Cecilie Bartholdy

Evaluation of the Benefit of Corticosteroid Injection Before Exercise Therapy in Patients With Osteoarthritis of the Knee A Randomized Clinical Trial

IMPORTANCE Osteoarthritis (OA) of the knee is the most frequent form of arthritis and a cause of pain and disability. Combined nonpharmacologic and pharmacologic treatments are recommended as the optimal treatment approach, but no evidence supports the recommendation. OBJECTIVE To assess the clinical benefits of an intra-articular corticosteroid injection given before exercise therapy in patients with OA of the knee. DESIGN, SETTING, AND PARTICIPANTS We performed a randomized, blinded, placebo-controlled clinical trial evaluating the benefit of intra-articular corticosteroid injection vs placebo injection given before exercise therapy at an OA outpatient clinic from October 1, 2012, through April 2, 2014. The participants had radiographic confirmation of clinical OA of the knee, clinical signs of localized inflammation in the knee, and knee pain during walking (score >4 on a scale of 0 to 10). INTERVENTIONS Participants were randomly allocated (1:1) to an intra-articular 1-mL injection of the knee with methylprednisolone acetate (Depo-Medrol), 40 mg/mL, dissolved in 4 mL of lidocaine hydrochloride (10 mg/mL) (corticosteroid group) or a 1-mL isotonic saline injection mixed with 4 mL of lidocaine hydrochloride (10 mg/mL) (placebo group). Two weeks after the injections, all participants started a 12-week supervised exercise program. MAIN OUTCOMES AND MEASURES The primary outcome was change in the Pain subscale of the Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire (range, 0-100; higher scores indicate greater improvement) at week 14. Secondary outcomes included the remaining KOOS subscales and objective measures of physical function and inflammation. Outcomes were measured at baseline, week 2 (exercise start), week 14 (exercise stop), and week 26 (follow-up). RESULTS One hundred patients were randomized to the corticosteroid group (n = 50) or the placebo group (n = 50); 45 and 44 patients, respectively, completed the trial. The mean (SE) changes in the KOOS Pain subscale score at week 14 were 13.6 (1.8) and 14.8 (1.8) points in the corticosteroid and placebo groups, respectively, corresponding to a statistically insignificant mean difference of 1.2 points (95% CI, -3.8 to 6.2; P = .64). We found no statistically significant group differences in any of the secondary outcomes at any time point. CONCLUSIONS AND RELEVANCE No additional benefit results from adding an intra-articular injection of 40 mg of corticosteroid before exercise in patients with painful OA of the knee. Further research is needed to establish optimal and potentially synergistic combinations of conservative treatments. TRIAL REGISTRATION clinicaltrialsregister.eu Identifier: 2012-002607-18; clinicaltrials.gov Identifier: NCT01945749.

The role of muscle strengthening in exercise therapy for knee osteoarthritis: A systematic review and meta-regression analysis of randomized trials

OBJECTIVES To analyze if exercise interventions for patients with knee osteoarthritis (OA) following the American College of Sports Medicine (ACSM) definition of muscle strength training differs from other types of exercise, and to analyze associations between changes in muscle strength, pain, and disability. METHODS A systematic search in 5 electronic databases was performed to identify randomized controlled trials comparing exercise interventions with no intervention in knee OA, and reporting changes in muscle strength and in pain or disability assessed as standardized mean differences (SMD) with 95% confidence intervals (95% CI). Interventions were categorized as ACSM interventions or not-ACSM interventions and compared using stratified random effects meta-analysis models. Associations between knee extensor strength gain and changes in pain/disability were assessed using meta-regression analyses. RESULTS The 45 eligible trials with 4699 participants and 56 comparisons (22 ACSM interventions) were included in this analysis. A statistically significant difference favoring the ACSM interventions with respect to knee extensor strength was found [SMD difference: 0.448 (95% CI: 0.091-0.805)]. No differences were observed regarding effects on pain and disability. The meta-regressions indicated that increases in knee extensor strength of 30-40% would be necessary for a likely concomitant beneficial effect on pain and disability, respectively. CONCLUSION Exercise interventions following the ACSM criteria for strength training provide superior outcomes in knee extensor strength but not in pain or disability. An increase of less than 30% in knee extensor strength is not likely to be clinically beneficial in terms of changes in pain and disability (PROSPERO: CRD42014015344).

Changes in ultrasound assessed markers of inflammation following intra-articular steroid injection combined with exercise in knee osteoarthritis: exploratory outcome from a randomized trial

OBJECTIVE Knee osteoarthritis (KOA) is a multifactorial joint disease affecting many people worldwide. Recommended treatments for KOA include exercise and steroid injections, or a combination of these. The objective of this exploratory outcome analysis of a randomized trial was to assess changes in inflammation markers assessed by ultrasound imaging (US) in KOA secondary to intra-articular corticosteroid injection given prior to exercise therapy. DESIGN This study is a sub-study to a larger clinical trial which compared the clinical effects of steroid injection in KOA to placebo injection, both given prior to exercise therapy. The US outcomes were changes from baseline in US-assessed synovial size, Doppler activity presence in the synovial membrane, and numbers of US-detected Bakers cysts. US was performed at baseline, week 14 (exercise stop), and week 26 (follow-up). RESULTS Fifty participants received steroid injection, and 50 received placebo injection. All participants received 12 weeks of exercise. Forty-five and 44, respectively, completed the study. At week 14, the group difference in the change in synovium thickness was 2.2 mm (95%, confidence interval (CI) -0.5 to 4.8), P = 0.11. There were no group differences in the changes in distribution of patients with presence of synovial Doppler activity (P = 0.98) or Bakers cysts (P = 0.35). There were no statistically significant differences between groups at week 26 in any outcome. CONCLUSION Intra-articular steroid injection of KOA-patients prior to a 3 months exercise programme did not reduce synovial hypertrophy, synovial Doppler activity, or Bakers cyst presence more than a placebo saline injection according to US-assessments. TRIAL REGISTRATION EudraCT: 2012-002607-18.

Intra-Articular Corticosteroids in Addition to Exercise for Reducing Pain Sensitivity in Knee Osteoarthritis: Exploratory Outcome from a Randomized Controlled Trial

Objective To assess the effects of one intra-articular corticosteroid injection two weeks prior to an exercise-based intervention program for reducing pain sensitivity in patients with knee osteoarthritis (OA). Design Randomized, masked, parallel, placebo-controlled trial involving 100 participants with clinical and radiographic knee OA that were randomized to one intra-articular injection on the knee with either 1 ml of 40 mg/ml methylprednisolone (corticosteroid) dissolved in 4 ml lidocaine (10 mg/ml) or 1 ml isotonic saline (placebo) mixed with 4 ml lidocaine (10 mg/ml). Two weeks after the injections all participants undertook a 12-week supervised exercise program. Main outcomes were changes from baseline in pressure-pain sensitivity (pressure-pain threshold [PPT] and temporal summation [TS]) assessed using cuff pressure algometry on the calf. These were exploratory outcomes from a randomized controlled trial. Results A total of 100 patients were randomized to receive either corticosteroid (n = 50) or placebo (n = 50); 45 and 44, respectively, completed the trial. Four participants had missing values for PPT and one for TS at baseline; thus modified intention-to-treat populations were analyzed. The mean group difference in changes from baseline at week 14 was 0.6 kPa (95% CI: -1.7 to 2.8; P = 0.626) for PPT and 384 mm×sec (95% CI: -2980 to 3750; P = 0.821) for TS. Conclusions These results suggest that adding intra-articular corticosteroid injection 2 weeks prior to an exercise program does not provide additional benefits compared to placebo in reducing pain sensitivity in patients with knee OA. Trial Registration EU clinical trials (EudraCT): 2012-002607-18

The effects of intra-articular glucocorticoids and exercise on pain and synovitis assessed on static and dynamic magnetic resonance imaging in knee osteoarthritis: exploratory outcomes from a randomized controlled trial

OBJECTIVE The aims of the present knee osteoarthritis (KOA)-study were to: (1) describe and compare the changes in magnetic resonance imaging (MRI)-measures of synovitis following an exercise program preceded by an intra-articular injection of either corticosteroid or isotonic saline and (2) investigate if any of the changes in patient reported outcome measures (PROMs) were associated with changes in MRI-measures of synovitis. DESIGN We performed a randomized, double-blinded, placebo-controlled clinical trial evaluating the effects of intra-articular corticosteroid vs placebo injections given before exercise therapy in KOA-patients. PROMs were assessed using the KOOS (knee injury and osteoarthritis outcome score). Synovitis was assessed on conventional non-contrast-enhanced, conventional contrast-enhanced (CE) and dynamic contrast-enhanced (DCE) MRI. PROMs and MRIs were obtained prior to the intra-articular injection, after termination of the exercise program (week 14-primary time point) and week 26. RESULTS Of 100 randomized participants (50 in each allocation group), 91 had complete MRI-data at baseline (63% female, mean age: 62 years, median Kellgren-Lawrence-grade: 3). There were no statistically significant differences between the two interventions in regards of changes in MRI-measures of synovitis at any time-point. At week 14, we found no statistical significant MRI-explanatory variables of either of the PROMs. CONCLUSIONS The present study does not justify the use of intra-articular corticosteroids over intra-articular saline when combined with an exercise program for reduction of synovitis in KOA. The improvement in pain and function following the intervention with intra-articular corticosteroids/saline and exercise could not be explained by a decrease in synovitis on MRI indicating other pain causing/relieving mechanisms in KOA.

Local and Systemic Changes in Pain Sensitivity After 4 Weeks of Calf Muscle Stretching in a Nonpainful Population: A Randomized Trial

Stretching is often used in clinical practice for a variety of purposes, including pain therapy. The possible mechanism behind the effect of stretching remains to be clarified.

Exercise therapy after ultrasound-guided corticosteroid injections in patients with subacromial pain syndrome: a randomized controlled trial

BackgroundSubacromial pain syndrome (SAPS) accounts for around 50 % of all cases of shoulder pain. The most commonly used treatments are glucocorticosteroid (steroid) injections and exercise therapy; however, despite treatment SAPS patients often experience relapse of their symptoms. Therefore the clinical effect of combining steroid and exercise therapy is highly relevant to clarify. The aim of this randomized controlled trial was to investigate if exercise therapy added to steroid injection in patients with SAPS will improve the effect of the injection therapy on shoulder pain.MethodsIn this two-arm randomized trial running over 26 weeks, patients with unilateral shoulder pain (> 4 weeks) and thickened subacromial bursa (> 2 mm on US) were included. At baseline all participants received two steroid injections into the painful shoulder with an interval of one week. Subsequently they were randomized (1:1) to either 10 weeks exercise of the involved shoulder (intervention group) or exercise of the uninvolved shoulder (control group). The patients were re-examined after the exercise program (at week 13) and again at week 26. The primary outcome assessed after 26 weeks was change in shoulder pain analyzed using the intention-to-treat principle (non-responder imputation).ResultsNinety-nine SAPS patients (58 female) participated (49 intervention/50 control). At both follow up visits (week 13 and 26) no statistically significant between-group differences in pain changes on a visual analog scale (mm) were seen (13 weeks: pain at rest 1.7 (95 % CI –3.6 to 7.0; P = 0.53); pain in activity 2.2 (95 % CI –6.5 to 10.9; P = 0.61), 26 weeks: rest 5.6 (95 % CI –0.9 to 12.1; P = 0.09); activity 2.2 (95 % CI –6.8 to 11.2; P = 0.62). The reduction in pain was most evident in the control group at all four pain measurements. The only difference between groups was seen by US examination at week 13, where fewer participants with impingement were observed in the intervention group compared with the controls (9 vs. 19 participants; P = 0.03).ConclusionExercise therapy in the painful shoulder in SAPS patients did not improve the effectiveness of steroid injections for shoulder pain in patients with unilateral SAPS and enlarged subacromial bursa on US examination.Trial registrationClinicalTrials.gov (NCT01506804). Registration date 5 May 2011.

Test-retest reliability of non-linear methods to assess walking dynamics

The present study investigated the day-to-day reliability (quantified by the absolute and relative reliability) of nonlinear methods that assess human locomotion dynamics. Twenty-four participants completed 5 minutes of treadmill walking at self-selected preferred speed on two separate days. Lower limb kinematics were recorded at 100Hz and hip, knee and ankle joint angles, three dimensional sacrum marker displacement and stride time intervals were extracted for 170 consecutive strides. The largest Lyapunov exponent and correlation dimension were calculated for the joint angle and sacrum displacement data using three different state space reconstruction methods (group average, test-retest average, individual time delay and embedding dimension). Sample entropy and detrended fluctuation analysis were applied to the stride time interval time series. Relative reliability was assessed using intra-class correlation coefficients and absolute reliability was determined by measurement error (ME). The group average state space reconstruction method resulted in the best relative and absolute reliability of the LyE parameter when compared to the individual and test-retest average methods. The detrended fluctuation analysis exhibited good reliability, while sample entropy showed poor reliability. The results comprise a reference material that can inspire and guide future studies of non-linear gait dynamics.The present study investigated the day-to-day reliability (quantified by the absolute and relative reliability) of nonlinear methods used to assess human locomotion dynamics. Twenty-four participants of whom twelve were diagnosed with knee osteoarthritis completed 5 min of treadmill walking at self-selected preferred speed on two separate days. Lower limb kinematics were recorded at 100 Hz and hip, knee, and ankle joint angles, three-dimensional (3D) sacrum marker displacement and stride time intervals were extracted for 170 consecutive strides. The largest Lyapunov exponent and correlation dimension were calculated for the joint angle and sacrum displacement data using three different state space reconstruction methods (group average, test-retest average, individual time delay and embedding dimension). Sample entropy and detrended fluctuation analysis (DFA) were applied to the stride time interval time series. Relative reliability was assessed using intraclass correlation coefficients and absolute reliability was determined using measurement error (ME). For both joint angles and sacrum displacement, there was a general pattern that the group average state space reconstruction method provided the highest relative reliability and lowest ME compared to the individual and test-retest average methods. The DFA exhibited good reliability, while the sample entropy showed poor reliability. The results comprise a reference material that can inspire and guide future studies of nonlinear gait dynamics.

Quadriceps-strengthening exercise and quadriceps and knee biomechanics during walking in knee osteoarthritis: A two-centre randomized controlled trial

Objective: To assess the effect of quadriceps strengthening on quadriceps muscle force, power, and work and tibio‐femoral compressive loads during walking in adults with knee osteoarthritis. Methods: Study design: Two‐center, randomized, controlled trial. Intervention: Patients with knee osteoarthritis were randomly allocated to quadriceps strengthening program (3 times weekly) or no attention control group. Main outcome measures: Primary outcome was change from baseline in peak quadriceps force during walking at 12 weeks. Secondary outcomes included quadriceps power and work, knee compression forces during walking estimated with musculoskeletal modeling, muscle strength and pain and function. Outcomes were measured at baseline and 12 weeks. Results: 30 patients were randomized to receive either training (n = 15) or no attention (n = 15). At follow‐up, there were no statistical differences between groups for maximum quadriceps force, quadriceps positive power, negative work, and positive work, and knee compressive force. Maximum negative quadriceps power in early stance was statistically significantly increased 36% in the training group compared to the control group which was most likely partially a response to faster walking velocity at follow‐up. Muscle strength and patient reported pain and function were improved in the training group compared to the control group. Conclusions: Quadriceps strength training leads to increased muscle strength and improved symptomatic and functional outcomes but does not change quadriceps or knee joint biomechanics during walking. The biomechanical mechanism of improved health with strength training in knee osteoarthritis patients remains unknown. ClinicalTrials.gov Identifier: NCT01538407.

Reliability and Construct Validity of the SENS Motion® Activity Measurement System as a Tool to Detect Sedentary Behaviour in Patients with Knee Osteoarthritis

Physical inactivity is important to address, and an objective way of measuring inactivity is by accelerometry. The objective of this study was to determine the reliability and construct validity of the SENS motion system to record physical activity and inactivity in patients with knee osteoarthritis. Participants with an age > 40 years and an average weekly pain above 0 on a numeric rating scale (0 = no pain, 10 = worst pain) were included. Participants had a total of two study visits and at each visit participants completed a standardized activity. Data from 24 participants were analysed. A mean agreement of 99% (SD 3%) for sedentary behaviour and a mean agreement of 97% (SD 9%) for active behaviour were found. The agreement for “walking” was 28% (SD 18%). Mean agreement between recordings on the two visits was 96% (SD 8%) for sedentary behaviour and 99% (SD 1%) for active behaviour. The SENS motion activity measurement system can be regarded as a reliable and valid device for measuring sedentary behaviour in patients with knee OA, whereas detection of walking is not reliable and would require further work.