A systematic review and meta-analysis comparing complications following total joint arthroplasty for rheumatoid arthritis versus for osteoarthritis.
ABSTRACT Most of the evidence regarding complications 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 complications in RA versus OA.
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 information 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.
Forty studies were included in this review. 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).
The findings of this literature review and meta-analysis indicate that, compared to patients with OA, patients with RA are at higher risk of dislocation following THA and higher risk of infection following TKA.
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ABSTRACT: A multidisciplinary approach is required to care for patients with rheumatoid arthritis (RA) in the perioperative period. In preparation for surgery, patients must have a cardiovascular risk assessment performed due to the high risk of heart disease in patients with RA. Treatment of RA is with immunomodulatory medications, which present unique challenges for the perioperative period. Currently, there is no consensus on how to manage disease modifying antirheumatic drug (DMARD) therapy in the perioperative setting. Much of the data to guide therapy is based on retrospective cohort data. Choices regarding DMARDs require an individualized approach with collaboration between surgeons and rheumatologists. Consensus regarding biologic therapy is to hold the therapy in the perioperative period with the length of time dictated by the half-life of the medication. Special attention is required at the time of surgery for potential need for stress dose steroids. Further, there must be close communication with anesthesiologists in terms of airway management particularly in light of the risk for cervical spine disease. There are no consensus guidelines regarding the requirement for cervical spine radiographs prior to surgery. However, history and exam alone cannot be relied upon to identify cervical spine disease. Patients with RA who undergo joint replacement arthroplasty are at higher risk for infection and dislocation compared to patients with osteoarthritis, necessitating particular vigilance in postoperative follow up. This review summarizes available evidence regarding perioperative management of patients with RA.World journal of orthopedics. 07/2014; 5(3):283-91.
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ABSTRACT: Patients with an inflammatory disease have an elevated risk for periprosthetic joint infections due to impairment of the immune system caused by the disease itself in combination with disease-modifying antirheumatic drugs (DMARD). These infections can cause life-threatening sepsis. Unfortunately recommendations on the diagnostics and treatment are mostly based on studies with a level of evidence grade IV or V. This article gives an overview of recent publications evaluating the level of evidence of recommendations on diagnostics and treatment of periprosthetic joint infections in patients with inflammatory diseases. A systematic literature search was performed in the Medline database in January and February 2014. The search included all articles on diagnostic and/or treatment of periprosthetic joint infections in patients with inflammatory diseases. Articles in languages other than English or German were excluded, as well as case reports, studies with less than 20 patients and articles only referring to patients with inflammatory diseases without periprosthetic infections. Nearly all recommendations are based on retrospective studies or expert opinions (level of evidence IV or V). Conflicting results are common but there is good evidence on preoperative aspiration of joint fluid (level of evidence I) and a doubled risk of joint infections under treatment with anti-tumor necrosis factor (level of evidence II). An increased mortality has been reported in multiple studies. Two-stage revision seems to have a slightly better outcome than retention of prosthesis or one-stage revision. Generally, therapeutic recommendations for periprosthetic joint infections lack a good level of evidence. Future studies are urgently needed.Zeitschrift für Rheumatologie 05/2014; · 0.46 Impact Factor
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ABSTRACT: GP88 (Progranulin; PGRN) is a secreted glycosylated protein with important functions in several processes, including immune response and cancer growth. Recent reports have shown that PGRN is a therapeutic target for rheumatoid arthritis (RA) because of its capability to bind with tumor necrosis factor receptor (TNFR). However, the serum PGRN level in RA patients has not been investigated. We used enzyme-linked immunosorbent assay (ELISA) to quantify the serum levels of PGRN in 417 healthy subjects, 56 patients with RA and 31 patients with osteoarthritis (OA). In RA patients, we also measured the serum TNF-α and sTNFR concentration. Immunohistochemical staining of PGRN was performed using synovectomy tissue of RA patients. The serum PGRN normal range was established as 40.1 ± 8.7 ng/ml. PGRN levels were not influenced by sex or age. A significant increase in serum PGRN levels was observed in RA (50.2 ± 11.1 ng/ml) and OA (45.4 ± 6.6 ng/ml) groups compared to those in age-matched healthy controls (40.4 ± 9.9 ng/ml) (p < 0.05, Tukey). Further, PGRN levels in the synovial fluid of RA patients (68.4 ± 3.4 ng/ml) were found to be significantly higher than those in OA patients (35.9 ± 16.8 ng/ml). Immunohistochemical staining of PGRN revealed that the highest positive signal was detected in macrophages. Circulating PGRN in RA patients was weakly associated with TNF-α and sTNFR 2 concentration. Furthermore, PGRN/TNF-α ratio was correlated the stage of the disease in RA patients. The concentrations of serum PGRN in RA were found to be significantly higher than those in age-matched healthy controls, although it remains to be clarified how blood PGRN is related to the pathogenesis of RA. Our results showed that the serum PGRN may be a useful approach to monitor the disease activity in RA patients.Inflammation 05/2014; 37(5). · 1.92 Impact Factor
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