Thousands of ESWT for NCST are currently performed in Europe [12
], even if the available evidence does not support the use of this technique with this indication [10
]. Because of the small number of studies on this topic and the few application protocols tested up to now [11
], we re-evaluated the efficacy of low energy ESWT for NCST using a new protocol. Indeed, it has been clearly demonstrated that different protocols considerably modify the success rate of ESWT [22
For the first time, we have demonstrated that patients suffering from NCST may benefit from ESWT. Our findings showed a significant CMS improvement in the ESWT but not in the control group six and twelve weeks after treatment. Furthermore, significant CMS differences between the groups at follow-up were also noted. The ESWT was found to be safe and well tolerated by the patients.
The best evidence for new treatments usually comes from randomized, placebo-controlled, double-blind studies and our work tried to provide compelling evidence that ESWT is effective in NCST. Our protocol included random sequence generation, allocation concealment, and blinding. A great effort was made to mask the real ESWT in order to eliminate subjective bias on the part of both experimental subjects and the experimenters. Indeed, the ESWT masking appeared less than optimal in previous similar studies [11
]. Because the minimum effect size of the CMS is not known [23
], we considered a clinically significant response a 30-point increase in the CMS [11
] which is considerably higher than the values chosen by others to evaluate ESWT [22
]. However, it should be noted that the 30-point difference it’s an arbitrary cut-off, not derived from research evidence. Interestingly, the study achieved a 100% rate of follow-up of patients, notwithstanding the presence of the placebo group.
Some limitations of the present investigation should also be acknowledged. The small sample size may have increased the risk of an underpowered randomized controlled trial. However, the differences in the CMS scores both within the ESWT group and between treatment groups at final follow-up were highly significant and the power analysis supported these findings, despite the small number of patients per group. Studies are considered to be adequately powered when there is about an 80% probability the study would show a treatment effect if it is present [24
The short-term follow-up may have limited the generalizability of our study, even if the same follow-up interval was used previously in similar ESWT trials [11
]. Notably, the short follow-up was useful to define the direct effects of ESWT on the clinical course of the condition and on the morphology of the supraspinatus tendon. Indeed, with a longer follow-up there might have been confusion between the effects of the treatment and spontaneous changes. A further restriction to increase the length of follow-up was the consideration that it is ethically and psychologically difficult to obtain informed consent to enter a study from patients presenting with chronic pain. The longer the duration of the study, the fewer are the individuals that would accept the possibility of receiving a sham treatment while suffering pain. Moreover, it should be noted that alternatives therapies are available to treat supraspinatus tendinopathy [3
], and when treatments for a disorder already exist, it could be argued that it is unethical to create a placebo group that will receive no treatment at all. A different study design should be proposed to evaluate ESWT over a longer period.
The demonstration of ESWT efficacy in the short-term period is still a valuable finding of this investigation. Indeed, previous studies showed satisfactory outcomes in the short-term after other conservative therapies such as physical therapy [26
] or subacromial cortisone injection [27
]. However, we showed an higher improvement of CMS in comparison to the values reported by others treating the supraspinatus tendinopathy with ultrasounds or rehabilitation program with the same follow-up [26
]. As for the corticosteroids, there is reasonably strong evidence that cortisone injection causes deleterious effects on the tendon and the outcomes deteriorates over time [30
]. Indeed, the continued use of a local corticosteroid is discouraged [31
]. On the contrary, no detrimental effects of ESWT for shoulder pain in the long-term period have been reported [32
] and this treatment could eventually be repeated in case of recurrence of symptoms.
Our data are in keeping with the results of a recent study reporting significant increase in function and reduction of pain after low or high-energy ESWT in patients with NCST [12
]. But our findings do not agree with the only two existing randomized, controlled studies that analyzed the efficacy of ESWT in NCST [11
]. Indeed, Schmitt and colleagues reported significant CMS improvements both in low energy ESWT and in the placebo group three months after treatment, but no difference in CMS between the groups was noted [11
], therefore shock waves were not recommended for NCST. However, in this study the method for administration of local anaesthetic involved use of a large bolus in the subacromial region (i.e. 10 cc of mepivacaine) and certain dosages of local anaesthetic are considered to be therapeutic [27
]. Further weakness in the sham design and the method of assessment of the supraspinatus tendon with either MRI or ultrasounds must be considered. The trial by Speed [13
] analyzed medium-energy ESWT in comparison with a placebo treatment for non-calcific tendinopathy of the rotator cuff, and confirmed the findings of Schmitt three months after the completion of therapies. However, some weakness appears also in this study due to the sham design. In the placebo group, the treatment head was deflated and contact with the skin was avoided, and no local anaesthesia was used. Since shockwaves may cause pain and discomfort, the ESWT masking here is less than optimal. Notwithstanding the limitations of these studies, any comparison with our findings is difficult because of the several variables that define the application parameters of ESWT. The shock wave generator, the number of impulses, the focusing of the shockwave with respect to the tendon insertion, the number and the interval between each treatment session, all are important factors that have to be carefully considered [6
]. It is possible that different treatment regimens may be more effective than others [22
] and, to our knowledge, the treatment protocol we used has not been utilized previously in a similar clinical setting.
Notably, to overcome at least in part the limitation of a short-term follow-up we performed a recall of patients nine years after treatments and an high satisfaction rate with treatment received together with a low recurrence of shoulder pain was noted.
We reported a successful treatment in 22% of our patients in the placebo group. This finding could be explained by the placebo effect rather than by the injection of a local anesthetic used to mask the treatment. Indeed, it is unlikely that a small dosage of local anesthetic into the subcutaneous fat of the shoulder would have a therapeutic effect. In fact, it was previously demonstrated that only higher dosages of this drug injected above the subacromial space are effective in the treatment of chronic rotator cuff tendinopathy [27
]. It should be noted that the regression to the mean due to the spontaneous improvement or fluctuations in symptoms can lead to a false impression of the placebo effect [34
One controlled prospective randomized trial on ESWT for calcifying tendinopathy of the rotator cuff has demonstrated that focusing the shock waves on the calcified area rather than on the insertion of the supraspinatus tendon is more effective [35
], but no data are available regarding the best area to focus the shock waves in NCST. We focused the shock waves at an area one cm proximal to the insertion of the tendon in the bone where areas of avascularity have been described [36
]. It has still not been determined whether vascular changes occur or are associated with rotator cuff pathology [39
], however, experimental studies have demonstrated that shockwaves improve the blood supply to the tendon tissue throughout a neovascularization process [40
] and low energy ESWT modulates the synthesis of nitric oxide [41
], a molecule that plays a critical role in the regulation of vascular tone, angiogenesis [42
], and in the degeneration of the tendon [43
]. Recently, it has been suggested that shock waves behave fairly differently according to the clinical phase of the disease, even reducing the pathological angiogenesis associated with rotator cuff disease [46
]. Further therapeutic mechanisms of ESWT in the treatment of tendinopathies have been hypothesized. ESWT have been shown to promote healing of tendinopathies by inducing TGF-beta1 and IGF-I [47
]. However, the therapeutic mechanism of shock waves in the treatment of supraspinatus tendinopathy is still uncertain.