1119111

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FAIXXX10.1177/10711007221119111Foot & Ankle InternationalMarchand et al

Article

Foot & Ankle International®

Greater Acute Articular Inflammatory

2022, Vol. 43(11) 1465­–1473
© The Author(s) 2022
Article reuse guidelines:
Response in Tibial Plafond Fractures as sagepub.com/journals-permissions
DOI: 10.1177/10711007221119111
https://doi.org/10.1177/10711007221119111

Compared to Ankle Fractures journals.sagepub.com/home/fai

Lucas S. Marchand, MD1 , David L. Rothberg, MD1,

Thomas F. Higgins, MD1, and Justin M. Haller, MD1

Abstract
Background: Several factors are thought to contribute to posttraumatic osteoarthritis (PTOA) development, including
the posttraumatic inflammatory response. The purpose of this study was to compare 2 injuries at the same joint with
a different severity and prognosis. This study compared the intra-articular inflammatory response after rotational ankle
fracture (lower energy and less PTOA) with tibial plafond fracture (higher energy and more PTOA).
Methods: This prospective comparative study was conducted at a level 1 trauma center between 2014-2019. Patients
between 18 and 60 years of age with acute ankle or tibial plafond fractures were enrolled. Patients with preexisting ankle
OA, autoimmune disease, additional injury, or open fractures were excluded. Synovial fluid aspirations were obtained
within 24 hours of injury. The concentrations of interleukin (IL)-1β, IL-1 receptor antagonist (IL-1RA), IL-6, IL-8, and IL-10
and matrix metalloproteinase (MMP)-1, MMP-3, and MMP-13 were quantified.
Results: Aspiration were obtained from 29 plafond fractures and 36 ankle fractures. Mean age was 43 years, and patients
were predominately female (64%). Age, gender, and comorbidities did not vary between cohorts. Of the plafond fractures,
13 were 43-B and 16 were 43-C injuries. Ankle fractures were predominately 44-B injuries, and 15 ankle fracture had
articular impaction. IL-10, IL-1β, IL-6, IL-8, MMP-1, MMP-3, and MMP-13 were all significantly higher in acute plafond
fractures as compared to acute ankle fractures.
Conclusion: This study compared articular inflammatory marker profiles after fractures of different severities. Several
cytokines were elevated in plafond fractures as compared to ankle fractures, suggesting a greater inflammatory response
with plafond fractures. Given the difference in prognosis for and higher rate of PTOA after plafond fractures, these data
strengthen the case that postinjury inflammatory response plays a role in PTOA development. Given that the postinjury
inflammatory response is one of the few modifiable variables of these injuries, future research in this area remains important.
Level of Evidence: Level II, prospective.

Keywords: posttraumatic osteoarthritis, synovial fluid, cytokines, ankle fracture

Introduction Understanding factors associated with the development of

Posttraumatic osteoarthritis (PTOA) can occur after a vari-
ety of joint injuries, but most predictably develops follow-
ing intra-articular trauma.10 The development of PTOA can
be disabling and is a common cause of secondary opera-
tions following injury.9,15 Clinical signs of pain and dys-
function may lag years or decades behind the initiating
injury, making it difficult to determine why some patients
develop PTOA.7 Although PTOA is estimated to cause only
12% of cases of symptomatic osteoarthritis overall, in con-
trast to the hip and knee joints, up to 90% of arthritic change
to the ankle may be posttraumatic in nature.7,26,28,30,31
PTOA is essential for possible prevention of this process.
Ankle PTOA typically affects younger patients and pro-
gresses more rapidly to end-stage disease when compared
to other lower extremity joints.10 This outcome can be
1
Department of Orthopaedic Surgery, University of Utah, Salt Lake City,
UT, USA
Corresponding Author:
Lucas S. Marchand, MD, Department of Orthopaedic Surgery, University
of Utah, 590 Wakara Way, Salt Lake City, UT 84108, USA.
Email: lucas.marchand@hsc.utah.edu
1466 Foot & Ankle International 43(11)

Figure 1.  Radiographic comparison of rotational ankle fracture and tibial plafond fracture. (A) Anteroposterior and (B) lateral
radiographs of a tibial plafond fracture with significant intra-articular involvement and joint impaction. (C) Anteroposterior and (D)
lateral radiographs of a rotational ankle fracture with minimal intra-articular joint involvement and no joint impaction.

particularly impactful to young, working patients as it may
have substantial impact on their productivity and career
longevity.19 This ultimately may result in increased duration
of joint pain, poor function, and increased economic impact
to society, collectively highlighting the importance of this
problem.7,27,28 Ankle injuries seem to have varying rates of
PTOA development, where 32% of low-energy rotational
ankle fractures develop significant arthrosis at 10-year fol-
low-up and more than 70% of plafond fractures develop
significant arthrosis at 5-year follow-up.21,25
Studying PTOA is appealing given that there is an iden-
tifiable inciting event that may allow clinicians a window
for intervention to attenuate or prevent its develop-
ment.1,4,9,22 Furthermore, we are able to study cellular and
subcellular events that correlate with and may contribute to
cartilage degeneration and the development of PTOA fol-
lowing injury. The initial traumatic injury involves articular
impaction, soft tissue disruption, a local inflammatory
response, abnormal joint loading, chondrocyte necrosis,
and apoptosis.10 Additional injury characteristics such as
instability, inflammation, and trauma severity (especially
the presence of an intra-articular fracture) are also recog-
nized contributors to PTOA.4,9 Although all of these factors
are thought to contribute to the development of PTOA, the
exact mechanisms that lead to progression from injury to
end-stage osteoarthritis are poorly understood.
The posttraumatic inflammatory response has been dem-
onstrated to have deleterious effects on the joint and can also
play a role in cartilage degeneration.1,2,11,12,14,15 Studies have
demonstrated a significant intra-articular inflammatory
response after tibial plafond fracture that is greater than the
response in tibial plateau fractures.14 However, these injuries
affect different joints and may not be fairly compared.
The effect of the initial posttraumatic inflammatory response
after intra-articular fracture on the development of PTOA
remains unknown. The purpose of this study was to compare
2 injuries involving the ankle joint that have a presumed dif-
ferent severity and prognosis. This study compared the
inflammatory response after acute rotational ankle fracture
with tibial plafond fracture. We hypothesized that the inflam-
matory profile would be greater in tibial plafond fractures
given their association with higher-energy mechanism and
more severe intra-articular injury, and higher rates of PTOA
at follow-up.
Methods
This was a Level II evidence prospective comparative
study. After receiving institutional review board approval,
we prospectively enrolled all patients older than 18 years
and younger than 60 years who presented to our level 1
trauma center with a rotational ankle fracture or tibial pla-
fond fracture from July 1, 2014, through January 1, 2019
(Figure 1). All subjects gave informed consent to participate
in the study. Exclusion criteria included an age greater than
60 years; any history of hip, knee, or ankle osteoarthritis
based on previous diagnosis, prior surgical intervention in
this regard, suggestive history, or radiographic findings;
regular use of nonsteroidal anti-inflammatory drugs; any
history of autoimmune disease; additional intra-articular
injury; pregnancy; open fracture; non–English speaking;
incarceration; and injury more than 24 hours prior to evalu-
ation. Additionally, if the ankle joint could not be aspirated
within 24 hours, the patient was excluded. Demographic
data including age, sex, and medical comorbidities were
recorded in the patient’s chart at the time of enrollment.
Marchand et al 1467
Fractures were classified according to the AO/OTA sys-
tem.17 The presence of articular impaction was also noted
through the review of computed tomography (CT) scans by
a fellowship-trained orthopaedic traumatologist (J.M.H.).
Injury Severity Scores were recorded for all patients.5 All
patients were treated by one of 3 fellowship-trained ortho-
paedic traumatologists (D.L.R., T.F.H., and J.M.H.).
Sample Acquisition
Ankle aspirations were performed within the first 24 hours
after injury at the time of closed reduction, spanning exter-
nal fixation, or open reduction and internal fixation (ORIF).
In cases where ORIF was performed, the aspiration was
performed at the start of the case prior to any surgical
approach or arthrotomy. A standardized protocol was used
for all aspirations. The skin was prepared in a sterile fash-
ion. As much fluid as possible was subsequently withdrawn
from the ankle. Techniques including joint manipulation,
changing limb position, and expressing fluid toward the
syringe were used to ensure a maximal amount of fluid
could be collected. The aspirated fluid was then transferred
to sterile centrifuge tubes and combined with protease
inhibitor cocktail (Roche Diagnostics, Indianapolis, IN).
The samples were then centrifuged at 2500 rpm for 15 min-
utes. The supernatant was aspirated using a micropipette,
placed in 2.0-mL cryopreservation tubes, and frozen at
–80°C until subsequent analysis.
Cytokine Analysis
The concentrations of 8 inflammatory cytokines and che-
mokines interleukin (IL)-1β, IL-1 receptor antagonist
(IL-1RA), IL-6, IL-8, IL-10, matrix metalloproteinase
(MMP)-1, MMP-3, and MMP-13 were determined from the
resulting supernatant with use of a human inflammatory
cytokine panel and the Millipore multiplex system
(Millipore, Billerica, MA) according to the manufacturer’s
protocol in a 96-well plate format. These particular cyto-
kines were selected based on previous results from this
study group.14,15 The assay uses antibodies linked to mag-
netic beads, and the relative concentration of each sample is
analyzed compared with the concentrations of the standard
controls provided by the manufacturer. The assays were
performed in triplicate by an investigator masked to the
patient injury characteristics.
Statistical Analysis
A power analysis was conducted to determine the number
of subjects needed for the study. This analysis is based on
results from a previous published study comparing the dif-
ference in inflammatory markers of tibial plafond and tibial
plateau fractures.14 Assuming a similar difference may exist
between rotational ankle and tibial plafond fractures, it was
determined that a total of 28 patients would be needed in
each cohort. The analysis was conducted to achieve 80%
power at an alpha level of 5% based on measurements from
the prior study.
Patient demographics and fracture characteristics were
summarized descriptively and stratified by plafond and
rotational ankle fractures. Continuous variables were sum-
marized as mean (SD), median (interquartile range) and
range, and compared between fracture types using a t test
for age and exact Wilcoxon rank sum tests for the other
variables that were right skewed. Sex was summarized as
number and percentage of males and compared using a χ2
test. Characteristics specific to fracture types were summa-
rized (Table 1).
Eight cytokine measures were summarized as median
and interquartile range stratified by fracture types (Table 2),
and also by subcategories within ankle fractures (Tables 3
and 4). Wilcoxon rank sum tests were used to compare each
cytokine measure between the groups. For the comparisons
between plafond and ankle fractures, we also provided P
values adjusting for age, sex, BMI, Injury Severity Score,
and CCI. Because of the challenging distributions of the
cytokine measures, we used generalized estimating equa-
tions (GEEs) and reported permutation P values from 3000
iterations.23 In each iteration rotational ankle or plafond
fracture types were randomly assigned to the individuals,
and regression coefficient for fracture type was estimated
using the same GEE model. Permutation P values were the
percentage coefficients that were more extreme than the
coefficient estimated using the original data.
All analyses were conducted in R v4.0.x and all tests
were 2 sided (R Core Team, Vienna, Austria).
Results
A total of 65 patients were prospectively enrolled in the
study, including 36 patients with rotational ankle fractures
and 29 patients with intra-articular plafond fractures.
Average age was 39.6 years (range 20-60 years) in the ankle
fracture group with 23 (64%) female and 13 (36%) male
patients (Table 1). Average age was 43 years (range 36-55
years) in the plafond fracture group, with 19 (66%) female
and 10 (34%) male patients. There was no significant differ-
ence in the average age or gender distribution between the 2
study cohorts (P = .18 and P = .78, respectively). There
were 14 partial articular fractures (AO/OTA 43B1-3) and 15
complete articular fractures (AO/OTA 43C1-3) in the tibial
plafond group. There were 13 bimalleolar fractures (AO/
OTA 44B2.3, 44B3.1, 44B3.2, 44C1.2) and 23 trimalleolar
fractures (AO/OTA 44B3.2, 44C3.3) in the ankle group. All
of the plafond fractures had articular impaction and 21
ankle fractures had notable articular impaction. The Injury
Severity Score for ankle fractures was 5.1 as compared to a
1468 Foot & Ankle International 43(11)

Table 1.  Patient Demographics and Fracture Characteristics.

Variable Plafond (n = 29) Ankle (n = 36) P Value

Age  
  Mean (SD) 43.6 (12.5) 39.6 (10.7) .18a
  Median (IQR) 45.0 (36.0, 55.0) 36.5 (33.5, 46.2) –
 Range (21.0, 60.0) (20.0, 60.0) –
Sex: male, n (%) 10 (34.4) 13 (36.1) .78b
BMI  
  Mean (SD) 27.6 (6.6) 31.4 (7.5) –
  Median (IQR) 26.0 (23.0, 30.3) 29.2 (25.6, 36.5) .032c
 Range (20.1, 54.2) (21.4, 49.5) –
ISS  
  Mean (SD) 5.0 (3.2) 5.1 (4.6) –
  Median (IQR) 4.0 (4.0, 4.0) 4.0 (4.0, 4.0) .68c
 Range (0.0, 17.0) (0.0, 27.0) –
CCI  
  Mean (SD) 0.5 (0.9) 1.2 (2.0) –
  Median (IQR) 0.0 (0.0, 1.0) 0.0 (0.0, 2.0) .28c
 Range (0.0, 4.0) (0.0, 8.0) –
Plafond type, n (%)  
 Partial 14 (48.3) – –
 Complete 15 (51.7) – –
Ankle type, n (%)  
 Bimalleolar – 13 (36.1) –
 Trimalleolar 23 (63.8)  
Impaction, n (%)  
 0 – 21 (58.3) –
 1 – 15 (41.7) –

Abbreviations: BMI, body mass index; CCI, Charlson Comorbidity Index; IQR, interquartile range; ISS, Injury Severity Score.
a
t test.
χ test.
b 2
c
Exact Wilcoxon rank sum test.

Table 2.  Cytokine Levels by Fracture Type.

Plafond, Ankle,
Median (IQR) Median (IQR)
Variable (n=29) (n=36) P Valuea P Valueb
IL-10c 50 (33, 179) 29 (11, 46) .001 .021
IL-1RAc 332 (68, 757) 407 (203, 637) .45 .06
IL-1β 2.5 (1.5, 8.1) 0.7 (0.0, 3.5) .007 <.001
IL-6 15 350 (8715, 21 565) 7949 (2066, 9643) <.001 <.001
IL-8 1429 (306, 2310) 143 (23, 709) <.001 .001
MMP-1 2024 (634, 10 935) 326 (144, 9664) .06 .06
MMP-3 435 123 (261 589, 958 092) 98 935 (27 246, 261 589) <.001 <.001
MMP-13 152 (0, 515) 0 (0, 292) .009 .07

Abbreviations: IL, interleukin; IL-1RA, IL-1 receptor antagonist; IQR, interquartile range; MMP, matrix metalloproteinase.
a
Exact Wilcoxon rank sum test.
b
Permutation test P values from linear generalized estimating equations adjusting for age, sex, body mass index, Injury Severity Score, and Charlson
Comorbidity Index.
c
Values reported in pg/mL, all others reported in ng/mL.
Marchand et al 1469

Table 3.  Cytokine Levels by Impaction Within Ankle Fractures.

Impaction, No Impaction,
Median (IQR) Median (IQR)
Variable (n=15) (n=21) P Valuea
IL-10b 21 (9, 64) 32 (13, 35) >.99
IL-1RAb 622 (418, 871) 317 (194, 430) .036
IL-1β 0.9 (0.0, 4.5) 0.7 (0.0, 2.2) .51
IL-6 8372 (5868, 12 314) 7714 (1044, 9032) .12
IL-8 180 (59, 1249) 97 (9, 274) .10
MMP-1 690 (203, 12 000) 246 (76, 9389) .36
MMP-3 160 639 (59 827, 261 589) 39 778 (14 433, 261 589) .23
MMP-13 0 (0, 386) 0 (0, 47) .30

Abbreviations: IL, interleukin; IL-1RA, IL-1 receptor antagonist; IQR, interquartile range; MMP, matrix metalloproteinase.
a
Exact Wilcoxon rank sum test.
b
Values reported in pg/mL, all others reported in ng/mL.

Table 4.  Cytokine Levels by Classification Within Ankle Fractures.

Bimalleolar, Trimalleolar,
Median (IQR) Median (IQR)
Variable (n=18) (n=18) P Valuea
IL-10b 27 (12, 45) 29 (12, 42) .86
IL-1RA b 366 (148, 482) 485 (218, 879) .25
IL-1β 0.3 (0.0, 0.9) 2.0 (0.1, 4.4) .11
IL-6 7949 (1040, 9027) 7992 (4925, 10852) .44
IL-8 55 (14, 223) 223 (74, 1257) .15
MMP-1 228 (115, 704) 4271 (259, 17109) .07
MMP-3 67 073 (26 210, 148 516) 256 320 (31 290, 261 589) .11
MMP-13 0 (0, 0) 24 (0, 392) .20

Abbreviations: IL, interleukin; IL-1RA, IL-1 receptor antagonist; IQR, interquartile range; MMP, matrix metalloproteinase.
a
Exact Wilcoxon rank sum test.
b
Values reported in pg/mL, all others reported in ng/mL.

score of 5 for plafond fractures, with no significant differ-
ence between the groups (P = .68).
Median cytokine levels from the ankle joint aspirate of
the ankle fracture group were as follows: 29 pg/mL (IL-10),
407 pg/mL (IL-1RA), 0.7 ng/mL (IL-1β), 7949 ng/mL (IL-
6), 143 ng/mL (IL-8), 326 ng/mL (MMP-1), 98 935 ng/mL
(MMP-3), and 0 ng/mL MMP-13. Median cytokine levels
from the ankle joint aspirate of the plafond fracture group
were as follows: 50 pg/mL (IL-10), 332 pg/mL (IL-1RA),
2.5 pg/mL (IL-1β), 15 350 ng/mL (IL-6), 1429 ng/mL (IL-
8), 2024 ng/mL (MMP-1), 435 123 ng/mL (MMP-3), and
152 ng/mL (MMP-13). Nearly all of the inflammatory cyto-
kines were elevated in the plafond fracture group as com-
pared to the ankle fracture group (Table 2). Only the levels
of IL-1RA were not significantly different between the 2
groups (P = .45).
Within the ankle fracture cohort cytokine measurements
were also compared in those ankle fractures with and with-
out articular impaction (Table 3). However, only IL-1RA
was elevated in the patients with impaction compared to
those without (P = .036). There was no difference noted
otherwise in this subgroup analysis. Furthermore, when
comparing the cytokine concentrations among the ankle
fracture cohort and stratifying by injury type (bimalleolar
vs trimalleolar injury), there was no significant difference
(Table 4).
Discussion
The literature has shown that PTOA occurs at a greater rate
in the ankle than other lower extremity joints, affects
younger patients on average, has significant economic
impact on society, and is the most common cause of arthritis
about the ankle joint, making this an ideal model for study-
ing PTOA.7,26,28,30,31 Furthermore, the traumatic inciting
events that ultimately lead to PTOA may offer a moment for
intervention to assuage or avoid the development of arthri-
tis altogether.1,4,9,22 Recent work has helped reveal part of
1470 Foot & Ankle International 43(11)
the cellular and subcellular events that may contribute to the
development of PTOA, but many questions remain in this
regard. This is the first study to compare the inflammatory
cytokine response about a single joint following 2 distinct
injury patterns. Importantly, this study demonstrates that
plafond fractures, which are known to be associated with
higher rates of PTOA, have higher concentrations of many
inflammatory cytokines following injury as compared to
ankle fractures that are aspirated within the same time frame
and analyzed via similar methods.
This study helps further our understanding of the acute
intra-articular inflammatory response that occurs following
joint trauma and may help further elucidate the role of this
response in the development of PTOA. Previous work has
demonstrated a significant intra-articular inflammatory
response after plafond fractures that is greater than the
inflammatory response in tibial plateau fractures.14
However, this difference may simply have been a result of
the different mechanical and cellular environment of ankle
and knee joints. The current study reveals that the inflam-
matory response is related to the type of injury sustained by
the joint and may therefore also play a primary role in the
development of PTOA. This information supports the
importance of the postinjury inflammatory response and
highlights the need for future investigations in this regard.
However, we must be clear that the primary finding of this
study has only demonstrated a correlation between an ele-
vated inflammatory response and more severe fractures.
Although the more severe fractures do have a higher rate of
PTOA in previous studies, the present work has not demon-
strated a causal pathway between the inflammatory response
and development of arthritis.
Tibial plafond fractures are typically high-energy inju-
ries that occur following an axial load mechanism such as a
fall from height or motor vehicle accident (Figure 1). Ankle
fractures are low-energy injuries that typically occur with a
rotational moment on the ankle that can occur with walking,
hiking, and sports. These injuries have different amounts of
bone, cartilage, and soft tissue injury that could play a role
in PTOA development. Patients are profoundly impaired
following a tibial plafond fracture where physical function
outcome is at least a standard deviation lower at 2 years
postinjury as compared to age-matched normal patients.20
Additionally, general health remains poor in these patients
over 3 years after the original injury and is similar to patients
with chronic medical conditions.24 Most patients who sus-
tain an ankle fracture are able to return to regular activities
within 1 year of injury and are able to maintain excellent
function over a decade from surgery.25
Similarly, joint arthrosis following a tibial plafond frac-
ture occurs more frequently and can develop early in the
recovery process when compared to PTOA that develops
following a rotational ankle fracture (Figures 2 and 3).
PTOA develops in up to 40% of plafond fractures at 2 years
and may increase to upward of 70% at a minimum of 5
years, a frequency which exceeds that known to be associ-
ated with rotational ankle injuries.16,21
Several studies have evaluated the posttraumatic intra-
articular inflammatory response through measuring cyto-
kine and MMP concentrations.1,2,6,11,14,15 These studies have
evaluated a variety of injuries to both the knee and ankle,
with synovial fluid aspirates collected at a variety of time
points following injury. Recently, Allen et al3 demonstrated
that exposure of uninjured cartilage to synovial fluid frac-
ture hematoma caused activation of cartilage damage path-
ways. The present study demonstrated a significant increase
in 7 of the 8 inflammatory markers measured when compar-
ing plafond to ankle fractures. The uninjured ankle was not
aspirated in this study as prior work has demonstrated a sig-
nificant difference between injured and uninjured ankles.17
It was not felt that further investigation regarding a com-
parison between injured and uninjured ankles was needed
given this data.
Prior work using animal models have correlated the
postinjury inflammatory response to the development of
PTOA.11-13,18,29 Additionally, these studies have suggested
that the inflammatory response is modifiable although mod-
ification of this process has yet to be successfully imple-
mented in clinical practice. Although the inflammatory
response in humans may also be contributing to PTOA, the
initial structural damage resulting from more severe frac-
tures in addition to any chondral injury likely also contrib-
utes. Further elucidation of the exact role each factor plays
in the development of PTOA may help guide future inter-
ventions and treatment.
We were unable to demonstrate any significant differ-
ence in the inflammatory response between ankle fracture
with and without joint impaction. Similarly, the present
study did not note any difference between the various types
of ankle fractures investigated (bimalleolar and trimalleolar
injuries). Although no studies have demonstrated increasing
rates of long-term PTOA in ankle fractures with impaction
or with distinct rotational ankle fracture patterns, it would
make sense that both articular impaction and increasing
severity of a rotational ankle injury would predispose to
PTOA. It would also, therefore, stand to reason that these
injuries would have a more significant acute inflammatory
response. The absence of this finding in the current study
may be a result of an underpowered analysis, as there were
relatively few patients in each subgroup.
The current study is not without limitation. Although the
current available evidence suggests that the postinflamma-
tory response contributes to PTOA, this cascade is a com-
plex and dynamic process that includes not only cytokines
and chemokines but also MMP’s proteins, stem cells, and
immunologic cells. The present study does not fully analyze
all of the contributing factors to PTOA and is undoubtedly
limited in this regard. Severity of initial cartilage injury and
Marchand et al 1471

Figure 2.  Radiographic outcome of rotational ankle and tibial plafond fractures. (A) Anteroposterior and (B) lateral radiographs
of a tibial plafond fracture 12 months status post open reduction and internal fixation with evidence of end-stage posttraumatic
osteoarthritis. (C) Anteroposterior and (D) lateral radiographs of a rotational ankle fracture with well-preserved joint space and no
evidence of posttraumatic arthritis.

Figure 3.  A/B - (A) Anteroposterior and (B) lateral radiographs of a rotational ankle fracture immediately following open reduction
and internal fixation. (C) Anteroposterior and (D) lateral radiographs of a tibial plafond fracture 12 months status post with a well
preserved joint and no evidence of post-traumatic osteoarthritis.
1472 Foot & Ankle International 43(11)
reduction quality were also not measured. Furthermore, the
study is limited by the lack of serum results. However,
serum testing has not been demonstrated to correlate with
synovial fluid biomarker concentrations.8,11 Lastly, we only
included those patients who could be aspirated within 24
hours from injury. Unfortunately, cytokine concentrations
can change within hours from injury, and this may further
add variability into our data and the subsequent analysis.
Despite the variability, these patient cohorts are the most
homogeneous in the literature, and it would be challenging
to collect synovial fluid aspirations with a narrower
window.
Conclusion
This is the first study to compare articular inflammatory
cytokine profiles after ankle fractures with that of tibial pla-
fond fractures. Several cytokines were significantly ele-
vated in plafond fractures as compared to ankle fractures,
suggesting the inflammatory response is greater in plafond
fractures. This is significant given that these injuries involve
the same joint, fluid samples were collected at the same
time point from acute injury, and aspirates were analyzed in
a parallel manner. Although this present study does not
prove causation of the inflammatory response in develop-
ment of PTOA, given the difference in prognosis for these
injuries these data strengthen the case that the postinjury
inflammatory response may play a role in the development
of PTOA and may serve as a target for therapeutic interven-
tion. Long-term follow-up on these patients will help to fur-
ther illuminate this topic and determine if an increased
acute inflammatory response correlates with the eventual
development of PTOA.
Acknowledgments
The authors would like to recognize Angela Presson and the Study
Design and Biostatistics Center for their assistance in statistical
interpretation of the data.
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with
respect to the research, authorship, and/or publication of this arti-
cle. ICMJE forms for all authors are available online.
Funding
The author(s) disclosed receipt of the following financial support
for the research, authorship, and/or publication of this article: This
study was supported by grants from the Orthopaedic Trauma
Association, the LS Peery Foundation, and AO North America.
These grants provided support for the research team and testing of
the synovial fluid samples. This investigation was supported by
the Design and Biostatistics Center, with funding in part from the
National Center for Research Resources and the National Center
for Advancing Translational Sciences, National Institutes of
Health, through grant 8UL1TR000105 (formerly UL1RR025764).
ORCID iDs
Lucas S. Marchand, MD, https://orcid.org/0000-0002-4499-
6669
Justin M. Haller, MD, https://orcid.org/0000-0002-8269-3925
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