Modern Rheumatology ISSN: 1439-7595 (Print) 1439-7609 (Online) Journal homepage: http://www.tandfonline.com/loi/imor20 Exercise therapy in patients with hip osteoarthritis: Effect on hip muscle strength and safety aspects of exercise—results of a randomized controlled trial Benjamin Steinhilber, Georg Haupt, Regina Miller, Pia Janssen & Inga Krauss To cite this article: Benjamin Steinhilber, Georg Haupt, Regina Miller, Pia Janssen & Inga Krauss (2016): Exercise therapy in patients with hip osteoarthritis: Effect on hip muscle strength and safety aspects of exercise—results of a randomized controlled trial, Modern Rheumatology, DOI: 10.1080/14397595.2016.1213940 To link to this article: http://dx.doi.org/10.1080/14397595.2016.1213940 Published online: 03 Aug 2016. Submit your article to this journal View related articles View Crossmark data Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=imor20 Download by: [University of Technology Sydney] Date: 04 August 2016, At: 00:57 http://www.tandfonline.com/imor ISSN 1439-7595 (print), 1439-7609 (online) Mod Rheumatol, 2016; Early Online: 1–10 ß 2016 Japan College of Rheumatology DOI: 10.1080/14397595.2016.1213940 ORIGINAL ARTICLE Exercise therapy in patients with hip osteoarthritis: Effect on hip muscle strength and safety aspects of exercise—results of a randomized controlled trial Benjamin Steinhilber1,2, Georg Haupt1, Regina Miller1, Pia Janssen1, and Inga Krauss1 Downloaded by [University of Technology Sydney] at 00:57 04 August 2016 1 Department of Sports Medicine, University Hospital, Tuebingen, Germany and 2Institute of Occupational Medicine, Social Medicine and Health Services Research, University Hospital, Tuebingen, Germany Abstract Purpose: To evaluate the effect of an exercise therapy concept (the Tübingen exercise therapy approach THüKo) for increasing hip muscle strength (HMS) in patients with hip osteoarthritis (OA), and to investigate whether patients do adhere to the intervention and if there are any adverse events related to the intervention. Methods: A total of 210 hip OA patients (89 females, 121 males) were randomized into a 12-week exercise intervention (THüKo) including group sessions (1/week) and home exercising (2/week), a placebo ultrasound group (1/week) or a control group (no treatment). HMS was measured as isometric peak torque of hip abduction, adduction, flexion, and extension. Adherence to exercise and safety aspects were monitored as additional outcomes. Results: Baseline adjusted post intervention HMS of the THüKo group were higher compared to the control group (differences of 0.11–0.27 Nm/kg, p50.01) and to the placebo ultrasound group (differences of 0.09–0.19 Nm/kg, p50.01). Adherence to exercise was high (about 90%). No subject had to refuse from training because of an exercise related adverse event and exercise related pain was only of intermittent nature without sustainable adverse effects. Conclusions: The Tübingen exercise therapy approach has shown to have a significant positive effect on HMS. Its implementation has shown to be feasible and safe according to the percentage of exercise participation and the absence of sustainable adverse events. Introduction Keywords Dose-response, Gender, Hip, Osteoarthritis, Strength training History Received 1 April 2016 Accepted 10 July 2016 Published online 2 August 2016 joint function [16,17]. Therefore, retaining and increasing HMS is recommended in international guidelines for the management of hip OA [18–20]. These guidelines further recommend introducing patients into exercise programs that can be proceeded autonomously after an initial period with professional support. Such programs may increase long-term adherence to exercise and address the economic burden of therapy costs in hip OA by reducing cost-intensive face to face contacts between therapist and patient [21]. The authors of this article recently reported scientific evidence of the effectiveness of an exercise intervention in terms of selfreported pain reduction and improvement in PF in patients suffering from hip OA [22]. The present article aims for the analysis of the effects of the Tübingen exercise therapy approach (THüKo) on HMS in comparison to sham ultrasound and a nontreated control. Additionally adherence and safety aspects of THüKo were analysed. Patients with hip osteoarthritis (OA) suffer from joint pain [1,2] and exhibit decreased levels of physical function (PF) [3], which result in impairments in quality of life [4,5]. A factor that is suggested to interact with both pain and PF is the strength of the surrounding hip joint muscles. Commonly, patients with hip OA have reduced hip muscle strength (HMS) compared to their contralateral hip joint in case of unilateral hip OA [6] and healthy agematched persons [7,8]. These impairments in HMS are mentioned to be the result of disuse atrophy [6,8], reflex arthrogenous inhibition of muscle contraction [9], and infiltration of noncontractile material such as fat in the muscle [10]. Cross-sectional studies reported an association of low HMS and reduced levels of PF in hip OA [3,11]. A 5-year epidemiologic follow-up study [12] indicated that reduced HMS fosters limitations of daily living. Some authors even consider weak hip muscles as a risk factor for idiopathic hip OA [13,14] similar to knee OA where quadriceps weakness increases the risk for becoming knee OA [15]. Strengthening exercise programs are suggested to be one of the most promising approaches to improve OA-related pain and Materials and methods Participants Correspondence to: Benjamin Steinhilber, Institute of Occupational medicine, Social Medicine and Health Services Research, University Hospital, Wilhelmstrasse 27, 72074 Tuebingen, Germany. E-mail: [email protected] A total of 218 hip OA patients (mean age 58.7 yr, standard deviation (SD) 10 yr; females ¼ 89, males ¼ 129) were recruited between 2010 and 2012 by newspaper advertisements and the outpatient clinic of the University Hospital. Sample size was based Downloaded by [University of Technology Sydney] at 00:57 04 August 2016 2 B. Steinhilber et al. Mod Rheumatol, 2016; Early Online: 1–10 Box 1. Inclusion and exclusion criteria for the study. Study design and study arms Inclusion criteria Age between 18 and 85 years Osteoarthritis (OA) of one or both hip joint(s) (clinical criteria of the American College of Rheumatology) The subject gives voluntary consent to study participation after receiving oral and written information about study content and objectives The subject has the time available to undertake the exercises and attend the measurings The subject is physically fit for the intervention measure (as ascertained during the examination conducted by the principal investigator) ‘‘Fitness’’ in this setting relates to the physical as well as the psychological condition of the subject. (Subjects will not be excluded if they have one hip endoprosthesis, as long as the contralateral hip is affected by osteoarthritis according to the listed criteria.) The subject has capacity to consent Measurements of the prospective study with a test-retest design were taken at baseline (t0) and immediately after the twelve week intervention period (t1). At t0 subjects were randomly assigned to an exercise intervention (Tübinger Hüftkonzept THüKo, the Tübingen exercise therapy approach), a control group receiving no intervention (CG), a placebo ultrasound group (PUG), and an experimental ultrasound group (UG). The rationale for including a placebo control is based on the fact, that placebo interventions in osteoarthritis are effective for pain relieve and improvements in self-reported joint function and stiffness [25]. It was therefore of special interest, if the exercise intervention has superior effects to attention control alone. An experimental ultrasound group with a small sample size was further included for ethical reasons. Randomization was stratified by sex. Allocation concealment was guaranteed by using a sealed opaque envelope that neither the investigators nor the participants were able to view. Patients of PUG and UG were single-blinded to the treatment applied. Randomization ratio of UG was 1:10 compared with the respective other groups. Due to its experimental characteristic, UG was not included into data analysis. Exclusion criteria Unstable anchoring of endoprosthetic hip joint Hip dislocation after endoprosthetic joint replacement Further disorders affecting the lower extremities or lower back that require treatment by a physician/therapist and which are not connected to the OA and are currently being treated The presence of osteoarthritis in several joints (for example, hip and knee) is NOT an exclusion criterion Medication or alcohol misuse Participation in a clinical study in the preceding 4 weeks Lack of compliance Acute illness Use of walking aids Previous trauma in the hip and pelvis area with accompanying development of secondary osteoarthritis Known endocrinological causes of hip osteoarthritis Confirmed metabolic causes of hip osteoarthritis State after aseptic bone necrosis (Perthes’ disease) Cardiocirculatory disorders or other comorbidities that result in severely restricted everyday physical capacity and that are contraindications to physical exertion (for example, heart failure NYHA III–IV, terminal renal failure stage IV) Medical exercise therapy, physiotherapy on resistance machines in the preceding 3 months, with a total treatment frequency of more than six units Systematic group or individual therapy to treat the osteoarthritis (systematic in the sense of a minimum of 1/week for 30 min or more) in the preceding 3 months Physical therapy to treat the osteoarthritis (systematic in the sense of regular, prescribed application at least 1/week) in the preceding 3 months Newly initiated exercise/movement therapy in the preceding 3 months (sports and movement therapy defined as taking place a minimum of 1/week, getting out of breath, minimum duration 30 min) Corticosteroid injection into the hip joint in the preceding 12 months on the subscale bodily pain of the 36-item Short Form questionnaire, which was the primary outcome of this trial [23]. The present article focuses on the secondary outcome HMS of this study. All participating subjects gave their written informed consent and the study received approval from the local ethics committee. The study was registered by the German Clinical Trials Register DRKS00000651. Inclusion criteria were age between 18 and 85 years and OA in at least one hip joint. Further, subjects had to be able to walk safely without walking aids and must have had a stable implantation of the artificial hip joint, if present in the contra lateral hip. Hip OA was assessed according to the clinical criteria of the American College of Rheumatology [24]. Exclusion criteria were the beginning of any kind of exercise or physical therapy within 3 months prior to the present study and any operation at the lower extremities during the last 3 months prior to the present study. A complete list of all in- and exclusion criteria are given in Box 1. Exercise intervention The Tübingen exercise therapy approach (THüKo) comprised 12 supervised institutional group sessions and 24 unsupervised homebased sessions within 12 weeks. The weekly indoor institutional group exercise sessions were supervised by a physical therapist and lasted 60–90 min. The maximum number of participants per group was restricted to 15. The sessions contained physical, social, and cognitive elements. Physical elements aimed for mobilization, strengthening, and improvement of postural control. The 24 home sessions included a progressive exercise program (two sessions per week) with exercises for mobilization, physical perception of movements, balance, and strengthening. Strengthening exercises accounted for about two-third of the training and were well balanced for hip abduction (HAB), hip adduction (HAB), hip flexion (HF), and hip extension (HE) with a progressive increase in exercise intensity throughout the program. All strengthening exercises were performed with the subjects’ own bodyweight, an elastic latex band, a ball, and weight-cuffs (examples are depicted in Figure 1). Some of the strengthening exercises were conducted for each lower extremity separately and some were performed bilaterally. The intensity of exercises was controlled and quantified by the subjects’ subjective rating using the 15 category Borg perceived exertion scale (Borg-Scale) from 6 to 20, where 6 is equivalent to no exertion ‘‘very very light’’ and 20 is equivalent to maximum exertion ‘‘very very hard’’ [26]. In order to enable the participants to exercise with the required exercise intensity throughout the program, exercises were provided with two performance levels (basic and difficult, see Figure 1) [27]. The program included three phases. Phase I was an adaptation phase (weeks one to three), phase II addressed strength endurance (weeks four to eight) and phase III aimed to stimulate improvements in cross-sectional area (weeks nine to twelve). During the adaptation phase subjects should exercise with exercise intensity below 30% of their maximum voluntary contraction (MVC) leading to low levels of perceived exertion. The strength endurance phase (phase II) is characterized by subjects performing exercises with 2–3 series and 20–25 repetitions, corresponding to 30–40% MVC. The third phase includes exercises with 3–4 series and 10–15 repetitions, corresponding to 70% MVC. The percentage MVC is estimated by the number of repetitions that can be conducted appropriately but with a subjective exertion level of at least 14 on the Borg-Scale at the end of each set [22,23]. Exercise therapy in hip OA Downloaded by [University of Technology Sydney] at 00:57 04 August 2016 DOI: 10.1080/14397595.2016.1213940 3 Figure 1. Examples for exercise therapy [27]. Placebo ultrasound The placebo ultrasound group received sham ultrasound onceweekly for 15 min. The transducer was gently moved over the hip region. The used ultrasound gel had no active component and the ultrasound itself was invisibly turned off. Outcome criteria Hip muscle strength (HMS). The Isomed 2000 (D&R GmbH, Hemau, Germany) isokinetic dynamometer was used to measure isometric peak torque for HAB, HAD, HF, and HE. Subjects were placed in a lateral position for HAB/HAD and in a supine position for HF/HE testing. The angles of the isometric measurements were 0 hip abduction for HAB, 20 hip abduction for HAD, 20 hip flexion for HF, and 40 hip flexion for HE. All measurements (prior and after the intervention period) were conducted at the same time of the day to control for circadian variation in performance. Details regarding standardization and procedures of the applied strength measurements are reported by Steinhilber et al. [28]. For each measure of HMS, the mean of both legs was calculated and relativized to subject’s body weight (Nm/kg). Adherence, dosage and safety of the interventions. Subjects of the THüKo had to fill out exercise logs including exercise frequency, duration, perceived exertion, and pain for each home session. The therapist supervising the institutional sessions monitored adherence to the sessions and was asked to report any adverse event in the context of the group sessions and to inquire information on any adverse event in the context of the home exercises. In PUG adherence was monitored by the person who applied the placebo ultrasound. Dosage was pre-specified by the protocol. Adherence was considered as the relation of intended exercise and ultrasound sessions, respectively and the number of completed sessions by all participating subjects. Dosage of exercise was quantified using information on duration, sets and repetitions of exercises and perceived exertion. Safety was quantified by analyzing withdrawals from exercise due to exercise related reasons, reports to the instructor on any adverse event in the context of the group sessions and the home based exercises as well as given information on perceived pain in the context of exercising. Pain levels were assessed before, during, and after exercising using an 11-point numerical rating scale (0– 10), where 0 indicated ‘‘no pain’’ and 10 ‘‘severe pain’’. Anthropometric data. Gender, age, body height, body weight, and body mass index (BMI) were determined. Statistics Data were analyzed by intention-to-treat with the last observation carried forward. Alpha level for statistically significance was set to 0.05. Normal distribution was rated according to histograms, normal quantile plots, skewness and curtosis for all metric variables. Statistical analyses were done using JMP 10.0.0 software (SAS Inc., Cary, NC). Group differences at baseline were tested by the Kruskal–Wallis Test. An analysis of covariance (ANCOVA) was used to evaluate changes between experimental groups in each isometric peak torque measure from t0 to t1. Baseline peak torque values were used as covariates [29] and group as well as the interaction term group*baseline peak torque was included in the statistical model as independent factors. Tukey–Kramer HSD (honestly significant difference) tests were used for post-hoc comparison in case of significant model effects. Differences of the adjusted post values between the experimental groups were expressed in percent (Equation 1): Equation 1: Calculation of percentage differences between adjusted post values of different groups. xGroupA xGroupB 100: ðxGroupA þ xGroupB Þ=2 Effect sizes (ES) were calculated according to Cohen [30] between all experimental groups (Equation 2). 4 B. Steinhilber et al. Mod Rheumatol, 2016; Early Online: 1–10 Equation 2: Calculation of effect sizes and pooled SD. ES ¼ ðx2 x1 ÞGroupA ðx2 x1 ÞGroupB SDpooled ; SDpooled sffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi ðnGroupA 1ÞSD2GroupA þ ðnGroupB 1ÞSD2GroupB , ¼ nGroupA þ nGroupB 2 Downloaded by [University of Technology Sydney] at 00:57 04 August 2016 where x2 is the non-adjusted mean value after the intervention period (t1) and x1 is the baseline (t0) mean value. SDpooled was calculated with SD values from the non-adjusted values at baseline. In addition, an exploratory data analysis was performed by a descriptive statistical approach to examine possible differences between male and female subjects. Therefore, the adjusted post values of the four isometric peak torque measures (which can be obtained by gender specific ANCOVA as described above) were given as mean percentage difference between experimental groups for male and female subjects separately. Adherence to exercise for the whole sample and each gender separately was quantified in a descriptive manner by evaluating the exercise logs regarding training frequencies, as well as medians and the first and third quartiles for subjective exhaustion after exercise and perceived pain. Figure 2. Dropout flow-chart. Exercise therapy in hip OA DOI: 10.1080/14397595.2016.1213940 Table 1. Characterization of the study population. Variable Group Mean (SD) n THüKo CG PUG THüKo CG PUG THüKo CG PUG THüKo CG PUG THüKo CG PUG 70 68 70 58 ± 19 60 ± 9 58 ± 10 80 ± 14 82 ± 13 83 ± 17 173 ± 9 173 ± 9 174 ± 10 27 ± 4 27 ± 3 27 ± 4 Age (yr) Body weight (kg) Body height (cm) Downloaded by [University of Technology Sydney] at 00:57 04 August 2016 BMI (kg/m2) 5 statistically significant difference between PUG and CG, the gender-specific analysis was not applied (Figure 3). Baseline group differences* Adherence and dosage of interventions n.s. n.s. n.s. n.s. THüKo: exercise group following the Hip Concept Tübingen; CG: control group; PUG: placebo ultrasound group; BMI: body mass index; SD: standard deviation; n.s.: not statistically significant. *Group differences were tested by the Kruskal–Wallis test. Results Dropouts and extreme values Figure 2 shows dropouts and reasons for dropouts. 210 subjects were randomly allocated to the experimental groups THüKo, CO, and PUG. Therefore, two subjects could not be analyzed because of missing values at t0: one subject in the THüKo group was not able to perform maximum peak torque measurements at t0 due to its physical condition after obstruction of the intestines, and one subject of the PUG was lost for data analysis due to failed storing of the measurement results at t0. 15 subjects were analyzed intention-to-treat because of non-participation at t1. The characteristics of the finally analyzed population (n ¼ 208) are shown in Table 1. Effects on hip muscle strength Baseline strength values, which were not normally distributed, were similar between all experimental groups. The residuals of each HMS measure were normally distributed and the interaction term group*baseline peak torque had no effect. The data therefore comply with the requirements to perform the ANCOVA. Table 2 illustrates HMS values for t0 and t1. The ANCOVA revealed statistically significant increased HMS of the THüKo group compared to CG and PUG in the adjusted peak torque values at t1 for all muscle groups (differences ranged from 7 to 15% (p50.01)). The differences in HF and HE between the THüKo group and CG were slightly higher than between the THüKo group and PUG (Table 2). No statistically significant differences were found between PUG and CG. Effect sizes indicate a medium effect of the exercise intervention. Additionally, a small effect of sham ultrasound appeared in two isometric peak torque measures (Table 3). The mean percentage change in HMS (Nm/kg) for male and female subjects from the THüKo group showed strength improvements for both genders compared to CG and PUG. However, the effect of the THüKo intervention on HMS seemed to be more pronounced in male subjects. Males from the THüKo group increased HMS by 11 and 10% compared to male subjects from CG and PUG while HMS in female subjects increased 9 and 4% compared to CG and PUG, respectively. Since there was no A total of 64 of 70 subjects completed the ultrasound program with an adherence of 92%. 65 of 70 subjects from the THüKo group completed the exercise program. Adherence (n ¼ 70) to the group sessions was 89% (males 90%, females 89%). According to the exercise logs, adherence to the home-based exercise program was 91% (males 95%, females 88%). Exercise logs further indicated that subjects were able to exercise with the required exercise intensity with low levels of perceived exertion during phase I and higher levels of perceived exertion during phase II and III. Males and females documented similar exertion levels in all phases (Table 4). Safety No participant of the THüKo group had to withdraw from the program due to exercise related adverse events. Overall, lowmedian pain levels during exercising increased throughout the 12-week intervention period (phase I ¼ 1, phase II ¼ 2, phase III ¼ 3). In contrast, median pain levels directly before and after exercising decreased from three in phase I to two in phases II and III. In males the median pain level in phase I was 1 and in phase II and III it was 2. Females reported a median pain level of 1 in phase I, 3 in phase II and 4 during phase III (Table 4). Discussion The aim of this randomized controlled clinical trial was to investigate the effect of an exercise therapy program (the Tübingen exercise therapy approach THüKo) with a substantial part of home-based strengthening exercises on hip muscle strength (HMS) in comparison to a non-treated control group (CG) and a sham ultrasound group (PUG). Additionally, a report on adherence to exercise and on safety aspects was provided. The results show a statistically significant increase of HMS in the THüKo group. Baseline adjusted peak torque values were 7– 15% higher compared to CG and PUG. Although not tested for statistical significance, increases in HMS were more pronounced in male subjects. The study design of this trial has a lot in common with a study from Bennell et al. They recently published data of a twelve week individualized multimodal physiotherapeutic intervention for patients with hip OA [31]. Aside of manual therapy techniques, education and advice in the context of 10 supervised sessions, four to six home exercises for strengthening, stretching and range of motion, as well as functional balance and gait drills were part of the program. Patients were introduced into the home exercises by supervised physiotherapeutic sessions and were then asked to continue autonomously at home four times a week. Three sets of hip abductor and quadriceps strengthening should be carried out in each training session and could be supplemented by another strengthening exercise for hip extensors and/or hip rotators [31,32]. Effects of this physiotherapeutic program were compared to a sham ultrasound treatment for the hip joint (once a week for twelve weeks with duration of 15 min). Both interventions reduced self-reported pain and improved PF. However, the effect of the active intervention was not superior to the effect induced by sham ultrasound which raises questions about the additional effect of a multimodal physiotherapeutic treatment as an active agent in comparison to attention control alone. In this regard, it has to be mentioned that the active intervention induced no statistically significant increase in muscle strength. By the authors own 0.83 p50.0001 0.82 p50.0001 0.80 p50.0001 0.83 p50.0001 1.68 (0.68) 1.61 (0.70) 0.08 (0.30) 1.69 (1.61–1.76) 1.18 (0.34) 1.14 (0.34) 0.03 (0.16) 1.15 (1.12–1.18) 1.25 (0.43) 1.28 (0.46) 0.03 (0.20) 1.34 (1.29–1.39) 1.28 (0.36) 1.28 (0.40) 0.00 (0.16) 1.30 (1.26–1.35) CG mean (SD) 1.87 (0.64) 1.86 (0.64) 0.01 (0.29) 1.76 (1.69–1.83) 1.21 (0.31) 1.20 (0.32) 0.01 (0.13) 1.18 (1.15–1.21) 1.37 (0.41) 1.38 (0.42) 0.02 (0.22) 1.34 (1.29–1.39) 1.33 (0.38) 1.33 (0.40) 0.00 (0.16) 1.31 (1.27–1.35) PUG mean (SD) 1.74 (0.77) 1.93 (0.87) 0.19 (0.33) 1.95 (1.88–2.03) 1.17 (0.29) 1.26 (0.33) 0.08 (0.14) 1.27 (1.23–1.30) 1.33 (0.48) 1.46 (0.49) 0.13 (0.22) 1.45 (1.40–1.50) 1.31 (0.41) 1.42 (0.44) 0.11 (0.19) 1.42 (1.38–1.46) THüKo mean (SD) 0.27 (0.14–0.39) 0.12 (0.06–0.17) 0.11 (0.02–0.19) 0.12 (0.05–0.18) mean (CI) 15 9 8 8 % difference THüKo–CG p50.001 p50.001 0.007 p50.001 p Value 0.19 (0.07–0.32) 0.09 (0.03 – 0.14) 0.11 (0.03–0.19) 0.11 (0.04–0.18) mean (CI) 10 7 8 8 % difference THüKo – PUG p50.001 0.002 0.006 p50.001 p Value 0.07 (0.05–0.20) 0.03 (0.03–0.09) 0.00 (0.09–0.08) 0.00 (0.07–0.07) mean (CI) 5 2 0 0 % difference PUG–CG 0.339 0.447 0.997 0.996 p Value B. Steinhilber et al. THüKo: exercise group following the Hip Concept Tübingen; CG: control group; PUG: placebo ultrasound group; ANCOVA: analysis of covariance; SD: standard deviation; 95%CI: confidence interval. *Differences in baseline values between groups were not statistically significant. **Baseline adjusted post-intervention values. Hip extension (Nm/kg) baseline* Post-intervention change (post baseline) ANCOVA** Hip flexion (Nm/kg) baseline* Post-intervention change (post baseline) ANCOVA** Hip adduction (Nm/kg) baseline* Post-intervention change (post baseline) ANCOVA** Hip abduction (Nm/kg) Baseline* Post-intervention change (post baseline) ANCOVA** ANCOVA r2 adj. p Value Table 2. Isometric hip muscle peak torque between the experimental groups. Downloaded by [University of Technology Sydney] at 00:57 04 August 2016 6 Mod Rheumatol, 2016; Early Online: 1–10 Exercise therapy in hip OA DOI: 10.1080/14397595.2016.1213940 Table 3. Effect sizes of hip muscle strength between the experimental groups. Isometric peak ES ES ES torque measure (THüKo and CG) (THüKo and PUG) (PUG and CG) Hip Hip Hip Hip abduction adduction flexion extension 0.3 0.2 0.4 0.4 0.3 0.3 0.3 0.3 0 0 0.1 0.1 Downloaded by [University of Technology Sydney] at 00:57 04 August 2016 THüKo: exercise group following the Hip Concept Tübingen; CG: control group; PUG: placebo ultrasound group; ES: effect size: 0.1 ¼ small effect, 0.3 ¼ medium effect, 0.5 ¼ large effect. Figure 3. Differences in experimental groups for male and female hip OA patients. THüKo: the Tübingen exercise therapy approach; m: males; f: females. admission, the combination of several exercise modalities reduced the dose of each of them. As such, the dosage of the applied exercises seemed to be too low to stimulate strength adaptations and superior treatment effects compared to placebo ultrasound [31,33]. In contrast, results of the present study show that exercise dosage was sufficient to improve HMS. Furthermore, the effects on pain and PF exceeded the effects by the sham ultrasound treatment [22]. This finding underlines the importance of an adequate composition and dosage of exercise therapy programs. Three aspects may be responsible for the differences in strength adaptations between the present study and the study by Bennell et al. (1) Low quality of exercise performance and low intensity can reduce the stimulus on target muscle and mitigate the impact of an exercise on strength adaptations [34,35]. The exercises applied in the present study were preliminary evaluated in a pilot study [28]. Subjects tended to exercise with an insufficient intensity. Consequently, in the present study, efforts were increased to support subjects’ motor learning in order to perform exercises with high performance quality and to support subjects’ ability to rate and adapt exercise intensity on the basis of perceived exertion. Patients were precisely introduced into the exercises during the group-based sessions and the first three weeks of home training focused on low intensity exercises to allow motor learning. We therefore hypothesized that subjects of the present study had a higher standard in exercise performance and were more compliant to the given exercise requirements. Subsequently, exercise 7 instructions, motor learning and control of exercise intensity seem to be important for an effective strengthening intervention program. (2) Aside of movement quality and exercise intensity, frequency and amount of exercises are relevant aspects of exercise dosage. Frequency of strengthening exercises was higher in the study of Bennell et al. [31] with four weekly home sessions in comparison to one group-based session and two home-based sessions in the THüKo program. However, adherence to exercise was higher in our study (91% compared to 85%) and the amount of exercises throughout the study period was larger as well: A rough estimate indicates that each subject of the study by Bennell et al. performed about 1500 repetitions for each target muscle or muscle group. The overall amount of repetitions including all exercises was about 3000 repetitions [31]. Subjects of the present study performed a similar amount of repetitions per muscle group (about 1300), but a distinctively greater overall amount (about 6000 repetitions). Since the repetitions per exercise for a given muscle group were comparable between the two studies, it is remarkable that an increase in muscle strength only occurred in the present study. The higher overall amount of exercise repetitions might account for this difference. Exercises for a target muscle simultaneously co activate other muscles [36,37]. Therefore, subjects from the THüKo group may have gained from additional stimuli by muscle co activation provided by the high overall amount of exercise repetitions. (3) Half of the applied exercises in the study by Bennell et al. [31] did not directly address the hip muscles. In contrast, exercises of THüKo specifically focused on the muscles surrounding the hip joint. Studies demonstrated that all major hip muscles are affected by hip OA [8,34,38]. Therefore, it seems reasonable that impaired HMS is more adequately addressed by joint specific exercises. At this point, it cannot be evaluated whether higher quality, intensity control, frequency, amount or specification of exercises improved exercise effectiveness in the present study. The results of these two studies illustrate the shortcomings of the current literature in exercise therapy for hip OA. Although strength training is recommended as first-line treatment in hip OA its optimum dosage (type, intensity, frequency, duration) still has to be defined [39] and in order to increase complexity of this issue it has to be mentioned that people may respond differently to the very same exercise intervention. In this regard French et al. conducted a secondary analysis of data from a multicenter randomized controlled trial to identify potential predictors of response to exercise therapy with or without adjunctive manual therapy in patients with hip OA [40]. Although French and colleagues failed to identify predictors, secondary analyses of trials with adequate sample sizes may provide hints or at least research hypotheses in order to further improve person-tailored exercise therapy programs in hip OA. The explorative analysis of gender effects indicated a more pronounced effect of the exercise intervention on HMS in male subjects. This could be partly explained by findings from exercise logs. Males of the THüKo group reported 7% higher adherence to home exercising and less perceived pain than female subjects. However, this minor incongruence between males and females might not be the only reason attributable to greater strength improvements in males. Häkkinen et al. found a positive correlation of serum testosterone levels and changes in maximal strength of the knee extensor muscles during a 6-month strength training in two groups of women (age 40 and 70). They concluded that a low level of testosterone, especially in older women, might be a factor that limits strength development [41]. In general higher age is reported to be a significant factor related to less adaptation to resistance exercises [42,43] and might be pronounced in female subjects at the age of menopause. On average, female subjects 8 B. Steinhilber et al. Mod Rheumatol, 2016; Early Online: 1–10 Table 4. Exercise modalities and outcomes of the exercise logs of the home-based strengthening exercises. Phase I Phase II Phase III Downloaded by [University of Technology Sydney] at 00:57 04 August 2016 Exercise modalities of strengthening exercises Week Sessions per week Exercises per session Sets per exercise Repetitions per exercise Exercise intensity (Borg value at the end of a set) Results from exercise logs Perceived exertion (Borg value: 6–20) Q3 Median Q1 Median male Median female Pain before exercising (0–10) Q3 Median Q1 Pain after exercising (0–10) Q3 Median Q1 Pain during exercising (0–10) P75 Median P25 Median male Median female Phase I adaptation Phase II strength endurance PhaseIII cross-sectional area 1–3 2 9–10 1 30 – 4–8 2 4 2–3 20–25 14 9–12 2 4 3–4 10–15 14 1 2 10 1 30 – 2 2 9 1 30 – 3 2 10 1 30 – 4 2 4 2 20 14 5 2 4 2 25 14 6 2 4 3 20 14 7 2 4 3 25 14 8 2 4 3 25 14 9 2 4 3 15 14 10 2 4 3 15 14 11 2 4 4 10 14 12 2 4 4 10 14 11 9 7 9 11 16 14 12 14 14 16 15 13 15 14 11 9 7 9 9 12 9 7 9 11 12 10 8 9 11 15 13 12 14 13 16 14 12 14 14 16 14 12 14 13 16 14 13 15 14 16 14 13 15 14 17 14 13 15 14 17 15 13 15 15 17 14 13 15 14 16 14 13 14 15 4 3 1 3 2 1 4 2 1 4 2 2 4 3 1 4 3 1 3 2 1 4 2 1 4 2 1 3 2 1 3 2 1 4 2 1 4 2 1 4 2 1 4 2 1 4 3 2 4 2 1 4 2 1 4 3 2 4 3 1 4 2 2 4 3 2 4 2 1 4 2 1 4 2 1 4 2 2 4 3 2 4 2 1 4 3 1 5 2 1 3 1 0 1 1 4 2 1 2 3 4 3 1 2 4 2 1 0 1 0 2 1 0 1 1 3 1 0 1 2 4 3 1 2 3 4 3 1 2 3 4 2 0 2 2 4 2 0 2 3 4 2 0 2 3 4 3 1 2 4 5 2 0 2 4 5 3 0 2 4 5 3 1 2 4 Q1: first quartile; Q3: third quartile. from the THÜKo group were 5 years older than male subjects. Therefore, different testosterone levels and age may contribute to lower effects of the intervention on HMS in female subjects. These finding have to be considered with caution since the study was not specifically designed to evaluate effects of THüKo between male and female subjects. Nonetheless, sex-related responses to exercise therapy in OA patients should be considered in future research projects because they may imply gender-specific therapeutic concepts as already indicated in two previous reviews on exercise therapy in knee OA [44,45]. Finally, we want to comment on the safety of the intervention. Only few data are available on safety aspects of exercise interventions in OA. It can generally be assumed that exercise is a safe treatment option with only few contra-indications that are mainly related to co-morbidities. Pain may increase, especially at the beginning of the intervention period and falls may occur while exercising, especially in person with reduced postural control and gait disturbances [46,47]. In our study, no sustainable adverse event was reported and no subject had to refuse from training because of an exercise related adverse event. Low-pain levels during exercising slightly increased throughout the exercise program, whereas pain levels before and after exercising slightly decreased. Almost exclusively, median pain levels during exercise were lower than pre- and post-exercise measures. Pain levels can be classified as low since subjects were not restricted from training. Aside of this general assumption, monitored increases in pain during the progressive exercise program may be related to higher exercise intensity which also increased throughout the home exercises. This has to be considered when informing participants about potential pain experiences during exercising. Subjects of the present study were given three hierarchically ordered recommendations to cope with notably increased pain during exercising: (1) Subjects should maintain repetitions and intensity but the exercise should be performed in a different body posture as provided by the exercise program. (2) If no mitigation of pain could be achieved by (1), subjects should reduce exercise intensity. (3) If exercising was still too painful this exercise should be removed from the current session. In any case the therapist who instructed the group sessions had to be contacted in order to control exercise performance or provide an alternative exercise. We cannot report how often subjects applied these recommendations as this was not monitored in detail. However, this procedure has face validity to be a helpful tool for hip OA patients to cope with pain during exercise. Conclusion The Tübinger Hip concept—a 12-week exercise intervention specifically designed for patients with hip OA—can increase hip muscle strength with superior effects in comparison to a nontreated control and a placebo ultrasound group. Its safety was demonstrated and it can therefore be concluded, that a wellinstructed exercise programs is safe and feasible. This statement has to be limited to patients that do not need gait aids. This study underlines the importance of training programs focusing on strengthening exercises in the treatment of hip OA. Further research is needed to evaluate predictors for exercise effectiveness such as gender aspects in order to provide person-tailored exercise therapy concepts. Acknowledgements The authors thank Artzt company for providing the exercise materials. Conflict of interest The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article. 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