The Journal of Arthroplasty 32 (2017) 2604e2611

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The Journal of Arthroplasty

journal homepage: www.arthroplastyjournal.org

Review

Arthrofibrosis Associated With Total Knee Arthroplasty

Victor A. Cheuy, PhD a, *, Jared R.H. Foran, MD b, Roger J. Paxton, PhD a,
Michael J. Bade, PT, PhD a, Joseph A. Zeni, PT, PhD c, Jennifer E. Stevens-Lapsley, PT, PhD a, d
a
Physical Therapy Program, Department of Physical Medicine and Rehabilitation, University of Colorado, Aurora, Colorado
b
Panorama Orthopaedics and Spine Center, Golden, Colorado
c
Department of Physical Therapy, University of Delaware, Newark, Delaware
d
Geriatric Research, Education and Clinical Center, Veterans Affairs Medical Center, Denver, Colorado

a r t i c l e i n f o a b s t r a c t

Article history: Background: Arthrofibrosis is a debilitating postoperative complication of total knee arthroplasty (TKA).
Received 17 August 2016 It is one of the leading causes of hospital readmission and a predominant reason for TKA failure. The
Received in revised form prevalence of arthrofibrosis will increase as the annual incidence of TKA in the United States rises into
3 January 2017
the millions.
Accepted 5 February 2017
Available online 14 February 2017
Methods: In a narrative review of the literature, the etiology, economic burden, treatment strategies, and
future research directions of arthrofibrosis after TKA are examined.
Results: Characterized by excessive proliferation of scar tissue during an impaired wound healing
Keywords:
arthrofibrosis
response, arthrofibrotic stiffness causes functional deficits in activities of daily living. Postoperative,
total knee supervised physiotherapy remains the first line of defense against the development of arthrofibrosis.
arthroplasty Also, adjuncts to traditional physiotherapy such as splinting and augmented soft tissue mobilization can
range of motion be beneficial. The effectiveness of rehabilitation on functional outcomes depends on the appropriate
stiffness timing, intensity, and progression of the program, accounting for the patient's ability and level of pain.
Invasive treatments such as manipulation under anesthesia, debridement, and revision arthroplasty
improve range of motion, but can be traumatic and costly. Future studies investigating novel treatments,
early diagnosis, and potential preoperative screening for risk of arthrofibrosis will help target those
patients who will need additional attention and tailored rehabilitation to improve TKA outcomes.
Conclusion: Arthrofibrosis is a multi-faceted complication of TKA, and is difficult to treat without an
early, tailored, comprehensive rehabilitation program. Understanding the risk factors for its development
and the benefits and shortcomings of various interventions are essential to best restore mobility and
function.
© 2017 Elsevier Inc. All rights reserved.

Characterizing Arthrofibrosis
Arthrofibrosis is a well-known complication of injury or trauma,
characterized by the production of excessive fibrous scar tissue in a
joint [1e4]. The major consequence of arthrofibrosis is the loss of
range of motion because of the painful stiffness of proliferated scar
tissue, which interferes with the patient's ability to adequately
perform functional tasks of daily living [5,6]. Arthrofibrosis is a
debilitating complication after knee surgery that may also result in
One or more of the authors of this paper have disclosed potential or pertinent
conflicts of interest, which may include receipt of payment, either direct or indirect,
institutional support, or association with an entity in the biomedical field which
may be perceived to have potential conflict of interest with this work. For full
disclosure statements refer to http://dx.doi.org/10.1016/j.arth.2017.02.005.
* Reprint requests: Victor A. Cheuy, PhD, Mail Stop C244, 13121 East 17th Ave.,
Aurora, CO 80045.
pain that does not subside at predictable time points, pain with
palpation, lack of patellar movement with quadriceps muscle
contraction, or a knee joint that is warm or swollen unrelated to
effusion [7,8].
There is a lack of consensus on the diagnostic criteria for
arthrofibrosis of the knee, which obscures its true prevalence after
surgical procedures [9,10]. The spectrum of classification ranges
from broadly assessing patient difficulty with activities of daily
living attributable to limited range of motion (including decreased
range of motion preoperatively), to quantitative thresholds of
flexion and/or extension loss [5,11]. These quantitative thresholds
vary and include a flexion contracture of >15 degrees and/or <75
degrees of flexion; >10 degrees of extension deficit and/or <95
degrees of flexion; or a total knee arc range of motion <70 degrees
[12e14]. Imaging techniques have been used to supplement patient
history and clinical examinations, and can be valuable in assisting

http://dx.doi.org/10.1016/j.arth.2017.02.005
0883-5403/© 2017 Elsevier Inc. All rights reserved.
 V.A. Cheuy et al. / The Journal of Arthroplasty 32 (2017) 2604e2611
Fig. 1. Risk factors for arthrofibrosis and typical postoperative care strategies. NSAIDs, nonsteroidal anti-inflammatory drugs; PT, physical therapy; RICE, rest-ice-compression-
elevation; ROM, range of motion; TKA, total knee arthroplasty.
with diagnosis and treatment planning [15]. Magnetic resonance
imaging (MRI) and ultrasound have both demonstrated the ability
to detect focal fibrous proliferation based on heterogeneous signal
intensity in the knee, ankle, and foot [15e17]. However, MRI is not
part of the standard of care, even with the development of metal
suppression sequences to reduce artifacts and improve image
quality [18,19]. Advanced imaging is used (if at all) only after patient
history, physical examination, and radiographs all fail to identify
the cause of pain and/or stiffness after total knee arthroplasty (TKA)
[20]. MRI also suffers from the drawbacks of cost, the time-
consuming nature of scans, and concerns over patient claustro-
phobia and keeping still for extended periods.
The etiology of arthrofibrosis is multifactorial, and numerous
preoperative, intraoperative, and postoperative risk factors have
been identified (Fig. 1). Decreased preoperative knee range of
motion, higher complexity surgery (ie, amount of trauma, length of
surgery), and history of surgery increase the risk of excessive scar
tissue after TKA [21]. Previous studies have shown the rate of
arthrofibrosis doubles or even triples when patients have under-
gone previous surgeries for multiple ligamentous injuries or sur-
geries that require immobilization [9,22,23]. Postoperative factors
contributing to arthrofibrosis include poor patient motivation and
immobility, delay in starting a rehabilitation program, lack of
2605
compliance with prescribed rehabilitation, poor pain tolerance, and
infection [5,9,23]. In addition, a genetic predisposition to forming
excessive intraarticular scar tissue after injury and/or surgery has
been implicated in several studies [24e26].
The exact pathophysiology of how these factors cause arthro-
fibrosis is not completely clear, but what is known is the coordi-
nation of cell growth, differentiation, and death controlled by
various cytokines and growth factor signaling is disrupted, directly
affecting tissue homeostasis and organization, and allowing for
uninhibited proliferation of fibroconnective tissue [9,22,27].
Fibrosis can occur in many different organs (eg, skin, liver, lungs),
and can ultimately lead to organ failure [25,28,29]. In the normal
wound healing response, the cascade of biological responses is
tightly regulated. The migration of inflammatory cells and the
proliferation of fibroblasts trigger the release of cytokines, growth
factors, and reactive oxygen species that are responsible for tissue
remodeling and restoring tissue integrity [30]. Once the healing
process is complete, the inflammatory cells undergo apoptosis
(ie, programmed cell death), the release of signaling molecules
stops, and the inflammatory response critical to restoring tissue to
its functional state subsides [30,31]. However, the arthrofibrotic
condition is characterized by a lack of apoptosis in the proin-
flammatory phase, resulting in an imbalance between synthesis
2606 V.A. Cheuy et al. / The Journal of Arthroplasty 32 (2017) 2604e2611
and degradation [29,31]. Persistent transforming growth factor-b
(TGF-b) and bone morphogenetic protein 2 (BMP2) secretion and
downstream responses are thought to contribute to a sustained
inflammatory response [25,28,31,32]. Without apoptosis to balance
proliferation during this time, pathologic scar formation is inevi-
table, where functional cell types are eventually replaced by con-
nective tissue [33,34]. Proteoglycans, collagens, and extracellular
matrix components aggressively accumulate in the intercellular
space and stiffen, creating a fibrotic state [25,30,31,33]. In-
terventions directed at some of these potential biological targets
have not been successful, and there has been no specific pharma-
cological therapy able to prevent or cure arthrofibrosis [29].
Association With TKA
TKA is the standard of care to manage the pain and disability
associated with end-stage knee osteoarthritis, with more than
700,000 TKA surgeries performed annually in the United States
[35]. Arthrofibrosis is a debilitating complication of TKA, with a
reported incidence of between 1% and 13% postoperatively
[4,6,10,13,36]. The range of values can be attributed to the varying
quantitative thresholds of flexion and/or extension loss used to
define arthrofibrosis, as described previously. As a predominant
failure mechanism, arthrofibrosis accounts for 28% of hospital
readmissions due to surgical complications within 90 days of
discharge, and 10% of all revisions within 5 years of initial surgery
within the United States [37,38]. Patients with arthrofibrosis are at
elevated risk for prolonged, high treatment costs, especially for
those whose limited range of motion persists despite varied
treatment techniques [38,39]. One quarter of patients treated with
a motion-restoring surgical procedure still required multiple sur-
geries, with only 37% reporting satisfactory results [22]. With the
incidence of TKA projected to reach 3.5 million by 2030, the
growing cohort of TKA patients with postoperative arthrofibrosis
provides an important target for research [40].
The excessive scar tissue formation in the knee joint with
arthrofibrosis results in decreased knee extension and flexion range
of motion, leading to tissue contracture, increased pain, and func-
tional deficits in many activities of daily living (eg, standing up,
walking, stair climbing) [11,41e44]. Previous studies have shown
that the functional deficits vary depending on the severity of
flexion loss; approximately 70 degrees of flexion are necessary for
typical gait, 80
-90
for stair ascent and descent, and at least 125

for squatting to pick an object up from the floor [9,43,45]. Loss of
extension can be even more incapacitating and difficult to manage,
as just small limitations in extension range of motion increase
energy consumption and place undue strain on the quadriceps
muscles [9,27,45]. As little as a 5
loss in extension results in altered
gait mechanics (eg, limping) and walking on a 15
flexed knee re-
quires 22% more extensor demand [9,46].
Economic Burden of Arthrofibrosis Post-TKA
TKA is generally a successful and cost-effective procedure, but
adverse outcomes like arthrofibrosis can lead to costly follow-up
procedures [47]. Although manipulation under anesthesia (MUA)
is typically the initial treatment option for post-TKA arthrofibrosis,
it is no guarantee of improved function, decreased pain, and
increased satisfaction [14,48]. More aggressive procedures may
improve knee range of motion, but are more traumatic and are
associated with an increased risk of continued postoperative
treatment. Furthermore, compared with a primary TKA, a revision
TKA is more costly (1.6 times less cost-effective for the same in-
crease in Western Ontario and McMaster Universities Arthritis In-
dex score, and an increased hospitalization cost of almost $7000
over a primary); those receiving a revision are also twice as likely to
require readmission (higher rates of complications such as infec-
tion); and those receiving a revision may have worse outcomes, as
patients may remain stiff even after their procedure [38,49e52]. If
the use of invasive techniques for management of arthrofibrosis
could be minimized while still achieving adequate range of motion,
the costs and incidence of complications associated with arthro-
fibrosis could be reduced. Rehabilitation is comparatively low cost,
at approximately $1500 per knee arthroplasty [53].
Importance of Initial Management
Physiotherapy rehabilitation is a fundamental component of the
postoperative care after primary TKA. The arthrofibrotic knee rep-
resents a difficult challenge for the therapist that requires careful
attention and skill to improve functional outcomes and potentially
save the health care system tens of thousands of dollars per patient
in future medical costs. An effective rehabilitation program em-
phasizes (1) the management of inflammation, swelling, and pain,
(2) frequent monitoring, and (3) maintaining or restoring range of
motion as soon as arthrofibrosis is recognized [27,54e56]. This is in
contrast to the typical intervention after TKA, in which the
emphasis is on increasing muscle strength of the quadriceps as well
as managing inflammation and swelling. However, because range
of motion is the limiting factor in patients with arthrofibrosis, the
intervention needs to prioritize range of motion deficits early
before the fibrotic tissue has a chance to mature and become
resistant to physiotherapy later on [10]. The arthrofibrotic knee
requires intensive, structured, and well-monitored rehabilitation to
aggressively treat range of motion deficits, and its effectiveness is
also highly dependent on patient motivation and compliance
[5,11,22,57e59]. Concurrently, adequate pain management must be
maintained and progress should be monitored closely [55]. The
intensity of rehabilitation should be aggressive, as intense physical
therapy was found to be the most influential factor for post-
operative flexion, while a decrease in days of aggressive inpatient
physical therapy correlated with an increased rate of MUAs [60,61].
Preoperative educational meetings can also engage patients as
active participants in their own healthcare to address motivation
and compliance; attendance of educational meetings was associ-
ated with a significantly decreased risk of postoperative stiffness
requiring MUA [59]. Several supplements to a prescribed rehabili-
tation program exist that target range of motion, with a long-term
goal of avoiding additional operations if possible. These adjuncts to
rehabilitation may help maintain or even promote range of motion
gains achieved with physical therapy, with implementation and
timing of these treatment modalities typically customized to each
patient (see below) [22,41].
Nonsteroidal Anti-Inflammatory Drugs and the Rest-Ice-
Compression-Elevation Method
Nonsteroidal anti-inflammatory drugs and the rest-ice-
compression-elevation method assist with decreasing the inflam-
matory response, pain, and swelling. Shortening the inflammatory
phase decreases the pathogenesis of scar tissue, whereas proper
pain and swelling management allow rehabilitation to begin or to
continue without excessive patient discomfort [62]. Such symptom
management is important for patient motivation and adherence to
therapy, which are both crucial to successful outcomes, as gains in
range of motion may be lost because of lack of activity or immo-
bility [63]. Therapist supervision is vital in determining if acute
inflammation persists through treatment. Although immediate and
aggressive range of motion exercises improve outcomes for pa-
tients with early motion problems, if inflammation is not well
 V.A. Cheuy et al. / The Journal of Arthroplasty 32 (2017) 2604e2611
Fig. 2. Management algorithm for arthrofibrosis of the knee after total knee arthroplasty.
controlled, such aggressive intervention may have the opposite
effect and actually promote scar tissue formation [64]. In these
cases, a milder, but consistently implemented range of motion
exercise intervention might achieve the best results.
Continuous Passive Motion Devices
Although active motion training is preferred, continuous passive
motion (CPM) devices are occasionally used to promote flexion.
However, several studies have found no advantage in improving
range of motion or any greater benefit when paired with physio-
therapy [65e67]. Boese et al [68] randomized a total of 160 subjects
into 3 groups: CPM device on and moving from the immediate
postoperative period, CPM device on and stationary at 90
flexion for
the first night and then moving throughout the rest of their stay, and
no CPM. They found no significant differences in all outcome vari-
ables (range of motion, swelling, blood loss, and pain scores) and
that CPM provided no benefit to patients recovering from TKA [68].
Bracing
Static bracing is often used to maintain full extension range of
motion [8,69]. Unfortunately, an extension brace may worsen
arthrofibrosis due to limited flexion and, if bracing is used, the
recommendation is alternating periods of bracing with periods of
motion so as to limit development of stiffness [8,70]. Bracing is
common practice after anterior cruciate ligament (ACL) recon-
struction, and although it is a different pathology of the knee, a
2607
systematic review of 12 randomized controlled trials investigating
bracing after ACL reconstruction rehabilitation found no evidence
that range of motion was affected by brace use, findings which may
extend to bracing after TKA as well [69]. Both static progressive
splints, which use stress relaxation to stretch tissues, and dynamic
progressive splints, which apply a low-grade force to the joint to
gradually flex or extend the joint, have been shown to improve
knee flexion deficits by 19
and knee flexion contractures by 7
-19

[39,71]. However, research in this area is limited to only 2 small
cohort studies.
Neuromuscular Electrical Stimulation
Neuromuscular electrical stimulation applies an electrical cur-
rent that overrides voluntary activation deficits to help re-educate
the quadriceps muscle to contract normally [72]. Improving muscle
function increases the speed of recovery and long-term functional
performance, and may help reduce or prevent extension lag
[41,72,73].
Soft Tissue Mobilization
Mechanical soft-tissue stimulation with hand-held instruments
(Astym, Performance Dynamics Inc, Muncie, Indiana) has also been
shown to improve knee flexion deficits by 35
and knee flexion
contractures by 12
in a small cohort of individuals who had failed
to respond to traditional rehabilitation and MUA [74]. The rationale
is the topical application of appropriate shear force and pressure
2608 V.A. Cheuy et al. / The Journal of Arthroplasty 32 (2017) 2604e2611
Table 1
Indications and Contraindications for Surgical Treatment Modalities.
Procedure Indications
MUA [75,76]  90 degrees of flexion at 6-wk follow-up
 Within 3 mo of primary TKA
Arthroscopic and open debridement [6,77]  Recurrent stiffness after physical therapy and MUA
 First attempt arthroscopic, then open
 More than 3 mo after primary TKA
Revision total knee arthroplasty [4]  Clear diagnosis for cause of stiffness, which can be
corrected operatively
 Preferably within 2 y of primary TKA
MUA, manipulation under anesthesia.
stimulates regeneration of damaged tissues and breakdown of scar
tissue.
Treatment Modalities Post-TKA After Physical Therapy
Arthrofibrosis is a challenging complication after primary TKA
because deficits in range of motion can persist, mitigating the
therapeutic effects of rehabilitation [41]. Treatment options avail-
able after physical therapy are MUA, debridement, and revision TKA
(Fig. 2), whose indications and contraindications are summarized
in Table 1.
MUA
Management of arthrofibrosis with MUA is typically the first
option when range of motion has not improved with physiotherapy
in the early postoperative period, as it is the least invasive operative
procedure and the scar tissue has not yet matured [10,48,78,79].
The reported incidence of patients undergoing a MUA after TKA to
address limited range of motion is between 2% and 6%
[48,58,75,76]. The most common technique for MUA is general
anesthesia, muscle relaxants, and a combination of administered
hip and knee flexion [80]. While the patient is under anesthesia, the
physician flexes the hip to 90
, and progressively flexes and extends
the knee while receiving auditory and tactile feedback of the ad-
hesions breaking away, culminating with several 20-30 second
holds at the new maximal knee positions [81].
Historically, there has been disagreement on the optimal in-
terval of time between TKA and MUA [75]. Initially, no major dif-
ferences were found in knee flexion improvement between MUA
performed early (12 weeks postop) and late (>12 weeks postop)
[82,83]. However, recent research has found an inverse relation-
ship between time to MUA postoperatively and final range of
motion, where earlier MUA increased flexion range of motion 30
-
42
and overall knee range of motion 31
-47
[13,75,78,80,84,85].
Namba and Inacio [48] compared patients who received MUA
within or beyond 3 months of surgery (1.8 [SD 0.7] vs 5.5 [SD 3.0]
months, respectively), and found that those patients who received
MUA beyond 3 months gained approximately half the flexion
range of motion of the cohort who had MUA within 3 months (17

vs 33
). Issa et al [86] found that patients who underwent
manipulation within 12 weeks achieved double the mean gain in
flexion (36.5
vs 17
), over 20
more in total arc range of motion
(119
vs 95
), and had higher Knee Society objective and function
scores than those who had late MUA. No significant differences in
these outcomes were found between patients who received an
MUA within 6 weeks and between 7 and 12 weeks. A recent survey
of 82 surgeons found confirmatory attitudes toward MUA timing,
where 71% performed MUA within 3 months, while only 19% per-
formed manipulations between 3 and 6 months postoperatively
Contraindications
 Infection, wound problems
 >10 degrees of extension loss (fracture concern)
 Component malalignment
 Infection, wound problems
 Component malalignment
 Extrinsic source of stiffness
 Insufficient pain and functional limitation to outweigh
risk of additional surgery
[5]. With patients typically returning to clinic 4-6 weeks post-
operatively, manipulation of those with severely limited motion
should not be delayed much longer, as potential range of motion
gains begin to decrease and incidence of subsequent revision TKA
increase (from 3.8%-5.3%) after 8 weeks post-TKA [58,75,76]. MUA
may not be effective for the severely stiff knee, in which flexion
range of motion is less than 70
, or for those who require multiple
sessions of MUA, as both these clinical presentations tend to have
poorer outcomes and require more aggressive treatment
[14,84,87]. When assessing the clinical benefits of MUA, the pa-
tient and surgeon must also weigh the potential complications,
which include fracture, wound dehiscence, patellar tendon avul-
sions, quadriceps strain or rupture, hemarthrosis, heterotopic bone
formation, and pulmonary embolism [79,85].
Debridement
When previous interventions like an MUA have failed to restore
adequate range of motion, or if the patient is more than 3 months
post-TKA, arthroscopic or open debridementdalso known as lysis
of adhesionsdis typically considered [10,11]. The reported inci-
dence of patients undergoing a debridement after TKA to address
limited range of motion is 0.8% [88]. Arthroscopic debridement is a
minimally invasive surgical procedure that introduces various
cutting or shaving instruments through multiple arthroscopic
portals to break up focal and diffuse arthrofibrosis [77]. The focus of
the procedure is on the release of adhesions within the supra-
patellar pouch, the lateral and medial gutters, and the intercondylar
notch [89]. Previous studies have found arthroscopic debridement
improved flexion range of motion 24
-34
, extension range of
motion 12
-23
, and overall knee range of motion 24
-31

[83,88,90,91]. When arthrofibrosis is severe enough that nonop-
erative and arthroscopic techniques fail, open debridement is the
more invasive alternative [6,10,45,62]. During the open surgery,
blunt and sharp tools are used to break up adhesions with
enhanced visualization and easier access to all the articular struc-
tures that require debridement [62]. Improvement in overall knee
range of motion range averaged 39
with the open method
[13,83,92e94]. Because the gains in range of motion for both
arthroscopic and open debridement are comparable with those
from an MUA, the utility of debridement (specifically open) may
only exist for those patients with severe arthrofibrosis and who
have not responded to any previous treatments [6]. A recent survey
of 82 surgeons found that a majority (55%) do not perform open or
arthroscopic debridement, and only 4% routinely performed
debridement [5]. Although debridement is generally a safe treat-
ment modality, the risks associated with it include damage to the
metal prosthesis, hemarthrosis, extensor mechanism injury, frac-
ture, infection, and neurovascular injury [77].
 V.A. Cheuy et al. / The Journal of Arthroplasty 32 (2017) 2604e2611
Revision TKA
Revision TKA is the final treatment option available for persis-
tent limited motion if all previous treatments have failed. Previous
research has found that 10% of all revisions within 5 years of initial
surgery are due to arthrofibrosis [37]. A revision involves a partial
or complete replacement of the original prosthesis. Previous liter-
ature is scant on the outcomes of revision surgery for arthrofibrosis,
but Ries et al did find an improvement in range of motion in 6
patients, averaging a 50
increase in total knee range of motion
[14,95]. Unfortunately, pain and function scores after revision TKA
for arthrofibrosis have been shown to still lag behind scores for
revision TKA for other reasons (eg, infection, instability, wear, and
loosening) [96]. Arthrofibrosis may still occur after a revision due to
the surgical trauma, postsurgical rehabilitation process, or patient
predisposition, as those patients who require a revision due to
arthrofibrosis are also those with the highest risk for the persistent
development of severe fibrosis. Kim et al [57] found that over 25% of
revision TKAs due to stiffness required a second revision. Greidanus
et al [97] asserted that “most revision patients will never experi-
ence an outcome as favorable as their primary procedure.” The
additional risks associated with a revision are similar for primary
TKA surgery and as mentioned previously, including infection,
hemarthrosis, and neurovascular injury [98].
Future Directions
Novel Treatments
Novel operative and nonoperative treatment options for
arthrofibrosis after TKA are being developed, although most still
require larger, prospective, randomized studies. Saltzman et al [99]
has described supplementing arthroscopic debridement with the
use of indwelling epidural catheters begun preoperatively that
continue postoperatively for 6 weeks. The rational for extended
pain analgesia is that inadequate postoperative pain control pre-
vents knee flexion, resulting in adhesion formation and knee
stiffness [5]. Although the retrospective analysis was completed on
a small cohort (n ¼ 20), those receiving epidural catheters showed
improved knee extension, knee flexion, and self-reported pain
levels, with 70% maintaining range of motion success long-term
(6-month follow-up) and minimal complications [99]. Formby
et al [100] used hydraulic distension, a technique typically used to
treat adhesive capsulitis, as a substitute for an MUA. Hydraulic
distension of the knee involves (1) aspirating the suprapatellar
pouch, (2) distending the capsule with irrigation fluid and anes-
thesia until rupture, (3) aspirating the distension fluid, and (4)
injecting corticosteroid coupled with manipulation of the knee. The
3 patients receiving hydraulic distension showed a 23
increase in
knee flexion postoperatively, which was maintained at follow-up
(average 12 months) with no complications [100].
Smith et al [101] performed a prospective, randomized, double-
blinded, placebo-controlled trial comparing the use of botulinum
toxin A vs placebo for the treatment of knee flexion contracture
after TKA in patients without a specific preexisting neuromuscular
disorder. The authors postulated that botulinum toxin A can been
used to relieve hamstring tightness that developed secondary to a
flexion contracture. The results for 15 knees were that a single in-
jection into the hamstring musculature resulted in a significant
improvement in extension at 1 month and a greater amount of
improvement at 1 year compared with placebo, although both
groups recovered near full extension at the 1-year time point [101].
Treatment options are targeting inhibition of the fibrotic process as
well: Farid et al evaluated low-dose irradiation immediately before
constrained revision TKA to suppress fibroblastic proliferation;
2609
Dixon et al hypothesize an interleukin-1 receptor antagonist, ana-
kinra, can have an inhibitory effect on fibroblasts; and animal
models reveal novel anti-inflammatory agents may reduce knee
stiffness [102e104]. These studies serve as impetus for further
work into interventions during all perioperative phases of TKA.
Screening
Certain individuals may develop arthrofibrosis as part of their
healing process, indicative of a genetic component to arthrofibrosis
[26,105]. The development of an assessment of patient suscepti-
bility to arthrofibrosis would aid healthcare professionals in opti-
mizing perioperative care, targeting those at high risk of
complication. For example, a physical therapist could tailor the
rehabilitation program more effectively through improving timing,
level of aggressiveness, and speed of progression based on the
patient's risk level, resulting in faster recovery and better functional
outcomes. Differences in genetic disposition and gene expression
between patients with and without arthrofibrosis is a promising
area of future study.
The genetic targets of interest would be those genes and
signaling pathway regulators that relate most to the fibrogenic
process, capsular remodeling, and long-term inflammatory re-
actions, all associated with changes in extracellular matrix and
collagen production [25,27]. Although allelic association studies
have implicated a genetic predisposition toward forming excessive
joint scar tissue after injury and/or surgery, a genome-wide asso-
ciation study (GWAS) would offer a far more robust approach for
establishing a genetic risk profile [24,25,106]. A GWAS takes into
account the entire genome, unbiased with respect to selecting
certain single nucleotide polymorphisms. A meta-analysis of mul-
tiple GWAS could identify target single nucleotide polymorphisms
associated with arthrofibrosis and better inform future candidate
gene studies. Determining the genetic variation and what is
differentially expressed in those with postoperative arthrofibrosis
could then be applied preoperatively through a screening tool to
determine patient risk. This knowledge would guide the health care
professionals in modifying the timing and aggressiveness of
noninvasive postoperative care before the rapid formation of scar
tissue, and ideally prevent the need for invasive procedures such as
arthroscopic/open arthrolysis or revision TKA in the future. Iden-
tification of those individuals at high risk for severe arthrofibrosis
could even become a contraindication to receiving a primary TKA.
Conclusion
Arthrofibrosis is a multi-faceted complication of TKA, and is
difficult to treat without an early, tailored, comprehensive reha-
bilitation program. Understanding the risk factors for its develop-
ment, as well as the benefits and shortcomings of various
interventions are essential to best restore mobility and function
(Fig. 1). Future studies investigating early diagnosis and potential
preoperative screening for risk of arthrofibrosis will help target
those patients who will need additional attention to prevent pro-
longed, expensive healthcare costs.
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