declaration of interest
The authors report no conflicts of interest. The authors alone
are responsible for the content and writing of the paper.
References
[1] Blackwell DL, Lucas JW, Clarke TC. Summary health statistics for
U.S. adults: National health interview survey, 2012. Vital Health
Stat 10 2014;260:1–161.
[2] Arroll B, Goodyear-Smith F. Corticosteroid injections for osteoar-
thritis of the knee: meta-analysis. BMJ 2004;328:869–70.
[3] Pekarek B, Osher L, Buck S, Bowen M. Intra-articular corticoste-
roid injections: a critical literature review with up-to-date findings.
Foot 2011;21:66–70.
[4] Aspden RM. Osteoarthritis: a problem of growth not decay? Rheu-
matology 2008;47:1452–60.
[5] Newton R. Anti-inflammatory glucocorticoids: changing concepts.
Eur J Pharmacol 2014;724:231–6.
[6] Bellamy N, Campbell J, Robinson V, et al. Intraarticular corticoste-
roid for treatment of osteoarthritis of the knee. Cochrane Database
Syst Rev 2005:CD005328.
[7] Creamer P. Intra-articular corticosteroid treatment in osteoarthritis.
Curr Opin Rheumatol 1999;11:417–21.
[8] Godwin M, Dawes M. Intra-articular steroid injections for painful
knees. Systematic review with meta-analysis. Can Fam Physician
2004;50:241.
[9] Farkas B, Kvell K, Czo€mpo€ly T, et al. Increased chondrocyte death
after steroid and local anesthetic combination. Clin Orthop Relat
Res 2010;468:3112–20.
[10] Hepper CT, Halvorson JJ, Duncan ST, et al. The efficacy and dura-
tion of intra-articular corticosteroid injection for knee osteoarthritis:
a systematic review of level I studies. J Am Acad Orthop Surg
2009;17:638–46.
[11] Bannuru RR, Natov NS, Obadan IE, et al. Therapeutic trajectory of
hyaluronic acid versus corticosteroids in the treatment of knee
osteoarthritis: a systematic review and meta-analysis. Arthritis
Rheum 2009;61:1704–11.
[12] Cole BJ, Schumacher HR Jr. Injectable corticosteroids in modern
practice. J Am Acad Orthop Surg 2005;13:37–46.
[13] Orozco L, Munar A, Soler R, et al. Treatment of knee osteoarthritis
with autologous mesenchymal stem cells: a pilot study. Transplan-
tation 2013;95:1535–41.
[14] Park Y, Lee SC, Nam HS, et al. Comparison of sonographically
guided intra-articular injections at 3 different sites of the knee.
J Ultrasound Med 2011;30:1669–76.
[15] Kon E, Filardo G, Drobnic M, et al. Non-surgical management of
early knee osteoarthritis. Knee Surg Sports Traumatol Arthrosc
2012;20:436–49.
[16] Habib G. Systemic effects of intra-articular corticosteroids. Clin
Rheumatol 2009;28:749–56.
[17] Hunter JA, Blyth TH. A risk-benefit assessment of intra-articular
corticosteroids in rheumatic disorders. Drug Saf 1999;21:353–65.
[18] Cardone DA, Tallia AF. Joint and soft tissue injection. Am Fam
Physician 2002;66:283–8.
[19] Kallock E, Neher J. Do intra-articular steroid injections affect glyce-
mic control in patients with diabetes? J Fam Pract 2010;59:709–10.
Available from Academic Search Premier, Ipswich, MA.
[20] Douglas RJ. Corticosteroid injection into the osteoarthritic knee:
drug selection, dose, and injection frequency. Int J Clin Pract
2012;66:699–704.
[21] Jacobs TF, Vansintjan PS, Roels N, et al. The effect of Lidocaine
on the viability of cultivated mature human cartilage cells: an in
vitro study. Knee Surg Sports Traumatol Arthrosc 2011;19:
1206–13.
[22] Behrens F, Shepard N, Mitchell N. Alterations of rabbit articular
cartilage by intra-articular injections of glucocorticoids. J Bone
Joint Surg Am 1975;57:70–6.
[23] Blanco I, Krahenbuhl S, Schlienger RG. Corticosteroid-associated
tendinopathies: an analysis of the published literature and spontane-
ous pharmacovigilance data. Drug Saf 2005;28:633–43.
[24] Berthelot J-M, Le Goff B, Maugars Y. Side effects of corticosteroid
injections: what’s new? Joint Bone Spine 2012;80:363–7.
 DOI: 10.1080/00913847.2015.1017440 Current concepts of corticosteroid injections for knee osteoarthritis
[25] Balch HW, Gibson JMC, El-ghobarey AF, et al. Repeated cortico-
steroid injections into knee joints. Rheumatology 1977;16:137–40.
[26] Keagy RD, Keim HA. Intra-articular steroid therapy: repeated use
in patients with chronic arthritis. Am J Med Sci 1967;253:45–51.
[27] Neustadt DH. Intra-articular injections for osteoarthritis of the
knee. Cleve Clin J Med 2006;73:897.
[28] Schumacher HR, Chen LX. Injectable corticosteroids in treatment
of arthritis of the knee. Am J Med 2005;118:1208–14.
[29] AIUM practice guideline for the performance of a musculoskeletal
ultrasound examination. J Ultrasound Med 2012;31:1473–88.
[30] Lawson A, Kelsberg G, Safranek S. Clinical inquiry: does ultra-
sound guidance improve outcomes for steroid joint injections?
J Fam Pract 2013;62:763a.
[31] Cunnington J, Marshall N, Hide G, et al. A randomized, double-
blind, controlled study of ultrasound-guided corticosteroid injection
into the joint of patients with inflammatory arthritis. Arthritis
Rheum 2010;62:1862–9.
[32] Berkoff DJ, Miller LE, Block JE. Clinical utility of ultrasound
The Physician and Sportsmedicine Downloaded from informahealthcare.com by Kainan University on 04/28/15
guidance for intra-articular knee injections: a review. Clin Interv
Aging 2012;7:89.
[33] Sibbitt WL, Band PA, Chavez-Chiang NR, et al. A randomized
controlled trial of the cost-effectiveness of ultrasound-guided
intraarticular injection of inflammatory arthritis. J Rheumatol
2011;38:252–63.
For personal use only.
5
[34] Centeno LM, Moore ME. Preferred intraarticular corticosteroids
and associated practice: a survey of members of the American Col-
lege of Rheumatology. Arthritis Care Res 1994;7:151–5.
[35] Ringdahl E, Pandit S. Treatment of knee osteoarthritis. Am Fam
Physician 2011;83:1287–92.
[36] Saunders SF. Injection techniques in musculoskeletal medicine a
practical manual for clinicians in primary and secondary care. 4th
ed. Edinburgh: Churchill Livingstone/Elsevier; 2012.
[37] Braun HJ, Wilcox-Fogel N, Kim HJ, et al. The effect of local anes-
thetic and corticosteroid combinations on chondrocyte viability.
Knee Surg Sports Traumatol Arthrosc 2012;20:1689–95.
[38] Stephens MB, Beutler AI, O’Connor FG. Musculoskeletal
injections: a review of the evidence. Am Fam Physician
2008;78:971–6.
[39] Courtney P, Doherty M. Joint aspiration and injection. Best Pract
Res Clin Rheumatol 2005;19:345–69.
[40] Bellamy N, Campbell J, Robinson V, et al. Viscosupplementation
for the treatment of osteoarthritis of the knee. Cochrane Database
Syst Rev 2006:CD005321.
[41] Ishijima M, Nakamura T, Shimizu K, et al. Intra-articular hyalur-
onic acid injection versus oral non-steroidal anti-inflammatory
drug for the treatment of knee osteoarthritis: a multi-center,
randomized, open-label, non-inferiority trial. Arthritis Res Ther
2014;16:R18–18.