Abstract: We included 32 trials (1836 participants). No trial compared a combination of manual therapy and exercise versus placebo or no intervention. Seven trials compared a combination of manual therapy and exercise versus other interventions but were clinically heterogeneous, so opportunities for meta-analysis were limited. The overall impression gained from these trials is that the few outcome differences between interventions that were clinically important were detected only up to seven weeks. Evidence of moderate quality shows that a combination of manual therapy and exercise for six weeks probably results in less improvement at seven weeks but a similar number of adverse events compared with glucocorticoid injection. The mean change in pain with glucocorticoid injection was 58 points on a 100-point scale, and 32 points with manual therapy and exercise (mean difference (MD) 26 points, 95% confidence interval (CI) 15 points to 37 points; one RCT, 107 participants), for an absolute difference of 26% (15% to 37%). Mean change in function with glucocorticoid injection was 39 points on a 100-point scale, and 14 points with manual therapy and exercise (MD 25 points, 95% CI 35 points to 15 points; one RCT, 107 participants), for an absolute difference of 25% (15% to 35%). Forty-six per cent (26/56) of participants reported treatment success with manual therapy and exercise compared with 77% (40/52) of participants receiving glucocorticoid injection (risk ratio (RR) 0.6, 95% CI 0.44 to 0.83; one RCT, 108 participants), with an absolute risk difference of 30% (13% to 48%). The number reporting adverse events did not differ between groups: 56% (32/57) reported events with manual therapy and exercise, and 53% (30/57) with glucocorticoid injection (RR 1.07, 95% CI 0.76 to 1.49; one RCT, 114 participants), with an absolute risk difference of 4% (-15% to 22%). Group differences in improvement in overall pain and function at six months and 12 months were not clinically important. We are uncertain of the effect of other combinations of manual therapy and exercise, as most evidence is of low quality. Meta-analysis of two trials (86 participants) suggested no clinically important differences between a combination of manual therapy, exercise, and electrotherapy for four weeks and placebo injection compared with glucocorticoid injection alone or placebo injection alone in terms of overall pain, function, active range of motion and quality of life at six weeks, six months and 12 months (though the 95% CI suggested function may be better with glucocorticoid injection at six weeks). The same two trials found that adding a combination of manual therapy, exercise and electrotherapy for four weeks to glucocorticoid injection did not confer clinically important benefits over glucocorticoid injection alone at each time point. Based on one high quality trial (148 participants), following arthrographic joint distension with glucocorticoid and saline, a combination of manual therapy and supervised exercise for six weeks conferred similar effects to those of sham ultrasound in terms of overall pain, function and quality of life at six weeks and at six months, but provided greater patient-reported treatment success and active shoulder abduction at six weeks. One trial (119 participants) found that a combination of manual therapy, exercise, electrotherapy and oral non-steroidal anti-inflammatory drug (NSAID) for three weeks did not confer clinically important benefits over oral NSAID alone in terms of function and patient-reported treatment success at three weeks. On the basis of 25 clinically heterogeneous trials, we are uncertain of the effect of manual therapy or exercise when not delivered together, or one type of manual therapy or exercise versus another, as most reported differences between groups were not clinically or statistically significant, and the evidence is mostly of low quality. The best available data show that a combination of manual therapy and exercise may not be as effective as glucocorticoid injection in the short-term. It is unclear whether a combination of manual therapy, exercise and electrotherapy is an effective adjunct to glucocorticoid injection or oral NSAID. Following arthrographic joint distension with glucocorticoid and saline, manual therapy and exercise may confer effects similar to those of sham ultrasound in terms of overall pain, function and quality of life, but may provide greater patient-reported treatment success and active range of motion. High-quality RCTs are needed to establish the benefits and harms of manual therapy and exercise interventions that reflect actual practice, compared with placebo, no intervention and active interventions with evidence of benefit (e.g. glucocorticoid injection).

Plain-language summary: This summary of an updated Cochrane review presents what we know from research about the benefits and harms of manual therapy and exercise in people with frozen shoulder. After searching for all relevant studies published up to May 2013, we included 32 trials (1836 participants). Among the included participants, 54% were women, average age was 55 years and average duration of the condition was six months. The average duration of manual therapy and exercise interventions was four weeks. —manual therapy and exercise compared with glucocorticoid (a steroid that reduces inflammation) injection into the shoulder Pain (higher scores mean worse pain) People who had manual therapy and exercise for six weeks did not improve as much as people who had glucocorticoid injection—improvement in pain was 26 points less (ranging from 15 to 37 points less) at seven weeks (26% absolute less improvement). • People who had manual therapy and exercise rated their change in pain score as 32 points on a scale of 0 to 100 points. • People who had glucocorticoid injection rated their change in pain score as 58 points on a scale of 0 to 100 points. Function (lower scores mean better function) People who had manual therapy and exercise for six weeks did not improve as much as people who had glucocorticoid injection—improvement in function was 25 points less (ranging from 15 to 35 points less) at seven weeks (25% absolute less improvement). • People who had manual therapy and exercise rated their change in function as 14 points on a scale of 0 to 100 points. • People who had glucocorticoid injection rated their change in function as 39 points on a scale of 0 to 100 points. Treatment success 31 fewer people out of 100 rated their treatment as successful with manual therapy and exercise for six weeks compared with glucocorticoid injection—31% absolute less improvement (ranging from 13% to 48% less improvement). • 46 out of 100 people reported treatment success with manual therapy and exercise. • 77 out of 100 people reported treatment success with glucocorticoid injection. Side effects Out of 100 people, three had minor side effects such as temporary pain after treatment with manual therapy and exercise for six weeks compared with glucocorticoid injection. • 56 out of 100 people reported side effects with manual therapy and exercise. • 53 out of 100 people reported side effects with glucocorticoid injection. Evidence of moderate quality shows that the combination of manual therapy and exercise probably improves pain and function less than glucocorticoid injection up to seven weeks, and probably does not result in more adverse events. Further research may change the estimate. Low-quality evidence suggests that (1) the combination of manual therapy, exercise and electrotherapy (such as therapeutic ultrasound) may not improve pain or function more than glucocorticoid injection or placebo injection into the shoulder, (2) the combination of manual therapy, exercise, electrotherapy and glucocorticoid injection may not improve pain or function more than glucocorticoid injection alone and (3) the combination of manual therapy, exercise, electrotherapy and oral non-steroidal anti-inflammatory drug (NSAID) may not improve function more than oral NSAID alone. Further research is likely to change the estimate. High-quality evidence shows that following arthrographic joint distension, the combination of manual therapy and exercise does not improve pain or function more than sham ultrasound, but may provide greater patient-reported treatment success and active range of motion. Further research is very unlikely to change our confidence in the estimate of effect. No trial compared the combination of manual therapy and exercise versus placebo or no intervention.