Phys Ther 2012 Ioppolo 1376 85

doi: 10.2522/ptj.20110252Originally published online June 28, 2012

2012; 92:1376-1385.PHYS THER. Cacchio and Valter SantilliAttanasi, Teresa Venditto, Marila Servidio, Angelo Francesco Ioppolo, Maria Tattoli, Luca Di Sante, CarmineClinical Trial Comparing Two Different Energy LevelsSupraspinatus Calcifying Tendinitis: A Randomized Extracorporeal Shock-Wave Therapy for

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Extracorporeal Shock-Wave Therapyfor Supraspinatus CalcifyingTendinitis: A Randomized ClinicalTrial Comparing Two DifferentEnergy LevelsFrancesco Ioppolo, Maria Tattoli, Luca Di Sante, Carmine Attanasi,Teresa Venditto, Marila Servidio, Angelo Cacchio, Valter Santilli

Background. Extracorporeal shock-wave therapy (ESWT) represents a validintervention in the treatment of people with supraspinatus calcifying tendinitis (SCT),but there is limited evidence for the useful range of ESWT doses.

Objective. The aim of this study was to compare 2 different ranges of energy fluxdensity in treatment of SCT with ESWT.

Design. This study was designed as a single-blind randomized clinical trial.

Setting. This study was performed in a university hospital.

Patients. Forty-six patients with SCT were randomly assigned to 2 groups thatreceived different therapeutic energy doses of ESWT: (1) group A received ESWT atan energy level of 0.20 mJ/mm2, and (2) group B received ESWT at an energy levelof 0.10 mJ/mm2.

Intervention. The treatment protocol consisted of 4 sessions performed once aweek.

Measurements. The change in mean Constant Murley Scale (CMS) scores at 3and 6 months was the primary endpoint. The change in the mean visual analog scale(VAS) scores from baseline to 3 and 6 months after the intervention and radiographicchange in size of calcium deposits were evaluated as secondary endpoints. At 12months, pain relief was assessed using a numeric rating scale.

Results. Significant clinical improvement based on mean CMS scores was observedafter 6 months in group A (X79.43, SD10.33) compared with group B (X57.91,SD6.53). Likewise, after 6 months, a significant decrease in VAS scores was foundin group A (X2.09, SD1.54) compared with group B (X5.36, SD0.78). Calcificdeposits disappeared in the same percentage of patients in both groups.

Limitations. The small sample size and lack of a control group were limitationsof the study.

Conclusions. In ESWT for SCT, an energy level of 0.20 mJ/mm2 appears to bemore effective than an energy level of 0.10 mJ/mm2 in pain relief and functionalimprovement.

F. Ioppolo, MD, PhD, PhysicalMedicine and Rehabilitation Unit,Azienda Policlinico Umberto I,School of Medicine, La SapienzaUniversity of Rome, Rome, Italy.

M. Tattoli, MD, PhD, Departmentof Biomedical Sciences andHuman Oncology, MedicalSchool, University of Bari AldoMoro, Bari, Italy, and Depart-ment of Physical and Rehabilita-tive Medicine, School of Medicine,La Sapienza University of Rome.

L. Di Sante, MD, PhD, PhysicalMedicine and Rehabilitation Unit,Azienda Policlinico Umberto I,School of Medicine, La SapienzaUniversity of Rome, Piazzale AldoMoro 5, 00185 Rome, Italy.Address all correspondence toDr Di Sante at: [email protected].

C. Attanasi, MD, Department ofPhysical and Rehabilitative Medi-cine, School of Medicine, LaSapienza University of Rome.

T. Venditto, MD, Department ofPhysical and Rehabilitative Medi-cine, School of Medicine, LaSapienza University of Rome.

M. Servidio, MD, Department ofPhysical and Rehabilitative Medi-cine, School of Medicine, LaSapienza University of Rome.

A. Cacchio, MD, PhD, Depart-ment of Health Sciences, PhysicalMedicine and Rehabilitation Unit,School of Medicine, Universityof LAquila, LAquila, Italy, andDepartment of Physical and Reha-bilitative Medicine, School ofMedicine, La Sapienza Univer-sity of Rome.

Author information continues onnext page.

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Supraspinatus calcifying tendini-tis (SCT) represents an acuteor chronic disease caused byinflammation around calcium depos-its situated upon tendons, with par-ticular involvement of the supraspi-natus tendon in its proximal portionof the humerus. It is most commonamong people between 30 and 50years of age.1 The prevalence of SCThas been reported to range from 7%to 36% of the population,2 and theincidence is estimated to be between2.5% and 20%.1,3 Clinical features ofthis disease are pain-triggering lossof muscular strength, decrease inrange of motion (ROM), and disabil-ity of the shoulder. Furthermore,pain localized in the deltoid region ismore often present during the night,when calcium undergoes reabsorp-tion.4 This phase can last from 2weeks in its acute form to up to 3months in its chronic form.5

According to Bosworth et al,6 cal-cium deposits can be divided into 3categories according to size and clin-ical impairment: tiny (0.5 cm),medium (0.51.5 cm), and large(1.5 cm). Gartner and Simons7

classified these calcifications in rela-tion to their radiological features:(1) type 1pasting and not clear inradiographs, (2) type 2pasting andclear in radiographs, and (3) type3without clear limits and with ahigh tendency toward spontaneousresolution. The mechanisms underly-ing the etiology of intratendinousdeposits of carbonated apatite arenot fully understood.8

Uhthoff et al5 demonstrated that SCTis a dynamic phenomenon in whichcalcium goes through a cyclical pro-cess of formation, reabsorption, andremodeling. Treatment of peoplewith SCT may be conservative orsurgical.9 Conservative treatment10

includes therapeutic exercise,11 anal-gesic and nonsteroidal anti-inflammatory drugs, transcutaneouselectrical nerve stimulation,12 steroid

injections,13 and shock-wave therapy(SWT).1417 During the chronic state,arthroscopic-guided surgical resec-tion of the calcification is indi-cated.18 Shock waves, defined as asequence of single sonic pulses char-acterized by high peak pressure (100mPa), a fast rise in pressure (10nanoseconds), and a short life cycle(10 microseconds), are conveyed byan appropriate generator to a spe-cific target area. Short-wave therapycan be classified according to itsenergy levels.19,20 A simpler classifi-cation distinguishes between low-energy SWT, having an energy fluxdensity (EFD) of less than 0.12mJ/mm2, and high-energy SWT, hav-ing an EFD between 0.12 and 0.38mJ/mm2.1921

During the last 10 years, extracorpo-real shock-wave therapy (ESWT) hasbeen used successfully in peoplewith tendon and muscle tissue dis-ease.14,15,22 It was found that ESWTinduces a long-term tissue regenera-tion effect in addition to having amore immediate antalgic and anti-inflammatory outcomes.23 A wash-out of chemical inflammation medi-ators, a trigger to neovascularization,and a nociceptive inhibition (gatecontrol theory) have been reportedas the main biological effects ofESWT on tissues.24,25

To date, various molecular workingmechanisms of shock waves havebeen demonstrated.23,2628 Twophysical effects are produced byshock-wave application: (1) thestress-related phenomenon inducedby an ultrashort rise time of about5 nanoseconds and (2) cavitationbubbles produced at the interfacebetween the solid and the surround-ing liquid.29 The latter effect inducesvessel rupture and angiogenesis insoft tissues. In in vitro studies, ESWTat an EFD lower than 0.09 mJ/mm2 isreported to produce a neoangio-genic effect by increasing expressionof vascular endothelial growth factor

V. Santilli, MD, Department of Physical andRehabilitative Medicine, School of Medicine,La Sapienza University of Rome.

[Ioppolo F, Tattoli M, Di Sante L, et al. Extra-corporeal shock-wave therapy for supraspi-natus calcifying tendinitis: a randomizedclinical trial comparing two different energylevels. Phys Ther. 2012;92:13761385.]

2012 American Physical Therapy Association

Published Ahead of Print: June 28, 2012Accepted: June 21, 2012Submitted: June 13, 2011

Extracorporeal Shock-Wave Therapy for Supraspinatus Calcifying Tendinitis

November 2012 Volume 92 Number 11 Physical Therapy f 1377 by guest on December 21, 2014http://ptjournal.apta.org/Downloaded from

(VEFG) and its receptor Flt-1.30 Sev-eral studies have shown that thereis a direct relationship betweendose and effect for ESWT.3133 Gotteet al34 also demonstrated that ESWTinduces a nonenzymatic productionof nitric oxide and a subsequent sup-pression of NF-B (nuclear factor-kappaB) activation responsible forthe clinically beneficial action on tis-sue inflammation.

The number of cells destroyed (vac-uolization) after ESWT increases in away that is dose and number depen-dent. It would seem that the destruc-tion of cells is a short-term effectof high shock-wave doses, whereascells stimulation is a medium-termeffect.35 On the other hand, a disor-ganization of matrix structure andchanges in degraded collagen levelshave been described in normal ten-dons after EWST and might repre-

sent the trigger for repair in chronictendinopathy.28

Furthermore, side effects have beenreported as consequences of theeffect of ESWT on tissues.25,36

Indeed, an EFD between 0.04 and0.22 mJ/mm2 has very few sideeffects, such as pain, local soft tissueswelling, cutaneous erosions, ery-thema, and local subcutaneoushematomas.22,37 Only one casereport of osteonecrosis of thehumeral head has been published.38

To date, it is not yet clear whichenergy level is the most effectivein pain relief and clinical improve-ment of shoulder function afterESWT.24,3941 Indeed, Gerdesmeyeret al15 found that 2 sessions of 1,500high-dose impulses (0.32 mJ/mm2)appeared to be superior to 2 sessionsof 6,000 low-dose impulses (0.08

mJ/mm2) in terms of pain reduction,clinical improvement, and radiologi-cal calcium deposit resorption,although they stated that thresholdenergy has yet to be defined.Schofer et al42 found an increase inshoulder function and a reduction ofpain in 2 groups treated with 6,000impulses in 3 sessions. They used anenergy level of 0.78 mJ/mm2 in thefirst group and an energy level of0.33 mJ/mm2 in the second group,but did not observe any differencebetween groups.

Therefore, treatment parameters ofESWT remain empirical becausethere is no consensus on appropriatesessions and doses.16,18,22,39 In ourstudy, 2 different protocols weredesigned: one protocol bounded bythe upper limit of low dose (0.040.12 mJ/mm2) and the other proto-col bounded by the lower limitof high dose (0.12 mJ/mm2). Wetested low-energy procedures in ourstudy because they do not requireany kind of anesthesia, which gener-ally was applied when high-energyprotocols were used.43 Moreover,it recently has been demonstratedthat local anesthesia substantiallyalters the biological responses ofESWT.25,44 It also been shown thatboth high- and low-energy protocolprocedures are similarly effective ifthe total energy applied is approxi-mately the same. Thus, with thelow-energy protocol, more impulseshad to be applied in more treatmentsessions to achieve a similar result.44

However, in our study, we chose tocompare the effects of the 2 treat-ment protocols using the sameimpulses and number of sessions.

MethodDesign OverviewA single-blind randomized clinicaltrial with assessment at baseline(admission to the clinic) and at 3, 6,and 12 months after the end of thetreatment was conducted.

The Bottom Line

What do we already know about this topic?

Several studies suggest the effectiveness of extracorporeal shock-wavetherapy (ESWT) as an intervention for reducing pain and improvingshoulder function in people with supraspinatus calcifying tendinitis(SCT); however, there is limited evidence about the useful range of ESWTdoses.

What new information does this study offer?

This study contributes to the standardization of treatment of SCT and canhelp clarify the most appropriate energy flux density (EFD) levels, numberof sessions, and number of impulses of shock waves in SCT treatment. Inthis study, 2 different energy levels were tested: 0.10 mJ/mm2 in the firstgroup, and 0.20 mJ/mm2 in the second group. The group that received thehigher energy level showed a greater reduction in pain and a greaterimprovement in shoulder function than the other group. The study alsorevealed that the clinical improvement of patients was not related to thereabsorption of or a decrease in size of calcific deposits.

If youre a patient, what might these findings meanfor you?

If you have SCT, the destruction of calcifications is not necessary toreduce your pain and improve your shoulder function.



Setting and ParticipantsConsecutive outpatients of theDepartment of Physical and Rehabil-itative Medicine (School of Medi-cine, La Sapienza University ofRome) with clinical and radiologicalfeatures of SCT from November2008 to June 2010 were invited toparticipate in the study.

All patients had a current episode ofshoulder pain that had been in prog-ress for at least 4 to 6 months. A totalof 68 consecutive patients affectedby shoulder pain (40 women and 28men) were screened for eligibility.If they had undergone previous con-servative treatment with no visibleclinical benefits, they were includedin the study. Patients with mediumand large calcific deposits accordingto the Bosworth classification6 andwith type I and II calcific depositsaccording to the Gartner classifica-tion7 were included. Individualswith clinical signs of partial or com-plete tear of the rotator cuff (evalu-ated with Jobe and full can tests)45

were excluded. Dinnes et al46

reported that clinical examinationhas a sensitivity of 90% and a speci-ficity of 54% in the detection of rota-tor cuff tears. Four patients weresubjected to magnetic resonanceimaging to eliminate doubts aboutsupraspinatus tendon tears.

Moreover, patients with the pres-ence of tiny calcific deposits accord-ing to the Bosworth classification6

and type III calcific deposits accord-ing to the Gartner classification7

were excluded because of the highprobability of spontaneous resolu-tion.47 Further exclusion criteriawere: age of less than 18 years, dia-betes, coagulation diseases or under-going anticoagulant therapy, tumors,bone infections, previous shouldersurgery, pregnancy, use of a pace-maker, acute bursitis demonstratedby ultrasound imaging, rheumatoidarthritis, or other connective tissuediseases.48

At the end of the evaluation, 46patients (31 women and 15 men;mean age54.3 years, SD14.8,range2978) fulfilled the selectioncriteria. They agreed to participate,signed informed consent statements,and were enrolled in the study. Theright shoulder was affected in 70% ofthe participants, and the left shoul-der was affected in 30%. The meanduration of condition at time of treat-ment was 7.1 months (SD1.16,range69). The enrolled patientsdid not receive any conservativetreatment in the 4 weeks beforeESWT, and this was the first time thatthey received ESWT. A flow diagram

of participant recruitment and reten-tion is shown in Figure 1.

Randomization andInterventionsUpon consenting to be involved inthe study, patients were asked byan interviewer blinded general ques-tions regarding age, symptom dura-tion, current medicine intake, andaverage pain intensity over the pre-vious week. A research assistant ran-domly assigned participants to studygroups by the use of a computer-based 1:1 randomization scheme.Participants were randomly assignedto receive 1 of 2 treatment protocols:(1) group A received ESWT at an

Randomized(n=46)

Excluded (n=22) because of: Coagulation disease (n=4) Acute bursitis (n=5) Previous shoulder surgery (n=4) Connective acute diseases (n=3) Refused to participate (n=6)

Assessed for eligibility(n=68)

Allocated to energylevel of 0.10 mJ/mm2

(n=23)

Allocated to energylevel of 0.20 mJ/mm2

(n=23)

23 completed6-month assessment






Figure 1.Flow diagram of participants in the study.



energy level of 0.20 mJ/mm2, and(2) group B received ESWT at anenergy level of 0.10 mJ/mm2. Bothgroups received 2,400 pulses once aweek for 4 weeks. Baseline measure-ments were taken by a second inter-viewer who was blinded to ESWTdosage, and the participants com-pleted the questionnaire adminis-tered. Treatment allocation wasconcealed in a numbered, opaqueenvelope, which subsequently wasopened by the physician.

Participants were instructed to useoral nonsteroidal anti-inflammatorydrugs (dexibuprofene, 400 mg) 1hour before treatment to providepain relief during treatment. Localanesthesia was not administered, asin previous studies.25,49

We utilized an ESWT device (Modu-lith SLK system, Storz Medical, Tager-wilen, Switzerland), with an electro-magnetic extra-corporeal shock-wavegenerator equipped with an in-lineultrasound positioning system onthe target zone. Participants under-went ESWT by lying on a bed withthe affected arm positioned in adduc-tion, the elbow flexed at 90 degrees,and the hand on the abdomen(Fig. 2).

Outcome and Follow-upThe Constant Murley Scale (CMS)50

and a visual analog scale (VAS)51

were administered before treatmentand at 3 and 6 months after the endof the ESWT. The primary endpointwas the change in mean CMS scoresfrom baseline to the 3- and 6-monthfollow-ups. Secondary endpointswere the change in VAS scores frombaseline to the 3- and 6-monthfollow-ups and the numerical ratingscale (NRS) score at the 12-monthfollow-up, as well as radiographiccalcific deposit size at the 6-monthfollow-up.

The CMS evaluates shoulder functionwith high accuracy, test-retest reli-ability (intraclass correlation coeffi-cient.80), and reproducibility.52 Itis a cumulative scale, consisting ofa 100-point scoring system, withassessment of patient-reported painand function accounting for up to35 points and quantitative assess-ment of ROM and strength account-ing for up to 65 points. Its emphasisis on symptoms and functional diffi-culties, and the patient-report com-ponent documents pain and diffi-culty in activities of daily life, work,sports, and sleep. Higher scoresreflect an improvement in shoulderfunction.

Shoulder pain was assessed using theVAS, which represents a valid mea-sure of acute pain with a good con-struct validity.53 It consists of a10-cm horizontal line (with 0 cmreferring to no pain and 10 cmreferring to worst pain ever) onwhich participants were invited tomark a line indicating pain intensity.The distance is measured, and painis recorded on a 10-point scale.54 Inthe acute pain setting, the VAS hasbeen shown to have very good test-retest reliability (intraclass correla-tion coefficient.99).55

Dworkin et al56 suggested that rawscore changes of approximately 1point or percentage changes ofapproximately 15% to 20% representthe minimal clinically important dif-ference (MCID) for the VAS and sim-ilar NRS measures (010) for painintensity. All outcomes before ESWTand at the scheduled 3- and 6-monthfollow-ups were assessed by a thirdblinded independent observer.

To further assess pain relief in bothgroups, at 12 months, the third inter-viewer, who was blinded to theenergy level of treatment, adminis-tered an 11-point NRS (group A:n20; group B: n16) by telephone.The NRS usually is an 11-, 21-, or(rarely) 101-point scale, with num-bers in boxes that are anchored with2 extremes at the ends of the scale.57

The 11-point scale NRS consists ofintegers from 0 through 10, with 0representing no pain and 10 repre-senting worst imaginable pain.The NRS recently has been demon-strated to possess good psycho-metric properties. High correlationswere observed between the NRS andVAS scores. The patient acceptablesymptomatic state (PASS) was 3.3.58

Calcifications of each patient werefirst detected in a previous visit byradiography or ultrasound beforetreatment with a standardized tech-nique in terms of position of theshoulder and arm, distance from

Figure 2.Participants underwent extracorporeal shock-wave therapy while lying on a bed withthe affected arm positioned in adduction, the elbow flexed at 90 degrees, and the handupon the abdomen.



the radiographic film, and exposure.The size of the calcific deposit wasdefined as the difference in measure-ments at the 6-month follow-up com-pared with baseline values.

Statistical AnalysisStatistical analysis was performedaccording to the principle of inten-tion to treat, with missing dataimputed with the last observationcarried forward technique. All anal-yses were performed with SAS statis-tical software, version 9.1 (SAS Insti-tute Inc, Cary, North Carolina).Computed P values were 2-sided,and P.05 was used to determinestatistical significance. Two-wayanalyses of variance (ANOVAs) forrepeated measures of CMS and VASscores were performed with group(treatments) as the between-subjectsfactor and time and group interac-tions time as the within-subjectsfactors.

Preplanned time-repeated contrastswere done. Two-tailed unpaired ttests and the Fisher exact test wereapplied when appropriate. The par-ticipants baseline characteristics areshown in the Table.

Sample SizeSample size and power calculationswere performed with nQuery Advi-sor 7 statistical software (StatisticalSolutions, Saugus, Massachusetts).We computed that a sample size of46 participants achieved a powerover 80% to detect a 15% differencein CMS score. The statistical level ofsignificance was set at alpha.05,and the assumed standard deviationwas set at 17.7 points based on theresults of a study by Loew et al.24

Role of the Funding SourceThis study was supported by a grantfrom La Sapienza University ofRome.

ResultsAll patients participated in the 3- and6-month follow-ups. As shown inthe Table, the baseline clinical anddemographic characteristics of theparticipants were homogenous inthe 2 groups.

Repeated-measures 2-way ANOVAsfor CMS and VAS scores showed asignificant effect of treatment (CMS:F1,4425.04, P.000; VAS: F1,4432.39, P.000) and a significanttreatment-time interaction (CMS:F2,8820.14, P.000; VAS: F2,88

46.23, P.000). A significant changein test performance over time alsowas observed in both groups (CMS:F2,8872.52, P.001; VAS: F2,88337.48, P.000).

Using preplanned contrasts, weobserved a significant increase inCMS values compared with baselinevalues at 3 months in both treatmentgroups (time effect: F1,4484.24,P.000), with no significant differ-ence between treatment groups(interaction effect: F1,440.18,P.672). A further improvement

Table.Baseline Demographic and Clinical Characteristics of Participants With ChronicSupraspinatus Tendinitis in Groups A and Ba

CharacteristicGroup A(n23)

Group B(n23) P

Age (y) .21b

X 57.09 51.65

SD 16.40 12.23

Range 2778 3178

95% CI 50.0064.18 46.3656.94

Time since onset of pain (mo) .44b

X 6.95 7.22

SD 1.06 1.20

Range 69 610

95% CI 6.497.41 6.697.74

Sex (female/male) 15/8 16/7 1.00c

Treatment side (right/left) 16/7 14/9 .76c

Type of calcificationd

I 5 6 1.00c

II 18 17 1.00c

CMS score .62b

X 49.26 47.70

SD 8.56 12.23

95% CI 45.4652.96 42.4152.99

VAS score .68b

X 8.45 8.36

SD 0.67 0.78

95% CI 8.178.74 8.038.69

a Group A received extracorporeal shock-wave therapy (ESWT) at an energy level of 0.20 mJ/mm2, andgroup B received ESWT at an energy level of 0.10 mJ/mm2. 95% CI95% confidence interval,CMSConstant-Murley Scale (0100 points), VASvisual analog scale (010 points).b As determined by an independent 2-sample t test.c As determined by Fisher exact test.d Gartners classification.7



over the time at the 6-monthfollow-up was observed (time effect:F1,4411, P.000); however, theimprovement was present in groupA but not in group B (interactioneffect: F1,4442.01, P.000) (Fig. 3).

The effect on pain relief was percep-tible at the 3-month follow-up versusbaseline in both groups (time effect:F1,44174.92, P.000), although itwas more evident in group A than ingroup B (interaction effect: F1,446.04, P.018). Comparing scoresobtained at the 6-month follow-upwith those obtained at the 3-monthfollow-up, the effect was still moreobvious in group A (time effect:F1,44151.58, P.000; interactioneffect: F1,4445.69, P.000) (Fig. 4).

Furthermore, statistical analysis(2-tailed unpaired t test) of NRSscores obtained at 12 monthsshowed a significantly lower level ofpain (P.045) in group A than ingroup B (group A: X 2.60, SD2.1,95% confidence interval [95% CI]1.62 to 3.58; group B: X4.56,SD3.5, 95% CI2.69 to 6.44).Moreover, 7 participants in group Aand 10 participants in group B hadNRS scores greater than 3.3, and 13participants in group A and 6 partic-ipants in group B had NRS scoreslower than 3.3.

The complete disappearance of cal-cification deposits was observedafter 6 months in approximately 50%of the patients treated in bothgroups. In particular, we found thatcalcifications had disappeared in23 (50%) of the 46 participants. Ofthese, 11 (47.8%) were in group A,and 12 (52.2%) were in group B. Fur-thermore, there was no difference(t-test value.22) between treat-ments in mean change of calcificdeposit size at 6 months from base-line (group A: X135.91, SD71.69, 95% CI100.37 to 166.29;group B: X109.73, SD75.73,95% CI50.69 to 134.44). No

Time (mo)

Group AGroup B

80

70

60

50

40

630

CM

S M

argi

nal M

eans

Figure 3.Time course of Constant Murley Scale (CMS) scores at baseline (0) and at 3- and6-month follow-ups. Data are expressed as marginal means. A significant increase inCMS values with respect to the baseline at 3 months in both treatment groups (timeeffect: F1,4484.24, P.000), with no significant difference between treatment groups(interaction effect: F1,440.18, P.672), was observed using preplanned contrasts. Afurther improvment at the 6-month follow-up was observed in group A (time effect:F1,4411, P.000) but not in group B (interaction effect: F1,4442.01, P.000).

Group AGroup B

8

6

4

2

VAS

Mar

gina

l Mea

ns

0 3 6Time (mo)

Figure 4.Time course of visual analog scale (VAS) scores at baseline (0) and at 3- and 6-monthfollow-ups. Data are expressed as marginal means. Using preplanned contrasts, thedecrease of pain was present at the 3-month follow-up versus baseline in both groups(time effect: F1,44174.92, P.000), although it was more evident in group A than ingroup B (interaction effect: F1,446.04, P.018). At the 6-month versus 3-monthfollow-ups, the effect was still more obvious in group A (time effect: F1,44151.58,P.000) than in group B (interaction effect: F1,4445.69, P.000).



correlation between clinical improve-ment and calcium deposit changewas observed in either treatmentgroup. Finally, no side effects wereobserved in participants after treat-ment or reported by participantsafterward.

DiscussionAccording to the literature, whenprevious conservative treatment isnot effective, ESWT is a valid alterna-tive in the management of SCTbecause it reduces pain andimproves the function of the shoul-der joint.39,59 There is no consensusas to the appropriate EFD, number ofsessions, and impulses of SWT, andit is not known whether and, if so,to what degree a correlation existsbetween decreased pain and func-tional recovery, on the one hand,and the resorption of calcific depos-its, on the other.

Peters et al22 reported that therapywas more effective in the high-energy group (0.44 mJ/mm2) thanin the low-energy group (0.15mJ/mm2) in achieving clinicalimprovement and dissolving calcifi-cations at 6 months from the end oftreatment. Gerdesmeyer et al15 alsoobserved a better clinical responsein the high-energy group (0.32mJ/mm2), with a rate of completedisappearance of calcific depositsof 60% at the 6-month follow-up and86% at the 12-month follow-up. Bycontrast, in the low-energy group(0.08 mJ/mm2), the rate of dissolu-tion was 21% at 6 months and 25% at12 months.

Albert et al60 observed that a high-energy level of ESWT significantlydecreased symptoms in individualswith SCT at a 3-month follow-up,but the results of our study indicatedthat clinical improvement was notrelated to resorption of calcificdeposits. Indeed, the calcific depos-its disappeared from the radiographsat 3 months in only 15% and 5% of

the patients in the high-energy andlow-energy groups, respectively.

The results of our study showed thatthe improvement in mean (SD, 95%CI) CMS scores was higher in groupA: 79.43 (10.33, 74.9783.90) thanin group B: 57.91 (6.53, 55.0960.74) at 6-month follow-up. Indeed,the change from baseline in 6-monthCMS scores was 61% in group A:49.26 (8.56, 45.5652.96) and21% in group B: 47.70 (12.23,42.4152.99).

To date, there are no studies provid-ing data on the MCID for CMS scores.However, assuming a 30% increasein CMS score from baseline as clini-cally relevant improvement,18 wecould speculate that only an EFD of0.20 mJ/mm2 induced a clinically rel-evant improvement of shoulder func-tion over time.

Both treatments produced a reduc-tion of pain, although varyingaccording to dose. At 6 months, theVAS score mean (SD, 95% CI) changewas 75% in group A: 2.09 (1.54,1.422.76) and 37% in group B: 5.36(0.78, 5.035.70), from the respec-tive baseline values (group A: 8.45[0.67, 8.178.74]; group B: 8.36[0.78, 8.038.69]), which was bothstatistically (P.001) and clinicallysignificant. Indeed, as described byDworkin et al,56 a reduction inchronic pain intensity of at least 10%to 20% appears to reflect minimallyimportant changes. Furthermore,group A showed better effects forlevel of pain than group B at 12months, assuming that an NRS scorelower than 3.3 points is related to anacceptable state of pain.

Moreover, we found that clinicalimprovement was not related to thedisappearance or reduction in size ofcalcifications, according to the cur-rent data,61 because they were stilldetectable in approximately 50% ofour participants in both groups after

6 months. Although some authorshave emphasized the potential effectsof ESWT for disintegrating calcifieddeposits upon the supraspinatustendon, the real mechanisms remainunknown.62,63

The exact biological effects bywhich ESWT acts are still in ques-tion. A study conducted on rabbitsshowed that ESWT increases neovas-cularization at the tendon-bonejunction through release of angio-genetic growth and proliferating fac-tors such as VEFG and endothelialnitric oxide synthase, which stimu-late increased blood flow in tendonsand seem to relieve shoulder symp-toms.28 Another study carried outon rabbits showed some short-termtendon pathologies associated withESWT energy levels of at least 0.6mJ/mm2.64 However, neither ten-dons nor the cartilage of joints havebeen found to be injured by shockwaves lower than this energy level.Despite a previous report,42 theenergy level used in our study wasranged in doses suitable for softtissue diseases.1921 We did notobserve any side effects in the par-ticipants in our study.

It also should be emphasized thatthese results were obtained usingenergy levels below those reportedin the literature because we wantedto compare the effectiveness of 2energy levels, ranging in the low lev-els. It can be hypothesized, on thebasis of our findings, that at the low-energy level used in our study (0.10mJ/mm2), the ESW produces imme-diate analgesic and anti-inflammatoryeffects, washing out the inflamma-tory mediators and turning off theassociated neoangiogenesis process.This efficacy possibly could beexplained by an increased synthesisof nitric oxide, which has beenshown to be produced in vitro by anEFD of 0.03 mJ/mm2.27 At 0.20mJ/mm2, ESWT probably led to inte-grated anti-inflammatory and regen-



erative actions on the different tissuecomponents, and these combinedmechanisms could explain the betterclinical results observed in group Ain our study. However, the limita-tions of the present study include thesmall sample size and the lack of acontrol group receiving a placebo.The efficacy of this therapy is betterand longer lasting in patients treatedwith an energy level of 0.20 mJ/mm2

than in those treated with an energylevel of 0.10 mJ/mm2.

So far, from what we know from theliterature, this is the first study thatused the same number of impulsesand number of sessions in the rangeof low-energy levels in order to stan-dardize a therapeutic protocol withbetter clinical results for SCT ther-apy. Certainly, it must be taken intoaccount, as already stated, that thepresence of a control group, as wellas a larger sample size, would haveallowed us to confirm the obtainedresults.

Nevertheless, in clinical practice theresults of this study could be helpfulto clarify the most appropriate EFD,number of sessions, and impulses ofshock waves in SCT treatment, sur-passing what is currently the mostused empirical approach in clinicalpractice. In addition, many patients,and even some physicians, believethat the effect of treatment withEWST is due to the destruction ofcalcific deposits. On the contrary,our results, in line with those of thestudy by Albert et al,60 showed thatthe destruction of calcifications isnot necessary to reduce pain andimprove function.

Further studies are needed to con-firm the most appropriate energythreshold in ESWT to obtain the bestresults in reducing pain and improv-ing shoulder function. The results ofthe present study are promising, butstudies with larger samples, longer

follow-up, and possible comparisonwith a control group are needed.

Dr Ioppolo, Dr Tattoli, Dr Di Sante, Prof Cac-chio, and Prof Santilli provided concept/idea/research design. Dr Ioppolo, Dr Tattoli,Dr Di Sante, Dr Venditto, Dr Servidio, andProf Cacchio provided writing. Dr Tattoli andDr Di Sante provided data collection. Dr Tat-toli, Dr Di Sante, and Dr Attanasi provideddata analysis. Dr Ioppolo, Dr Attanasi, andProf Santilli provided project management.Dr Attanasi and Dr Venditto provided facili-ties/equipment. Dr Di Sante, Prof Cacchio,and Prof Santilli provided consultation(including review of manuscript beforesubmission).

This study was approved by the local ethicscommission.

This study was supported by a grant fromLa Sapienza University of Rome.

ClinicalTrials.gov Identifier: NCT01602653.

DOI: 10.2522/ptj.20110252

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doi: 10.2522/ptj.20110252Originally published online June 28, 2012

2012; 92:1376-1385.PHYS THER. Cacchio and Valter SantilliAttanasi, Teresa Venditto, Marila Servidio, Angelo Francesco Ioppolo, Maria Tattoli, Luca Di Sante, CarmineClinical Trial Comparing Two Different Energy LevelsSupraspinatus Calcifying Tendinitis: A Randomized Extracorporeal Shock-Wave Therapy for

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