ARTHRITIS & RHEUMATISM
Vol. 64, No. 12, December 2012, pp 3839–3849
© 2012, American College of Rheumatology
A Systematic Review and Meta-Analysis Comparing
Complications Following Total Joint Arthroplasty for
Rheumatoid Arthritis Versus for Osteoarthritis
Bheeshma Ravi,1Benjamin Escott,1Prakesh S. Shah,1Richard Jenkinson,1
Jas Chahal,1Earl Bogoch,1Hans Kreder,1and Gillian Hawker2
Objective. Most of the evidence regarding compli-
cations following total hip arthroplasty (THA) and total
knee arthroplasty (TKA) is based on studies of patients
with osteoarthritis (OA), with little being known about
outcomes in patients with rheumatoid arthritis (RA).
The objective of the present study was to review the
current evidence regarding rates of THA/TKA compli-
cations in RA versus OA.
Methods. Data sources used were Medline,
EMBase, Cinahl, Web of Science, and reference lists of
articles. We included reports published between 1990
and 2011 that described studies of primary total joint
arthroplasty of the hip or knee and contained informa-
tion on outcomes in >200 RA and OA joints. Outcomes
of interest included revision, hip dislocation, infection,
90-day mortality, and venous thromboembolic events.
Two reviewers independently assessed each study for
quality and extracted data. Where appropriate, meta-
analysis was performed; if this was not possible, the
level of evidence was assessed qualitatively.
Results. Forty studies were included in this re-
view. The results indicated that patients with RA are at
increased risk of dislocation following THA (adjusted
odds ratio 2.16 [95% confidence interval 1.52–3.07]).
There was fair evidence to support the notion that risk
of infection and risk of early revision following TKA are
increased in RA versus OA. There was no evidence of
any differences in rates of revision at later time points,
90-day mortality, or rates of venous thromboembolic
events following THA or TKA in patients with RA versus
OA. RA was explicitly defined in only 3 studies (7.5%),
and only 11 studies (27.5%) included adjustment for
covariates (e.g., age, sex, and comorbidity).
Conclusion. The findings of this literature review
and meta-analysis indicate that, compared to patients
with OA, patients with RA are at higher risk of disloca-
tion following THA and higher risk of infection follow-
Total joint arthroplasty (TJA) is considered one
of the most successful health care interventions for
end-stage arthritis of the hip or knee (1–3). Among
medical and surgical interventions, estimates of cost
utility consistently rank TJA at or near the top for
cost-effectiveness and patient satisfaction (4–6). This
success is reflected in the increasing rates of total hip
arthroplasty (THA) and total knee arthroplasty (TKA).
Outcomes following THA and TKA are generally excel-
lent, with low complication rates. However, some com-
plications have significant consequences, including early
revision, infection or dislocation, venous thromboembo-
lism, and death (7–11).
The vast majority of THA and TKA procedures
are performed for osteoarthritis (OA), which is the most
common form of arthritis (12,13). Thus, most of the
literature regarding outcomes of TJA and their predic-
tors is based on the experience in patients with OA.
Among the inflammatory arthritides, rheumatoid arthri-
tis (RA) is the most common. RA affects ?0.8% of the
1Bheeshma Ravi, MD, Benjamin Escott, MBBS, Prakesh S.
Shah, MD, FRCPC, Richard Jenkinson, MD, FRCSC, Jas Chahal,
MD, MSc, FRCSC, Earl Bogoch, MD, FRCSC, Hans Kreder, MD,
MPH, FRCSC: University of Toronto, Toronto, Ontario, Canada;
2Gillian Hawker, MD, MSc: University of Toronto and Women’s
College Hospital, Toronto, Ontario, Canada.
Dr. Bogoch has received consulting fees, speaking fees, and/or
honoraria from Eli Lilly, Procter & Gamble, Merck Frosst Canada,
Merck Sharpe & Dohme, Novartis Canada Ltd., and the Alliance for
Better Bone Health (less than $10,000 each) and has received unre-
stricted research grants from Amgen Canada, Novartis Canada Ltd.,
Warner-Chilcott, and the Alliance for Better Bone Health.
Address correspondence to Bheeshma Ravi, MD, Women’s
College Hospital, 76 Grenville Street, 8th Floor, Room 815, Toronto,
Ontario M5S 1B2, Canada. E-mail: email@example.com.
Submitted for publication April 5, 2012; accepted in revised
form August 28, 2012.
population of North America (0.3–2.1%); in 80% of
cases, RA develops between the ages of 35 and 50 years
(14,15). As in OA, TJA is indicated for the management
of end-stage hip and knee arthritis in RA. Estimates of
the prevalence of RA among TJA recipients vary con-
siderably, in part because of the difficulty in accurately
establishing this diagnosis using arthroplasty registries.
However, a recent study that evaluated the medical
history of TJA recipients in Ontario, Canada showed
that ?13% of these recipients had RA (10), correspond-
ing to ?170,000 TJAs from 2002 to 2010.
As RA is fundamentally different from OA in
terms of pathogenesis, prognosis, and medical manage-
ment, systematic differences in TJA outcomes would be
expected (16). However, few studies have examined
outcomes of TJA or their predictors in patients with RA,
or have investigated whether there are differences in
outcomes for patients with RA versus OA. Those that
have examined this have yielded conflicting results. For
example, Furnes et al (17) and Rud-Sorensen et al (18)
found no difference in risk of revision following THA
for RA versus OA, whereas Stea and colleagues re-
ported a higher risk in RA (19). This lack of clarity
regarding TJA outcomes, and their determinants, in
patients with RA impedes patient-physician decision-
making regarding when, and in which RA patients, TJA
should be considered. We undertook the present study
to compare the odds of complications following THA
and TKA in patients with RA versus OA, using meta-
analysis or systematic literature review.
Protocol, criteria for patient and study inclusion,
and outcomes. This review was conducted using a predefined
protocol and in accordance with guidelines suggested by the
Meta-analyses of Observational Studies in Epidemiology
Participants. Ambulatory adult patients (age ?18 years)
with RA or OA were included in this review. We included
studies reporting data on RA patients in comparison with OA
patients; the criteria used to establish the RA diagnosis were
recorded when available. For studies that utilized diagnostic
codes for RA from administrative databases or arthroplasty
registries, we noted whether any information on the validity of
these diagnostic codes was provided. We excluded TJA per-
formed secondary to fracture, malignancy, “juvenile RA,” or
Studies. We included peer-reviewed cohort, case–
control, or case series studies published from 1990 (to more
closely reflect current clinical practice) through December
2011 that examined primary TJA of the hip or knee. We
excluded studies on partial knee arthroplasty, hip hemiarthro-
plasty, and hip resurfacing. We limited our selection to studies
that examined outcomes in both OA and RA patients, with
results in at least 200 joints described. We chose this sample
size to have sufficient statistical power to evaluate the effect of
multiple factors on rare outcomes, such as death or revision.
Studies examining revision rates and those examining peri-
operative complications were required to have at least 1 year
and 90 days of followup, respectively. We did not include
annual reports from arthroplasty registries unless they were
published in a peer-reviewed journal. We did not include
meeting abstracts, as they did not contain enough information
to assess for bias. We excluded editorials, commentaries,
letters to the editor, and reviews, but they were read to iden-
tify any potential articles. We e-mailed the corresponding
author of each report selected for inclusion, to clarify any
details and to request access to patient-level data. The criteria
for study eligibility/inclusion are summarized in Supplemen-
tary Table 1, on the Arthritis & Rheumatism web site at http://
Outcomes. Studies of various TJA complications in
patients with RA in comparison to patients with OA were
evaluated. The following complications were included in the
assessment: 1) revision, defined as exchange of any or all of
the components due to any cause, 2) infection of the arthro-
plasty requiring therapy with antibiotics (any route) or surgery,
3) dislocation following THA, 4) mortality from any cause
within 90 days of surgery, and 5) venous thromboembolic event
within 90 days of surgery.
Information sources and search strategy. With the aid
of an experienced librarian, we searched 4 bibliographic data-
bases (Medline, EMBase, Cinahl, Web of Science) without
language restriction for reports published between January
1990 and December 2011. MeSH (Medical Subject Headings)
terms and key words used for the search are shown in
Supplementary Table 2 (http://onlinelibrary.wiley.com/journal/
10.1002/(ISSN)1529-0131). We also reviewed the bibliogra-
phies of included studies.
Study selection. Two of the authors (BR, BE) reviewed
the titles of all citations generated by the literature search
and removed any that did not address THA or TKA. We
reviewed the abstracts of the remaining studies and removed
those that did not address RA or inflammatory arthritis.
Thirty-eight abstracts were not available online or at the
University of Toronto libraries; all were from non-English
journals and were excluded from the review. Two additional
authors (RJ, JC) independently reviewed all excluded citations
to determine appropriateness of exclusion. Three citations
were found to be inappropriately excluded and were restored.
The abstract of each remaining citation was assessed (BR, BE)
for its primary outcome and sample size. We excluded reports
of studies that did not examine at least one of our outcomes of
interest, or if they did not meet our sample size requirements.
Data collection process and data items. The complete
articles from the 217 eligible citations were assessed by 3 of the
authors (BR, BE, RJ) for data abstraction. At least 2 authors,
who were not blinded with regard to citation identifiers,
independently abstracted data from each article. Briefly, for
each study, we determined the following: number of replaced
joints (RA and OA), number of centers, outcome measure,
mean followup time, criteria used to establish arthritis diag-
nosis, and the type of implant(s) used. Discrepancies were
resolved by consensus. Data from each article are summarized
3840 RAVI ET AL
in Table 1 and in Supplementary Table 3 (http://onlinelibrary.
wiley.com/journal/10.1002/(ISSN)1529-0131). We excluded
173 studies in which the outcome measure was not stratified by
arthritis diagnosis. For all selected studies, we attempted to
contact the corresponding author for additional details.
Assessment of risk of bias. For each included study,
risk of bias was evaluated using published validity criteria (21).
The domains included case definition (i.e., RA/OA classifica-
tion), patient selection, followup, outcome assessment, and
analyses. An additional criterion assessed data validation for
Figure 1. Search results and study selection. THA ? total hip arthro-
plasty; TKA ? total knee arthroplasty; RA ? rheumatoid arthritis;
IA ? inflammatory arthritis; TJA ? total joint arthroplasty; VTE ?
venous thromboembolic event.
Characteristics of the 40 included studies*
Author, year (ref.) Primary outcome measure
Allami et al, 2006 (24)
Bengtson and Knutson, 1991 (49)
Berry et al, 2002 (50)†
Bongartz et al, 2008 (29)
Chesney et al, 2008 (51)
Conroy et al, 2008 (52)†
Domsic et al, 2010 (53)†
Elke et al, 1995 (54)†
Furnes et al, 2001 (17)†
Gill et al, 2003 (9)
Hedlundh et al, 1995 (55)†
Himanen et al, 2005 (25)†
Jamsen et al, 2009 (27)
Johnsen et al, 2006 (41)†
Kang et al, 2010 (56)†
Kesteris et al, 1998 (57)†
Khatod et al, 2006 (32)†
Laskin and O’Flynn, 1997 (58)†
Mallory et al, 1999 (59)†
Nafei et al, 1996 (60)†
Niki et al, 2010 (31)
Partio et al, 1994 (61)†
Partio et al, 1994 (62)†
Paterson et al, 2010 (10)†
Pedersen et al, 2010 (63)†
Purtill et al, 2001 (64)†
Rand and Ilstrup, 1991 (65)†
Ritter et al, 1994 (66)†
Ritter, 2009 (67)†
Rud-Sorensen et al, 2010 (18)†
Schrama et al, 2010 (26)†
Sochart and Porter, 1997 (68)†
Soohoo et al, 2010 (69)†
TKA infection, THA infection
THA dislocation, THA revision
THA revision, TKA revision
THA revision, TKA revision
TKA infection, THA infection
THA dislocation, THA revision
Stea et al, 2009 (19)†
Van Heereveld et al, 2001 (70)
Weir et al, 1996 (71)†
White et al, 1990 (30)
Wymenga et al, 1992 (28)
Zwartele et al, 2004 (72)†
Zwartele et al, 2008 (73)†
* Additional details on each study, including study years, arthritis
diagnosis (rheumatoid arthritis or osteoarthritis) and how the diagno-
sis was determined, outcomes, total hip arthroplasty (THA) and total
knee arthroplasty (TKA) approach, means of outcome assessment and
analysis, and bias score, are available in Supplementary Table 3, on the
Arthritis & Rheumatism web site at http://onlinelibrary.wiley.com/
† Included in quantitative synthesis.
Grading the strength of the evidence
Good There is good evidence for or against an association
between the complication and rheumatoid
Determined by: consistent results across studies;
?3 studies; at least 1 study graded as “low” bias
There is fair evidence for or against an association
between the complication and RA
Determined by: consistent results across studies
but limited by quantity (3 studies) or quality
(no studies graded as “low” bias)
There is inconsistent evidence for or against an
association between the complication and RA
Determined by: studies had conflicting results
There is insufficient evidence for or against an
association between the complication and RA
Determined by: inadequate number of studies
evaluating the risk factor (?3 studies)
COMPLICATIONS FOLLOWING TJA IN RA VERSUS OA3841
database studies (2) (Supplementary Table 4). Articles with
scores of ?10 were classified as having a low risk of bias, scores
of 7–9 indicated moderate risk of bias, and scores of ?6
indicated high risk of bias.
Summary measures. Studies were stratified by the
joint replaced (hip versus knee), outcome of interest, and
duration of followup. For revision, we stratified followup into
3 periods: early (?5 years), middle (6–10 years), and late (?10
years). When possible, studies were also stratified by the type
of prosthesis and the use of bone cement. Studies were
evaluated within each group to determine if meta-analysis was
feasible and appropriate. If appropriate, meta-analyses were
performed using random-effects models with Review Manager
software (version 5.1). Meta-analytic estimates of proportion,
unadjusted odds ratio (OR), adjusted OR, unadjusted relative
risk (RR), and adjusted RR with 95% confidence intervals
(95% CIs) were reported. For study reports that provided
adjusted estimates but also provided information on the num-
ber of patients with OA and RA for both the treatment and the
outcome, unadjusted estimates were calculated for pooling
with other unadjusted estimates. The relative weight of each
individual study in the meta-analysis was calculated based on
the inverse of variance. Clinical heterogeneity among studies
was assessed based on the clinical criteria described above.
Statistical heterogeneity was assessed using I-square statistics.
Where meta-analysis was not appropriate, a systematic review
of relevant studies was conducted and the overall direction of
evidence summarized qualitatively.
Synthesis of results. Evidence based on meta-analysis
was assumed to be “good” if there was adjustment for potential
confounders, and “fair” if adjustment was not performed.
For outcomes where meta-analysis was not possible, 2 review-
ers (BR and BE) independently graded the overall strength of
the evidence as good, fair, inconsistent, or insufficient (Table
2). A third reviewer (JC) resolved any differences. Grades
were assigned using 3 criteria: quality, quantity, and consis-
tency of findings. Quality was assessed based on the study’s risk
of bias, as defined above. Quantity was assessed based on the
number of studies that evaluated each risk factor. Consistency
was assessed based on similarity of findings reported across a
range of study populations and study designs. The findings are
reported using the guidelines included in the Preferred Re-
porting Items for Systematic Reviews and Meta-Analyses
Risk of bias across studies. It was decided a priori that
for meta-analyses that included ?10 studies, publication bias
would be assessed using funnel plot asymmetry (23).
Study selection and quality of included studies.
The results of the search, the study selection log, and the
number of studies are shown in Figure 1. Forty studies
were included in this review. The results of the assess-
ment of the overall risk of bias in the included studies
are reported in Supplementary Table 3 (on the Arthritis
& Rheumatism web site at http://onlinelibrary.wiley.com/
journal/10.1002/(ISSN)1529-0131). Seventeen studies
had low risk of bias, 17 had moderate risk of bias, and 6
had high risk of bias. We were unable to obtain patient-
level data for any of the studies selected for inclusion.
Funnel plots were not assessed for asymmetry as none of
the meta-analyses included 10 or more studies.
Figure 2. Analysis of the likelihood of dislocation of the index hip within 5 years of hip arthroplasty in patients with rheumatoid arthritis (RA)
versus patients with osteoarthritis (OA), without (A) and with (B) adjustment for confounders. 95% CI ? 95% confidence interval.
3842 RAVI ET AL
Hip dislocation. Five studies compared the rates
of hip dislocation in patients with RA versus OA within
5 years of THA (risk of bias moderate in 4, high in 1)
(Supplementary Table 5). Meta-analysis of these 5 stud-
ies, all of which reported unadjusted comparative data,
revealed an increased risk of hip dislocation within 5
years of THA in patients with RA relative to those with
OA (unadjusted OR 2.74 [95% CI 1.73–4.34]; I2? 27%
[n ? 2,842 RA patients and 61,861 OA patients])
(Figure 2A). This increased risk was also found after
meta-analysis of 4 studies that reported comparative
data, adjusted for several variables (including age, sex,
surgical approach, and surgeon volume) (adjusted OR
2.16 [95% CI 1.52–3.07]; I2? 0% [n ? 1,637 RA
patients and 61,810 OA patients]) (Figure 2B).
Hip revision. Fifteen studies addressed THA
revision (risk of bias low in 9, moderate in 5, high in 1)
(Supplementary Table 6). For our analysis, these studies
were grouped according to the amount of time between
initial arthroplasty and revision (early, middle, or late, as
Hip revision at ?5 years. Meta-analysis of 4 stud-
ies that reported unadjusted comparative data revealed
increased odds of early revision among RA patients
versus OA patients (unadjusted OR 1.33 [95% CI 1.03–
1.71]; I2? 6% [n ? 3,913 RA patients and 76,221 OA
patients]) (Figure 3A). However, a study that adjusted
for age, sex, and comorbidity did not show increased
odds of revision within 1 year of THA in patients with
RA (adjusted OR 1.11 [95% CI 0.82–1.51] [n ? 3,805
RA patients and 23,412 OA patients]) (10).
Hip revision at 6–10 years. Meta-analysis of 7
studies revealed no difference in the unadjusted odds of
revision at 6–10 years in RA patients versus OA patients
overall (unadjusted OR 1.16 [95% CI 0.94–1.43]; I2?
46% [n ? 9,118 RA patients and 210,674 OA patients])
(Figure 3B). Allami et al also found no difference in the
unadjusted risk of revision at 10 years in RA patients
Figure 3. Analysis (unadjusted) of the likelihood of revision of the index arthroplasty in patients with RA versus patients with OA, within 5 years
of total hip arthroplasty (A), 6–10 years after total hip arthroplasty (B), and ?10 years after total hip arthroplasty (C). See Figure 2 for definitions.
COMPLICATIONS FOLLOWING TJA IN RA VERSUS OA3843
versus OA patients (unadjusted hazard ratio [HR] 3.33
[95% CI 0.4–24.5]) (24). Similarly, meta-analysis of 2
studies in which the investigators adjusted for age and
sex (among other covariates) revealed no difference in
the risk of revision between RA patients and OA
patients following THA (adjusted RR 0.91 [95% CI
0.74–1.11]; I2? 86% [n ? 2,110 RA patients and 88,103
OA patients]). Additionally, Furnes et al found no
difference in the odds of revision after adjustment for
age, sex, and type of prosthesis (adjusted OR 1.10
[95% CI 0.90–1.35]) (17).
Hip revision at ?10 years. Meta-analysis of 2
studies revealed lower unadjusted odds of late revi-
sion in RA patients versus OA patients for cemented
implants (unadjusted OR 0.28 [95% CI 0.17–0.47];
I2? 0% [n ? 229 RA patients and 1,710 OA patients])
Knee revision. Eleven studies reported on knee
revision (risk of bias low in 4, moderate in 4, high in 3)
(Supplementary Table 7) (http://onlinelibrary.wiley.
com/journal/10.1002/(ISSN)1529-0131). These studies
were analyzed in groups categorized by the duration
between initial arthroplasty and revision.
Knee revision at ?5 years. Meta-analysis of 3
studies indicated slightly increased odds of early revision
in patients with RA versus OA (unadjusted OR 1.24
[95% CI 1.10–1.40]; I2? 0% [n ? 8,479 RA patients and
35,274 OA patients]) (Figure 4A). Himanen et al found
no difference in the likelihood of revision at 4 years
(unadjusted RR 1.25 [95% CI 0.87–1.8]) (25). Paterson
and colleagues controlled for potential confounders
(age, sex, comorbidity, provider volume) and found no
significant difference in revision rates at 1 year (adjusted
OR 1.08 [95% CI 0.78–1.50]) (10).
Knee revision at 6–10 years. Meta-analysis of 6
studies revealed no difference between RA and OA
patients in the odds of revision at 6–10 years (unadjusted
OR 2.02 [95% CI 0.96–4.28]; I2? 69% [n ? 3,116 RA
patients and 29,670 OA patients]) (Figure 4B). This was
not affected by stratification by prosthesis type, i.e.,
Figure 4. Analysis (unadjusted) of the likelihood of revision of the index arthroplasty in patients with RA versus patients with OA, within 5 years
of total knee arthroplasty (A), 6–10 years after total knee arthroplasty (B), and ?10 years after total knee arthroplasty (C). See Figure 2 for
3844RAVI ET AL
cruciate-retaining prostheses (unadjusted OR 3.90
[95% CI 0.46–33.17] [n ? 235 RA patients and 1,171 OA
patients]) or posterior-stabilized prostheses (unadjusted
OR 1.11 [95% CI 0.56–2.18] [n ? 298 RA patients
and 6,743 OA patients]). Schrama and colleagues spe-
cifically assessed revision due to infection after 6 years
of followup, and demonstrated an unadjusted RR of 1.6
(95% CI 1.06–2.38) (26).
Knee revision at ?10 years. Meta-analysis of 2
studies that reported unadjusted comparative data on
cemented implants revealed no difference between
RA and OA patients in the odds of late revision (un-
adjusted OR 2.46 [95% CI 0.70–8.70]; I2? 50%
[n ? 297 RA patients and 256 OA patients]) (Figure
4C). No studies that provided adjusted estimates were
Infection. Five studies compared the rates of
index joint infection in patients with RA versus OA
following TJA (risk of bias low in 2, moderate in 2, high
in 1) (Table 1 and Supplementary Table 3, http://
0131). Meta-analysis was not possible due to variable
definitions of infection and preoperative antibiotic pro-
tocols (with some centers forgoing antibiotics alto-
gether), and pooling of primary and revision arthro-
plasty cases. In a study controlling for age, sex,
prosthesis type, and antibiotic cement, Jamsen and
colleagues found that patients with RA had an adjusted
HR of 1.86 (95% CI 1.31–2.63) for infection following
TKA, relative to OA patients (27). In a study by
Wymenga et al the risk of infection following TKA was
increased in patients with RA compared to those with
OA (unadjusted RR 4.8 [95% CI 1.2–19]) (28). Bongartz
and colleagues matched 402 RA patients (primary and
revision THA/TKA) to OA patients by age, time of
surgery, sex, and site of surgery (29). Compared with
matched OA controls, RA patients had higher odds of
infection in the first year (OR 10.30 [95% CI 1.31–
80.26]). Among those with RA, increased infection risk
was associated with prior infection in the replaced joint,
prior infection in any joint, and longer duration of
operating time (HR 1.36 per 60-minute increase [95%
CI 1.02–1.81]). That study revealed no association with
perioperative systemic corticosteroid use (HR 1.28 [95%
CI 0.46–3.60]) or with withdrawal of biologic treatment
prior to surgery (HR 0.65 [95% CI 0.09–4.95]) (29).
Mortality within 90 days of TJA. Four studies
reported on mortality following TJA (risk of bias low in
1, moderate in 3) (Table 1 and Supplementary Table 3).
Meta-analysis of 2 studies revealed no difference be-
tween RA and OA patients in the odds of mortality
within 90 days of THA (adjusted OR 1.40 [95% CI
0.82–2.39]; I2? 68%). Similarly, meta-analysis of 2
studies examining rates of death within 90 days of TKA
showed no difference between RA and OA patients
(adjusted OR 0.86 [95% CI 0.66–1.12]; I2? 0%). In a
study of 3,048 TKAs, Gill and colleagues reported 14
deaths occurring within 90 days of surgery (2,871 in OA
patients, 177 in RA patients); all of the deaths occurred
in patients with OA (9).
Venous thromboembolism within 90 days of TJA.
Five studies reported on venous thromboembolic events
following TJA (risk of bias low in 3, moderate in 2)
(Table 1 and Supplementary Table 3). Meta-analysis of
2 studies revealed no difference in the odds of venous
thromboembolic events within 90 days of THA in pa-
tients with RA versus those with OA (adjusted OR 0.84
[95% CI 0.28–2.54]; I2? 85%). Similarly, White et al
found that the unadjusted rates of in-hospital venous
thromboembolic events were similar among RA and OA
patients (P ? 0.07) (30). Niki and colleagues found no
difference in the rates of proximal deep vein thrombosis
on routine ultrasound performed 7 days after TKA in
patients with RA versus those with OA (unadjusted OR
0.81 [95% CI 0.26–2.52]) (31).
To our knowledge, this is the first systematic
review to assess rates of complications following THA
and TKA in patients with RA versus OA. In this review
of 40 studies, we found strong evidence for increased
risk of hip dislocation following THA, and fair evidence
for increased risk of infection following TKA, in patients
with RA versus OA. We also found fair evidence for
increased risk of early revision following TKA, but no
evidence to support any differences in later revision
rates, 90-day mortality, or rates of venous thromboem-
bolic events following THA or TKA in patients with RA
The increased risk of dislocation following THA
in patients with RA versus OA was an unexpected
finding which, to our knowledge, has not been well
recognized previously, possibly due to the lack of meta-
analysis. Susceptibility to dislocation could be the result
of poorer soft tissue quality in RA relative to OA,
resulting in suboptimal hip abductor strength postoper-
atively. Other potential explanations include systematic
differences in surgical approach, head size, or use of
bone cement between groups. However, Khatod et al
adjusted for surgical approach as well as head size, and
still noted an increased risk of dislocation among RA
COMPLICATIONS FOLLOWING TJA IN RA VERSUS OA 3845
patients (32). Further research is warranted to confirm
this finding and elucidate potential modifiable risk fac-
tors such as head size, surgical approach, or use of
It makes intuitive sense that risk of infection
following TJA would be increased in patients with RA
versus OA due to differences in the pathogenesis and
medical management of these conditions. As a systemic
autoimmune disease, RA is typically treated with immu-
nosuppressive agents, including systemic corticosteroids,
methotrexate, antimalarial drugs, and more recently,
biologic agents, e.g., adalimumab and etanercept (33–
35). Evidence regarding the effect of these medications
on the rate of postoperative infection is inconsistent
Our review revealed fair evidence to support the
notion of an increased risk of infection following TKA in
patients with RA versus OA. Three of four studies
showed increased infection risk following TKA in pa-
tients with RA, and 2 of these studies had a low risk of
bias. This is consistent with our finding that RA patients
had higher odds of revision within 5 years of TKA
(although this did not include adjustment for confound-
ers). Only 1 study showed an increased risk of infection
following THA in patients with RA, and this study had a
low risk of bias (29). In that study it was also found that
perioperative systemic corticosteroid use and withdrawal
of biologic treatment prior to surgery did not have any
effect on the rate of infection following THA or TKA in
patients with RA (29). However, most of the study
reports included no comment on the role of drug use in
the rate of infection following arthroplasty. Our review
has identified the need for larger studies to confirm the
present findings regarding infection risk after TKA in
RA patients and if they are confirmed, to determine the
effect of specific medical therapies and other factors on
risk of infection in RA.
Although dislocation rates following THA were
higher in RA patients than in OA patients, this was not
reflected in an increased rate of early revision following
THA. Potential explanations for this disparity include
the following: 1) there may be systematic differences
in the management of dislocations between RA and
OA, with the former being preferentially managed with
closed reduction and activity modification due to either
surgeon or patient preference (37), or 2) it may be that
an increased rate of early revision in RA does exist, but
was not observed in our study due to lack of power.
We also did not find a difference between RA
and OA patients in terms of 90-day mortality or venous
thromboembolic events following THA or TKA. How-
ever, as the reported risk of these complications is low,
the studies reviewed may have been inadequately pow-
ered to detect significant differences in rates between
the 2 patient groups.
RA can be a challenging diagnosis to establish
clinically, particularly early in the disease (38). Reports
of only 3 of the 40 studies (7.5%) discussed the process
by which the diagnosis of RA was established. One of
these used the 1987 American College of Rheumatology
criteria (39), and the other 2 used a referral diagnosis
from an internist or rheumatologist. Sixteen studies
(40%) utilized administrative databases or arthro-
plasty registries to establish the diagnosis of RA; of
these, only 1 report provided information on the validity
of the codes. The data in administrative databases are
typically collected for non-research purposes, and with-
out appropriate reabstraction and validation, the diag-
nosis may be inaccurate (40). Even a diagnosis recorded
by the surgeon intraoperatively may be inaccurate, as the
index joint of a patient with RA may have an appearance
that is more consistent with OA, and be recorded as the
latter (23). While these patients may have joint and/or
bone characteristics more similar to those found in OA,
they will still have the other risk factors for complica-
tions associated with RA, and should be classified as
such. The misclassification of RA patients as having OA
would reduce our ability to identify differences between
these groups. Thus, we may have underestimated differ-
ences in TJA outcomes between OA and RA patients,
where they exist.
Despite the large numbers of patients included
in the studies reviewed, variable adjustment for con-
founders limited our ability to pool results, and ulti-
mately lowered our statistical power. Most of the studies
reviewed (29 of 40 [72.5%]) did not, or were inade-
quately powered to, adjust for potential confounders,
including age, sex, and comorbidity.
It has been established that younger patients
(?70 years old) have a higher revision rate following
TJA, which is hypothesized to be due to increased
activity leading to wearing out of the prosthesis (41).
While this assumption may not apply to younger patients
with RA, who may have more activity-limiting poly-
articular joint involvement than patients with OA at a
comparable age, lack of controlling for the effect of age
is a significant limitation (42). Increased comorbidity,
including specific conditions such as diabetes, is associ-
ated with early infection and subsequent revision (43),
while cardiovascular disease may increase the risk of
mortality following TJA (44). RA is a systemic disease
characterized by an increased risk of cardiovascular
3846 RAVI ET AL
disease (45), while OA is associated with a high preva-
lence of concomitant obesity, diabetes, hypertension,
and heart disease (46,47). Although our focus was on
elective primary TJA procedures, in which patients are
typically medically fit for surgery, the presence of co-
morbid conditions contributes to differential risk of TJA
complications in patients with RA versus OA. Adequate
consideration of and control for comorbidity is war-
ranted in future studies examining the rates of revision
and other complications in RA versus OA.
Since none of the meta-analyses that were in-
cluded contained pooled results on 10 or more studies,
we did not assess funnel plots for asymmetry. However,
we did assess differences between studies via I-square
values, which describe the percentage of total variation
across studies that is due to heterogeneity rather than
chance (48). I-square values of 25%, 50%, and 75% are
considered low, moderate, and high, respectively. Our
analyses yielded a broad range of I-square values (0–
85%), although values were ?50% in most of our
meta-analyses (8 of 11). This degree of heterogeneity is
consistent with our pooling of studies that utilized
diverse types of implants, variable surgical approaches
and techniques, and differing diagnostic criteria to de-
fine RA versus OA.
In summary, compared with TJA recipients with
OA, we found that those with RA were at higher risk of
dislocation following THA and higher risk of infection
following TKA. However, after adjustment for covari-
ates, we found no difference regarding risk of revision,
90-day-mortality, or venous thromboembolic events
within 90 days of either THA or TKA. Adequately
powered studies, which incorporate validated definitions
for RA and OA diagnosis and control for appropriate
confounders and other covariates, are needed to con-
firm these findings. Where differences are confirmed,
further research is warranted to elucidate potential
explanations, including the role of prosthesis type, med-
ication use (e.g., biologic therapies), comorbidity, and
bone quality. The results of such studies would be useful
to guide decision-making regarding TJA in the setting
All authors were involved in drafting the article or revising it
critically for important intellectual content, and all authors approved
the final version to be published. Dr. Ravi had full access to all of the
data in the study and takes responsibility for the integrity of the data
and the accuracy of the data analysis.
Study conception and design. Ravi, Shah, Jenkinson, Bogoch, Kreder,
Acquisition of data. Ravi, Escott, Jenkinson, Chahal.
Analysis and interpretation of data. Ravi, Shah, Hawker.
1. Ethgen O, Bruyere O, Richy F, Dardennes C, Reginster JY.
Health-related quality of life in total hip and total knee arthro-
plasty: a qualitative and systematic review of the literature. J Bone
Joint Surg Am 2004;86-A:963–74.
2. Santaguida PL, Hawker GA, Hudak PL, Glazier R, Mahomed NN,
Kreder HJ, et al. Patient characteristics affecting the prognosis of
total hip and knee joint arthroplasty: a systematic review. Can
J Surg 2008;51:428–36.
3. Towheed TE, Hochberg MC. Health-related quality of life after
total hip replacement. Semin Arthritis Rheum 1996;26:483–91.
4. NIH consensus conference: total hip replacement. NIH Consensus
Development Panel on Total Hip Replacement. JAMA 1995;273:
5. NIH consensus statement on total knee replacement. NIH
Consens State Sci Statements 2003;20:1–34.
6. Chang RW, Pellisier JM, Hazen GB. A cost-effectiveness analysis
of total hip arthroplasty for osteoarthritis of the hip. JAMA
7. Dislocation rate after hip arthroplasty within the first postopera-
tive year: 36mm versus 28mm femoral heads. Hip Int 2011;21:
8. Antti-Poika I, Josefsson G, Konttinen Y, Lidgren L, Santavirta S,
Sanzen L. Hip arthroplasty infection: current concepts. Acta Orthop
9. Gill GS, Mills D, Joshi AB. Mortality following primary total knee
arthroplasty. J Bone Joint Surg Am 2003;85-A:432–5.
10. Paterson JM, Williams JI, Kreder HJ, Mahomed NN, Gunraj N,
Wang X, et al. Provider volumes and early outcomes of primary
total joint replacement in Ontario. Can J Surg 2010;53:175–83.
11. Xing KH, Morrison G, Lim W, Douketis J, Odueyungbo A,
Crowther M. Has the incidence of deep vein thrombosis in patients
undergoing total hip/knee arthroplasty changed over time? A
systematic review of randomized controlled trials. Thromb Res
12. Busija L, Bridgett L, Williams SR, Osborne RH, Buchbinder R,
March L, et al. Osteoarthritis. Best Pract Res Clin Rheumatol
13. Dreinhofer KE, Dieppe P, Sturmer T, Grober-Gratz D, Floren M,
Gunther KP, et al. Indications for total hip replacement: compar-
ison of assessments of orthopaedic surgeons and referring physi-
cians. Ann Rheum Dis 2006;65:1346–50.
14. Pratt AG, Isaacs JD, Mattey DL. Current concepts in the patho-
genesis of early rheumatoid arthritis. Best Pract Res Clin Rheu-
15. Scott DL. Early rheumatoid arthritis. Br Med Bull 2007;81–82:
16. Breedveld FC, Combe B. Understanding emerging treatment
paradigms in rheumatoid arthritis. Arthritis Res Ther 2011;13
17. Furnes O, Lie SA, Espehaug B, Vollset SE, Engesaeter LB,
Havelin LI. Hip disease and the prognosis of total hip replace-
ments: a review of 53,698 primary total hip replacements reported
to the Norwegian Arthroplasty Register 1987–99. J Bone Joint
Surg Br 2001;83:579–86.
18. Rud-Sorensen C, Pedersen AB, Johnsen SP, Riis AH, Overgaard
S. Survival of primary total hip arthroplasty in rheumatoid arthritis
patients: findings in 1,661 arthroplasties in 1,395 patients from the
Danish Hip Arthroplasty Registry. Acta Orthop 2010;81:60–5.
19. Stea S, Bordini B, De Clerico M, Petropulacos K, Toni A. First hip
arthroplasty register in Italy: 55,000 cases and 7 year follow-up.
Int Orthop 2009;33:339–46.
20. Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD,
Rennie D, et al, for the Meta-analysis Of Observational Studies in
Epidemiology (MOOSE) Group. Meta-analysis of observational
COMPLICATIONS FOLLOWING TJA IN RA VERSUS OA3847
studies in epidemiology: a proposal for reporting. JAMA 2000;
21. Hudak PL, Cole DC, Haines AT. Understanding prognosis to
improve rehabilitation: the example of lateral elbow pain. Arch
Phys Med Rehabil 1996;77:586–93.
22. Moher D, Liberati A, Tetzlaff J, Altman DG, Group P. Preferred
reporting items for systematic reviews and meta-analyses: the
PRISMA statement. BMJ 2009;339:b2535.
23. Higgins JP, Green S. Cochrane handbook for systematic reviews of
interventions: version 5.1.0. 2011. URL: www.cochrane-handbook.
24. Allami MK, Fender D, Khaw FM, Sandher DR, Esler C, Harper
WM, et al. Outcome of Charnley total hip replacement across a
single health region in England: the results at ten years from a
regional arthroplasty register. J Bone Joint Surg Br 2006;88:
25. Himanen AK, Belt E, Nevalainen J, Hamalainen M, Lehto MU.
Survival of the AGC total knee arthroplasty is similar for arthrosis
and rheumatoid arthritis: Finnish Arthroplasty Register report on
8,467 operations carried out between 1985 and 1999. Acta Orthop
26. Schrama JC, Espehaug B, Hallan G, Engesaeter LB, Furnes O,
Havelin LI, et al. Risk of revision for infection in primary total hip
and knee arthroplasty in patients with rheumatoid arthritis com-
pared with osteoarthritis: a prospective, population-based study on
108,786 hip and knee joint arthroplasties from the Norwegian
Arthroplasty Register. Arthritis Care Res (Hoboken) 2010;62:
27. Jamsen E, Huhtala H, Puolakka T, Moilanen T. Risk factors for
infection after knee arthroplasty: a register-based analysis of
43,149 cases. J Bone Joint Surg Am 2009;91:38–47.
28. Wymenga AB, van Horn JR, Theeuwes A, Muytjens HL, Slooff
TJ. Perioperative factors associated with septic arthritis after
arthroplasty: prospective multicenter study of 362 knee and 2,651
hip operations. Acta Orthop Scand 1992;63:665–71.
29. Bongartz T, Halligan CS, Osmon DR, Reinalda MS, Bamlet WR,
Crowson CS, et al. Incidence and risk factors of prosthetic joint
infection after total hip or knee replacement in patients with
rheumatoid arthritis. Arthritis Rheum 2008;59:1713–20.
30. White RH, McCurdy SA, Marder RA. Early morbidity after total
hip replacement: rheumatoid arthritis versus osteoarthritis. J Gen
Intern Med 1990;5:304–9.
31. Niki Y, Matsumoto H, Hakozaki A, Mochizuki T, Momohara S.
Rheumatoid arthritis: a risk factor for deep venous thrombosis
after total knee arthroplasty? Comparative study with osteoarthri-
tis. J Orthop Sci 2010;15:57–63.
32. Khatod M, Barber T, Paxton E, Namba R, Fithian D. An analysis
of the risk of hip dislocation with a contemporary total joint
registry. Clin Orthop Relat Res 2006;447:19–23.
33. Bhattacharyya T, Iorio R, Healy WL. Rate of and risk factors for
acute inpatient mortality after orthopaedic surgery. J Bone Joint
Surg Am 2002;84-A:562–72.
34. Michaud KD, Fehringer E, Garvin K, O’Dell JR, Mikuls TR.
Rheumatoid arthritis (RA) is associated with increased mortality
in patients undergoing total joint arthroplasty [abstract]. Arthritis
Rheum 2011;63 Suppl:S822.
35. Aglietti P, Buzzi R, Segoni F, Zaccherotti G. Insall-Burstein
posterior-stabilized knee prosthesis in rheumatoid arthritis. J Ar-
36. Momohara S, Kawakami K, Iwamoto T, Yano K, Sakuma Y,
Hiroshima R, et al. Prosthetic joint infection after total hip or knee
arthroplasty in rheumatoid arthritis patients treated with nonbio-
logic and biologic disease-modifying antirheumatic drugs. Mod
37. Soong M, Rubash HE, Macaulay W. Dislocation after total hip
arthroplasty. J Am Acad Orthop Surg 2004;12:314–21.
38. Banal F, Dougados M, Combescure C, Gossec L. Sensitivity and
specificity of the American College of Rheumatology 1987 criteria
for the diagnosis of rheumatoid arthritis according to disease
duration: a systematic literature review and meta-analysis. Ann
Rheum Dis 2009;68:1184–91.
39. Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF,
Cooper NS, et al. The American Rheumatism Association 1987
revised criteria for the classification of rheumatoid arthritis.
Arthritis Rheum 1988;31:315–24.
40. Singh JA, Holmgren AR, Noorbaloochi S. Accuracy of Veterans
Administration databases for a diagnosis of rheumatoid arthritis.
Arthritis Rheum 2004;51:952–7.
41. Johnsen SP, Sorensen HT, Pedersen AB, Lucht U, Soballe K,
Overgaard S. Patient-related predictors of implant failure after
primary total hip replacement in the initial, short- and long-term:
a nationwide Danish follow-up study including 36,984 patients.
J Bone Joint Surg Br 2006;88:1303–8.
42. Knutson K, Robertsson O. The Swedish Knee Arthroplasty Reg-
ister (www.knee.se). Acta Orthop 2010;81:5–7.
43. Lutonsky M, Kucera T, Karpas K. Complications after knee joint
replacement in patients with rheumatoid arthritis. Ceska Revma-
tologie 2006;14:149–53. In Czech.
44. Gaston MS, Amin AK, Clayton RA, Brenkel IJ. Does a history of
cardiac disease or hypertension increase mortality following pri-
mary elective total hip arthroplasty? Surgeon 2007;5:260–5.
45. Galvin EM, O’Donnell D, Leonard IE. Rheumatoid arthritis: a
significant but often underestimated risk factor for perioperative
cardiac morbidity. Anesthesiology 2005;103:910–1.
46. Rosemann T, Joos S, Szecsenyi J, Laux G, Wensing M. Health
service utilization patterns of primary care patients with osteo-
arthritis. BMC Health Serv Res 2007;7:169.
47. Sowers MR, Karvonen-Gutierrez CA. The evolving role of obesity
in knee osteoarthritis. Curr Opin Rheumatol 2010;22:533–7.
48. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring
inconsistency in meta-analyses. BMJ 2003;327:557–60.
49. Bengtson S, Knutson K. The infected knee arthroplasty: a 6-year
follow-up of 357 cases. Acta Orthop Scand 1991;62:301–11.
50. Berry DJ, Harmsen WS, Cabanela ME, Morrey BF. Twenty-five-
year survivorship of two thousand consecutive primary Charnley
total hip replacements: factors affecting survivorship of acetabular
and femoral components. J Bone Joint Surg Am 2002;84-A:171–7.
51. Chesney D, Sales J, Elton R, Brenkel IJ. Infection after knee
arthroplasty: a prospective study of 1509 cases. J Arthroplasty
52. Conroy JL, Whitehouse SL, Graves SE, Pratt NL, Ryan P,
Crawford RW. Risk factors for revision for early dislocation in
total hip arthroplasty. J Arthroplasty 2008;23:867–72.
53. Domsic RT, Lingala B, Krishnan E. Systemic lupus erythema-
tosus, rheumatoid arthritis, and postarthroplasty mortality: a
cross-sectional analysis from the nationwide inpatient sample.
J Rheumatol 2010;37:1467–72.
54. Elke R, Meier G, Warnke K, Morscher E. Outcome analysis
of total knee-replacements in patients with rheumatoid arthritis
versus osteoarthritis. Arch Orthop Trauma Surg 1995;114:330–4.
55. Hedlundh U, Hybbinette CH, Fredin H. Influence of surgical
approach on dislocations after Charnley hip arthroplasty. J Ar-
56. Kang JH, Hsieh MS, Lin HC. Comparison of treatment outcomes
following total knee arthroplasty among patients with rheumatoid
arthritis and osteoarthritis: a nationwide population-based study.
Rheumatology (Oxford) 2010;49:1409–10.
57. Kesteris U, Robertsson O, Wingstrand H, Onnerfalt R. Cumula-
tive revision rate with the Scan Hip Classic I total hip prosthesis:
1,660 cases followed for 2-12 years [published erratum appears in
Acta Orthop Scand 1998;69:330]. Acta Orthop Scand 1998;69:
58. Laskin RS, O’Flynn HM. Total knee replacement with posterior
3848 RAVI ET AL
cruciate ligament retention in rheumatoid arthritis: problems and Download full-text
complications. Clin Orthop Relat Res 1997;345:24–8.
59. Mallory TH, Lombardi AV Jr, Fada RA, Herrington SM, Eberle
RW. Dislocation after total hip arthroplasty using the antero-
lateral abductor split approach. Clin Orthop Relat Res 1999;358:
60. Nafei A, Kristensen O, Knudsen HM, Hvid I, Jensen J. Survivor-
ship analysis of cemented total condylar knee arthroplasty: a
long-term follow-up report on 348 cases. J Arthroplasty 1996;11:
61. Partio E, von Bonsdorff H, Wirta J, Avikainen V. Survival of the
Lubinus hip prosthesis: an eight- to 12-year follow-up evaluation of
444 cases. Clin Orthop Relat Res 1994;303:140–6.
62. Partio E, Orava T, Lehto MU, Lindholm ST. Survival of the
Townley knee: 360 cases with 8 (0.1-15) years’ follow-up. Acta
Orthop Scand 1994;65:319–22.
63. Pedersen AB, Sorensen HT, Mehnert F, Overgaard S, Johnsen SP.
Risk factors for venous thromboembolism in patients undergoing
total hip replacement and receiving routine thromboprophylaxis.
J Bone Joint Surg Am 2010;92:2156–64.
64. Purtill JJ, Rothman RH, Hozack WJ, Sharkey PF. Total hip
arthroplasty using two different cementless tapered stems. Clin
Orthop Relat Res 2001;393:121–7.
65. Rand JA, Ilstrup DM. Survivorship analysis of total knee arthro-
plasty: cumulative rates of survival of 9200 total knee arthro-
plasties. J Bone Joint Surg Am 1991;73:397–409.
66. Ritter MA, Herbst SA, Keating EM, Faris PM, Meding JB.
Long-term survival analysis of a posterior cruciate-retaining total
condylar total knee arthroplasty. Clin Orthop Relat Res 1994;309:
67. Ritter MA. The Anatomical Graduated Component total knee
replacement: a long-term evaluation with 20-year survival analysis.
J Bone Joint Surg Br 2009;91:745–9.
68. Sochart DH, Porter ML. The long-term results of Charnley
low-friction arthroplasty in young patients who have congenital
dislocation, degenerative osteoarthrosis, or rheumatoid arthritis.
J Bone Joint Surgery Am 1997;79:1599–617.
69. SooHoo NF, Farng E, Lieberman JR, Chambers L, Zingmond DS.
Factors that predict short-term complication rates after total hip
arthroplasty. Clin Orthop Relat Res 2010;468:2363–71.
70. Van Heereveld HA, Laan RF, van den Hoogen FH, Malefijt MC,
Novakova IR, van de Putte LB. Prevention of symptomatic
thrombosis with short term (low molecular weight) heparin in
patients with rheumatoid arthritis after hip or knee replacement.
Ann Rheum Dis 2001;60:974–6.
71. Weir DJ, Moran CG, Pinder IM. Kinematic condylar total knee
arthroplasty: 14-year survivorship analysis of 208 consecutive
cases. J Bone Joint Surg Br 1996;78:907–11.
72. Zwartele RE, Brand R, Doets HC. Increased risk of dislocation
after primary total hip arthroplasty in inflammatory arthritis: a
prospective observational study of 410 hips. Acta Orthop Scand
73. Zwartele R, Peters A, Brouwers J, Olsthoorn P, Brand R, Doets C.
Long-term results of cementless primary total hip arthroplasty
with a threaded cup and a tapered, rectangular titanium stem in
rheumatoid arthritis and osteoarthritis. Int Orthop 2008;32:581–7.
COMPLICATIONS FOLLOWING TJA IN RA VERSUS OA3849