Effectiveness of sub-acromial injections in rotator cuff injuries: A systematic review and meta-analysis

Table 1 Search strategies presented to the main databases

Databases	Search strategy
Medline/PubMed	(“Rotator cuff” OR shoulder impingement syndrome OR subacromial bursitis OR subacromial impingement OR rotator cuff injuries OR rotator cuff tendinosis OR shoulder pain OR supraspinatus OR infraspinatus OR subscapular OR teres minor) AND (hyaluronic acid OR hyaluronic acid injection OR sodium hyaluronate OR hyaluronate sodium OR viscosupplement platelet rich plasma injection OR platelet rich plasma OR PRP OR corticoid injection OR glucocorticoid OR corticosteroid injection OR prolotherapy OR dextrose injection) NOT (arthroscopy OR surgery OR adhesive capsulitis OR frozen shoulder)
	Filters: Humans, randomized controlled trial, controlled clinical trial, randomized, from 1900/1/1-2023/3/1
The Cochrane Library	#1 (rotator cuff): ti, ab, kw* #2 (shoulder impingement syndrome): ti, ab, kw #3 (subacromial bursitis): ti, ab, kw #4 (rotator cuff tendinosis): ti, ab, kw #5 (subacromial impingement): ti, ab, kw #6 (rotator cuff injuries): ti, ab, kw #7 (rotator cuff lesions): ti, ab, kw #8 (hyaluronic acid): ti, ab, kw #9 (hyaluronate sodium): ti, ab, kw #10 (viscosupplement): ti, ab, kw #11 (platelet rich plasma): ti, ab, kw #12 (PRP): ti, ab, kw #13 (corticoid): ti, ab, kw #14 (corticosteroid): ti, ab, kw #15 (glucocorticoid): ti, ab, kw #16 (prolotherapy): ti, ab, kw #17 (dextrose): ti, ab, kw #18 (arthroscopy): ti, ab, kw #19 (surgery): ti, ab, kw #20 (adhesive capsulitis): ti, ab, kw #21 (frozen shoulder): ti, ab, kw #22 (#1 OR #2 OR #3 OR #4 OR #5 OR #6 OR #7) #23 (#8 OR #9 OR #10 OR #11 OR #12 OR #13 OR #14 OR #15 OR #16 OR #17)
EMBASE	(“rotator cuff” OR “shoulder impingement syndrome” OR “subacromial bursitis” OR “subacromial impingement” OR “rotator cuff injuries” OR “rotator cuff tendinosis” OR “rotator cuff lesions” OR “shoulder pain” OR “supraspinatus” OR “infraspinatus” OR “subscapular” OR “teres minor”) AND (“hyaluronic acid” OR “viscosupplement” OR “hyaluronate sodium” OR “PRP” OR “platelet rich plasma” OR “corticoid” OR “corticosteroid” OR “glucocorticoid” OR “prolotherapy” OR “dextrose injection”) NOT (“arthroscopy” OR “surgery” OR “adhesive capsulitis” OR “frozen shoulder”)
LILACS	TW*: (“rotator cuff” or “shoulder impingement syndrome” or " “rotator cuff injuries" or “rotator cuff lesions” or “rotator cuff tendinosis” or “subacromial bursitis” or “subacromial impingement”) AND (“hyaluronic acid” or “viscosupplement” or “hyaluronate sodium” or “PRP” or “platelet rich plasma” or “corticoid” or “corticosteroid injection” or “glucocorticoid” or “prolotherapy” or “dextrose injection”) AND NOT (“arthroscopy” OR “surgery” OR “adhesive capsulitis” OR “frozen shoulder”)

Table 2 The main characteristics of the included studies for partial-thickness rotator cuff tears

Ref.	Technique	Follow-up			Intervention						Pain score	Functional score	Complementary imaging examination	Adverse effects
		S	M	L	PL	HA	PRP	HA+PRP	CE	PR
Partial-thickness rotator cuff tears
Cai et al[44]	Guided by US sub-acromial	Yes	Yes	Yes	47	44	45	48	-	-	VAS	ASES CMS	MRI	NE
Chou et al[45]	Not guided by US sub-acromial	Yes	No	Yes	26	25	-	-	-	-	VAS	CMS	NE	None
Kesikburun et al[46]	Guided by US intratendineous	Yes	Yes	Yes	20	-	20	-	-	-	VAS	ROM SPADIWORC	NE	NE
Moghtaderi et al[47]	Guided by US sub-acromial	Yes	Yes	No	20	20	-	-	-	-	VAS	CMS	NE	NE
Shams et al[48]	Not guided by US sub-acromial	Yes	Yes	No	-	-	20	-	20	-	NE	ASES CMS SST	MRI	NE
Schwitzguebel et al[49]	Guided by US sub-acromial	No	Yes	Yes	39	-	41	-	-	-	VAS	ASES CMS SANE	MRI	Local pain for more than 48h, frozen shoulder, and lesion progression
Kwong et al[50]	Guided by US sub-acromial	Yes	Yes	Yes	-	-	47	-	52	-	VAS	ASESWORC	US	None
Dadgostar et al[51]	Guided by US sub-acromial + intratendineous	Yes	Yes	No	-	-	30	-	28	-	VAS	DASHROMWORC	US	NE
Sari and Eroglu[52]	Guided by US sub-acromial	Yes	Yes	No	30	-	30	-	30	30	VAS	ASESWORC	NE	NE

S: Short-term; M: Medium-term; L: Long-term; PL: Placebo; HA: Hyaluronic acid; PRP: Platelet rich plasma; CE: Corticoid; PR: Prolotherapy; VAS: Visual Analogue Scale; CMS: Constant-Murley Score; ASES: American Shoulder and Elbow Surgeons Score; WORC: Western Ontario Rotator Cuff Index; SPADI: Shoulder, Pain and Disability Index; ROM: Range of Motion; SST: Simple Shoulder Test; SANE: Single assessment numerical evaluation; DASH: Disabilities of arm, shoulder, and hand score; UCLA: University of California at Los Angeles Shoulder Score; SF-36: 36-item Short-Form Health Survey; SDQ: Shoulder disability questionnaire; US: Ultrasound; MRI: Magnetic resonance imaging; NE: Not evaluated.

Table 3 The main characteristics of the included studies for rotator cuff tendinopathy

Ref.	Technique	Follow-up			Intervention						Pain score	Functional score	Complementary imaging examination	Adverse effects
		S	M	L	PL	HA	PRP	HA+PRP	CE	PR
Rotator cuff tendinopathy
Akgün et al[33]	Not guided by US sub-acromial	Yes	Yes	No	16	-	-	-	32*	-	VAS	CMS	NE	Dyspepsia
Alvarez et al[34]	Not guided by US sub-acromial	Yes	Yes	No	28	-	-	-	30	-	VAS	ASES DASH ROM WORC	NE	NE
Barreto et al[35]	Not guided by US sub-acromial	Yes	Yes	No	-	-	26	-	25	-	NE	CMS DASH UCLA	NE	None
Lin et al[36]	Guided by US intratendineous	Yes	Yes	No	28	-	-	-	-	29	VAS	ROM SPADI	US	NE
Chang et al[37]	Guided by US sub-acromial	Yes	Yes	No	25	-	-	-	-	25	VAS	ROM SPADI	US	NE
Kim et al[38]	Guided by US sub-acromial	Yes	Yes	No	-	38	-	-	42	-	VAS	ASES ROM	NE	Nasopharynx, musculoskeletal pain, local pain, and cough
Cole et al[39]	Guided by US sub-acromial + intratendineous	Yes	Yes	No	-	-	-	-	19	17	Likert	ROM	US	NE
Hsieh et al[40]	Guided by US sub-acromial	Yes	Yes	No	58	60	-	-	68	-	VAS	ROM SD SF-36 SPADI	NE	NE
Damjanov et al[41]	Guided by US peritendineous + enthesis	Yes	Yes	No	-	-	15	-	16	-	VAS	CMS	NE	Headache, arterial hypertension, facial erythema, and moon face
Lin et al[42]	Guided by US intratendineous	Yes	No	No	15	-	-	-	-	6	VAS	ROM SPADI	US	None
Meloni et al[43]	Guided by US sub-acromial	Yes	Yes	Yes	28	28	-	-	-	-	VAS	ROM	US	None

S: Short-term; M: Medium-term; L: Long-term; PL: Placebo; HA: Hyaluronic acid; PRP: Platelet rich plasma; CE: Corticoid; PR: Prolotherapy; VAS: Visual Analogue Scale; CMS: Constant-Murley Score; ASES: American Shoulder and Elbow Surgeons Score; WORC: Western Ontario Rotator Cuff Index; SPADI: Shoulder, Pain and Disability Index; ROM: Range of Motion; SST: Simple Shoulder Test; SANE: Single assessment numerical evaluation; DASH: Disabilities of arm, shoulder, and hand score; UCLA: University of California at Los Angeles Shoulder Score; SF-36: 36-item Short-Form Health Survey; SDQ: Shoulder disability questionnaire; US: Ultrasound; MRI: Magnetic resonance imaging; NE: Not evaluated.

Table 4 Summary of findings

	Short-term	Medium-term	Long-term
Pain (VAS)	HA1 HA + PRP1	HA1	HA, PRP and corticoids: Little-to-no effect3
Function	CMS: HA + PRP1 HA1	ASES: HA + PRP3	CMS: HA + PRP1 (great improvement)
			PRP1
			HA1 (small improvement)
			ASES: HA + PRP1 (great improvement)
			PRP1
			Corticoid2 (small improvement)
			HA2 (small improvement)

¹Moderate certainty of evidence.

²Low certainty of evidence.

³Very low certainty of evidence.

SPADI, SST and WORC: No differences at any time. VAS: Visual Analogue Scale; CMS: Constant-Murley Score; ASES: American Shoulder and Elbow Surgeons Society Standardized Shoulder Assessment Score; HA: Hyaluronic Acid; PRP: Platelet-Rich Plasma; SPADI: Shoulder Pain Disability Index; SST: Simple Shoulder Test; WORC: Western Ontario Rotator Cuff Index.

Table 5 League Table with the results of the network meta-analysis for pain improvement Visual Analogue Scale in the short term

	Hyaluronic acid	HA + PRP	Corticosteroids	PRP	Prolotherapy	Placebo
Network meta-analysis-MD	-0.28 [-1.86; 1.30]
	-0.56 [-1.54; 0.42]	-0.28 [-1.90; 1.35]
	-0.92 [-2.00; 0.16]	-0.64 [-2.22; 0.93]	-0.37 [-1.25; 0.52]
	-1.43 [-2.66; -0.20]	-1.15 [-2.90; 0.60]	-0.88 [-1.99; 0.24]	-0.51 [-1.67; 0.65]
	-1.48 [-2.37; -0.59]	-1.20 [-2.74; 0.34]	-0.92 [-1.73; -0.12]	-0.56 [-1.45; 0.33]	-0.05 [-0.95; 0.86]

HA: Hyaluronic acid; PRP: Platelet-rich plasma; MD: Mean difference.

Table 6 League Table with the results of the network meta-analysis for function improvement Constant Murley Score in the short term

	HA + PRP	Hyaluronic acid	PRP	Corticosteroids	Placebo
Network meta-analysis-MD	0.53 [-6.22; 7.28]
	3.15 [-3.89; 10.18]	2.62 [-3.89; 9.12]
	5.84 [-4.07; 15.75]	5.31 [-4.00;14.62]	2.69 [-5.51; 10.89]
	10.7 [4.01; 17.42]	10.18 [4.96; 15.41]	7.57 [1.31; 13.82]	4.87 [-3.69; 13.43]

HA: Hyaluronic acid; PRP: Platelet-rich plasma; MD: Mean difference.

Table 7 League Table with the results of the network meta-analysis for function improvement American Shoulder and Elbow Surgeons Standardized Shoulder Assessment in the short term

	HA + PRP	Corticosteroids	Hyaluronic acid	Placebo	Prolotherapy	PRP
Network meta-analysis-MD	6.15 [-5.00; 17.31]
	7.09 [-3.79; 17.97]	0.93 [-7.47; 9.34]
	8.97 [-1.61; 19.55]	2.82 [-4.94; 10.57]	1.88 [-7.18; 10.94]
	9.95 [-4.36; 24.25]	3.79 [-7.41; 15.00]	2.86 [-10.01; 15.73]	0.98 [-10.38; 12.34]
	10.61 [0.11; 21.11]	4.45 [-2.37; 11.28]	3.52 [-5.23; 12.26]	1.64 [-6.00; 9.27]	0.66 [-10.44; 11.76]

HA: Hyaluronic acid; PRP: Platelet-rich plasma; MD: Mean difference.

Table 8 League Table with the results of the network meta-analysis for pain improvement Visual Analogue Scale in the medium term

	Hyaluronic acid	PRP	Placebo	Corticosteroids
Network meta-analysis-MD	-0.24 [-2.21; 1.74]
	-1.50 [-3.48; 0.48]	-1.27 [-2.38; -0.16]
	-1.80 [-4.01; 0.41]	-1.56 [-2.88; -0.25]	-0.30 [-1.51; 0.91]

PRP: Platelet-rich plasma; MD: Mean difference.

Table 9 League Table with the results of the network meta-analysis for function improvement Constant Murley Score in the medium term

	HA + PRP	PRP	Hyaluronic acid	Corticosteroids	Placebo
Network meta-analysis-MD	13.81 [-12.54; 40.16]
	15.87 [-12.23; 43.97]	2.06 [-24.30; 28.41]
	21.42 [-16.63; 59.48]	7.61 [-19.84; 35.06]	5.55 [-32.50; 43.61]
	22.73 [-3.62; 49.08]	8.92 [-11.28; 29.11]	6.86 [-19.49; 33.21]	1.30 [-32.78; 35.38]

HA: Hyaluronic acid; PRP: Platelet-rich plasma; MD: Mean difference.

Table 10 League Table with the results of the network meta-analysis for function improvement American Shoulder and Elbow Surgeons Standardized Shoulder Assessment in the medium term

	HA + PRP	PRP	Hyaluronic acid	Prolotherapy	Corticosteroids	Placebo
Network meta-analysis-MD	19.09 [0.37; 37.81]
	20.29 [-0.38; 40.76]	1.10 [-17.67; 19.87]
	23.63 [-1.58; 48.84]	4.54 [-14.22; 23.30]	3.44 [-21.81; 28.69]
	26.44 [4.86; 48.02]	7.35 [-6.09; 20.80]	6.25 [-15.37; 27.88]	2.81 [-16.37; 22.00]
	26.72 [8.02; 45.41]	7.63 [-3.98; 19.23]	6.53 [-12.23; 25.28]	3.09 [-15.71; 21.89]	0.27 [-13.34; 13.88]

HA: Hyaluronic acid; PRP: Platelet-rich plasma; MD: Mean difference.

Table 11 League Table with the results of the network meta-analysis for pain improvement Visual Analogue Scale in the long term

	Hyaluronic acid	PRP	Corticosteroids	Placebo
Network meta-analysis-MD	-0.48 [-5.72; 4.76]
	-1.59 [-9.41; 6.23]	-1.11 [-6.91; 4.69]
	-2.59 [-7.83; 2.65]	-2.11 [-5.49; 1.27]	-1.00 [-7.72; 5.71]

PRP: Platelet-rich plasma; MD: Mean difference.

Table 12 League Table with the results of the network meta-analysis for function improvement Constant Murley Score in the medium term

	HA + PRP	PRP	Hyraluronic acid	Placebo
Network meta-analysis-MD	8.24 [7.26; 9.22]
	19.47 [18.51; 20.43]	11.23 [10.20; 12.26]
	32.64 [31.66; 33.62]	24.40 [23.35; 25.45]	13.17 [12.14; 14.20]

HA: Hyaluronic acid; PRP: Platelet-rich plasma; MD: Mean difference.

Table 13 League Table with the results of the network meta-analysis for function improvement American Shoulder and Elbow Surgeons Standardized Shoulder Assessment in the long term

	HA + PRP	Corticosteroids	Hyaluronic acid	Placebo	Prolotherapy	PRP
Network meta-analysis-MD	6.15 [-5.00; 17.31]
	7.09 [-3.79; 17.97]	0.93 [-7.47; 9.34]
	8.97 [-1.61; 19.55]	2.82 [-4.94; 10.57]	1.88 [-7.18; 10.94]
	9.95 [-4.36; 24.25]	3.79 [-7.41; 15.00]	2.86 [-10.01; 15.73]	0.98 [-10.38; 12.34]
	10.61 [0.11; 21.11]	4.45 [-2.37; 11.28]	3.52 [-5.23; 12.26]	1.64 [-6.00; 9.27]	0.66 [-10.44; 11.76]

HA: Hyaluronic acid; PRP: Platelet-rich plasma; MD: Mean difference.