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Musculoskelet Surg (2013) 97 (Suppl 1):S49–S56
Ultrasound-guided subacromial injections of sodium hyaluronatefor the management of rotator cuff tendinopathy: a prospectivecomparative study with rehabilitation therapy
G. Merolla • P. Bianchi • G. Porcellini
Received: 20 December 2012 / Accepted: 3 March 2013 / Published online: 21 April 2013Ó Istituto Ortopedico Rizzoli 2013
Reduction in overall pain in the HA group was
Rotator cuff (RC) tendinopathy is a common
statistically significant at week 2 (p 0.05) week 4 (p
cause of pain and shoulder dysfunction. The literature evi-
0.05), week 12 comparing to baseline. Similarly, pain sub-
dence suggests that a combination of overuse and extrinsic
scores (at night and with activity) were significantly lower
compression may induce chronic RC tendinopathy. Aim of
at week 2 (p 0.05), week 4 (p 0.05), and week 12
the current study was to compare the results of subacromial
(p 0.05), respectively. In the Physio group, pain decreased
sodium hyaluronate injections with rehabilitation therapy.
significantly at week 2 (p 0.05) but not maintained at week
Materials and methods
We enrolled 48 patients (M/F:
4 (p [ 0.05), week 12 (p [ 0.05), and week 24 (p [ 0.05). CS
26/22; mean age: 50 years; shoulder right/left: 29/19) with
and OSS in the HA group increased significantly at week 2
persistent shoulder pain for at least 4 months. Exclusion cri-
(p 0.05), week 4 (p 0.05), and week 12 (p 0.05). A
teria were as follows: RC tear, calcifying tendinitis, gleno-
non-statistically significant increase in clinical scores was
found at week 24 (p [ 0.05). A significant improvement of CS
physical therapy and/or injection in the previous 4 months,
and OSS we found in the Physio group at week 2 (p 0.05),
shoulder surgery, anesthetic nerve block, trauma, and severe
but not at weeks 4, 12, and 24 (p [ 0.05).
medical diseases. The included subjects received either two
Subacromial HA injections could be an
ultrasound-guided subacromial hyaluronic acid (HA) injec-
effective and safe alternative treatment for patients suffering
tions (25 patients, HA group) at baseline and 14 days, or
from RC tendinopathy. We believe that the results of this study
underwent rehabilitation therapy (23 patients, Physio group)
are encouraging but not lasting and we might suppose that a
including active shoulder mobilization, soft tissue stretching
series of three to four subacromial sodium hyaluronate injec-
and humeral head positioner and propeller muscles strength-
tions could provide good mid- and long-term clinical benefits.
ening for 30 days (3 sessions every week). Clinical assess-ment of shoulder function was performed with visual analog
Shoulder Injection Sodium hyaluronate
scale score for pain (0–100), Oxford Shoulder Score (OSS),
Rotator cuff Tendinopathy
and Constant–Murley Score (CS). Overall, patients wereexamined at baseline, week 2, week 4, week 12, and week 24.
Statistical significance was set at 5 % (p 0.05).
Rotator cuff (RC) tendinopathy is a common source of pain
G. Merolla (&) G. Porcellini
and shoulder dysfunction that affects both the young and
Unit of Shoulder and Elbow Surgery, D. Cervesi Hospital,
older population [] mainly in arduous overhead workers
Via L. V. Beethowen 46, Cattolica, Italye-mail:
[email protected];
The available research findings emphasize the multi-
factorial origin of RC tendinopathy that begins as a failurein the tendon fibers due to the overuse and cyclic loading
on their internal side Under these conditions, the
Department of Orthopedics, Traumatology, Rehabilitationand Plastic Surgery, Second University of Naples, Naples, Italy
subunits of the RC tendons undergo internal compressive
Musculoskelet Surg (2013) 97 (Suppl 1):S49–S56
forces which induce the development of fibrocartilage in
or complete RC tears, calcifying tendinitis, previous
these regions particularly, fibrocartilage develops on
arthroscopic or open shoulder surgery, shoulder instability,
the articular side of the supraspinatus tendon close to its
infections or neoplasm, symptomatic cervical spine dis-
insertion, where the articular fibers are subjected to less
ease, rheumatoid arthritis or immune diseases, gout and
strain than the non-articular side [, Fibrocartilage is
uric acid diseases, severe medical conditions, or were
less capable of withstanding tension load, and joint-side
pregnant. Patients were also assessed for their mental status
fibers have half the force of the bursal-side fibers
and excluded if they presented with cognitive limitations
Furthermore, the supraspinatus and infraspinatus are
that could prevent them expressing a valid consent, or
inserted into a cable located 1.5 cm from the humeral
undergo subjective and objective evaluations. We also
insertion of the fibers and the ‘‘crescent'' region is
excluded subjects with known allergic or adverse reactions
located between the cable and the humerus insertion where
to previous nonsteroid or hyaluronan injections. All eval-
the tendon fibers are thinner and close to the hypovascu-
uations were performed by two experienced shoulder sur-
larized region and therefore are more susceptible to
geons. The diagnosis of RC tendinopathy was performed
degeneration This evidence suggests that a combina-
by trained musculoskeletal radiologists who depicted a
tion of overuse and extrinsic compression may induce
high tendon signal intensity that was anatomically intact on
chronic RC tendinopathy. Conservative therapies, includ-
the MRI in T2-weighted images. During the screening, 10
ing rehabilitation, physical therapies analgesics, and non-
patients were excluded because they refused the treatment
steroid anti-inflammatory drugs (NSAIDs), are commonly
or failed to comply with the inclusion criteria. We allowed
recommended to restore shoulder function in chronic RC
a rescue medication of oral paracetamol at a maximum
tendinopathy. Physiotherapy is based on the correction of
dosage of 4 g/day, and the amount taken by each patient
the flexibility, motion, and strength that are the cause of
was recorded at the four follow-up visits. Withdrawal of
painful shoulder []. Subacromial supplementation with
rescue medication (paracetamol) 24 h prior to each follow-
sodium hyaluronate or hyaluronic acid (HA) has been
up visit was recommended by the assessor and confirmed
proposed to treat RC dysfunction [due to its action as a
by the patients during the examination. There were no
lubricant [and suppressor of the joint inflammatory
statistically significant differences between the two groups
process ]. To our knowledge, no studies in the literature
of treatment with respect to demographic characteristics at
have compared physiotherapy and subacromial HA injec-
baseline (Table ).
tion; therefore, the purpose of the current research was toassess the efficacy and safety of sodium hyaluronate
Table 1 Demographic and anthropometric data of the population
injection versus physiotherapy in a population of patients
enrolled in the study
with painful chronic RC tendinopathy.
Materials and methods
Mean age (years ± SD)
Mean height (cm ± SD)
The study was approved by the Hospital Institutional
Mean weight (kg ± SD)
review board (Prot. 4232/2011/I.5/186), and all patients
gave informed consent prior to enrollment. This was a
prospective non-randomized comparative study involving a
study population of 60 patients with RC tendinopathy aged
Interval from symptoms
from 47 to 53 years old, seen in the outpatient office of our
to treatment (months)
Shoulder and Elbow Unit between June 2010 and March
Injection approach
2011 (Table ).
Patients were considered eligible for subacromial ther-
apy if they were 18 years or older, had persistent shoulder
pain for at least 4 months, clinical diagnosis of RC ten-
dinopathy detected with MRI, no previous treatment with
articular or subacromial steroid injections within the last
4 months, availability for the duration of the study. Patients
were excluded if they refused to consent to such a proce-
dure, had a positive history of shoulder trauma, partial
SD standard deviation
Musculoskelet Surg (2013) 97 (Suppl 1):S49–S56
Fig. 1 Anatomical landmark with the two sites of injections drawn
Fig. 2 The preparation is injected under ultrasound assistance taking
for the anterolateral approach to the subacromial space
care to direct the needle medially and posteriorly, on the insertionarea of the supraspinatus tendon
(GIRD) and the coracoid base muscles tightness was
We recruited an intent-to-treat population to be assigned to
treated using open stretch in the supine position and rota-
two treatment groups with the objective of gaining an
tion stretch exercises with the scapula stabilized. Scapula
improvement in the pain score of 4 points and in the
control was obtained performing exercises for lower tra-
Constant–Murley scale of 10 points. According to these
pezius and serratus anterior with the arm below 90°
parameters and a power value of 0.8, we had enrolled 50
abduction. RC activation exercises were allowed after a
patients consecutively: the first half in the hyaluronic acid
stable scapular base was established and included hori-
group (HA group, N = 25) and the second half in the
zontal and vertical closed-chain exercises, horizontal open-
physiotherapy group (Physio group, N = 25).
chain exercises, and diagonal closed-chain exercises. Thefinal sequence was completed with open-chain plyometric
The study material was a specific preparation (SportVisTM,
Outcome measurements
MDT Int'l SA, Switzerland), whose main content is aSTABHATM (Soft Tissue Adapted Biocompatible Hyalu-
Primary outcome measurements were the visual analog
ronic Acid) of 1 million of daltons contained in a pre-filled
scale (VAS) for pain.
syringe (12 mg/1.2 ml).
Secondary outcomes measurements were the Constant–
The procedure was performed in a standardized way in
Murley scale (CS) ] and the Oxford Shoulder Score
the outpatients' office with the patient in the upright
(OSS) , the Patient Global Assessment (PGA), the
position using local disinfection, sterile drape, and marking
tolerability and any adverse events after each injection.
the site of injection (Fig. ). A shoulder surgeon (MG) with
Pain included overall pain, pain at night, pain with
10 years of experience injected all the shoulders using an
activity, and pain without activity and was rated subjec-
ultrasound-guided anterolateral approach and the same GE
tively on a scale ranging from 1 (no pain) to 10 (severe
Logiq 7 ultrasound machine (7.5–14 MHz). We first
pain). Patients were invited to write their average pain rate
checked the tendon thickness and its superior limitant.
for the previous 48 h. The CS included a subjective ques-
Subsequently, a 22G needle was introduced beneath the
tionnaire for pain, the ability to perform daily living
anterolateral acromial edge above the tendon (Fig.
activity (DLA), an objective evaluation of active range of
taking care not to overcome the superior limitant. The
motion (ROM) and strength. Pain was scored on a 15-point
preparation was injected allowing it to spread over the
scale (0 severe pain, 15 no pain), while DLA was scored on
superior tendon surface (Fig.
a 20-point scale, with lower scores associated with greaterimpairment on DLA. ROM was measured using a standard
goniometer between the upper arm and the upper part ofthe thorax. Shoulder strength was assessed using the
We set a standard protocol of physiotherapy [] for
Lafayette handheld dynamometer (Lafayette Instruments,
30 days, following three sessions a week. The loss of
Lafayette, Ind, USA) that has a microprocessor with a
flexibility due to the glenohumeral internal rotation deficit
resolution of 0.4 lb (0.2 kg) in the range 0–50 pounds
Musculoskelet Surg (2013) 97 (Suppl 1):S49–S56
Table 2 Overall pain scores in the HA and Physio groups
Data refer to mean ± SD values
p values refer to analysis versus baseline
Fig. 3 Ultrasound image showing the needle (red arrow) placed in
Statistical analysis
the subacromial bursa, on the superior limitant of the supraspinatustendon. The blue arrows emphasize the preparation that expanded
Statistical analysis was performed using the Kruskal–
above the tendon surface (color figure online)
Wallis test for the equality of populations and the ANOVAtest for the variables, setting the significance at 5 %.
Bravais–Pearson correlation coefficient was calculated to
(0–22.6 kg), 0.03 % accuracy with two calibration points:
analyze the variability of the two independent observations.
0.25 and 50 lbs (0.11 and 22.6 kg). Data were recorded andanalyzed using SPSS version 10 software (SPSS Inc,Chicago, IL, USA). We assigned 1 point for each 0.5 kg of
The OSS is a 12-item patient-reported outcome measure
All the 25 patients with persistent shoulder pain due to RC
specifically used for assessing the impact of RC tendin-
tendinopathy considered for subacromial injection treat-
opathy on the patient's quality of life. Each question on the
ment with hyaluronic acid (HA group) from June to July
OSS is scored 0–4, with 4 representing the best; the twelve
2010 completed the follow-up evaluations (Table ).
items are summed to produce overall scores ranging from 0
Among the 25 patients who were assigned to the phys-
to 48. Interpreting the OSS: a score 0–19 indicates a severe
iotherapy group (Physio group) from August to October
shoulder condition, a score 20–29 indicates a moderate to
2010, two cases were excluded: one case because he
severe shoulder condition, a score 30–39 indicates a mild
refused to consent to the use of his data for research pur-
to moderate shoulder condition, a score 40–48 may indicate
poses at the time of the enrollment and one case due to
a satisfactory shoulder function.
incomplete evaluation (lost at last follow-up examination)(Table
Pain score and subscores
Overall, patients were assessed immediately before thetreatment (baseline), at the time of the second injection
In the HA group, we registered a remarkable decrease in
(week 2), and subsequently at week 4, week 12, and week
overall pain score from baseline to the week 2 (p 0.05),
24. The value of the subjective pain score was recorded by
week 4 (p 005), and week 12 (p 0.05), and it was
each patient using a printed analogic scale. Data were then
always statistically significant. The pain reduction was
entered on an electronic worksheet (Microsoft Excel for
recorded at week 24, but no statistically significant dif-
Mac OS 2011) which calculated the average values for pain
ference was found (p [ 0.05) (Table ). Similarly, pain
overall and relative subscores. CS and OSS were obtained
subscores (at night and with activity) were significantly
as the numeric sum of the subjective and objective evalu-
lower compared with baseline values, respectively, at week
ations using a dedicated electronic version of both scales
2 (p 0.05), week 4 (p 0.05), and week 12 (p 0.05),
(that gave the final score at
while at week 24, such reduction was maintained but not
the end of the questionnaire. Overall clinical scores were
statistically significant (p [ 0.05) (Table
collected by two independent observers who had not per-
In the Physio group at follow-up evaluation, we found
formed the injections.
that pain decreased significantly at week 2 (p 0.05) while
Musculoskelet Surg (2013) 97 (Suppl 1):S49–S56
Table 3 Pain with activity and pain at night in the HA and Physio groups
Pain with activity
Pain with activity
Data refer to mean ± SD values
p values refer to analysis versus baseline
higher values were registered at week 4 (p [ 0.05), week
be similar at week 2 and 4 in both groups, and higher from
12 (p [ 0.05), and week 24 (p [ 0.05) (Table ). Pain at
the week 12 to the week 24 in the Physio group.
night and pain with activity had similar trend with a sig-nificant decreasing at week 2 (p 0.05) and persistent
higher values at week 4 (p [ 0.05), week 12 (p [ 0.05),and week 24 (p [ 0.05) (Table ).
The CS showed no significant difference at baseline andweek 2 between the groups (p [ 0.05). There was a persis-
Constant–Murley Score and Oxford Shoulder Score
tently statistically significant higher score at week 4 andweek 12 in the HA group versus physiotherapy group
The average values of CS and OSS in the HA group
(p 0.05), and maintained at week 24 follow-up but without
increased significantly comparing to baseline at week 2
statistical significance (p [ 0.05). The OSS in the two
(p 0.05), week 4 (p 0.05), and week 12 (p 0.05). A
groups had the same values at baseline, but significantly
non-statistically significant increase in clinical scores was
higher scorers registered in the HA group at weeks 4 and 12
found at week 24 (p [ 0.05). In the Physio group, we
(p 0.05) and such improvement difference maintained at
recorded significantly higher values of CS and OSS at
week 24 but with no significant difference (p [ 0.05). Inter-
week 2 (p 0.05), but at week 4, 12, and 24, there was no
observer agreement resulted in k values ranging from 0.81 to
significant difference compared with baseline values
0.85 for CS and from 0.80 to 0.88 for OSS; good intra-
(p [ 0.05) (Tables
observer agreement was registered with k = 0.85–0.90.
Comparison between HA and Physio groups
Patient global assessment and adverse events
Overall pain and subscores
The PGA showed good patient compliance with no seriousadverse events registered during the experimentation. The
Overall pain and subscores were stratified to evaluate the
anterolateral approach injections, with US assistance,
difference in pain scores between the two groups of treat-
proved to be safe and well tolerated by all the patients
ment. There was no statistically significant difference in
enrolled for the study.
overall pain scores between the groups at baseline and atweek 2 (p [ 0.05). We found an average difference of 2.22points at week 4 (p = 0.0149) and 2.16 points at week 12
(p = 0.0168), while the difference at week 24 was notstatistically significant (p [ 0.05) (Table ). Subscores for
Sodium hyaluronate is effective in managing acute or
pain at night were significantly different at week 4
chronic ligaments and tendon injuries, like ankle sprains
(p = 0.0487), and remained at week 12, while the average
and epicondylalgia [HA is believed to integrate
difference found at week 24 was not significant (p [ 0.05).
into the extracellular fibrin matrix to help realignment of
A similar trend was found for pain with activity which
fibrils thanks to electrostatic interactions. Thus, stability of
registered a significant difference at week 4 (p = 0.0318)
form and function is then restored allowing healing to
and maintained at week 12 and but not at week 24
occur in structures (ligaments and tendons) and shorten-
(p [ 0.05). Rescue medication consumption was found to
ing the rehabilitation process. Recent research findings
Musculoskelet Surg (2013) 97 (Suppl 1):S49–S56
Table 4 Comparison of Constant–Murley Score in the HA and Physio groups
p value within HA group
p value within Physio group
p value between HA and Physio groups
Data refer to mean ± SD values
p values refer to analysis versus baseline
Table 5 Comparison of Oxford Shoulder Score in the HA and Physio groups
p value within HA group
p value within Physio group
p value between HA and Physio groups
Data refer to mean ± SD values
p values refer to analysis versus baseline
demonstrated that repeated periarticular injections of the
and in the long-term placebo injections showed the best
study materials were more effective in pain relief and joint
results. In the current study, physiotherapy was selected for
function improvement, compared to placebo or standard
the comparator because it is proven to be effective in
conservative treatment for ankle sprains and lateral
shoulder tendinopathy management [and is recom-
epicondylalgia. Long-term follow-up by investigators
mended by the recent European guidelines (2008). A
confirmed the therapeutic effects persist after 12 and
standard program of physiotherapy is recommended to
24 months [, ].
correct inflexibility, loss of strength and mobility in RC,
Several trials using sodium hyaluronate in the treatment
and associated structures, but it is common that these
for chronic shoulder pain have been documented, on
conditions persist despite a proper rehabilitation program
shoulder osteoarthritis RC tears ], peri-arthritis
which is phased into a maintenance program to reduce the
[] adhesive capsulitis ], and chronic shoulder pain
risk of reinjury The current study compared directly
of different etiologies ].
the effects of HA injections and physiotherapy, and we
The effectiveness of subacromial injections of HA alone
found that both treatments produced good results in pain
in patients with chronic RC tendinopathy is also reported in
and clinical scores in the short term, with a significant pain
the literature. In an open label multicenter study, Itokazu
decrease at week 2 of 3.3 points in the HA group and 2.8
et al. [observed a significant pain and range of motion
points in the Physio group. In midterm, the pain score
improvement after subacromial high-molecular weight
maintained a significant improvement at week 4 and week
sodium hyaluronate injection for 5 weeks or more, and
12 only in the HA group, while the improvement found in
they conclude that this treatment was effective in patients
the Physio group was not significant at week 4 and week 12
with periarthritis of the shoulder. Kim et al. [in a
compared to the baseline. Pain subscores at night and
prospective randomized single-blind comparative study on
during activity in the HA group showed a significant
105 patients with subacromial impingement, found that
reduction from the start of the study throughout follow-up,
hyaluronate injections produced more significant pain
except for week 24, while in the Physio group, the reduc-
reduction and similar functional improvement comparing
tion in pain subscores was not significant from week 2 to
to corticosteroid at 12 weeks. On the contrary, respect to
week 24. CS and OSS showed a course similar to overall
our results, Penning et al. ] reported a significant
pain, with a significant improvement in both treatment
reduction in pain at short- and long-term follow-up with
groups at week 2, persistent pain relief in the HA group
corticosteroid injections compared with hyaluronic acid
only at week 4 and week 12, and a return to lower but
Musculoskelet Surg (2013) 97 (Suppl 1):S49–S56
non-statistically significant scores with respect to baseline,
injections could provide good mid- and long-term clinical
at week 24 in both groups. The consumption of rescue
medication was higher in the Physio group from week 12 toweek 24, but at the end of the study, such differencebecame not significant. These results suggest that suba-
cromial HA injections are effective in inducing betterclinical outcomes and pain relief compared to physiother-
Despite the limitations of the current research, such as no
apy from the start of the study up to week 12, the thera-
randomization and relatively small sample size, we may
peutic effects became less important at 6 months when
conclude that subacromial HA injections could be an
symptoms gradually returned. Stratifying the results, we
effective and safe alternative treatment for patients suf-
found that five patients in the Physio group had worsening
fering from RC tendinopathy. Our results are encouraging
VAS scores at the end of study, whereas this was seen in
but not lasting, and we might suppose that further
only two patients in the HA group. The two patients in the
investigation with a larger sample size into the optimal
HA group were young in age and have relative high daily
injection regime and possible combination with current
activities on the shoulder in life, that is, regular fitness
standard therapies, so as to provide long-term benefits, are
training and therefore higher risk to develop overuse ten-
dinopathy and subacromial bursitis. The procedure forshoulder injection was safe without any adverse events
Conflict of interest
registered in all the enrolled subjects.
We used the same anterolateral approach with ultra-
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prepared in collaboration with the WHO Collaborating Centre for International Drug Monitoring, The aim of the Newsletter is to disseminate information on the safety and efficacy of pharmaceutical products, The WHO Pharmaceuticals Newsletter provides you with the latest information on the safety of medicines and based on communications received
O'Shaughnessy's • Winter 2015/16 —7— Cannabis in the Treatment of Pediatric Epilepsy By Bonni Goldstein, MD The author documents the progress of more than 100 patients using CBD-rich cannabis oil to treat seizure disorders. I have been a medical cannabis physician seeing adult tion they are going to give their child. They cannot give oil, the added expense of testing every bottle becomes pro-