The Journal of Arthroplasty xxx (2014) xxx–xxx
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No Clinical Benefit of High-Flex Total Knee Arthroplasty. A Meta-Analysis of Randomized Controlled Trials Huichao Fu, MD, Jiaxing Wang, MD, Wen Zhang, MD, Tao Cheng, MD, Xianlong Zhang, MD, PhD Department of Orthopaedic Surgery, Shanghai Sixth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China
a r t i c l e
i n f o
Article history: Received 10 September 2014 Accepted 27 October 2014 Available online xxxx Keywords: high flex posterior stabilized range of flexion total knee arthroplasty meta-analysis
a b s t r a c t The application of high-flex prosthesis in total knee arthroplasty (TKA) is an area of continuing debate. Thus, we conducted a meta-analysis of randomized controlled trials (RCTs). A literature search was performed in PubMed, EMBASE and the Cochrane database. 10 trials involving 1230 knee joints were eligible for our meta-analysis. No significant difference was observed between the two designs regarding postoperative range of flexion, clinical scores, quality of life outcomes, or complication rate. Moreover, the advantage of high-flex implants for patients with high preoperative range remained not statistically significant and high-flex design in NexGen system showed a marginal improvement in the postoperative range of flexion. Based on current findings, high-flex prosthesis did not appear to confer any benefit as compared to standard prosthesis. © 2014 Elsevier Inc. All rights reserved.
Total knee arthroplasty (TKA) is performed primarily to relieve pain, but the restoration of postoperative range of flexion is an important aspect of outcome as many daily activities depend on it such as stair climbing or getting out of a chair (90°–120°) [1], kneeling or squatting (110°–165°) [2,3], bathtub use (135°) [4], and yoga or gardening (N150°) [3,4]. Although TKA gains better than 90% satisfaction with relatively low morbidity and mortality [5,6], patients rarely achieve greater than 120° of flexion after TKA [7,8]. Many factors affect the range of flexion after TKA, including preoperative knee motion, surgical technique, prosthetic design, and rehabilitation issues. Several clinical studies reported that even patients with good preoperative range of motion often lost deep flexion after TKA [1,8–15]. In the past decade, newly designed implants have promptly emerged with the aim of accommodating or even facilitating greater knee flexion and improving function. The benefit of so-called “high-flex” TKA remains a subject of debate. There are various studies comparing clinical outcomes and range of flexion between the high-flex and the standard TKAs [16–24]. However, no final conclusion has been drawn. The latest meta-analyses of high-flex TKAs were done in 2010 and published in 2011 [25,26], incorporating randomized controlled trials (RCTs), prospective studies, and retrospective studies. Since then, many RCTs have been conducted, and it is necessary to perform a further analysis containing these latest RCTs. We therefore conducted a meta-analysis
Conflict of interest: No benefits or funds were received in support of the study. The Conflict of Interest statement associated with this article can be found at http:// dx.doi.org/10.1016/j.arth.2014.10.032. Reprint requests: Xianlong Zhang, M.D., Ph.D., Department of Orthopaedic Surgery, Shanghai Sixth People’s Hospital, Shanghai Jiao Tong University School of Medicine, 600 Yishan Road, Shanghai 200233, People’s Republic of China.
of all available RCTs comparing TKAs with posterior stabilized (PS) high-flex implants or standard implants to evaluate the efficacy of this new design.
Materials and Methods Identification and Selection of Studies A systematic review was conducted according to the guidelines described in the Cochrane Handbook for Systematic Reviews of Interventions and PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) Statements [27]. To identify published reports of relevant RCTs we carried out highly sensitive electronic searches of relevant databases, including MEDLINE (1966 to August 2014), EMBASE (1980 to August 2014), and the Cochrane Library (1992 to August 2014). The following key words were considered: “total knee arthroplasty”, “high flex”, “high flexion”, “range of motion”. Articles had to fulfill the following criteria for inclusion: (1) comparison of PS high-flex implants with standard implants in patients treated for end-stage arthritis undergoing primary TKAs; (2) inclusion of at least one of the outcome measures, such as range of flexion, clinical scores, quality of life outcomes and complication rate; (3) details of the high-flex implants design; (4) more than one year of the follow-up duration. Exclusion criteria were as follows: unpublished data, proceedings of meetings, non-randomized controlled studies, experimental reports on cadavers and case series that had no comparison group. Publications involving the same patient population were pooled as one study, choosing the most recent publication, to prevent double-counting patients.
http://dx.doi.org/10.1016/j.arth.2014.10.032 0883-5403/© 2014 Elsevier Inc. All rights reserved.
Please cite this article as: Fu H, et al, No Clinical Benefit of High-Flex Total Knee Arthroplasty. A Meta-Analysis of Randomized Controlled Trials, J Arthroplasty (2014), http://dx.doi.org/10.1016/j.arth.2014.10.032
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H. Fu et al. / The Journal of Arthroplasty xxx (2014) xxx–xxx
Fig. 1. Flow diagram shows the process of selecting studies to be included in the review. RCT: randomized controlled trial.
Data Extraction and Synthesis Two reviewers independently abstracted the following data from each literature: first author, country, year of publication, study population, participants' characteristics, inclusion and exclusion criteria, duration of follow-up, details of implant used, pre-operative range of flexion, post-operative range of flexion, clinical scores (KSS, HSS, WOMAC), and quality of life outcome (SF-36). Assessment of Methodological Quality The methodological quality of each included study was assessed by two reviewers with respect to rating of the randomization procedure; allocation concealment; blinding of patients, surgeons, assessors; statistical analysis of individual trials, and number of patients lost to the final follow-up. Any disagreements on study quality were resolved through reviewing the study and discussing the discrepancy. Statistical Analysis Analyses were conducted using Review Manager version 5.3 software (The Nordic Cochrane Centre, The Cochrane Collaboration, Oxford, England). For each study, we combined dichotomous outcome data
using risk ratio (RR) and 95% confidence interval (CI), while the weighted mean difference (WMD) and 95% confidence interval (CI) were calculated for continuous data. Heterogeneity was determined by chisquared test. A P value of 0.10 was considered a significant difference, and I values were used for the evaluation of statistical heterogeneity (I value of 50% or more indicated the presence of heterogeneity). A fixed-effect model was used to synthesize data when heterogeneity was absent; otherwise, a random-effect model would have been used. Publication bias was assessed using a funnel plot of the outcome measure recorded in the largest number of clinical trials. Results Study Identification and Study Characteristics The electronic search methodology identified 579 potentially relevant publications. After detailed evaluation, 10 randomized controlled trials [28–37], with a total of 1230 knees, met the inclusion criteria and were eligible for the current study (Fig. 1). The high-flex group consisted of 618 knees with an average age range of 62.6–71.1 years, whereas the standard group comprised 612 knees with an average age range of 62–72 years. The sample sizes of the trials ranged from 50 to 278 knees. The mean follow-up period range was from 12 months to
Table 1 Characteristics of Included Studies. Number of Knees
Gender (Male/Female)
BMI (kg/m2)
Age (Years)
Study
Year
Country
A
B
A
B
A
B
A
B
Guild et al [28] Singh et al [29] Hamilton et al [30] Seng et al [31] Choi et al [32] Wohlrab et al [33] McCalden et al [34] Nutton et al [35] Weeden et al [36] Kim et al [37]
2014 2012 2011 2011 2010 2009 2009 2008 2007 2005
America India America Singapore South Korea Germany Canada United Kingdom America South Korea
138 100 71 41 85 30 50 28 25 50
140 100 69 35 85 30 50 28 25 50
67/71 0/100 34/37 7/34 6/79 14/16 23/27 17/11 10/15 2/48
73/67 0/100 27/42 11/24 3/82 12/18 25/25 12/16 9/16 2/48
64.8 ± 8.5 64 ± 3 65 67 71.1 ± 6 66.5 ± 5.34 70 71 62.6
64 ± 8.1 68 ± 6 62 68 70.1 ± 5.8 65.52 ± 9.05 72 68 62.3
NR 30.7 ± 4.9 30.9 27 26.5 ± 3.5 24.1 ± 5.9 32.8 NR 34.1
NR 31.1 ± 5.3 30.2 28 26.6 ± 3.2 24.4 ± 6.6 32.1 NR 34.4
68
NR
A = high-flex group; B = standard group; NR = not reported; BMI = body mass index.
Please cite this article as: Fu H, et al, No Clinical Benefit of High-Flex Total Knee Arthroplasty. A Meta-Analysis of Randomized Controlled Trials, J Arthroplasty (2014), http://dx.doi.org/10.1016/j.arth.2014.10.032
H. Fu et al. / The Journal of Arthroplasty xxx (2014) xxx–xxx
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Table 2 Characteristics of Included Studies. Diagnostic
Pre-Op ROM Flexion (°)
Prosthesis Designs
Study
OA
Others
A
B
Follow-Up
Guild et al [28] Singh et al [29] Hamilton et al [30] Seng et al [31] Choi et al [32] Wohlrab et al [33] McCalden et al [34] Nutton et al [35] Weeden et al [36] Kim et al [37]
267 200 140 76 170 60 100 56 39 98
11 0 0 0 0 0 0 0 11 2
113 ± 11.2 111.7 ± 13.5 119.1 ± 50.3 123 ± 23 110 ± 18 108.5 ± 14.75 111 108 ± 15 120.2 127 ± 21.7
114.7 ± 11 110.5 ± 13.7 120.3 ± 50.3 122 ± 12 112 ± 18.3 105.67 ± 17.8 114 107 ± 15 119 126 ± 21.7
2y 2.1 y 12 m 5y 2y 5y 2.7 y 12 m 12 m 2.1 y
A
B
Study Conclusion of ROM Flexion
NexGen LPS-Flex NexGen LPS-Flex PFC sigma RP-F PS NexGen LPS-Flex PFC sigma RP-F PS NexGen LPS-Flex Genesis II PS H-F NexGen LPS-Flex NexGen LPS-Flex NexGen LPS-Flex
NexGen LPS NexGen LPS PFC sigma PS PFC sigma PS PFC sigma PS NexGen LPS Genesis II PS NexGen LPS NexGen LPS NexGen LPS
Neutral Favours A Neutral Favours A Neutral Neutral Neutral Neutral Favours A Neutral
OA = osteoarthritis; A = high-flex group; B = standard group; NR = not reported; PS = posterior stabilized.
The methodological quality of the included RCTs was variable. The method of allocation sequence generation varied among studies and included random number tables, randomized lists, block randomizations, and the use of computers. Details of randomization were not reported in the remaining four studies [29,30,34,36]. Randomization appeared to have been concealed in two studies, in which sealed envelopes had been used [31,35]. In orthopedic surgery trials, triple-blinding was difficult to be exercised, especially blinding of the surgeon. It was not known whether patients were blinded to the procedure in most studies and they were blinded in three studies [30,31,35]. The outcome assessors were described as blinded in the majority of the studies [28,31,32,34,35,37]. Loss to final follow-up was relatively low, except for one study in which follow-up duration was 5 years, ranging between 0% and 17.1%. Table 3 presented the qualities of the included RCTs.
using a fixed-effect model (WMD =1.69°; 95% CI = 0.13°–3.26°; P = 0.03; I2 = 28%) (Fig. 3). PFC sigma system was implanted in two trials [30,32] while the comparison of postoperative range of flexion showed no difference between two groups (WMD = −2.06°; 95% CI = −5.39°– 1.26°; P = 0.22; I2 = 0%) (Fig. 4). Similarly, McCalden et al [34] did not find significant benefit of Genesis II PS high-flex in range of flexion (MD =1.00°; 95% CI = −1.77°–3.77°; P = 0.81). The mean preoperative range of flexion in four studies [30,31,36,37] was close to or even greater than 120°, which was defined as high preoperative range of flexion. Application of high-flex implant did improve the range of flexion in these patients. However, the additional 3° did not achieve its statistical significance (WMD = 3.85°; 95% CI = − 0.22°– 7.93°; P = 0.06; I2 = 39%) (Fig. 5). When comparing postoperative and preoperative range of flexion of the two groups separately, eight studies were involved in the analysis [28–33,35,37]. Both groups showed a significant improvement (highflex: WMD = 9.51°; 95% CI = 6.66°–12.35°; P b 0.00001; I2 = 51%; standard: WMD =7.47°; 95% CI =3.38°–11.56°; P = 0.0003; I2 = 77) (Figs. 6 and 7). The analysis of studies using NexGen LPS-Flex and NexGen LPS implants demonstrated 8.99° of improvement in the high-flex group (95% CI = 7.17°–10.82°; P b 0.00001; I2 = 30%) and 7.47° in the standard group (95% CI = 5.66°–9.28°; P b 0.00001; I2 = 49%).
Range of Flexion
Clinical Scores and Quality of Life Outcomes
All selected trials reported preoperative and postoperative range of flexion. In these studies a goniometer was generally used. The metaanalysis of the postoperative range of flexion showed no significant difference between two groups (WMD =1.14°; 95% CI = −0.11°–2.39°; P = 0.07; I2 = 39%) (Fig. 2). Of all 10 trials, six employed same implants in the high-flex group (NexGen LPS-Flex) and in the standard group (NexGen LPS) [28,29,33,35–37]. There was a statistically significant difference in postoperative range of flexion in favor of NexGen LPS-Flex
Five studies assessed the Knee Society Score (KSS) [28,29,32,35,37]; five studies assessed the Hospital for Special Surgery Score (HSS) [28,29,32,33,37]; and two studies assessed the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score [32,35]. These studies reported no significant statistical differences between high-flex and standard groups on all knee scores measures. Although statistical heterogeneity was present in the assessment of WOMAC pain (I2 = 65%), data from meta-analysis did not show significant
5 years. In most of these included studies, the demographic features of both groups were well balanced at baseline. Furthermore, most studies had clear inclusion or exclusion criteria. The 10 eligible studies noted the use of three different high-flex implant designs: NexGen LPS-Flex, PFC sigma RP-F PS, and Genesis II PS H-F. Tables 1 and 2 showed additional details about study characteristics and participant demographics. Methodological Quality Assessment
Table 3 Quality of Included Studies.
Study
Randomization Method
Guild et al [28] Singh et al [29] Hamilton et al [30] Seng et al [31] Choi et al [32] Wohlrab et al [33] McCalden et al [34] Nutton et al [35] Weeden et al [36] Kim et al [37]
Random number tables NR NR Computer-generated random numbers Computer-generated block randomizations Randomized lists NR Computer-generated cards NR Random number tables
Allocation Concealment NR NR NR Sealed envelopes NR NR NR Sealed envelopes NR NR
Blinding Patient
Surgeon
Assessor
Baseline Comparability
Similarity of Care Program
Sample-Size Calculation
NR NR Yes Yes NR NR NR Yes NR NR
NR NR NR NR NR NR NR NR NR NR
Yes NR NR Yes Yes NR Yes Yes NR Yes
Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes
Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes
NR NR Yes NR Yes NR Yes NR NR Yes
Loss to Follow-Up 12.6% 0% 8.6% 17.1% 11.8% 31.7% 2% 6.7% 0% 0%
NR = not reported.
Please cite this article as: Fu H, et al, No Clinical Benefit of High-Flex Total Knee Arthroplasty. A Meta-Analysis of Randomized Controlled Trials, J Arthroplasty (2014), http://dx.doi.org/10.1016/j.arth.2014.10.032
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H. Fu et al. / The Journal of Arthroplasty xxx (2014) xxx–xxx
Fig. 2. Forest plot shows the weighted mean difference in postoperative range of flexion between high-flex group and standard group.
Fig. 3. Forest plot shows the weighted mean difference in postoperative range of flexion between high-flex group and standard group using NexGen system.
statistical differences between the two groups on all knee scores measures (Table 4). Quality of life was measured using the Short Form 36 (SF-36) questionnaire. Two studies reported details for further analysis [28,35]. No significant difference was noted in physical scale (WMD = − 0.03; 95% CI = −4.11–4.06; P = 0.99; I2 = 62%) (Table 4).
Complications Seven of these studies, for a total of 998 knees, provided information on postoperative complications [28–30,32–34,36]. Altogether, 34 complications occurred in 499 knees treated with high-flex implants, and 33 complications occurred in 499 knees treated with standard implants. There was no evidence of differences in mobilization for stiffness under anaesthesia, anterior knee pain, surgery for patellar crepitus, or radiolucent lines between the two groups (Table 5).
Publication Bias Publication bias was assessed with funnel plots, which demonstrate the relationship between the study sample size and the precision in estimating the treatment effect. The funnel plot visually demonstrated mild asymmetry, suggesting minimal evidence of publication bias (Fig. 8).
Discussion By this meta-analysis of 10 randomized trials, we found that both groups achieved significant improvement in the range of flexion after TKA. However, the use of high-flex implants had no significant effect on postoperative range of flexion, clinical scores, quality of life outcomes, or complication rate as compared to standard implants. When only involving the groups of high preoperative range of flexion, highflex implants did gain certain degrees of range but no significant difference. In the evaluation of each implant system, only NexGen system demonstrated a tiny improvement with high-flex design, which was of questionable clinical relevance. The strengths of this meta-analysis study lay in the large sample size and the inclusion of only RCTs. All 10 trials balanced the equality of baseline characteristics, which minimized potential bias introduced by preoperative patient-related factors such as age, body weight, and preoperative range of flexion. The measurement of the range of flexion was uniform. A goniometer was universally used. Moreover, we attempted to compare implant systems of different manufacturers separately. Nevertheless, our study had a number of limitations. First, the follow-up period was short. Only 2 studies accomplished follow-up duration of more than five years [31,33]. The data collected reported outcomes which represented early outcomes for TKA. Long term conclusions could not be made based on this early data. Second, our data pertain to different implant systems. We separately made analysis
Fig. 4. Forest plot shows the weighted mean difference in postoperative range of flexion between high-flex group and standard group using PFC sigma system.
Please cite this article as: Fu H, et al, No Clinical Benefit of High-Flex Total Knee Arthroplasty. A Meta-Analysis of Randomized Controlled Trials, J Arthroplasty (2014), http://dx.doi.org/10.1016/j.arth.2014.10.032
H. Fu et al. / The Journal of Arthroplasty xxx (2014) xxx–xxx
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Fig. 5. Forest plot shows the weighted mean difference in postoperative range of flexion between high-flex group and standard group for groups with high preoperative range.
Fig. 6. Forest plot shows the weighted mean difference in range of flexion between post-op and pre-op in high-flex design.
of different manufacturers. However, except for NexGen system, no sufficient data could be collected from other systems of implant as to further analyze. More studies of knee implant in different systems were needed before our conclusion could be applied to various designs. Third, even though all 10 studies declared to be an RCT, four of them [29,30,34,36] did not detail their randomization methods and only 2 declared to be double-blinding [31,35]. Thus, some conclusions should be interpreted carefully. The need for high-flex total knee arthroplasty is based on the increasing demands in the range of motion for people’s daily activities and on the fact that standard prosthesis designs have failed to fulfill this goal [7,8]. Compared to the standard design, the high-flex implant has three principle design modifications: extension of the posterior femoral condyles and posterior condylar radii to increase contact area, an increased cam height, and cut out in the polyethylene insert to prevent patellar tendon impingement. Theoretically these design modifications may lead to greater postoperative range of flexion, longer survivorship, and improved clinical outcomes. Some studies have reported the benefits of high-flex implants. Bin et al [21] prospectively compared 180 total knee arthroplasties, showing significantly greater knee range of flexion at one year in patients receiving high-flex prostheses. Lee et al [38] retrospectively reviewed data of postoperative range of flexion on 41 knees in the high-flex group and 39 knees in the standard group with a minimum of 2 years of follow-up. The study suggested that
patients with severe preoperative flexion limitation could achieve more postoperative gain in flexion when a high-flex prosthesis was used, compared to the flexion obtained using a standard prosthesis. However, in literature, seven of the ten trials did not find any superiority of high-flex implant [28,30,32–35,37]. A meta-analysis by Luo et al [26] found no difference in the range of flexion or clinical outcome between PS high-flex and standard implants. Sumino et al [25] analyzed the change in range of knee flexion from preoperative values between high-flex group and standard group and found that improvement of preoperative flexion after TKA using high-flex prosthesis was similar to that of standard prosthesis. After a minimum duration of follow-up of ten years, Kim et al [39] found that there were no significant differences between NexGen LPS-Flex and NexGen LPS groups with regard to implant survivorship, functional outcome, knee motion, or prevalence of osteolysis. The conclusions of these studies were consistent with our findings. Anouchi et al [8] prospectively studied three groups of patients with different range of preoperative knee flexion using standard prosthesis. They found that the patients with preoperative motion less than 90° gained the most in postoperative range, whereas the group of greater than 105° gained the least after TKA. Yamakado et al [15] tried to obtain a good postoperative range of motion with standard prosthesis by loosely balancing the gap of articulation. The result showed that the mean preoperative and postoperative range of motion was 124° and
Fig. 7. Forest plot shows the weighted mean difference in range of flexion between post-op and pre-op in standard design.
Please cite this article as: Fu H, et al, No Clinical Benefit of High-Flex Total Knee Arthroplasty. A Meta-Analysis of Randomized Controlled Trials, J Arthroplasty (2014), http://dx.doi.org/10.1016/j.arth.2014.10.032
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Table 4 Clinical Scores and Quality of Life Outcomes.
Clinical Score KSS knee score KSS function score HSS score SF-36 physical scale WOMAC pain WOMAC stiffness WOMAC function
Number of Study
WMD
95% CI
4 4 5 2 2 2 2
−0.45 0.10 0.04 −0.03 0.36 −0.05 −0.11
−1.28, 0.38 −1.49, 1.70 −0.83, 0.90 −4.11, 4.06 −1.33, 2.05 −0.48, 0.39 −1.89, 1.67
P Value
Heterogeneity
n.s. n.s. n.s. n.s. n.s. n.s. n.s.
I2 I2 I2 I2 I2 I2 I2
= = = = = = =
28% 30% 0% 62% 65% 0% 0%
KSS = The Knee Society Score; HSS = The Hospital for Special Surgery Score; WOMAC = Western Ontario and McMaster Universities Osteoarthritis Index; SF-36 = the Short Form 36 questionnaire; WMD = weighted mean difference; CI = confidence interval; n.s. = not significant.
112°, respectively. Thus the issue was pointed out that patients with good preoperative range of motion often did not gain or even lost deep flexion after standard TKA. We presented in this literature that the groups with high preoperative range of flexion using high-flex implants gained more range after TKA than using standard implants. Though no significant difference was detected, the P value was 0.06 with a limited sample size, implying that more involved patients might achieve a statistical difference. In the presented study, we assessed the range of flexion in patients using NexGen system. Analysis of one certain manufacturer was to some extent more convincing because in this way the bias of the implant design was eliminated. Both groups gained important improvement from preoperative range of flexion. The high-flex group achieved 1° greater in the postoperative range of flexion than the standard group. However, based on the finding that a difference of less than 5° in range of flexion was not clinically relevant [40], the acquisition of 1° seemed not sufficient to illustrate the benefit of high-flex design. Though we have supposed that when balancing baseline data, the high-flex prosthesis would gain more in the postoperative range of flexion than the standard prosthesis in consideration with the theoretical advantages, our study refuted this hypothesis. Several previous literatures [41,42] concluded that as an independent variable, the high-flex design did not correlate with better clinical outcomes or greater postoperative range of flexion. Other characteristics, such as preoperative flexion, intraoperative flexion, preoperative tibio-femoral alignment, posterior capsular release, the removal of posterior osteophytes and patient’s motivation to participate in physical therapy altogether determined postoperative range of flexion [43]. One of the concerns in high-flex implants was that the extra bone resection of femur would lead to instability and more difficult revision surgery. Moreover, extreme flexion might increase patella-femoral joint stress and cause anterior knee pain [44,45]. Han et al [46] reported a 38% rate of early loosening of the femoral component and 15 revisions in a series of 47 knees with the high-flex prosthesis. Nevertheless, we did not observe any obviously increased rate of early loosening, anterior knee pain or patellar crepitus in patients using high-flex implants. Many current literatures [21,41,42,47–50] supported our findings.
Fig. 8. Funnel plot for the postoperative range of flexion, demonstrating evidence of publication bias.
Conclusion In conclusion, our meta-analysis demonstrated that both high-flex prosthesis and standard prosthesis significantly improved range of flexion and that no obvious statistical difference was found between two groups in terms of the postoperative range of flexion, clinical scores, quality of life outcomes, or complication rate. The application of high-flex implant to patients with high preoperative range of flexion did gain range as compared to standard design, but a significant difference would need a larger sample size. A tiny improvement in the postoperative range of flexion was found with the NexGen LPS-Flex implant, which was clinically irrelevant.
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Table 5 Complication Rates. Number of Knee Complications Mobilization for stiffness Anterior knee pain Surgery for patellar crepitus Radiolucent line
A
B
7/336 8/169 5/142 14/164
7/333 6/170 7/136 13/170
Risk Ratio 0.99 1.32 0.69 1.12
95% CI 0.38–2.59 0.49–3.56 0.22–2.12 0.54–2.31
P Value n.s. n.s. n.s. n.s.
Heterogeneity I2 I2 I2 I2
= = = =
33% 0% 0% 0%
A = high-flex group; B = standard group; CI = confidence interval; n.s. = not significant.
Please cite this article as: Fu H, et al, No Clinical Benefit of High-Flex Total Knee Arthroplasty. A Meta-Analysis of Randomized Controlled Trials, J Arthroplasty (2014), http://dx.doi.org/10.1016/j.arth.2014.10.032
H. Fu et al. / The Journal of Arthroplasty xxx (2014) xxx–xxx 11. Insall JN, Dorr LD, Scott RD, et al. Rationale of the Knee Society clinical rating system. Clin Orthop Relat Res 1989;248:13. 12. Insall JN, Hood RW, Flawn LB, et al. The total condylar knee prosthesis in gonarthrosis. A five to nine year follow-up of the first one hundred consecutive replacements. J Bone Joint Surg Am 1983;65:619. 13. McAuley JP, Harrer MF, Ammeen D, et al. Outcome of knee arthroplasty in patients with poor preoperative range of motion. Clin Orthop Relat Res 2002;404:203. 14. Tew M, Forster IW, Wallach WA. Effect of total knee arthroplasty on maximal flexion. Clin Orthop Relat Res 1989;247:168. 15. Yamakado K, Kitaoka K, Yamada H, et al. Influence of stability on range of motion after cruciate-retaining TKA. Arch Orthop Trauma Surg 2003;123:1. 16. Argenson JN, Komistek RD, Mahfouz M, et al. A high flexion total knee arthroplasty design replicates healthy knee motion. Clin Orthop Relat Res 2004;428:174. 17. Li G, Most E, Sultan PG, et al. Knee kinematics with a high-flexion posterior stabilized total knee prosthesis: an in vitro robotic experimental investigation. J Bone Joint Surg Am 2004;86-A:1721. 18. Coughlin KM, Incavo SJ, Doohen RR, et al. Kneeling kinematics after total knee arthroplasty: anterior–posterior contact position of a standard and a high-flex tibial insert design. J Arthroplasty 2007;22:160. 19. Ng FY, Wong HL, Yau WP, et al. Comparison of range of motion after standard and high-flexion posterior stabilised total knee replacement. Int Orthop 2008;32:795. 20. Malik A, Salas A, Ben Ari J, et al. Range of motion and function are similar in patients undergoing TKA with posterior stabilised and high-flexion inserts. Int Orthop 2010; 34:965. 21. Bin SI, Nam TS. Early results of high-flex total knee arthroplasty: comparison study at 1 year after surgery. Knee Surg Sports Traumatol Arthrosc 2007;15:350. 22. Kanekasu K, Banks SA, Honjo S, et al. Fluoroscopic analysis of knee arthroplasty kinematics during deep flexion kneeling. J Arthroplasty 2004;19:998. 23. Laskin RS. The effect of a high-flex implant on postoperative flexion after primary total knee arthroplasty. Orthopedics 2007;30:86. 24. Huang HT, Su JY, Wang GJ. The early results of high-flex total knee arthroplasty: a minimum of 2 years of follow-up. J Arthroplasty 2005;20:674. 25. Sumino T, Gadikota HR, Varadarajan KM, et al. Do high flexion posterior stabilised total knee arthroplasty designs increase knee flexion? A meta analysis. Int Orthop 2011;35:1309. 26. Luo SX, Su W, Zhao JM, et al. High-flexion vs conventional prostheses total knee arthroplasty: a meta-analysis. J Arthroplasty 2011;26:847. 27. Moher D, Liberati A, Tetzlaff J, et al. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 2009;6:e1000097. 28. Guild III GN, Labib SA. Clinical outcomes in high flexion total knee arthroplasty were not superior to standard posterior stabilized total knee arthroplasty. A multicenter, prospective, randomized study. J Arthroplasty 2014;29:530. 29. Singh H, Mittal V, Nadkarni B, et al. Gender-specific high-flexion knee prosthesis in Indian women: a prospective randomised study. J Orthop Surg (Hong Kong) 2012; 20:153. 30. Hamilton WG, Sritulanondha S, Engh Jr CA. Prospective randomized comparison of high-flex and standard rotating platform total knee arthroplasty. J Arthroplasty 2011;26:28. 31. Seng C, Yeo SJ, Wee JL, et al. Improved clinical outcomes after high-flexion total knee arthroplasty: a 5-year follow-up study. J Arthroplasty 2011;26:1025.
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32. Choi WC, Lee S, Seong SC, et al. Comparison between standard and high-flexion posterior-stabilized rotating-platform mobile-bearing total knee arthroplasties: a randomized controlled study. J Bone Joint Surg Am 2010;92:2634. 33. Wohlrab D, Hube R, Zeh A, et al. Clinical and radiological results of high flex total knee arthroplasty: a 5 year follow-up. Arch Orthop Trauma Surg 2009;129:21. 34. McCalden RW, MacDonald SJ, Bourne RB, et al. A randomized controlled trial comparing “high-flex” vs “standard” posterior cruciate substituting polyethylene tibial inserts in total knee arthroplasty. J Arthroplasty 2009;24:33. 35. Nutton RW, van der Linden ML, Rowe PJ, et al. A prospective randomised doubleblind study of functional outcome and range of flexion following total knee replacement with the NexGen standard and high flexion components. J Bone Joint Surg (Br) 2008;90:37. 36. Weeden SH, Schmidt R. A randomized, prospective study of primary total knee components designed for increased flexion. J Arthroplasty 2007;22:349. 37. Kim YH, Sohn KS, Kim JS. Range of motion of standard and high-flexion posterior stabilized total knee prostheses: a prospective, randomized study. J Bone Joint Surg Am 2005;87:1470. 38. Lee BS, Kim JM, Lee SJ, et al. High-flexion total knee arthroplasty improves flexion of stiff knees. Knee Surg Sports Traumatol Arthrosc 2011;19:936. 39. Kim YH, Park JW, Kim JS. High-flexion total knee arthroplasty: survivorship and prevalence of osteolysis: results after a minimum of ten years of follow-up. J Bone Joint Surg Am 2012;94:1378. 40. Chaudhary R, Beaupré LA, Johnston DW. Knee range of motion during the first two years after use of posterior cruciate-stabilizing or posterior cruciate-retaining total knee prostheses. A randomized clinical trial. J Bone Joint Surg Am 2008;90:2579. 41. Kim YH, Choi Y, Kwon OR, et al. Functional outcome and range of motion of high-flexion posterior cruciate-retaining and high-flexion posterior cruciate-substituting total knee prostheses. A prospective, randomized study. J Bone Joint Surg Am 2009;91:753. 42. Seon JK, Park SJ, Lee KB, et al. Range of motion in total knee arthroplasty: a prospective comparison of high-flexion and standard cruciate-retaining designs. J Bone Joint Surg Am 2009;91:672. 43. Ritter MA, Harty LD, Davis KE, et al. Predicting range of motion after total knee arthroplasty. Clustering, log-linear regression, and regression tree analysis. J Bone Joint Surg Am 2003;85-A:1278. 44. Ritter MA. High-flexion knee designs: more hype than hope? In the affirmative. J Arthroplasty 2006;21:40. 45. Ranawat CS. Design may be counterproductive for optimizing flexion after TKR. Clin Orthop Relat Res 2003;416:174. 46. Han HS, Kang SB, Yoon KS. High incidence of loosening of the femoral component in legacy posterior stabilised-flex total knee replacement. J Bone Joint Surg (Br) 2007; 89:1457. 47. Gupta SK, Ranawat AS, Shah V, et al. The P.F.C. Sigma RP-F TKA designed for improved performance: a matched-pair study. Orthopedics 2006;29:S49. 48. Minoda Y, Aihara M, Sakawa A, et al. Range of motion of standard and high-flexion cruciate retaining total knee prostheses. J Arthroplasty 2009;24:674. 49. Lee BS, Chung JW, Kim JM, et al. High-flexion prosthesis improves function of TKA in Asian patients without decreasing early survivorship. Clin Orthop Relat Res 2013; 471:1504. 50. Nakamura S, Ito H, Kobayashi M, et al. Are the long term results of a high-flex total knee replacement affected by the range of flexion? Int Orthop 2014;38:761.
Please cite this article as: Fu H, et al, No Clinical Benefit of High-Flex Total Knee Arthroplasty. A Meta-Analysis of Randomized Controlled Trials, J Arthroplasty (2014), http://dx.doi.org/10.1016/j.arth.2014.10.032
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No Clinical Benefit of High-Flex Total Knee Arthroplasty. A Meta-Analysis of Randomized Controlled Trials Huichao Fu, MD, Jiaxing Wang, MD, Wen Zhang, MD, Tao Cheng, MD, Xianlong Zhang, MD, PhD Department of Orthopaedic Surgery, Shanghai Sixth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China
a r t i c l e
i n f o
Article history: Received 10 September 2014 Accepted 27 October 2014 Available online xxxx Keywords: high flex posterior stabilized range of flexion total knee arthroplasty meta-analysis
a b s t r a c t The application of high-flex prosthesis in total knee arthroplasty (TKA) is an area of continuing debate. Thus, we conducted a meta-analysis of randomized controlled trials (RCTs). A literature search was performed in PubMed, EMBASE and the Cochrane database. 10 trials involving 1230 knee joints were eligible for our meta-analysis. No significant difference was observed between the two designs regarding postoperative range of flexion, clinical scores, quality of life outcomes, or complication rate. Moreover, the advantage of high-flex implants for patients with high preoperative range remained not statistically significant and high-flex design in NexGen system showed a marginal improvement in the postoperative range of flexion. Based on current findings, high-flex prosthesis did not appear to confer any benefit as compared to standard prosthesis. © 2014 Elsevier Inc. All rights reserved.
Total knee arthroplasty (TKA) is performed primarily to relieve pain, but the restoration of postoperative range of flexion is an important aspect of outcome as many daily activities depend on it such as stair climbing or getting out of a chair (90°–120°) [1], kneeling or squatting (110°–165°) [2,3], bathtub use (135°) [4], and yoga or gardening (N150°) [3,4]. Although TKA gains better than 90% satisfaction with relatively low morbidity and mortality [5,6], patients rarely achieve greater than 120° of flexion after TKA [7,8]. Many factors affect the range of flexion after TKA, including preoperative knee motion, surgical technique, prosthetic design, and rehabilitation issues. Several clinical studies reported that even patients with good preoperative range of motion often lost deep flexion after TKA [1,8–15]. In the past decade, newly designed implants have promptly emerged with the aim of accommodating or even facilitating greater knee flexion and improving function. The benefit of so-called “high-flex” TKA remains a subject of debate. There are various studies comparing clinical outcomes and range of flexion between the high-flex and the standard TKAs [16–24]. However, no final conclusion has been drawn. The latest meta-analyses of high-flex TKAs were done in 2010 and published in 2011 [25,26], incorporating randomized controlled trials (RCTs), prospective studies, and retrospective studies. Since then, many RCTs have been conducted, and it is necessary to perform a further analysis containing these latest RCTs. We therefore conducted a meta-analysis
Conflict of interest: No benefits or funds were received in support of the study. The Conflict of Interest statement associated with this article can be found at http:// dx.doi.org/10.1016/j.arth.2014.10.032. Reprint requests: Xianlong Zhang, M.D., Ph.D., Department of Orthopaedic Surgery, Shanghai Sixth People’s Hospital, Shanghai Jiao Tong University School of Medicine, 600 Yishan Road, Shanghai 200233, People’s Republic of China.
of all available RCTs comparing TKAs with posterior stabilized (PS) high-flex implants or standard implants to evaluate the efficacy of this new design.
Materials and Methods Identification and Selection of Studies A systematic review was conducted according to the guidelines described in the Cochrane Handbook for Systematic Reviews of Interventions and PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) Statements [27]. To identify published reports of relevant RCTs we carried out highly sensitive electronic searches of relevant databases, including MEDLINE (1966 to August 2014), EMBASE (1980 to August 2014), and the Cochrane Library (1992 to August 2014). The following key words were considered: “total knee arthroplasty”, “high flex”, “high flexion”, “range of motion”. Articles had to fulfill the following criteria for inclusion: (1) comparison of PS high-flex implants with standard implants in patients treated for end-stage arthritis undergoing primary TKAs; (2) inclusion of at least one of the outcome measures, such as range of flexion, clinical scores, quality of life outcomes and complication rate; (3) details of the high-flex implants design; (4) more than one year of the follow-up duration. Exclusion criteria were as follows: unpublished data, proceedings of meetings, non-randomized controlled studies, experimental reports on cadavers and case series that had no comparison group. Publications involving the same patient population were pooled as one study, choosing the most recent publication, to prevent double-counting patients.
http://dx.doi.org/10.1016/j.arth.2014.10.032 0883-5403/© 2014 Elsevier Inc. All rights reserved.
Please cite this article as: Fu H, et al, No Clinical Benefit of High-Flex Total Knee Arthroplasty. A Meta-Analysis of Randomized Controlled Trials, J Arthroplasty (2014), http://dx.doi.org/10.1016/j.arth.2014.10.032
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H. Fu et al. / The Journal of Arthroplasty xxx (2014) xxx–xxx
Fig. 1. Flow diagram shows the process of selecting studies to be included in the review. RCT: randomized controlled trial.
Data Extraction and Synthesis Two reviewers independently abstracted the following data from each literature: first author, country, year of publication, study population, participants' characteristics, inclusion and exclusion criteria, duration of follow-up, details of implant used, pre-operative range of flexion, post-operative range of flexion, clinical scores (KSS, HSS, WOMAC), and quality of life outcome (SF-36). Assessment of Methodological Quality The methodological quality of each included study was assessed by two reviewers with respect to rating of the randomization procedure; allocation concealment; blinding of patients, surgeons, assessors; statistical analysis of individual trials, and number of patients lost to the final follow-up. Any disagreements on study quality were resolved through reviewing the study and discussing the discrepancy. Statistical Analysis Analyses were conducted using Review Manager version 5.3 software (The Nordic Cochrane Centre, The Cochrane Collaboration, Oxford, England). For each study, we combined dichotomous outcome data
using risk ratio (RR) and 95% confidence interval (CI), while the weighted mean difference (WMD) and 95% confidence interval (CI) were calculated for continuous data. Heterogeneity was determined by chisquared test. A P value of 0.10 was considered a significant difference, and I values were used for the evaluation of statistical heterogeneity (I value of 50% or more indicated the presence of heterogeneity). A fixed-effect model was used to synthesize data when heterogeneity was absent; otherwise, a random-effect model would have been used. Publication bias was assessed using a funnel plot of the outcome measure recorded in the largest number of clinical trials. Results Study Identification and Study Characteristics The electronic search methodology identified 579 potentially relevant publications. After detailed evaluation, 10 randomized controlled trials [28–37], with a total of 1230 knees, met the inclusion criteria and were eligible for the current study (Fig. 1). The high-flex group consisted of 618 knees with an average age range of 62.6–71.1 years, whereas the standard group comprised 612 knees with an average age range of 62–72 years. The sample sizes of the trials ranged from 50 to 278 knees. The mean follow-up period range was from 12 months to
Table 1 Characteristics of Included Studies. Number of Knees
Gender (Male/Female)
BMI (kg/m2)
Age (Years)
Study
Year
Country
A
B
A
B
A
B
A
B
Guild et al [28] Singh et al [29] Hamilton et al [30] Seng et al [31] Choi et al [32] Wohlrab et al [33] McCalden et al [34] Nutton et al [35] Weeden et al [36] Kim et al [37]
2014 2012 2011 2011 2010 2009 2009 2008 2007 2005
America India America Singapore South Korea Germany Canada United Kingdom America South Korea
138 100 71 41 85 30 50 28 25 50
140 100 69 35 85 30 50 28 25 50
67/71 0/100 34/37 7/34 6/79 14/16 23/27 17/11 10/15 2/48
73/67 0/100 27/42 11/24 3/82 12/18 25/25 12/16 9/16 2/48
64.8 ± 8.5 64 ± 3 65 67 71.1 ± 6 66.5 ± 5.34 70 71 62.6
64 ± 8.1 68 ± 6 62 68 70.1 ± 5.8 65.52 ± 9.05 72 68 62.3
NR 30.7 ± 4.9 30.9 27 26.5 ± 3.5 24.1 ± 5.9 32.8 NR 34.1
NR 31.1 ± 5.3 30.2 28 26.6 ± 3.2 24.4 ± 6.6 32.1 NR 34.4
68
NR
A = high-flex group; B = standard group; NR = not reported; BMI = body mass index.
Please cite this article as: Fu H, et al, No Clinical Benefit of High-Flex Total Knee Arthroplasty. A Meta-Analysis of Randomized Controlled Trials, J Arthroplasty (2014), http://dx.doi.org/10.1016/j.arth.2014.10.032
H. Fu et al. / The Journal of Arthroplasty xxx (2014) xxx–xxx
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Table 2 Characteristics of Included Studies. Diagnostic
Pre-Op ROM Flexion (°)
Prosthesis Designs
Study
OA
Others
A
B
Follow-Up
Guild et al [28] Singh et al [29] Hamilton et al [30] Seng et al [31] Choi et al [32] Wohlrab et al [33] McCalden et al [34] Nutton et al [35] Weeden et al [36] Kim et al [37]
267 200 140 76 170 60 100 56 39 98
11 0 0 0 0 0 0 0 11 2
113 ± 11.2 111.7 ± 13.5 119.1 ± 50.3 123 ± 23 110 ± 18 108.5 ± 14.75 111 108 ± 15 120.2 127 ± 21.7
114.7 ± 11 110.5 ± 13.7 120.3 ± 50.3 122 ± 12 112 ± 18.3 105.67 ± 17.8 114 107 ± 15 119 126 ± 21.7
2y 2.1 y 12 m 5y 2y 5y 2.7 y 12 m 12 m 2.1 y
A
B
Study Conclusion of ROM Flexion
NexGen LPS-Flex NexGen LPS-Flex PFC sigma RP-F PS NexGen LPS-Flex PFC sigma RP-F PS NexGen LPS-Flex Genesis II PS H-F NexGen LPS-Flex NexGen LPS-Flex NexGen LPS-Flex
NexGen LPS NexGen LPS PFC sigma PS PFC sigma PS PFC sigma PS NexGen LPS Genesis II PS NexGen LPS NexGen LPS NexGen LPS
Neutral Favours A Neutral Favours A Neutral Neutral Neutral Neutral Favours A Neutral
OA = osteoarthritis; A = high-flex group; B = standard group; NR = not reported; PS = posterior stabilized.
The methodological quality of the included RCTs was variable. The method of allocation sequence generation varied among studies and included random number tables, randomized lists, block randomizations, and the use of computers. Details of randomization were not reported in the remaining four studies [29,30,34,36]. Randomization appeared to have been concealed in two studies, in which sealed envelopes had been used [31,35]. In orthopedic surgery trials, triple-blinding was difficult to be exercised, especially blinding of the surgeon. It was not known whether patients were blinded to the procedure in most studies and they were blinded in three studies [30,31,35]. The outcome assessors were described as blinded in the majority of the studies [28,31,32,34,35,37]. Loss to final follow-up was relatively low, except for one study in which follow-up duration was 5 years, ranging between 0% and 17.1%. Table 3 presented the qualities of the included RCTs.
using a fixed-effect model (WMD =1.69°; 95% CI = 0.13°–3.26°; P = 0.03; I2 = 28%) (Fig. 3). PFC sigma system was implanted in two trials [30,32] while the comparison of postoperative range of flexion showed no difference between two groups (WMD = −2.06°; 95% CI = −5.39°– 1.26°; P = 0.22; I2 = 0%) (Fig. 4). Similarly, McCalden et al [34] did not find significant benefit of Genesis II PS high-flex in range of flexion (MD =1.00°; 95% CI = −1.77°–3.77°; P = 0.81). The mean preoperative range of flexion in four studies [30,31,36,37] was close to or even greater than 120°, which was defined as high preoperative range of flexion. Application of high-flex implant did improve the range of flexion in these patients. However, the additional 3° did not achieve its statistical significance (WMD = 3.85°; 95% CI = − 0.22°– 7.93°; P = 0.06; I2 = 39%) (Fig. 5). When comparing postoperative and preoperative range of flexion of the two groups separately, eight studies were involved in the analysis [28–33,35,37]. Both groups showed a significant improvement (highflex: WMD = 9.51°; 95% CI = 6.66°–12.35°; P b 0.00001; I2 = 51%; standard: WMD =7.47°; 95% CI =3.38°–11.56°; P = 0.0003; I2 = 77) (Figs. 6 and 7). The analysis of studies using NexGen LPS-Flex and NexGen LPS implants demonstrated 8.99° of improvement in the high-flex group (95% CI = 7.17°–10.82°; P b 0.00001; I2 = 30%) and 7.47° in the standard group (95% CI = 5.66°–9.28°; P b 0.00001; I2 = 49%).
Range of Flexion
Clinical Scores and Quality of Life Outcomes
All selected trials reported preoperative and postoperative range of flexion. In these studies a goniometer was generally used. The metaanalysis of the postoperative range of flexion showed no significant difference between two groups (WMD =1.14°; 95% CI = −0.11°–2.39°; P = 0.07; I2 = 39%) (Fig. 2). Of all 10 trials, six employed same implants in the high-flex group (NexGen LPS-Flex) and in the standard group (NexGen LPS) [28,29,33,35–37]. There was a statistically significant difference in postoperative range of flexion in favor of NexGen LPS-Flex
Five studies assessed the Knee Society Score (KSS) [28,29,32,35,37]; five studies assessed the Hospital for Special Surgery Score (HSS) [28,29,32,33,37]; and two studies assessed the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score [32,35]. These studies reported no significant statistical differences between high-flex and standard groups on all knee scores measures. Although statistical heterogeneity was present in the assessment of WOMAC pain (I2 = 65%), data from meta-analysis did not show significant
5 years. In most of these included studies, the demographic features of both groups were well balanced at baseline. Furthermore, most studies had clear inclusion or exclusion criteria. The 10 eligible studies noted the use of three different high-flex implant designs: NexGen LPS-Flex, PFC sigma RP-F PS, and Genesis II PS H-F. Tables 1 and 2 showed additional details about study characteristics and participant demographics. Methodological Quality Assessment
Table 3 Quality of Included Studies.
Study
Randomization Method
Guild et al [28] Singh et al [29] Hamilton et al [30] Seng et al [31] Choi et al [32] Wohlrab et al [33] McCalden et al [34] Nutton et al [35] Weeden et al [36] Kim et al [37]
Random number tables NR NR Computer-generated random numbers Computer-generated block randomizations Randomized lists NR Computer-generated cards NR Random number tables
Allocation Concealment NR NR NR Sealed envelopes NR NR NR Sealed envelopes NR NR
Blinding Patient
Surgeon
Assessor
Baseline Comparability
Similarity of Care Program
Sample-Size Calculation
NR NR Yes Yes NR NR NR Yes NR NR
NR NR NR NR NR NR NR NR NR NR
Yes NR NR Yes Yes NR Yes Yes NR Yes
Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes
Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes
NR NR Yes NR Yes NR Yes NR NR Yes
Loss to Follow-Up 12.6% 0% 8.6% 17.1% 11.8% 31.7% 2% 6.7% 0% 0%
NR = not reported.
Please cite this article as: Fu H, et al, No Clinical Benefit of High-Flex Total Knee Arthroplasty. A Meta-Analysis of Randomized Controlled Trials, J Arthroplasty (2014), http://dx.doi.org/10.1016/j.arth.2014.10.032
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Fig. 2. Forest plot shows the weighted mean difference in postoperative range of flexion between high-flex group and standard group.
Fig. 3. Forest plot shows the weighted mean difference in postoperative range of flexion between high-flex group and standard group using NexGen system.
statistical differences between the two groups on all knee scores measures (Table 4). Quality of life was measured using the Short Form 36 (SF-36) questionnaire. Two studies reported details for further analysis [28,35]. No significant difference was noted in physical scale (WMD = − 0.03; 95% CI = −4.11–4.06; P = 0.99; I2 = 62%) (Table 4).
Complications Seven of these studies, for a total of 998 knees, provided information on postoperative complications [28–30,32–34,36]. Altogether, 34 complications occurred in 499 knees treated with high-flex implants, and 33 complications occurred in 499 knees treated with standard implants. There was no evidence of differences in mobilization for stiffness under anaesthesia, anterior knee pain, surgery for patellar crepitus, or radiolucent lines between the two groups (Table 5).
Publication Bias Publication bias was assessed with funnel plots, which demonstrate the relationship between the study sample size and the precision in estimating the treatment effect. The funnel plot visually demonstrated mild asymmetry, suggesting minimal evidence of publication bias (Fig. 8).
Discussion By this meta-analysis of 10 randomized trials, we found that both groups achieved significant improvement in the range of flexion after TKA. However, the use of high-flex implants had no significant effect on postoperative range of flexion, clinical scores, quality of life outcomes, or complication rate as compared to standard implants. When only involving the groups of high preoperative range of flexion, highflex implants did gain certain degrees of range but no significant difference. In the evaluation of each implant system, only NexGen system demonstrated a tiny improvement with high-flex design, which was of questionable clinical relevance. The strengths of this meta-analysis study lay in the large sample size and the inclusion of only RCTs. All 10 trials balanced the equality of baseline characteristics, which minimized potential bias introduced by preoperative patient-related factors such as age, body weight, and preoperative range of flexion. The measurement of the range of flexion was uniform. A goniometer was universally used. Moreover, we attempted to compare implant systems of different manufacturers separately. Nevertheless, our study had a number of limitations. First, the follow-up period was short. Only 2 studies accomplished follow-up duration of more than five years [31,33]. The data collected reported outcomes which represented early outcomes for TKA. Long term conclusions could not be made based on this early data. Second, our data pertain to different implant systems. We separately made analysis
Fig. 4. Forest plot shows the weighted mean difference in postoperative range of flexion between high-flex group and standard group using PFC sigma system.
Please cite this article as: Fu H, et al, No Clinical Benefit of High-Flex Total Knee Arthroplasty. A Meta-Analysis of Randomized Controlled Trials, J Arthroplasty (2014), http://dx.doi.org/10.1016/j.arth.2014.10.032
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Fig. 5. Forest plot shows the weighted mean difference in postoperative range of flexion between high-flex group and standard group for groups with high preoperative range.
Fig. 6. Forest plot shows the weighted mean difference in range of flexion between post-op and pre-op in high-flex design.
of different manufacturers. However, except for NexGen system, no sufficient data could be collected from other systems of implant as to further analyze. More studies of knee implant in different systems were needed before our conclusion could be applied to various designs. Third, even though all 10 studies declared to be an RCT, four of them [29,30,34,36] did not detail their randomization methods and only 2 declared to be double-blinding [31,35]. Thus, some conclusions should be interpreted carefully. The need for high-flex total knee arthroplasty is based on the increasing demands in the range of motion for people’s daily activities and on the fact that standard prosthesis designs have failed to fulfill this goal [7,8]. Compared to the standard design, the high-flex implant has three principle design modifications: extension of the posterior femoral condyles and posterior condylar radii to increase contact area, an increased cam height, and cut out in the polyethylene insert to prevent patellar tendon impingement. Theoretically these design modifications may lead to greater postoperative range of flexion, longer survivorship, and improved clinical outcomes. Some studies have reported the benefits of high-flex implants. Bin et al [21] prospectively compared 180 total knee arthroplasties, showing significantly greater knee range of flexion at one year in patients receiving high-flex prostheses. Lee et al [38] retrospectively reviewed data of postoperative range of flexion on 41 knees in the high-flex group and 39 knees in the standard group with a minimum of 2 years of follow-up. The study suggested that
patients with severe preoperative flexion limitation could achieve more postoperative gain in flexion when a high-flex prosthesis was used, compared to the flexion obtained using a standard prosthesis. However, in literature, seven of the ten trials did not find any superiority of high-flex implant [28,30,32–35,37]. A meta-analysis by Luo et al [26] found no difference in the range of flexion or clinical outcome between PS high-flex and standard implants. Sumino et al [25] analyzed the change in range of knee flexion from preoperative values between high-flex group and standard group and found that improvement of preoperative flexion after TKA using high-flex prosthesis was similar to that of standard prosthesis. After a minimum duration of follow-up of ten years, Kim et al [39] found that there were no significant differences between NexGen LPS-Flex and NexGen LPS groups with regard to implant survivorship, functional outcome, knee motion, or prevalence of osteolysis. The conclusions of these studies were consistent with our findings. Anouchi et al [8] prospectively studied three groups of patients with different range of preoperative knee flexion using standard prosthesis. They found that the patients with preoperative motion less than 90° gained the most in postoperative range, whereas the group of greater than 105° gained the least after TKA. Yamakado et al [15] tried to obtain a good postoperative range of motion with standard prosthesis by loosely balancing the gap of articulation. The result showed that the mean preoperative and postoperative range of motion was 124° and
Fig. 7. Forest plot shows the weighted mean difference in range of flexion between post-op and pre-op in standard design.
Please cite this article as: Fu H, et al, No Clinical Benefit of High-Flex Total Knee Arthroplasty. A Meta-Analysis of Randomized Controlled Trials, J Arthroplasty (2014), http://dx.doi.org/10.1016/j.arth.2014.10.032
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Table 4 Clinical Scores and Quality of Life Outcomes.
Clinical Score KSS knee score KSS function score HSS score SF-36 physical scale WOMAC pain WOMAC stiffness WOMAC function
Number of Study
WMD
95% CI
4 4 5 2 2 2 2
−0.45 0.10 0.04 −0.03 0.36 −0.05 −0.11
−1.28, 0.38 −1.49, 1.70 −0.83, 0.90 −4.11, 4.06 −1.33, 2.05 −0.48, 0.39 −1.89, 1.67
P Value
Heterogeneity
n.s. n.s. n.s. n.s. n.s. n.s. n.s.
I2 I2 I2 I2 I2 I2 I2
= = = = = = =
28% 30% 0% 62% 65% 0% 0%
KSS = The Knee Society Score; HSS = The Hospital for Special Surgery Score; WOMAC = Western Ontario and McMaster Universities Osteoarthritis Index; SF-36 = the Short Form 36 questionnaire; WMD = weighted mean difference; CI = confidence interval; n.s. = not significant.
112°, respectively. Thus the issue was pointed out that patients with good preoperative range of motion often did not gain or even lost deep flexion after standard TKA. We presented in this literature that the groups with high preoperative range of flexion using high-flex implants gained more range after TKA than using standard implants. Though no significant difference was detected, the P value was 0.06 with a limited sample size, implying that more involved patients might achieve a statistical difference. In the presented study, we assessed the range of flexion in patients using NexGen system. Analysis of one certain manufacturer was to some extent more convincing because in this way the bias of the implant design was eliminated. Both groups gained important improvement from preoperative range of flexion. The high-flex group achieved 1° greater in the postoperative range of flexion than the standard group. However, based on the finding that a difference of less than 5° in range of flexion was not clinically relevant [40], the acquisition of 1° seemed not sufficient to illustrate the benefit of high-flex design. Though we have supposed that when balancing baseline data, the high-flex prosthesis would gain more in the postoperative range of flexion than the standard prosthesis in consideration with the theoretical advantages, our study refuted this hypothesis. Several previous literatures [41,42] concluded that as an independent variable, the high-flex design did not correlate with better clinical outcomes or greater postoperative range of flexion. Other characteristics, such as preoperative flexion, intraoperative flexion, preoperative tibio-femoral alignment, posterior capsular release, the removal of posterior osteophytes and patient’s motivation to participate in physical therapy altogether determined postoperative range of flexion [43]. One of the concerns in high-flex implants was that the extra bone resection of femur would lead to instability and more difficult revision surgery. Moreover, extreme flexion might increase patella-femoral joint stress and cause anterior knee pain [44,45]. Han et al [46] reported a 38% rate of early loosening of the femoral component and 15 revisions in a series of 47 knees with the high-flex prosthesis. Nevertheless, we did not observe any obviously increased rate of early loosening, anterior knee pain or patellar crepitus in patients using high-flex implants. Many current literatures [21,41,42,47–50] supported our findings.
Fig. 8. Funnel plot for the postoperative range of flexion, demonstrating evidence of publication bias.
Conclusion In conclusion, our meta-analysis demonstrated that both high-flex prosthesis and standard prosthesis significantly improved range of flexion and that no obvious statistical difference was found between two groups in terms of the postoperative range of flexion, clinical scores, quality of life outcomes, or complication rate. The application of high-flex implant to patients with high preoperative range of flexion did gain range as compared to standard design, but a significant difference would need a larger sample size. A tiny improvement in the postoperative range of flexion was found with the NexGen LPS-Flex implant, which was clinically irrelevant.
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Table 5 Complication Rates. Number of Knee Complications Mobilization for stiffness Anterior knee pain Surgery for patellar crepitus Radiolucent line
A
B
7/336 8/169 5/142 14/164
7/333 6/170 7/136 13/170
Risk Ratio 0.99 1.32 0.69 1.12
95% CI 0.38–2.59 0.49–3.56 0.22–2.12 0.54–2.31
P Value n.s. n.s. n.s. n.s.
Heterogeneity I2 I2 I2 I2
= = = =
33% 0% 0% 0%
A = high-flex group; B = standard group; CI = confidence interval; n.s. = not significant.
Please cite this article as: Fu H, et al, No Clinical Benefit of High-Flex Total Knee Arthroplasty. A Meta-Analysis of Randomized Controlled Trials, J Arthroplasty (2014), http://dx.doi.org/10.1016/j.arth.2014.10.032
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Please cite this article as: Fu H, et al, No Clinical Benefit of High-Flex Total Knee Arthroplasty. A Meta-Analysis of Randomized Controlled Trials, J Arthroplasty (2014), http://dx.doi.org/10.1016/j.arth.2014.10.032
