Physical therapies for Achilles tendinopathy: systematic review and meta-analysis

Studies eligible for inclusion were RCTs evaluating the effect of at least one non-surgical, non-pharmacological intervention on pain and/or altered function associated with AT. Achilles tendinopathy was defined as participants experiencing one or more common signs or symptoms (tenderness on palpation, pain at rest or during activity, stiffness during activity, and impaired function), either in the midportion or insertional region of the Achilles tendon. The diagnosis of AT had to be made by a healthcare or medical practitioner. No restrictions were placed on the duration of participant symptoms, or length of treatment or follow up period. Studies were excluded if they included results that had been reported in previous publications, or if they included participants with symptoms related to Achilles rupture, rheumatological disease or the use of fluoroquinolone antibiotics. The search was limited to studies available in full-text, written in English and evaluating human participants.

A comprehensive search strategy was developed using the National Health and Medical Research Council guidelines [16]. Medline, EMBASE, Web of Science, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Health and Medical Complete, Proquest, Australian Medical Index (AMI), Australian Sport Database (AUSPORT), AUSPORT Medical, Physiotherapy Evidence Database (PEDro), and Clinical Evidence databases were searched from their earliest record to September 13^th 2011. The search strategy for Medline ( Additional file 1) was adapted for use in the other databases. Secondary searching was conducted by reviewing reference lists of eligible papers.

Titles, abstracts and full text articles, where necessary, were screened for eligibility by two independent reviewers (KC and SW). Discrepancies were discussed in a consensus meeting and the opinion of a third independent reviewer (AB) was sought if agreement could not be achieved.

A modified version of the Physiotherapy Evidence Database (PEDro) scale [17] was used to assess the methodological quality of included studies ( Additional file 2). Three additional criteria were added to the existing 11 PEDro criteria to evaluate sample size, validity and reliability of outcome measures, and reporting of adverse or side effects [18]. One point was awarded for each criterion that was clearly satisfied according to prespecified guidelines, and the 14 items summed to give a total methodological quality score out of 14. The modified PEDro scale has been used in previous systematic reviews [18‐20] and has good inter-rater reliability (κ 0.73 to 0.82) [18]. Two reviewers (SSL and AB) completed formal training for using the PEDro scale [17] and independently rated each eligible study. A consensus meeting was held to resolve any discrepancies between the reviewers. When the two reviewers could not reach agreement, a third independent reviewer was consulted (SW).

The risk of bias was established for each study, using specific criteria from the modified PEDro scale. These were chosen after consulting the PRISMA Statement [15] as well as recommendations made by the Cochrane Collaboration [21]. Six criteria were used in the assessment: i) adequacy of randomisation (criterion two); ii) allocation concealment (criterion three); iii) between-group baseline comparability (criterion four); iv) blinding of outcome assessors (criterion seven); v) adequate follow-up (more than 85%) (criterion eight), and; vi) intention to treat analysis (criterion nine). A score of five or six was considered to have a low risk of bias, three to four a moderate risk, and two or less a high risk. Studies that had a high risk of bias were excluded from further analyses.

The kappa (κ) statistic was used to calculate the inter-rater reliability of the modified PEDro scores. The magnitude of agreement was defined as per Hopkins [22], where 0.9 to 1.0 represented almost perfect to perfect agreement, 0.7 to 0.9 very high agreement, 0.5 to 0.7 high agreement, 0.3 to 0.5 moderate agreement, 0.1 to 0.3 small agreement, and 0.0 to 0.1 very small agreement.

Data extraction was performed by one author (SSL) and included participant characteristics, diagnostic criteria, AT characteristics, interventions, outcome measures and outcome data. For studies that utilised more than one outcome measure for pain and/or function, outcome data for a disease-specific outcome of pain and/or function was extracted. If this was not possible, a commonly-used outcome measure was chosen (e.g. pain visual analogue scale). If insufficient data were presented for calculation of effect sizes, an attempt was made to electronically contact the corresponding author for further information. Calculations of mean differences (SMD) and 95% confidence intervals (CI) were generated by Review Manager software [23] using an inverse variance method and fixed effects model for individual studies. Where studies had sufficient homogeneity in participant characteristics, interventions, outcome measures and follow up times, a meta-analysis of outcome data was performed. Meta-analyses were conducted using a random effects model, as some pooled studies had a heterogeneity greater than 50%, which was determined using an I² statistical assessment of inconsistency [24]. Interpretation of SMDs was conducted as per Hopkins [22], where an effect size of 4.0 was considered to represent an extremely large clinical effect, 2.0 to 4.0 a very large effect, 1.2 to 2.0 a large effect, 0.6 to 1.2 a moderate effect, 0.2 to 0.6 a small effect, and 0.0 to 0.2 a trivial effect. Negative values favoured the intervention of interest and a null effect was considered for 95% CIs that contained zero.

The two reviewers had initial agreement on 297 out of 322 criteria (κ = 0.941, 95% CI 0.904 to 0.978) (Table 1), and reached consensus on all criteria. The inter-rater reliability for individual criteria ranged from high to perfect (κ = 0.621 to 1.000). Quality assessment scores ranged between two and 12 out of a maximum of 14 (mean ± SD 7.8 ± 2.9). Reporting of random group allocation and the results of between-group statistical comparisons were scored by all studies. Criteria that were met by the least number of studies were blinding of therapists (one study), and reliability and validity of outcome measures (two studies). Four studies were considered to have a high risk of bias [28, 36, 37, 41], and were subsequently excluded from further analyses, leaving 19 studies remaining.

Characteristics of study participants are presented in Table 2. Most studies utilised chronic cohorts (symptoms greater than three months), with the minimum duration of symptoms ranging from six weeks to 12 months. Nine studies (47%) [29‐31, 33‐35, 38, 40, 42] included participants with symptom durations of three or more months. Clinical examination was the only diagnostic tool in 13 studies (68%) [25‐27, 29, 31‐33, 35, 39, 42, 44, 45, 47], while ultrasonography was considered in six studies (33%) [25‐27, 31, 40, 45]. Two-thirds of studies (67%) evaluated participants with only midportion symptoms, two studies (11%) [29, 32] included participants with mixed diagnoses of insertional or midportion AT, while the location was not reported in four studies [34, 42, 44, 46]. Seven studies (37%) [26, 29, 33, 34, 44‐46] included participants with a mean age of 40 years or less, and six studies (32%) [25‐27, 32, 35, 42] utilised groups with at least 50 percent females.

Six different measures of pain and/or function were reported across the 19 studies, with the evaluation of pain-only being most common (79% of studies). Combined measures of pain and function (47% of studies), and function-only measures (21% of studies) were also used. Visual analogue scales (VAS) (79% of studies) [25‐27, 29‐32, 35, 39, 40, 42, 43, 45, 46] and the Victorian Institute of Sport Assessment–Achilles (VISA-A) questionnaire (37% of studies) [25, 26, 33, 39, 43, 44, 47] were the most frequently used tools. The American Orthopedic Foot and Ankle Society hindfoot scale (AOFAS) (11%) [31, 42], Functional Index of the Leg and Lower Limb (FILLA) (11%) [32, 35], Pain Scoring System (5%) [34], General Assessment of function (5%) [34] and Heel-raise test (5%) [44] were also used. Reliability was reported for three outcome measures (VAS [48], VISA-A [49] and FILLA [50]) and only one measure had reported validity (VISA-A [49]). Additional data was requested for six of the 19 studies [33, 34, 38, 42, 46, 47], with three authors replying to correspondence [33, 38, 47], and one providing sufficient data for further evaluation [47].

Exercise modalities: Eccentric exercise was the most frequently investigated intervention (17 out of the 19 studies). Nine studies investigated eccentric exercise programs as a primary intervention of interest [25, 26, 29, 31, 33, 35, 38, 40, 46]. A further eight studies used eccentric exercise as a control or adjunct intervention [27, 30, 34, 39, 42, 43, 45, 47], and these will be considered under their respective primary interventions. The methodological quality of the nine studies ranged from four to 11 out of 14 (mean ± SD 7.6 ± 5.3). Four of these studies [25, 26, 29, 35] provided sufficient data for effect size calculation (Figure 2). Due to differences in comparator interventions, outcome measures and follow up times, pooling of data from these studies was not conducted.

Only one study compared eccentric exercise to a wait-and-see control [25], with findings of large significant effects favouring a 12-week eccentric exercise program (SMD −1.26, 95% CI −0.65 to −1.87). Similar effects were also seen when 12 weeks of eccentric exercise was compared to cryotherapy (−1.67,–0.50 to −2.83) [29]. In contrast, Petersen et al. [31] reported no significant differences in outcome over one year between those treated with 12 weeks of eccentric exercise and a heel brace (p > 0.05).

Three studies compared eccentric exercise to electrotherapeutic modalities. Effect sizes for Chester et al. [35] showed that eccentric exercise was not significantly different to therapeutic ultrasound at six weeks (0.63,–0.33 to 1.58) and 12 weeks (0.24,–0.69 to 1.17). Two studies compared 12 weeks of eccentric exercise to three weeks of shock wave therapy (SWT) [25, 26], with pooled data showing no significant differences at 16 weeks (VISA-A:–0.55,–2.21 to 1.11).

A 12-week eccentric exercise program was compared directly to concentric exercise by two studies [40, 46]. Although effect sizes could not be calculated for either study, Niesen-Vertommen et al. [46] reported significantly greater pain reduction in the eccentric exercise group at four, eight and 12 weeks (p < 0.05). Mafi et al. [40] did not present between-group comparisons for pain outcomes at 12 weeks. Silbernagel et al. [38] compared two rehabilitation programs, both using eccentric and concentric calf strengthening. Those randomised to the experimental group received a program of higher Achilles tendon loading that induced higher pain levels than the control program, although they received greater therapist monitoring than the control group. However, no conclusions could be drawn regarding comparative efficacy, due to the absence of between-group comparisons of pain, and effect estimates could not be calculated due to insufficient data.

Herrington and McCulloch [33] assessed the benefit of adding eccentric exercise to a multimodal program of deep friction massage, ultrasound and calf stretching. Pain and function outcomes assessed using the VISA-A questionnaire suggest that the eccentric exercise group experienced greater improvements after 12 weeks than the control group (p = 0.01); however, effect estimates could not be calculated due to insufficient data.

Silbernagel et al. [39] evaluated the effect of continued tendon loading while undergoing a rehabilitation program of eccentric exercises for AT. One group continued to participate in tendon loading activities (e.g. running or jumping activities) while the other limited this type of activity, and groups were followed over one year. Evaluation of pain and function outcomes found no significant effects for either program at six weeks (−0.32, -0.88 to 0.25), 12 weeks (−0.17,–0.73 to 0.39), 26 weeks (−0.12,–0.68 to 0.44) or one year (−0.55,–1.11 to 0.02) (Figure 2).

Electrophysical therapies: Five studies [25‐27, 32, 42] evaluated the efficacy of SWT on AT (Table 3), with a mean methodological quality of 11.2 ± 0.4 (range 11 to 12). Sufficient data for effect size calculations was available for all studies (Figure 3).

Evidence from meta-analysis of data from two studies comparing SWT to eccentric exercise [25, 26] found no significant effects for outcomes of pain and function (VISA-A:–0.55,–2.21 to 1.11) at 16 weeks. One of these studies specified that they evaluated individuals with insertional AT [26], while the other studied individuals with midportion AT [25]. A further study by Rompe and colleagues [27] examined the effects of SWT when added to eccentric exercise, with effect sizes showing moderate significant effects favouring combined SWT and eccentric exercise over eccentric exercise alone after 16 weeks (–0.76,–1.28 to–0.24).

The 2007 study by Rompe et al. [25] also included a wait-and-see group, allowing comparisons to be made between SWT and a no-treatment control. Moderate significant effects were found that favour SWT at 16 weeks (−1.03,–1.62 to–0.44). Two studies [32, 42] evaluated SWT using double-blind, placebo-controlled study designs, with effect sizes indicating similar outcomes. Costa et al. [32] compared SWT directly to application of sham SWT over 12 weeks. There were no significant pain effects favouring either SWT or sham at 12-week follow up (−0.44,–1.01 to 0.13). Although participants were followed up at 12 months, insufficient data was available to calculate effect sizes. Rasmussen et al. [42] investigated differences between SWT and sham SWT as an addition to a conservative therapy program that included eccentric exercise. After four weeks of intervention, no significant effects were found for either group (−0.52,–1.1 to 0.06). There was insufficient data to evaluate longer follow up periods.

Evidence from meta-analysis of data from two studies of higher methodological quality (10 and 12 out of 14) [43, 45] does not support the use of laser therapy (LT) in conjunction with eccentric exercise. Both studies compared LT with sham LT, used in conjunction with eccentric exercise, and evaluated pain outcomes on a VAS over 12 weeks. Pooled data showed no significant effects at 4 weeks (−0.31,–1.88 to 1.26), but significant effects favouring LT were found at 12 weeks (−0.59,–1.11 to −0.07) (Figure 3).

Microcurrent therapy was investigated as an intervention for AT by one study [34] with a methodological quality rating of 8 out of 14. Chapman-Jones and Hill [34] compared a combined intervention of microcurrent therapy and eccentric exercise to eccentric exercise alone. While effect estimates were unable to be calculated, the authors reported significantly greater improvements in pain after 12, 26 and 52 weeks in favour of those receiving microcurrent therapy (p < 0.001).

Braces and splints: Meta-analysis was conducted using data from two studies that evaluated the addition of a night splint to an eccentric exercise program (PEDro scores 9 [47] and 6 [44] out of 14). Pooling of data for pain and function outcomes (VISA-A) showed no significant effects at 12 weeks (−0.35,–1.44 to 0.74).

Two studies investigated the efficacy of a heel brace as an adjunct to eccentric exercise [30, 31]. Both studies had methodological quality ratings of 6 out of 14 and, due to insufficient data provided by Petersen et al. [31], pooling of data was unable to be performed. Effect size calculations for Knobloch et al. [29] showed no significant effects for the addition of a heel brace to an eccentric exercise program at 12 weeks (−0.29,–0.70 to 0.12) (Figure 4). Petersen and colleagues [31] also reported no significant between-group differences over a one-year period.