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Comparison of single platelet-rich plasma injection with hyaluronic acid injection for partial-thickness rotator cuff tears

Huang, Shou-Hsiena; Hsu, Po-Chengb,c; Wang, Kevin A.d,e; Chou, Chen-Liangb,c; Wang, Jia-Chib,c,*

Author Information
Journal of the Chinese Medical Association: June 2022 - Volume 85 - Issue 6 - p 723-729
doi: 10.1097/JCMA.0000000000000736
  • Open

Abstract

1. INTRODUCTION

Partial-thickness rotator cuff tears (PTRCTs) are common causes of shoulder pain and dysfunction, with incidence ranging from 13% to 37%.1,2 There is an increasing incidence with age.2–4 Although study found α1 type I procollagen mRNA near the tear area may be potential for repair,5 most studies found increased IL-1β, IL6, matrix metalloprotease-1, and COX2 may contribute to the progression rather than repair.5,6 Treatment of PTRCTs depends on the patient’s age, symptoms, activity level, previous treatment effect, and causes of PTRCTs. Surgical intervention of PTRCTs ranges from acromioplasty, debridement of tear with or without acromioplasty, to tendon repair.7,8 Nonoperative management of PTRCTs includes rest, activity modification, anti-inflammatory and pain medications, physical modalities, therapeutic exercises, and injections.5,9

Corticosteroids injection, alone or combined with anesthetics, has been used to treat PTRCTs.10 Nevertheless, there is emerging evidence to suggest the possible detrimental effect of corticosteroids on tendons, including loss of fibroblasts, decreased mechanical strength, reduced type I collagen secretion, fragmentation of collagen, and infiltration of inflammatory cells.11–13 The deleterious effects of corticosteroid injections correlate with the number of injections, and its therapeutic effects are relatively short term.14 Therefore, alternative injectates were proposed and applied for the treatment of PTRCTs.15,16

Hyaluronic acid (HA) is found in synovial fluid and extracellular matrix, where it has both biological and mechanical effects, including shock absorption, lubrication, and anti-inflammation.17 Most studies investigating HA for treating PTRCTs have shown improvement in symptoms including pain, range of motion (ROM), activities of daily living, and function without severe adverse effects.18,19 Nevertheless, tissue repair and spontaneous healing of PTRCTs after HA injection appears less likely, and intratendinous injection of HA can cause acute inflammation, although there is controversy regarding this.20

There has recently been a trend toward using regenerative medicine to treat musculoskeletal conditions and to alleviate pain, especially in the context of degenerative pathology. Platelet-rich plasma (PRP) is an autologous blood product containing high concentrations of platelet and growth factors, prepared by centrifugation of whole blood.21 PRP has showed promising effects in reduction of inflammation and healing of tendon injuries and has been widely used in both conservative and surgical management of PTRCTs.22–24 Nevertheless, there are few studies comparing the effect of HA and PRP in patients with PTRCTs, and the dosage of injections varied. Therefore, the aim of the present study was to compare the short-term therapeutic effects of ultrasound-guided injection of single PRP with three doses HA in treatment of PTRCTs.

2. METHODS

2.1. Study design

The prospective, nonrandomized comparative study was conducted at single medical center from April 2014 to March 2018. The flow chart for participants’ enrollment is presented in Fig. 1. Patients diagnosed with partial supraspinatus tendon tears on ultrasonography, including articular side, bursal side, full-thickness, and intrasubstance tear, were recruited from the rehabilitation clinic. Informed consent was obtained before enrollment. The inclusion criteria were as follows: (1) age 18–64 without cognitive impairment; (2) shoulder visual analog scale (VAS) >5; and (3) agreement to cease all pain control medications during the study period.

F1
Fig. 1:
Study flow diagram for the groups receiving ultrasound-guided PRP or HA injection. HA = hyaluronic acid; PRP = platelet-rich plasma.

The exclusion criteria were as follows: (1) abnormal coagulation function or acute medical illness; (2) uncontrolled infection; (3) cervical radiculopathy; (4) concurrent shoulder disease (eg, shoulder arthropathy, frozen shoulder, tear of other rotator cuff tendons); (5) history of major trauma, shoulder subluxation, dislocation, operation; and (6) recent shoulder injection within 3 months before pretrial evaluation.

The enrolled patients were instructed to the treatments option, procedure, and the possible adverse events of injection. They were asked to select the treatment by themselves, and were not blinded to the treatment.

The study protocol was approved by the local institutional review board (VGHIRB No.2014-02-005B) and was registered on ClinicalTrials.gov (registration number: NCT03548662).

2.2. Ultrasound-guided injection and rehabilitation program

Patients allocated to receive either a single ultrasound-guided intralesional and peritendinous single injection of 4 mL of PRP (Regenlab PRP Kit-RegenACR, Le Mont-sur-Lausanne Switzerland) and shoulder rehabilitation exercise (PRP group), or ultrasound-guided subacromial 2 mL high-molecular-weight HA (Hyruan Plus, LG Pharm Co., Seoul, Korea) injection three times with 2 weeks’ interval and shoulder rehabilitation exercise (HA group). All the injections were performed by the same physiatrist who had over 10 years of experience in ultrasound-guided interventions, by using a high-frequency (5–14 MHz) linear array transducer (Siemens Acuson S2000, Germany).

Therapeutic exercise following injection was instructed to each patient. The specific exercises composed of shoulder ROM, flexibility, scapular stabilization exercise and shoulder girdle strengthening exercise. Patients were asked to visit the physical therapist 2 times per week to follow up their progression and provide advice in home program. For those who underwent PRP injection, strengthening exercise were strictly started after 2 weeks after injection.

2.3. Clinical assessment and outcome measurement

The primary outcome was Chinese version of the Shoulder Pain and Disability Index (SPADI), composed of two dimensions (pain scale and disability scale), and 13 items with each item scored from 0 (no pain or no difficulty) to 10 (worst pain imaginable or so difficult that the patient requires help). The score of each dimension was averaged and transferred to a 100-point scale, with higher scores indicating worse pain (total pain score) or disability (total disability score). The scores of the two dimensions were summed, averaged, and transformed to the total SPADI scale.

Secondary outcome measurements were the ROM of the shoulder, including active flexion, passive flexion, active abduction, passive abduction, active external rotation, passive external rotation, active internal rotation, and passive internal rotation. Other data which were also recorded included the Constant-Murley Shoulder Score (CMSS), a 100-point scale composed of several parameters to determine pain and ability to carry out daily functions with higher scores indicating better pain and function of the shoulder, and the VAS for assessing pain, including pain during overhead activities, resting pain, and night pain. All outcome parameters were documented at baseline, 1 month, and 3 months after injections. Patients were asked to report any adverse effects during the study period and all evaluations were conducted by a therapist who was unaware of the treatment and research protocol.

2.4. Statistical analysis

Statistical analyses were completed using SPSS 23.0 (IBM, Armonk, NY). Continuous variables were expressed as mean ± SD and the 95% confidence interval, whereas categorical data were expressed as number and percentage. The normality of distribution was tested using the Shapiro-Wilk test for continuous variables. To compare baseline differences between two groups, the independent t-test (for normal distribution data) or the Mann-Whitney test (for non-normal distribution data) was used for continuous variables, and the categorical data were compared using the chi-squared test.

The effect of the interventions on SPADI scores, ROM, VAS scores, and CMSS was analyzed by comparing the differences (from baseline to each follow up) using the paired t-test (for normal distribution data) or the Wilcoxon signed-rank test (for non-normal distribution data). To compare the effects between two groups, the independent t-test (for normal distribution data) or the Mann-Whitney test (for non-normal distribution data) was administered. Due to baseline difference in pain during overhead activities, analysis of covariance was administered for between-group comparison of VAS during overhead activities. A value of p < 0.05 was considered statistically significant.

3. RESULTS

3.1. Patients

There were 54 patients referred for initial survey, and 6 patients were excluded due to hematological disease (n = 1), adhesive capsulitis (n = 1), amyloidosis (n = 1), recent injection (n = 1) and refusal of consent (n = 2). A total of 48 patients (37 women and 11 men) met the inclusion criteria and enrolled in the full study and completed the follow up (Fig. 1). The two groups were similar with respect to baseline clinical demographics and characteristics (Table 1).

Table 1 - Baseline characteristics
Variables PRP group (n = 24) HA group (n = 24) Between-group comparison, p
Age (y) 61.8 ± 2.5 61.5 ± 2.1 0.919
Women (number, %) 18 (75.0) 19 (79.2) 0.731
Right shoulder (number, %) 16 (66.7) 15 (62.5) 0.763
Duration (y) 9.7 ± 2.1 9.3 ± 2.2 0.843
Size (mm) 8.4 ± 0.7 8.4 ± 0.8 0.978
SPADI (pain) 40.1 ± 19.6 33.1 ± 17.0 0.193
SPADI (disability) 40.6 ± 23.5 40.2 ± 16.5 0.944
SPADI (total) 40.4 ± 21.6 37.5 ± 16.2 0.603
VAS 6.0 ± 2.1 6.2 ± 1.7 0.617
CMSS 49.4 ± 15.0 49.9 ± 11.0 0.896
ROM (degree)
 Active flexion 147.5 ± 35.0 150.5 ± 23.6 0.726
 Passive flexion 149.7 ± 35.6 152.6 ± 24.0 0.737
 Active abduction 109.0 ± 36.9 109.5 ± 26.7 0.954
 Passive abduction 112.4 ± 35.0 112.0 ± 25.4 0.963
 Active external rotation 65.5 ± 25.2 60.8 ± 26.8 0.564
 Passive external rotation 67.0 ± 25.1 62.5 ± 26.7 0.578
 Active internal rotation 69.2 ± 22.6 71.0 ± 18.5 0.777
 Passive internal rotation 71.2 ± 22.3 73.0 ± 17.7 0.778
Age, duration, size, SDADI scores, ROM, VAS scores, CMSS are given as mean ± SD.
CMSS = Constant-Murley Shoulder Score; ROM = range of motion; SPADI = Shoulder Pain and Disability Index; VAS = pain visual analog scale.

3.2. Outcomes

A significant decreased in the SPADI scores (pain, function, and total) and VAS pain score, and increased in CMSS were observed in 1-month and 3-month follow ups (Table 2; Fig. 2). Bedside, the SPADI scores (pain, function, and total), VAS pain score and CMSS in both groups were significant different between the point of 1-month and 3-month follow ups. There were no significant intergroup differences with respect to the SPADI scores (pain, function, and total) and VAS pain score at each follow-up timing. Both groups showed significant improvement in CMSS in the first month and the third month; however, the improvement was significantly greater in the PRP group in the third month.

Table 2 - SPADI scores at first and third month after the injection
Outcomes PRP group (n = 24) Difference from baseline HA group (n = 24) Difference from baseline p
SPADI (pain)
 First month 27.3 ± 13.2 a (21.7–32.9) –12.8 ± 11.3 (–17.5 to –8.0) 24.5 ± 14.3 a (18.4–30.6) –8.6 ± 11.0 (–13.2 to –3.9) 0.203
 Third month 18.5 ± 13.7 a , b (12.7–24.3) –21.6 ± 16.4 (–28.5 to –14.6) 19.1 ± 15.0 a , b (12.8–25.4) –14.0 ± 18.6 (–21.8 to –6.16) 0.098
SPADI (disability)
 First month 32.7 ± 20.6 a (24.0–41.4) –7.9 ± 9.0 (–11.7 to –4.1) 33.0 ± 15.4 a (26.5–39.5) –7.2 ± 6.0 (–9.8 to –4.7) 0.759
 Third month 21.3 ± 18.5 a , b (13.5–29.1) –19.3 ± 17.6 (–26.8 to –11.9) 26.5 ± 16.6 a , b (19.4–33.5) –13.8 ± 14.6 (–19.9 to –7.6) 0.445
SPADI (total)
 First month 30.6 ± 17.0 a (23.5–37.8) –9.7 ± 9.3 (–13.6 to –5.8) 29.7 ± 14.2 a (23.7–35.7) –7.8 ± 7.0 (–10.7 to –4.8) 0.415
 Third month 20.6 ± 15.8 a , b (14.0–27.3) –19.7 ± 16.3(–26.6 to –12.8) 23.6 ± 15.5 a , b (17.1–30.2) –13.8 ± 15.4 (–20.4 to –7.3) 0.403
CMSS
 First month 56.3 ± 12.0 a (51.3–61.4) 7.0 ± 7.5 (3.8 to 10.1) 54.3 ± 11.2 a (49.6–59.0) 4.4 ± 6.6 (1.6 to 7.2) 0.218
 Third month 65.9 ± 12.2 a , b (60.8–71.1) 16.5 ± 9.7 (12.5 to 20.6) 58.8 ± 10.5 a , b (54.3–63.2) 8.9 ± 9.3 (4.9 to 12.8) 0.008
VAS
 First month 3.8 ± 1.6 a (3.1–4.4) –2.25 ± 2.09 (–3.1 to –1.4) 4.0 ± 1.8 a (3.2–4.7) –2.25 ± 2.29 (–3.2 to –1.3) 0.351
 Third month 2.8 ± 2.0 a , b (1.9–3.6) –3.25 ± 2.40 (–4.3 to –2.2) 3.1 ± 2.7 a , b (2.0–4.3) –3.08 ± 3.34 (–4.5 to –1.7) 0.219
Scores are given as mean ± SD (95% confidence interval of mean). p pertain to between-group comparisons for differences from baseline
aSignificant difference compared with baseline.
bSignificant difference compared with first month.
CMSS = Constant-Murley Shoulder Score; HA = hyaluronic acid; PRP = platelet-rich plasma; SPADI = Shoulder Pain and Disability Index.

F2
Fig. 2:
Mean changes and the corresponding 95% confidence intervals pertaining to the pain domain of the SPADI scores (A), the function domain of the SPADI score (B), the total SPADI scores (C), the VAS scores (D), and CMSS (E). * p < 0.05 of between-group comparisons for differences from baseline. CMSS = Constant-Murley Shoulder Score; SPADI = Shoulder Pain and Disability Index; VAS = pain visual analog scale.

Regarding shoulder ROM, in the PRP group, active and passive flexion, abduction increased significantly from baseline and the first to the third month; active and passive external rotation improved significantly from baseline to the third month. In the HA group, active and passive flexion increased significantly from the baseline and from the first month to the third month; active abduction significantly increased in the third month and active internal rotation significantly improved in the first month, compared with the baseline. In terms of between-group comparison, there was significantly greater augmentation of passive abduction in the PRP group in the third month (Table 3; Fig. 3).

Table 3 - Shoulder ROM at first and third month after the injection
Outcomes PRP group (n = 24) Difference from baseline HA group (n = 24) Difference from baseline P
Active flexion
 First month 149.6 ± 31.6 (136.3–163.0) 2.2 ± 17.3 (–5.1 to 9.5) 152.4 ± 21.7 (143.3–161.6) 1.9 ± 15.4 (–4.6 to 8.4) 0.958
 Third month 160.7 ± 15.5 a , b (154.2–167.3) 13.3 ± 28.3 (1.3 to 25.2) 159.1 ± 14.4 a , b (153.0–165.2) 8.6 ± 16.3 (1.8 to 15.4) 0.487
Passive flexion
 First month 151.8 ± 31.1 (138.6–164.9) 2.1 ± 18.0 (–5.5 to 9.7) 154.9 ± 19.8 (146.6–163.3) 2.3 ± 14.9 (–4.0 to 8.6) 0.965
 Third month 162.6 ± 15.3 a , b (156.2–169.1) 13.0 ± 28.6 (0.9 to 25.0) 160.7 ± 14.2 a , b (154.7–166.7) 8.1 ± 16.0 (1.3 to 14.9) 0.470
Active abduction
 First month 113.8 ± 30.5 (101.0–126.7) 4.8 ± 23.3 (–5.0 to 14.7) 113.8 ± 32.1 (100.3–127.4) 4.3 ± 18.3 (–3.4 to 12.0) 0.929
 Third month 132.0 ± 29.6 a , b (119.6–144.5) 23.0 ± 29.4 (10.6 to 35.4) 118.3 ± 30.0 a (105.6–131.0) 8.8 ± 19.1 (0.7 to 16.8) 0.052
Passive abduction
 First month 115.7 ± 30.1 (103.0–128.4) 3.3 ± 21.5 (–5.8 to 12.4) 116.6 ± 29.9 (104.0–129.2) 4.6 ± 17.5 (–2.8 to 12.0) 0.821
 Third month 135.3 ± 29.2 a , b (122.9–147.6) 22.8 ± 28.7 (10.7 to 35.0) 119.4 ± 30.1 (106.7–132.1) 7.4 ± 19.5 (–0.9 to 15.6) 0.034
Active external rotation
 First month 55.7 ± 32.2 (42.1–69.3) 1.1 ± 21.3 (–7.9 to 10.1) 56.8 ± 29.2 (44.4–69.1) 1.0 ± 33.1 (–13.3 to 15.4) 0.992
 Third month 66.0 ± 28.2 b (54.1–77.9) 11.5 ± 31.4 (–1.8 to 24.7) 57.7 ± 30.3 (44.0–71.3) 2.0 ± 35.8 (–13.5 to 17.5) 0.340
Passive external rotation
 First month 57.0 ± 32.2 (43.4–70.6) 1.3 ± 21.8 (–8.0 to 10.5) 58.3 ± 29.0 (46.0–70.5) 1.0 ± 33.0 (–13.2 to 15.36) 0.980
 Third month 67.4 ± 28.0 b (55.6–79.2) 11.6 ± 32.4 (–2.1 to 25.3) 58.1 ± 30.6 (44.4–71.8) 0.9 ± 36.2 (–14.7 to 16.6) 0.291
Active internal rotation
 First month 60.2 ± 30.1 (47.5–72.9) 2.6 ± 22.4(–6.9 to 12.0) 73.8 ± 23.2 a (64.0–83.6) 9.1 ± 22.2 (–0.5 to 18.7) 0.320
 Third month 68.4 ± 26.9 (57.0–79.7) 10.8 ± 33.5 (–3.4 to 24.9) 71.0 ± 29.1 (57.4–84.6) 10.6 ± 33.2 (–4.1 to 25.3) 0.987
Passive internal rotation
 First month 61.5 ± 30.0 (48.9–74.2) 2.2 ± 23.3 (–7.6 to 12.1) 75.0 ± 23.2 (65.2–84.7) 8.4 ± 22.2 (–1.2 to 18.0) 0.354
 Third month 70.0 ± 26.7 (58.7–81.3) 10.7 ± 34.2 (–3.8 to 25.1) 71.6 ± 28.8 (58.1–85.1) 9.2 ± 33.4 (–5.6 to 24.0) 0.886
ROM are given as mean ± SD (95% confidence interval of mean). p pertain to between-group comparisons for differences from baseline.
aSignificant difference compared with baseline.
bSignificant difference compared with first month.
HA = hyaluronic acid; PRP = platelet-rich plasma; ROM = range of motion.

F3
Fig. 3:
Mean changes and the corresponding 95% confidence intervals pertaining to ROM of active flexion (A), passive flexion (B), active abduction (C), passive abduction (D), active external rotation (E), passive external rotation (F), active internal rotation (G), and passive internal rotation (H). * p < 0.05 of between-group comparisons for differences from baseline. ROM = range of motion.

4. DISCUSSION

This study demonstrated that ultrasound-guided injection with PRP and HA combined with rehabilitation are effective short-term measures in alleviating shoulder pain and improving shoulder function. This is one of the first few studies comparing the effectiveness of ultrasound-guided single PRP injection and three doses of HA injections as the main treatment in patients with PTRCTs. These results, in addition to the lack of significant side effects reported, provided evidence that both PRP and HA may have a role in conservative management of PTRCTs.

The clinical improvement of HA group was accordant with those of previous studies, which reported that injection of HA into either the subacromial space or the glenohumeral joint reduced pain and increased function in patients with rotator cuff tears,18,19 and the therapeutic effect was either superior or equal to that of corticosteroid injections.25,26 The biological effects of HA in facilitating tendon healing were proposed to be integration into extracellular fibrin matrix and aiding fibrillar realignment,27 and alleviated inflammation by mitigating inflammatory responses.17 Because of the tear, the subacromial bursa can be communicated with the tendon in bursal side tear, and the HA can infiltrate to the tear site and surrounding tissue. The subacromial bursa is crucial for normal shoulder function and subacromial gliding mechanism, as it contains extensive free nerve endings of nociceptive fibers, including A-delta and C-fibers.28 Subacromial HA injection may inhibit the proinflammatory cytokines and decreased pain,17,29 and subsequently improve shoulder function and ROM. Nevertheless, the numbers of injections varied from one to three times to five times,18,19,25 and the injection sites varied from intra-articular to subacromial space among current studies.18,19,25,26

The pathogenesis of PTRCTs is multifactorial and includes both intrinsic and extrinsic factors. The intrinsic factors include hypovascular critical zones close to the supraspinatus insertion, age-related decrease of blood supply to the tendon, fiber thinning, and granulation.9 PRP not only reduces inflammation by modulating the inflammatory enzyme expression and regulation but also being considered as a regenerative agent.30,31 It has been used to treat chronic tendon injuries, including tennis elbow as well as patellar and Achilles tendinopathies.32–34 The possible mechanism of PRP promotion involves tendon cell proliferation, gene expression, and synthesis of tendon matrix, collagen synthesis, and vascularization,18,22,35 all of which may counteract the pathogenesis of PTRCTs. Unlike the mechanism of HA, a superiority effect due to regeneration was expected. Our study revealed that most of the clinical outcome after single PRP injection were similar to HA group, with greater improvement in CMSS and abduction ROM. A significant improvement of abduction ROM was of interest because intact rotator cuff contributed to the shoulder abduction and joint stability by cadaveric study.36 The improvement of the ROM implicated the restoration of the rotator cuff function following injection, and corresponding stabilizing shoulder joint stability could be expected.

Previous studies reported that PRP injection for rotator cuff tears may be effective.35,37,38 A meta-analysis demonstrated a trend in functional improvement and pain reduction when using PRP to treat rotator cuff tears, particularly in long-term follow up39; however, the effects did not reach minimal clinically important differences. A recent study comparing the HA, PRP, and combination of HA with PRP in treating PTRCTs reported that combination of HA and PRP demonstrated a better clinical outcome than HA or PRP alone in a 12-month follow up.40 Our study demonstrated similar trend in alleviating pain and improving shoulder function at 3-month follow up; however, there were only slight significant difference between HA and PRP. Possible explanations included the dose responses to PRP; single PRP dose in our study compared with four injections in Cai et al. may not enough to exhibit obvious superiority in clinical efficacy over the HA group.40 Nevertheless, our study demonstrated that the short-term effect of a single PRP injection was similar to that of three doses of HA injection. Recent studies compared the cost-effectiveness of PRP and HA in treating knee osteoarthritis, indicated the PRP may not be more cost-effective than HA injections.41,42 Whenever medical expense is a concern, the comparable therapeutic effect of both injections could provide more options to the patient. Moreover, individual participants in our study were enrolled in postinjection rehabilitation program. Evidence suggested that conservative rehabilitation program for rotator cuff tear was similar to surgery.43–46 Therefore, synergistic effect of injection and exercise in PTRCTs should be considered in promoting the functional recovery and pain reduction.

There are several limitations regarding this study. First, the study was not randomized in allocation, and the patients were not blinded to the treatments, since blood sampling was needed in the PRP group. Second, the sample size of our study was relatively small, and we enrolled all the types of partial tear which might have masked some potential differences in outcome measurements. Third, the follow-up duration lasted only 3 months, which was relatively short. A further prospective cohort study with a longer follow-up period is needed to confirm the mid-term to long-term (>6 months) treatment effects. Fourth, our outcome measurements were only continuous variables; since the tendon healing model suggested that structural remodeling may last 1 year or more, objective measurements such as MRI or ultrasound images with a longer follow up could be considered in further studies. Fifth, there is still lack of consensus on the preparation procedure of PRPs, the optimal molecular weight of HAs, the injection sites of PRP and HA, the optimal number of injections, and the intervals between injections. There remains a need for more large-scale, prospective, randomized, controlled, double-blind trials to confirm our findings.

In conclusion, both ultrasound-guided peritendinous and intralesional PRP injection and subacromial HA injection combining rehabilitation were effective in pain management and improved function after PTRCTs. However, the therapeutic effects in the PRP group were more prominent, in terms of passive shoulder abduction ROM and CMSS at the 3-month follow up. Ultrasound-guided PRP injection should be considered a good option for treating PTRCTs. There is a need for more large-scale double-blinded, randomized controlled trial to determine the optimal preparation procedure, site, dose of injection, and the length of the therapeutic effects of PRP injection in PTRCTs.

ACKNOWLEDGMENTS

This work was supported by Taipei Veterans General hospital (Grant number: V108B-017), and Yen Tjing Ling Medical Foundation (Grant number: CI-107-30), Taipei, Taiwan, ROC. The funding source had no involvement in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the article for publication. We thank Miss Yu-Yang Chang for recruiting patients and data collection.

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Keywords:

Hyaluronic Acid; Injection; Platelet-Rich Plasma; Rotator Cuff Injuries; Ultrasonography

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