The Knee 21 (2014) 12–20 Contents lists available at ScienceDirect The Knee Review Lower limb strength following total knee arthroplasty: A systematic review Margaret B. Schache a,b,⁎, Jodie A. McClelland a,c, Kate E. Webster c a b c Department of Physiotherapy, School of Allied Health, La Trobe University, Melbourne, Australia Donvale Rehabilitation Hospital, Ramsay Health Care, Melbourne, Australia Lower Extremity and Gait Studies Program, School of Allied Health, La Trobe University, Melbourne, Australia a r t i c l e i n f o Article history: Received 8 March 2013 Received in revised form 5 July 2013 Accepted 5 August 2013 Keywords: Total knee arthroplasty Muscle Lower limb Strength a b s t r a c t Background: Total knee arthroplasty (TKA) is commonly performed for end-stage knee osteoarthritis to relieve pain and improve quality of life. Understanding specific muscle weakness following TKA is required in order to develop targeted rehabilitation programmes for TKA patients. The aim of this systematic review was to determine whether TKA patients have reduced strength in lower limb muscle groups compared to controls. Methods: A search of common scientific databases was conducted. A modified published checklist was used to assess the risk of bias. A meta-analysis was completed for each lower limb muscle group in three separate post-operative time periods (4–6 months, 1–3 years, and N 3 years). The GRADE approach was used to determine the quality of the evidence. Results: Fifteen studies met the inclusion criteria for this review. There was low quality evidence for all metaanalyses. The meta-analyses showed that TKA patients had weaker quadriceps than the controls at every postoperative time (pooled effect sizes between −2.81 and −0.53). The meta-analyses of hamstring strength for patients 1–3 years post-operatively also showed patient weakness (pooled effect size = −1.87) and no significant difference at N3 years post-operatively (pooled effect size = −0.20). Conclusion: There was low quality evidence of quadriceps and hamstring weakness following TKA. Further research is required to determine if other lower limb muscles also display similar muscle weakness. Strategies that specifically target strengthening of these muscle groups may need to be incorporated in rehabilitation to improve outcomes from TKA. Level of evidence: I. © 2013 Elsevier B.V. All rights reserved. Contents 1. 2. 3. Introduction . . . . . . . . . . . . . . . . Methods . . . . . . . . . . . . . . . . . . 2.1. Search strategy . . . . . . . . . . . . 2.2. Selection criteria . . . . . . . . . . . 2.3. Outcome measures . . . . . . . . . . 2.4. Assessment of risk of bias . . . . . . . 2.5. Data extraction . . . . . . . . . . . 2.6. Data analysis . . . . . . . . . . . . . 2.7. Assessment of risk of bias across studies Results . . . . . . . . . . . . . . . . . . . 3.1. Selection of studies . . . . . . . . . . 3.2. Assessment of risk of bias . . . . . . . 3.3. Study characteristics . . . . . . . . . 3.4. Outcome measures . . . . . . . . . . 3.4.1. Quadriceps strength . . . . . 3.4.2. Hamstring strength . . . . . 3.4.3. Calf strength . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13 13 13 13 13 13 13 13 14 14 14 14 14 14 14 16 16 ⁎ Corresponding author at: Department of Physiotherapy, La Trobe University, Health Sciences Building 3, Kingsbury Drive, Melbourne, Victoria 3086, Australia. Tel.: +61 3 9841 1257; fax: +61 3 9842 7276. E-mail address: schachem@ramsayhealth.com.au (M.B. Schache). 0968-0160/$ – see front matter © 2013 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.knee.2013.08.002 M.B. Schache et al. / The Knee 21 (2014) 12–20 4. Discussion . . . . . . . . . . . . . 5. Conclusion . . . . . . . . . . . . . 6. Conflict of interest statement . . . . Appendix 1. Search strategy . . . . . . Appendix 2. Modified Downs and Black . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16 18 18 18 18 20 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18 21 1. Introduction End-stage knee osteoarthritis (OA) is a significant health problem worldwide [1,2]. It results in pain and limited participation in many activities of daily living and functional activities. The most effective current treatment for end-stage knee OA is total knee arthroplasty (TKA). TKA is effective in providing pain relief and improving function in knee OA patients [3] with the assistance from post-operative rehabilitation programmes [4]. Post-operative rehabilitation programmes include gait re-education, knee range of movement exercises and strengthening exercises. Emphasis is placed on restoring optimal knee range of movement and quadriceps strength [5,6]. Hamstring, gluteal and calf strengthening exercises may also be included. Despite this, muscle weakness and functional limitations persist following TKA [7]. Patients walk more slowly and have greater difficulty negotiating stairs and performing activities of daily living than age-matched individuals without knee pathology [7,8]. These functional limitations are associated with persistent muscle weakness demonstrated in TKA patients when compared to agematched controls [9]. It is therefore important to have a better understanding of specific and persistent muscle weakness post TKA that will assist rehabilitation programmes to be more targeted and effective. The aim of this systematic review was to determine whether TKA patients have reduced lower limb strength compared to a healthy agematched population, and to identify which lower limb muscle groups are weaker. 2. Methods 2.1. Search strategy A search of the following databases was conducted from their inception to March 2012: Medline, Cinahl, Embase, Pedro and Cochrane. Combinations of the following search terms were used to define the population: total knee arthroplasty, replacement, prosthesis; and the outcome of interest: muscle, hip, knee, ankle, lower extremity, quadriceps, hamstring, gluteal, calf, strength, isometric, isokinetic, torque, force (Appendix 1). Search terms were matched to subject headings in Medline, Cinahl and Embase. After deleting duplicate articles from multiple databases, the titles and abstracts were assessed according to predetermined inclusion and exclusion criteria. Two examiners assessed the titles and abstracts independently and any discrepancies were resolved with discussion. The full text article was retrieved for potentially eligible studies and for those studies where the title and abstract did not provide sufficient information for exclusion. The selection criteria were applied to the full text article by two examiners. Any disagreements were resolved by discussion. Citation tracking was performed using ISI Web of Knowledge. The reference lists of included articles were also checked to supplement electronic searching. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . operative diagnoses included pathologies other than OA and the patients were reported as a single group, only studies where greater than 80% of the patient population had pre-operative OA were included. This decision was made because the disease process in other populations such as rheumatoid arthritis and tumour resections have been shown to affect the strength outcomes after TKA [10,11]. Revision arthroplasties were excluded because these procedures have been shown to have strength outcomes that may be different from primary knee arthroplasty [12,13]. Only studies that recorded maximum strength of isolated lower limb muscle groups measured on a continuous scale and compared data to a control group were included. A control group was chosen in preference to the uninvolved knee because of the high risk of undiagnosed or developing OA in the contralateral knee, which could have implications for muscle strength comparisons [14]. Authors were contacted where necessary to confirm whether multiple manuscripts reported on a common data set. 2.3. Outcome measures The primary outcome measure was muscle strength of the lower limb muscle groups. Maximum isometric, isokinetic or concentric muscle strength produced by isolated lower limb muscle groups was recorded. 2.4. Assessment of risk of bias A checklist published by Downs and Black [15] was used to assess the risk of bias of each included study independently by two raters. Discrepancies were resolved by discussion. This checklist was chosen for its suitability for non-randomised studies and was modified so that it contained items only relevant to the aim of this review (Appendix 2). Therefore, items that assessed risk of bias specific to randomised studies, treatment effects and losses to follow up were removed. The selected items are listed in Table 1. 2.5. Data extraction Reporting for the current systematic review followed the Preferred Reporting Items for Systematic reviews and Meta-analysis (PRISMA) guidelines [16]. The number of participants, study characteristics, participant characteristics, muscle strength assessment and muscle strength data were extracted from each study. Where studies presented muscle strength data in graph form only, an email was sent to the corresponding author requesting numerical data. If the author could not be contacted, numerical values were estimated from the published graph(s) [17,18]. The means and standard deviations of data for subgroups such as gender differences or prosthetic design [7,11,19,20] were collapsed using formulae for the weighted mean and square root of the pooled variance [21]. 2.6. Data analysis 2.2. Selection criteria Studies were included that investigated patients with a primary TKA for a diagnosis of OA published in English. In studies where the pre- Effect sizes were calculated for each comparison of strength between patients with TKA and controls. These effect sizes were then grouped according to the type of strength measurement (isometric or isokinetic), 14 M.B. Schache et al. / The Knee 21 (2014) 12–20 Table 1 Assessment of risk of bias. Downs and Black criteria [15] Item no. 1 Item no. 2 Item no. 3 Item no. 5 Item no. 6 Item no. 7 Item no. 10 Item no. 11 Item no. 12 Item no. 25 Item no. 27 Author Clear aim Outcomes described Patients described Confounders described Main findings described Estimates of random probability Probability values reported Subjects represent population Confounders comparable Adjustment for confounders Power calculation Aquino and Garcez Leme [43] Bade et al. [3] Berth et al. [38] Boonstra et al. [39] Borden et al. [41] Ciolac and Greve [40] Farquhar and Snyder-Mackler [25] Fuchs et al. [17] Gapeyeva et al. [18] Huang et al. [19] Kim et al. [20] Levinger et al. [42] Silva et al. [9] Walsh et al. [7] Wigren et al. [11] ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✗ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✗ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✗ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✗ ✔ ✔ ✔ ✗ ✔ ✗ ✔ ✔ ✔ ✔ ✗ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✗ ✗ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✗ ✔ ✔ ✔ ✔ ✔ ✔ ✗ ✗ ✗ ✗ ✗ ✗ ✔ ✗ ✗ ✗ ✔ ✗ ✔ ✔ ✗ ✔ ✔ ✗ ✔ ✗ ✗ ✔ ✗ ✔ ✗ ✔ ✔ ✗ ✔ ✗ ✔ ✔ ✔ ✗ ✔ ✔ ✔ ✗ ✔ ✗ ✔ ✗ ✔ ✗ ✗ ✔ ✔ ✔ ✗ ✗ ✔ ✔ ✗ ✔ ✔ ✗ ✔ ✔ ✗ ✗ ✗ ✔ ✗ ✗ ✔ ✔ ✗ ✗ ✔ ✗ ✔ ✗ ✗ ✗ ✗ muscle group (quadriceps or hamstrings), and time period postoperatively (4–6 months, 1–3 years or greater than 3 years). A metaanalysis using a random effects model was performed on each group using StatsDirect statistical software [22]. In studies where there were multiple assessments of a single population that occurred in the same category for time period, strength measurement and muscle group, only one assessment was included to avoid an individual subject being represented twice in the same meta-analysis. For the same reason, where studies assessed isokinetic strength at multiple speeds the lower speed was used as slower speeds have been shown to be more reliable [23]. 2.7. Assessment of risk of bias across studies All but five studies [11,18,38–40] used a fixed unit dynamometer to measure muscle strength. Quadriceps strength was measured by 14 studies of which ten measured isometric quadriceps strength [3,9,11,18,19,25,38,39,41,42] and five measured isokinetic quadriceps strength [7,17,19,20,43]. Ten studies measured hamstring strength. Five of these studies measured isometric hamstring strength [9,11,19,39,41], five measured isokinetic hamstring strength [7,17,19,20,43] and one study [40] measured concentric hamstring strength. One study also measured concentric calf strength [40]. 3.4. Outcome measures 3.4.1. Quadriceps strength Meta-analysis of findings was possible for the comparison of isometric quadriceps strength between patients and controls at all follow-up periods, and for isokinetic strength at the 1–3 year follow-up period (Fig. 2). For all meta-analyses the quality of evidence was The Grades of Research, Assessment, Development and Evaluation (GRADE) approach [24] was used to evaluate the quality of evidence in each meta-analysis. Each meta-analysis was graded using the following criteria: 1. Inconsistency (downgrade if I2 ≥ 75); 2. Indirectness (no downgrade applied as all studies measured muscle strength directly); 3. Imprecision (downgrade if upper or lower confidence interval crosses an effect size of 0.5 in either direction); and 4. Reporting bias (downgrade if modified Downs and Black score average b60%). Titles and abstracts identified and screened (n=3732) Papers excluded after screening title and abstract (n=3704) 3. Results Full text retrieved (n=28) 3.1. Selection of studies Fifteen studies were included in the review after an initial yield of 3732 (Fig. 1). Contact with authors confirmed multiple studies initially included in the review contained a common data set [25–29]. Of these, the study by Farquhar and Snyder-Mackler [25] was included as it had the largest number of participants. Contact with authors confirmed that multiple studies also contained another common data set [3,30,31]. For this dataset, the article by Bade et al. [3] was included as it contained the largest sample that reported numerical values. One study [32] was excluded because muscle strength was not measured as an isolated muscle group and six papers [12,33–37] were excluded because muscle strength was not measured as a maximum force. 3.2. Assessment of risk of bias Of a possible 11, the number of criteria satisfied by the included studies ranged from one to 10 (Table 1). In six of these studies factors that could confound strength outcomes such as age, gender, height, weight or BMI were not reported or were not equal between the two groups. Power calculations were not reported in 10 of the studies. 3.3. Study characteristics A summary of the included studies is presented in Table 2. The number of subjects in each individual study ranged from seven to 183 and there were 906 (495 female, 336 male, 75 not stated) participants in the overall review. Studies identified after searching reference lists (n=0) Papers excluded after evaluation of full text (n=13) Reasons: 1. Lower-limb strength not reported as isolated muscle groups (n=1) 2. Lower limb strength not measured as a maximum strength and recorded as a numerical value (n=6) 3. Research articles with no new data (n=6) Studies identified from citations (n=0) Eligible Studies (n=15) Fig. 1. Flow of studies through the selection process. Table 2 Summary of included studies (n = 15). Study TKA subjects Mean (SD) Control subjects Mean (SD) Age (yrs) Gender (M/F) BMI (kg/m2) Time post-op Surgical approach/prosthesis type Sample size Age (yrs) Gender BMI (kg/m2) (M/F) 17.8 (6) mths, range = 12–36 mths 6 mths 33 (8) mths 16.7 (5.7) mths Not stated 25 71.36 (3.24) 0/25 27.40★ Not stated 17 Approach not stated/un-constrained 23 Approach not stated/fixed bearing 31 66.8 (6.5) 63.2 65.4 (8.6) 9/8 8/15 12/19 27.2 (3.5) 26.2 28.4 (3.8) Approach not stated/PCL retaining 9 68 (6) 4/5 29.76★ Not stated 8 70.4 (5.3) 0/8 28.1 (5.2) Medial parapatellar/implant not stated Subvastus/Genesis-I-prosthesis 25 63.1 (8.4) 10/15 26.8 (4.2) 22 65.5 (8) 11/11 Not stated 10 0/10 9 (16 knees) 64 (range: 52– 75) 68.0 (5.1) Isokinetic quads & hams (60°/s, 180°/s) 27 (range: 21–32) Isometric quads (90° flex) Not stated Weight = 59.1 (12.0) kg 30 66 (4) 27.3 (3) 27 65 (11) 10 (15 knees) 62 (7.3) Not stated 12/14 3/7 25 (3) 28.9 (5.9) 40 62.8 (1.3) 22/18 25.6 (.69) 96 Not stated 40/46 Not stated 20 71.35 (3.23) 0/20 31.13⁎ 24 50 28 65 (9.4) 65.8 (5.6) 65.5 (8.9) 12/12 18/32 11/17 30.7 (4.1) 31 29.7 (5.2) Borden et al. [41] 8 70 (8) 3/5 29.76⁎ Ciolac and Greve [40] 7 75.3 (3.1) 0/7 32.4 (4.8) 66.4 (8.5) 101/82 30.6 (5.2) 68.1 (8) 8/11 Not stated Farquhar and 183 Snyder-Mackler [25] Fuchs et al. [17] 19 10 46 (14) mths, range = 30–72 mths 38.5 (18.5) range = 14–66 mths 3 yrs 24.6 (16.7) range = 4–80 mths 6 mths Huang et al. [19] 63.0 0/10 (range: 52–74) 36 (50 knees) 68 (6) Not stated 30.0 (range: 23–38) Weight = 67.9 7.6 (2.1) yrs (11.8) kg range = 6–13 yrs Kim et al. [20] 45 0/45 27.7 (4.1) Levinger et al. [42] Silva et al. [9] 35 67 (7) 16 (25 knees) 65.1 (8.1) 19/16 4/12 30 (4) 31.1 (4.4) Walsh et al. [7] 29 64.1 (1.5) 16/13 30.3 (1.4) Wigren et al. [11] 14 68 2/12 Not stated 67.5 (6.5) 14.8 mths range = 12–18 mths 4 mths N2 yrs (mean = 2.8, max = 6 yrs) 12.6 (1.5) mths, range: 11–17 mths 3 yrs Medial parapatellar/mixed PCL retaining and sacrificed Approach not stated/total condylar, mobile-bearing, PCL retained and sacrificed Medial parapatellar and mini midvastus/posterior stabilised Not stated Approach not stated/posterior stabilised Not stated Medial parapatellar incision/ Modular knee Isokinetic quads & hams (60°/s) Isometric quads (60° flex) Isometric quads (90° flex) Isometric quads & hams (not stated) Isometric quads & hams (45° flex) concentric hams and calf (not stated) Isometric quads (75° flex) Isometric (60° flex) and isokinetic (120°/s, 180°/s) quads & hams Isokinetic quads & hams (60°/s) Isometric quads (90° flex) Isometric quads & hams (75° flex) isokinetic quads & hams (90°/s, 120°/s) Isometric quads & hams (not stated) M.B. Schache et al. / The Knee 21 (2014) 12–20 Sample size Aquino and Garcez Leme [43] Bade et al. [3] Berth et al. [38] Boonstra et al. [39] Gapeyeva et al. [18] Strength outcome measure (angular velocity or knee flex angle) SD, standard deviation; yrs, years; mths, months; M, male F, female; BMI, body mass index (kg/m2); ⁎, BMI calculated from height and weight; quads, quadriceps muscle; hams, hamstring muscle; PCL, posterior cruciate ligament. 15 16 M.B. Schache et al. / The Knee 21 (2014) 12–20 low. At 4–6 months post-operatively, meta-analysis indicated isometric quadriceps weakness (pooled effect size = −2.56; 95% CI −4.43 to −0.68), and a single study reported reduced isokinetic strength (single effect size = −1.79; 95% CI −2.33 to −1.24). At 1–3 years following TKA, meta-analysis indicated that patients were weaker compared to controls for isometric (pooled effect size = −0.68; 95% CI −1.02 to −0.34) and isokinetic contractions (pooled effect size = −2.81; 95% CI −4.72 to −0.90). An additional study that could not be included in the meta-analysis [17] also found quadriceps strength to be significantly weaker (TKA = 45.07 Nm, Control = 92.05 Nm, p b 0.05) in TKA patients than controls. Similarly, when patients were more than 3 years following TKA, meta-analysis indicated reduced isometric strength (pooled effect size = −0.53; 95% CI −1.02 to −0.04) and a single study reported reduced isokinetic strength (single effect size = −0.54; 95% CI −1.11 to 0.03). 3.4.2. Hamstring strength Meta-analyses were possible for comparison of hamstrings strength at 1–3 years, and greater than 3 years post-operative (Fig. 3). The quality of the evidence was low for all meta-analyses. A single study compared patients 4–6 months following TKA and reported reduced isokinetic hamstring strength in the patient group (single effect size = −0.66; 95% CI −1.13 to −0.18). At 1–3 years following TKA, meta-analyses indicated there was no significant difference between groups for isometric hamstrings contraction (pooled effect size = −0.76; 95% CI −1.87 to 0.34), but patients had reduced isokinetic strength (pooled effect size = −1.87; 95% CI −3.65 to −0.08). The additional study that measured isokinetic hamstring strength but could not be included in the meta-analysis ([17] also found hamstring strength to be significantly weaker (TKA = 62.26 Nm, Control = 132.25 Nm, p b 0.05)) in TKA patients than controls. When patients were more than Isometric Quadriceps 4–6 months postvop 3 years following TKA, meta-analysis indicated no significant difference in hamstring strength for either isometric (pooled effect size = −0.23; 95% CI −1.02 to 0.56) or isokinetic contractions (pooled effect size = −0.20; 95% CI −1.01 to 0.61). 3.4.3. Calf strength The single study that measured calf strength [40] reported that the patient group had reduced strength compared to controls at greater than 3 years post-operative. The effect size was −1.23 (95% CI −2.26 to −0.06). 4. Discussion This systematic review showed that overall, TKA patients had reduced strength of multiple lower limb muscle groups when compared to unimpaired control groups, although the evidence for this is low quality. This muscle weakness was particularly evident for the quadriceps muscle group. The quality of evidence was low in each of the meta-analyses due to the high heterogeneity of results. There was no significant difference in hamstring strength between TKA patients and controls except for isokinetic strength at 4–6 months and 1–3 years post-operatively. Again there was low quality evidence for these findings due to high heterogeneity particularly in the 1–3 years postoperative period where two studies showed that TKA patients had weaker hamstrings and one showed that they had stronger hamstrings Isokinetic Quadriceps 4–6 months post-op Bade et al. (2010) Gapeyeva et al. (2007) Kim et al. (2011) Levinger et al. (2011) Total -8 -7 -6 -5 -4 -3 -2 -1 0 1 -8 -7 -6 Patients weaker -5 -4 -3 -2 -1 0 1 Patients weaker I2 (heterogeneity) = 92.7% Isometric Quadriceps 1–3 years post-op Farquhar and Snyder-Mackler (2010) Isokinetic Quadriceps 1–3 years post-op Aquino and Garcez Leme (2006) Wigren et al. (1983) Kim et al. (2011) Silva et al. (2003) Boonstra et al. (2008) Walsh et al. (1998) Berth et al. (2002) Total Total -8 -7 -6 -5 -4 -3 -2 -1 0 1 -8 -7 -6 -5 -4 -3 -2 -1 0 Patients weaker Patients weaker I2 (heterogeneity) = 58.8% I2 (heterogeneity) = 94.4% Isometric Quadriceps >3 years post op 1 Isokinetic Quadriceps >3 years post-op Huang et al. (1996) Huang et al. (1996) Borden et al. (1999) Total -8 -7 -6 -5 -4 -3 -2 -1 0 Patients weaker 1 -8 -7 -6 -5 -4 -3 -2 Patients weaker I2 (heterogeneity) = 0% Fig. 2. Forest plots and meta-analysis of isometric and isokinetic quadriceps strength for each separate post-operative period. -1 0 1 M.B. Schache et al. / The Knee 21 (2014) 12–20 than controls. Calf strength, measured in one study [40], was also reduced in the TKA group. The findings of this systematic review are particularly relevant to rehabilitation post TKA. The main goals of TKA surgery are to reduce pain and improve function. Optimizing quadriceps strength post TKA is considered extremely important for achieving good functional outcomes [44]. There are also many different rehabilitation protocols for TKA patients that acknowledge the high importance of quadriceps strengthening [3,5,11,18,45] as well as research to discover more innovative and effective methods to strengthen the quadriceps following TKA such as neuromuscular electrical stimulation [46–48]. Despite the emphasis on quadriceps strengthening in most documented protocols, the patients continue to be weaker than age-matched controls well beyond 3 years post-operatively. The cause of the persistent quadriceps weakness in TKA patients more than three years post surgery is unclear from this systematic review. It is possible that current rehabilitation programmes may be inadequate with respect to type of quadriceps exercises, intensity, timing post-operatively or duration. It is also possible that the aberrant kinematic patterns adopted by patients following TKA surgery, in particular the reduced knee flexion angles during loading phase of gait, reinforce an avoidance of regular quadriceps use [49,50]. 17 It would therefore be useful for future research to investigate if patients who engage in quadriceps strength training at higher levels or for longer periods of time could achieve quadriceps strength closer to that of the normal population. In order to maximise our patients' outcome following TKA, rehabilitation programmes must aim to achieve muscle strength equal to that of healthy individuals. The strength of lower limb muscle groups other than quadriceps are also likely to affect functional outcome in patients with TKA. Although there was a trend towards hamstrings weakness in patients, there were not enough studies, and there was poor heterogeneity between studies to draw conclusions based on strong evidence. Calf strength was investigated by only one study. Weak hamstrings and calf muscles have implications for the gait patterns of patients with TKA. Reduced hamstring strength along with reduced quadriceps strength may affect the patients' balance as co-contraction of the hamstrings and quadriceps is important for knee proprioception and joint stability [51]. The ankle plantar flexors are critical to both supporting the body and achieving fast speeds of walking, and in people with gait abnormalities it has been shown that poor ankle plantar flexor function during gait is a strong predictor of poor mobility outcome [52]. Adequate plantar flexor function is also important in stair ascent [53]. Therefore, reduced calf Isokinetic Hamstrings 4 6 months post-op Kim et al. (2011) -5 -4 -3 -2 -1 0 1 Patients weaker Isometric Hamstrings 1 3 years post-op Isokinetic Hamstrings 1 3 years post-op Boonstra et al. (2008) Aquino and Garcez Leme (2006) Silva et al. (2003) Kim et al. (2011) Wigren et al. (1983) Walsh et al. (1998) Total Total -5 -4 -3 -2 -1 0 1 -5 -4 -3 -2 -1 0 1 Patients weaker Patients weaker I2 (heterogeneity) = 92.3% I2 (heterogeneity) = 95.2% Isometric Hamstrings >3 years post-op Isokinetic Hamstrings >3 years post-op Borden et al. (1999) Huang et al. (1996) Huang et al. (1996) ∗Ciolac and Greve 2011 (concentric) Total Total -5 -4 -3 -2 -1 0 1 -5 -4 -3 -2 -1 0 Patients weaker Patients weaker I2 (heterogeneity) = 51.4% I2 (heterogeneity) = 50.1% 1 Fig. 3. Forest plots and meta-analysis of isometric and isokinetic hamstring strength for each separate post-operative period. ⁎Ciolac and Greve (2011) is included in isokinetic meta-analysis. 18 M.B. Schache et al. / The Knee 21 (2014) 12–20 strength may contribute to difficulty experienced in stair climbing by many patients with TKA. There is growing interest in improving hip strength following TKA and recent evidence suggests hip strength is important in TKA outcomes [6]. Hinman et al. [54] have demonstrated hip muscle weakness in individuals with medial knee osteoarthritis and it is expected that this deficit is likely to persist following TKA. However, none of the studies included in this review compared the strength of the hip abductors with a control group. Piva et al. [6] investigated the contribution of hip abductor strength to physical function in patients with TKA. They found that hip abductor weakness had a greater effect than quadriceps weakness on physical function. Hip strength following TKA and its beneficial effect on function should be investigated in more detail to ensure rehabilitation programmes address any significant persistent muscle strength deficits. The strength of muscles in the contralateral limb was also not investigated by any of the studies in this review. Recent evidence [55] suggests that the contralateral limb strength is the strongest predictor of outcome following TKA, therefore, it is surprising that little is known about the strength of the contralateral limb compared to normal. This is an obvious gap in this area that needs to be addressed to ensure that rehabilitation programmes are targeting strength impairments that may be most effective in improving patient outcomes from TKA surgery. It is possible that the location of the surgical incision may affect the strength outcome of lower limb muscles following TKA surgery. However, only five of the included studies provided information about the incision approach, which was insufficient to warrant analysis of the outcome of strength from these subgroups. Furthermore, there was a variety of TKA prostheses used in the included studies. Whilst it would be of interest to know whether different prosthesis design characteristics such as retention or resection of the posterior cruciate ligament lead to different strength outcomes, there were an insufficient number of studies with similar prostheses to allow further analysis. To understand the impact of surgical procedures on strength outcomes following TKA, further research is needed. There was large variability in the methodology among the studies. Nine of the fifteen studies had comparable confounders between their two groups and nine studies normalized their data for confounding factors. Knee flexion varied from 45° to 90° in isometric strength testing and the angular velocity in isokinetic testing varied from 60°/s to 180°/s. These factors should be considered when interpreting these results however they did not appear to significantly affect the final outcome. Despite the fact that these factors may affect the heterogeneity of the results, all of the included studies found similar muscle weaknesses. Previous research has noted persistent quadriceps deficit, and whilst this is likely to be the case, this review shows that the overall evidence is weak and highlights the need for further research in this area. This review has summarised the evidence of persistent quadriceps weakness post TKA. Further research is warranted to determine if quadriceps strength can be improved more substantially post TKA. Further research is required to determine if the hip abductors also display similar muscle weakness post-TKA. Also, given that hip strengthening reduces symptoms in patients with medial knee osteoarthritis [56] it would be beneficial to determine the effects of targeted hip strengthening on functional outcomes following TKA. The calf and contralateral limb muscle strength should also be assessed. These muscle groups can then be specifically targeted in rehabilitation in the future. 5. Conclusion Compared to a control group, muscle weakness exists in the quadriceps and hamstring muscle groups following TKA but the evidence base is weak. Further research is required to determine if other lower limb muscles such as the hip abductors, calf and contralateral limb also display similar muscle weakness following TKA so they can be specifically targeted in rehabilitation. 6. Conflict of interest statement None of the authors have any personal or financial relationships that may result in a conflict of interest in the preparation of this manuscript. Appendix 1. Search strategy Medline and Embase (inception to March 2012) 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. 32. 33. 34. 35. 36. 37. 38. 39. 40. 41. 42. 43. 44. 45. 46. 47. 48. 49. 50. 51. Arthroplasty, Replacement, Knee/ arthroplasty/or arthroplasty, replacement/ Knee Prosthesis/ knee replacement$ total knee replacement$ knee arthroplast$ total knee arthroplast$ knee prosthes$ TKR TKA joint replacement$ arthroplast$ 1 or 2 or 3 or 4 or 5 or 6 or 7 or 8 or 9 or 10 or 11 or 12 muscles/or muscle, skeletal/ knee/ Hip/ Ankle/ exp Lower Extremity/ Quadriceps Muscle/ muscle knee hip ankle lower limb quadricep$ hamstring$ knee extens$ knee flex$ glute$ hip abduct$ hip extens$ calf plantarflex$ tibialis anterior dorsiflex$ 14 or 15 or 16 or 17 or 18 or 19 or 20 or 21 or 22 or 23 or 24 or 25 or 26 or 27 or 28 or 29 or 30 or 31 or 32 or 33 or 34 or 35 Muscle Strength/ muscle contraction/or isometric contraction/or isotonic contraction/ torque/ Muscle Weakness/ Muscular Atrophy/ strength force isometric isokinetic torque dynamometer weak$ atrophy 38 or 39 or 40 or 41 or 42 or 43 or 44 or 45 or 46 or 47 or 48 or 49 13 and 36 and 50 M.B. Schache et al. / The Knee 21 (2014) 12–20 Appendix 2. Modified Downs and Black 10. Have the actual probability values been reported (e.g. 0.035 rather than b 0.05) for the main outcomes except where the probability value is less than 0.001? Reporting 1. Is the hypothesis/aim/objective of the study clearly described? Yes No ✔ ✗ Yes No 2. Are the main outcomes to be measured clearly described in the Introduction or Methods section? If the main outcomes are first mentioned in the Results section, the question should be answered no. Details of each outcome measure, no. of trials of strength measurements, position of strength measurements, equipment used must be stated. ✔ ✗ Yes No 3. Are the characteristics of the patients included in the study clearly described including at least 2 of the following: - pre-operative diagnosis - time since surgery - other disorders affecting muscle strength, e.g.: osteoarthritis in other joints, rheumatoid arthritis, and neurological conditions? In cohort studies and trials, inclusion and/or exclusion criteria should be given. In case-control studies, a case-definition and the source for controls should be given. ✔ ✗ Yes No 5. Are the distributions of principal confounders in each group of subjects to be compared clearly described? Descriptions of study subjects and control subjects must include more than 2 of the following to score a tick: Yes No age gender height weight BMI All the following criteria attempt to address the representativeness of the findings of the study and whether they may be generalized to the population from which the study subjects were derived. 11. Were the subjects asked to participate in the study representative of the entire population from which they were recruited? The study must identify the source population for patients and describe how the patients were selected. Patients would be representative if they comprised the entire source population, an unselected sample of consecutive patients, or a random sample. Random sampling is only feasible where a list of all members of the relevant population exists. Where a study does not report the proportion of the source population from which the patients are derived, the question should be answered as unable to determine. Yes No Unable to determine ✔ ✗ ✗ 12. Were the subjects and controls comparable regarding confounding factors? The control population should be matched to the study subjects according to age, gender, height, weight, or BMI. To score a tick, all study groups must be compared on age, gender and one other factor. Points not awarded if descriptions of subjects and controls only. ✔ ✗ Internal validity — confounding (selection bias) ✔ ✗ ✔ ✗ 7. Does the study provide estimates of the random variability in the data for the main outcome? In non-normally distributed data the inter-quartile range of results should be reported. In normally distributed data the standard error, standard deviation or confidence intervals should be reported. If the distribution of the data is not described, it must be assumed that the estimates used were appropriate and the question should be answered yes. Yes No ✔ ✗ External validity Yes No 6. Are the main findings of the study clearly described? Simple outcome data (including denominators and numerators) should be reported for all major findings so that the reader can check all major analyses and conclusions. This question does not cover statistical tests, which are considered below. Yes No 19 ✓ ✗ 22. Were study subjects in different intervention groups (trials and cohort studies) or were the cases and controls (case–control studies) recruited over the same period of time? For a study that does not specify the time period over which patients were recruited, the question should be answered as unable to determine. Yes No Unable to determine ✔ ✗ ✗ 25. Was there adequate adjustment for confounding in the analyses from which the main findings were drawn? i.e.: were results normalized to a. body weight b. height c. or BMI This question should be answered no for trials if: the main conclusions of the study were based on analyses of treatment rather than intention to treat; the distribution of known confounders in the different treatment groups was not described; or the distribution of known confounders differed between the treatment groups but was not taken into account in the analyses. In non-randomised studies if the effect of the main confounders was not investigated or 20 M.B. Schache et al. / The Knee 21 (2014) 12–20 confounding was demonstrated but no adjustment was made in the final analyses the question should be answered no. 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