Platelet-rich plasma in the management of rotator cuff tendinopathy

Batuhan Bahadir; Baran Sarikaya

doi:10.52312/jdrs.2024.1586

Batuhan Bahadir, Baran Sarikaya

Department of Orthopedics and Traumatology, Ankara Bilkent City Hospital, Ankara, Türkiye

Keywords: Platelet-rich plasma, rotator cuff, tear, tendinopathy, tendinosis, tendonitis.

Abstract

Platelet-rich plasma (PRP) is an autologous blood-derived product that has gained significant attention in the treatment of tendinopathies as one of many treatment modalities in the field of regenerative medicine. Rotator cuff pathologies are the leading cause of shoulder pain. Despite the high success rate with conservative treatment and arthroscopic surgical repair, the search for a nonsurgical treatment has made PRP a trending topic recently. The purpose of this article is to review the recent literature data on the possible role of PRP in different rotator cuff pathologies. The limited data in the literature about isolated tendinopathies without a tear (tendonitis and tendinosis) suggests potential benefit from conservative treatment with PRP. Many studies exist for the treatment of rotator cuff tears solely using PRP or as an augmentation to arthroscopic repair. Despite the large number of randomized clinical trials and meta-analyses about the topic, there is no consensus in favor of routine application of PRP in this patient population. The existing reliable evidence of benefit seems to be restricted to its use in only inflammatory tendinopathies with preserved tendon integrity.

Introduction

Platelet-rich plasma (PRP) is an autologous blood-derived product that has gained significant attention in the treatment of various orthopedic problems recently. The first use of PRP in orthopedics dates back to 1998.[1] Since then, it has been frequently utilized to treat a variety of conditions such as osteoarthritis, epicondylitis, and tendinopathy as one of many treatment modalities in the field of regenerative medicine.

Shoulder pain is a common disabling symptom of shoulder pathologies, being the third most common musculoskeletal complaint.[2] Rotator cuff pathologies are the leading cause of shoulder pain, accompanying more than half of the shoulder pain cases applying to orthopedic clinics.[3] Despite the high success rate with arthroscopic surgical treatment, complications such as postoperative retears and patients' preference for nonsurgical treatment have recently made PRP applications a trending topic as an alternative to physical therapy solely or even to surgical management.

This study aimed to review the recent literature on the possible role and outcomes of PRP in different rotator cuff pathologies. Before discussing the effectiveness of PRP, different types of rotator cuff pathologies should be classified. In rotator cuff tendonitis, inflammation is the predominant event, often accompanying the distortion of lubrication mechanisms such as bursae, whereas tendinosis is a condition in which mechanical structure of the tendon is disturbed and largely occurs due to overuse. Tears can be classified according to their extent in terms of thickness: partial and full-thickness tears.

TENDONITIS AND TENDINOSIS

Although tendonitis and tendinosis are distinct terms, they are commonly used interchangeably in the literature, and in many studies, no clear distinction is made. Most of the time, tendonitis is an abrupt short-term condition in which inflammation is the result of a direct injury. As the condition persists or recurs by repetitive trauma or just simply due to the fact that the tendon is not healing, structural integrity of the tendon begins to deteriorate. The term tendinosis is used to refer to this stage.

In the early inflammatory stage (tendonitis), anti-inflammatory agents and rehabilitation programs, including exercise and electrotherapeutic modalities, are usually successful in controlling the disease.[4] Healing is prolonged or never occurs in chronic tendinopathies (tendinosis) because the tendon becomes less vascular, and inflammatory cells begin to appear less frequently as the pathology progresses.[5-7] Inflammatory cells and biologically active factors such as growth factors, cytokines, chemokines, and cell-adhesion molecules secreted by them are the fundamental prerequisites for tissue regeneration and repair. Their absence, when paired with repetitive use and injury, results in a vicious cycle. This creates an advantageous environment for PRP to break the cycle and demonstrate benefits.

There are many studies reporting improvement in shoulder function, Visual Analog Scale score, and range of motion as a result of PRP application. However, the literature is very limited in terms of studies on tendinopathy patients without a tear. Rha et al.[8] compared two sets of PRP injections with dry needling procedure in 39 patients and revealed that PRP injections resulted in greater relief of pain and arm functional improvement, but no difference was found in terms of shoulder range of motion. In another study comparing the effectiveness of PRP and corticosteroid injections in 58 patients, a significantly greater improvement in pain score was reported, but the difference in range of motion was not that obvious.[9] A recent meta-analysis of eight randomized controlled trials involving the data of more than 500 patients revealed that PRP was significantly better in controlling pain symptoms in 6- and 12-month follow-ups compared to control interventions.[1] However, according to the same study, the effect of PRP on functional outcomes was controversial, obtaining different results with different types of questionnaires.

One of the common features of studies about the outcomes of PRP on rotator cuff tendinopathies is having different concentration of platelets and formulas of PRP and working on heterogenous patient populations, including the ones with tears in some studies. Another point is that tendonitis-tendinosis discrimination was not made by almost any of these studies; therefore, it is hard to determine whether both pathologies benefit from the treatment or which one benefits more.

ROTATOR CUFF TEARS

In contrast to the cases without a tear, the literature on the use of PRP in cases with rotator cuff tears is quite rich. A study involving tenocyte cell cultures obtained from human rotator cuff tear lesions showed that PRP gel promotes cell proliferation and enhances the synthesis of tendon matrix by tenocytes.[10]

Many studies deal with patient groups having isolated tendinopathy and partial tears at the same time without any distinction and report favorable outcomes.[9,11,12] Rossi et al.[13] reported that PRP results in less functional improvement in patients with a partial rotator cuff tear compared to the ones with isolated tendinopathy without any tear. Another study conducted by Prodromos et al.[14] in 2021 included tendinopathy patients who failed conservatory treatment and evaluated them according to their tear status (no tear, partial tears of <50% or >50%, and full-thickness tear) after having two PRP injections. In contrast to the previous study, this study found that at the one-year follow-up, the Q-DASH (quick disabilities of the arm, shoulder, and hand) scores of partial tear groups with tear thicknesses of 50% and >50% improved significantly more than the score of the group with no tear. The results were similar at the six-month and two-year follow-ups. At this point, studies involving patients solely with a tear should be considered.

As far as we know, two prospective randomized studies exist that include only patients with partial rotator cuff tears and compare PRP injection with placebo or physical therapy (Table I).[15,16] In both studies, no significant difference could be demonstrated between the groups in terms of pain, range of motion, or functional score on behalf of PRP, except for the DASH score in one of them. Another randomized study comparing the effectiveness of PRP with sodium hyaluronate (SH), PRP + SH, and placebo on partial thickness tear cases revealed that PRP was more effective than placebo and SH alone.[17] Interestingly, the same study found that the PRP + SH combination was more effective than PRP alone in the treatment of partial thickness rotator cuff tears, and they suggested that SH might be providing a network that can increase the residence time of the growth factors and facilitate their release to the injured rotator cuff. Another randomized controlled study combining PRP with bone marrow concentrate revealed that the combination is more effective than exercise therapy in the treatment of partial and full-thickness rotator cuff tears.[18] There are two randomized controlled studies demonstrating PRP's indisputable superiority over other treatment modalities, and they are not in the majority.[9,19]

Table 1. Characteristics and main results of randomized clinical trial samples conducted on patients with rotator cuff tendinopathy with the application of PRP

Year	Author	Sample size	Type of rotator cuff tendinopathy	Intervention group (n)		Control group (n)		Follow-up (months)	Main measures of outcome	Summary of the outcomes
2013	Kesikburun et al.^[15]	40	Tendonitis and partial tear	PRP	20	Placebo	20	12	WORC, VAS, ROM	No more effective than placebo in improving function or pain.
2015	llhanli et al.^[l6]	62	Chronic partial tear	PRP	30	Physical therapy	32	12	DASH, VAS, ROM	Better improvement in pain and ROM with physical therapy. DASH score improved more in PRP group.
2018	Kim et al.^[26]	24	Partial tear	PRP + BMAC	12	Physical therapy	12	3	ASES, VAS, tear size	Improved shoulder functions and pain, no significant difference in tear size.
2021	Kwong et al .^[27]	99	Partial tear	PRP	47	Corticosteroid	52	12	ASES, VAS	Better improvement in short term, no sustained benefit at the end of 12 months.
2021	Dadgostar et al.^[9]	58	Tendonitis and partial tear	PRP	29	Corticosteroid	29	3	WORC, VAS, ROM	Significantly better improvement.
2023	Vaquerizo et al.^[19]	79	Chronic tear	3 PRP injections with one week intervals	39	3 corticosteroid injections with one week intervals	40	12	CMS, UCLA	Significantly superior and sustained pain relief and functional improvement.
PRP: Platelet-rich plasma; WORC: Western Ontairo Rotator Cuff Index; VAS: Visual Analog Scale; ROM: Range of motion; DASH: Disabilities of arm, shoulder and hand questionnaire; BMAC: Bone marrow aspirate concentrate; ASES: American shoulder and elbow surgeons score; CMS: Constant-Murley Shoulder outcome score; UCLA: The University of California-Los Angeles Shoulder Scale.

Another popular method and compelling research area of PRP use in the treatment of cuff tears is combining it with surgical repair (Table II). One of the earliest randomized controlled studies conducted by Ruiz-Moneo et al.[20] in 2011 found no benefit of adding plasma rich in growth factors to the arthroscopic rotator cuff repair at the end of a one-year follow-up. Malavolta et al.[21] reported similar results in another study evaluating single-row repair with and without intraoperative use of PRP at the end of a two-year follow-up later in 2014. In 2016, Pandey et al.[22] reported that PRP-augmented repair reduced retear rate in large tears and resulted in better functional scores in all sizes of degenerative tears. Many others followed these short-term studies with different results. A 2021 meta-analysis by Xu and Xue[23] reported that intraoperative PRP application significantly reduced retear rate and improved shoulder function only in large and massive rotator cuff tears. Two other meta-analyses conducted on randomized controlled trials published recently found that the addition of intraoperative PRP to both single-row and double-row repair improved functional results and retear rates.[23,24] However, a recent study reporting the longest follow-up period with arthroscopic repair and PRP combination conducted by Randelli et al.[25] in 2021 found no significant superiority of PRP at the end of a 10-year follow-up.[31]

Table 2. Characteristics and main results of randomized clinical trial samples conducted on patients with rotator cuff tear with the application of PRP-augmented arthroscopic repair

Year	Author	Sample size	Type of rotator cuff tendlnopathy	Intervention group (n)		Control group (n)		Follow-up (months)	Main measures of outcome	Summary of the outcomes
2015	Jo et al.^[10]	74	Partial and full thickness tear	PRP-augmented repair		Conventional repair		3	CMS, VAS, ROM, retear rate	Better functional scores, reduced retear rates.
2015	Wang et al.^[28]	60	Partial and full thickness tear	PRP injections in postoperative 7^thand 14^th days	30	Conventional repair	30	4	OSS, VAS with serial assessments in early postoperative period, MRI in 16^th week	PRP augmentation did not improve early healing or functional recovery.
2016	Pandey et al.^[22]	102	Partial and full thickness, degenerative tear	PRP-augmented repair	52	Conventional repair	50	24	CMS, UCLA, VAS, retear rate	Better functional scores, reduced retear rate only in large tears.
2016	Flury et al.^[29]	120	Full thickness tear	PRP-augmented repair	60	Ropivacaine injection + repair	60	24	CMS, pain, retear rate	No significant difference in functional scores or retear rates.
2022	Zhang et al.^[30]	104	Partial and full thickness tear	3 PRP injections during double-row repair, at days 7 and 14 after surgery	52	Conventional double-row repair	52	24	CMS, UCLA, VAS, fatty infiltration, retear rate	Reduced fatty infiltration and retear rates in PRP group, but no significant difference in functional outcomes.
2022	Randelli et al.^[25]	38	Full thickness tear	PRP-augmented repair	17	Conventional repair	21	120	CMS, UCLA, ASES, VAS, re tear rate	Minor differences observed at two-year
PRP: Platelet-rich plasma; CMS: Constant-Murley Shoulder Outcome Score; VAS: Visual Analog Scale; ROM: Range of motion; OSS: Oxford shoulder score; MRI: Magnetic resonance imaging; UCLA: The University of California-Los Angeles Shoulder Scale; ASES: American Shoulder and Elbow Surgeons Score.

In conclusion, at least a subgroup of patients having isolated tendonitis has a strong potential to benefit from PRP treatment. Although there is some evidence suggesting the benefit of PRP with or without surgical repair in rotator cuff tears, there is no consensus in favor of routine application of PRP in this large patient population. The existing reliable evidence of benefit appears to be restricted to its use in tendonitis cases only. More large-scale and long-term research focusing on subgroups of rotator cuff tears with homogenous methodology on the application of PRP is needed.

Citation: Bahadir B, Sarikaya B. Platelet-rich plasma in the management of rotator cuff tendinopathy. Jt Dis Relat Surg 2024;35(2):462-467. doi: 10.52312/jdrs.2024.1586.

Author Contributions

Literature review, interpretation and writing: B.B.; Idea and concept: B.S.

Conflict of Interest

The authors declared no conflicts of interest with respect to the authorship and/or publication of this article.

Financial Disclosure

The authors received no financial support for the research and/or authorship of this article.

Data Sharing Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

References

Bhan K, Singh B. Efficacy of Platelet-Rich Plasma injection in the management of rotator cuff tendinopathy: A review of the current literature. Cureus 2022;14:e26103. doi: 10.7759/ cureus.26103.
Urwin M, Symmons D, Allison T, Brammah T, Busby H, Roxby M, et al. Estimating the burden of musculoskeletal disorders in the community: The comparative prevalence of symptoms at different anatomical sites, and the relation to social deprivation. Ann Rheum Dis 1998;57:649-55. doi: 10.1136/ard.57.11.649.
Alqunaee M, Galvin R, Fahey T. Diagnostic accuracy of clinical tests for subacromial impingement syndrome: A systematic review and meta-analysis. Arch Phys Med Rehabil 2012;93:229-36. doi: 10.1016/j.apmr.2011.08.035.
Landry M. Brukner & Khan's clinical sports medicine. Physiother Can 2014;66:109-10. doi: 10.3138/ptc.66.1.rev2.
Riley GP, Goddard MJ, Hazleman BL. Histopathological assessment and pathological significance of matrix degeneration in supraspinatus tendons. Rheumatology (Oxford) 2001;40:229-30. doi: 10.1093/ rheumatology/40.2.229.
Kannus P, Józsa L. Histopathological changes preceding spontaneous rupture of a tendon. A controlled study of 891 patients. J Bone Joint Surg Am 1991;73:1507-25.
Hashimoto T, Nobuhara K, Hamada T. Pathologic evidence of degeneration as a primary cause of rotator cuff tear. Clin Orthop Relat Res. 2003 Oct;(415):111-20. doi: 10.1097/01. blo.0000092974.12414.22.
Rha DW, Park GY, Kim YK, Kim MT, Lee SC. Comparison of the therapeutic effects of ultrasound-guided platelet-rich plasma injection and dry needling in rotator cuff disease: A randomized controlled trial. Clin Rehabil 2013;27:113-22. doi: 10.1177/0269215512448388.
Dadgostar H, Fahimipour F, Pahlevan Sabagh A, Arasteh P, Razi M. Corticosteroids or platelet-rich plasma injections for rotator cuff tendinopathy: A randomized clinical trial study. J Orthop Surg Res 2021;16:333. doi: 10.1186/s13018- 021-02470-x.
Jo CH, Kim JE, Yoon KS, Shin S. Platelet-rich plasma stimulates cell proliferation and enhances matrix gene expression and synthesis in tenocytes from human rotator cuff tendons with degenerative tears. Am J Sports Med 2012;40:1035-45. doi: 10.1177/0363546512437525.
Wesner M, Defreitas T, Bredy H, Pothier L, Qin Z, McKillop AB, et al. A pilot study evaluating the effectiveness of platelet-rich plasma therapy for treating degenerative tendinopathies: A randomized control trial with synchronous observational cohort. PLoS One 2016;11:e0147842. doi: 10.1371/journal.pone.0147842.
Rha DW, Park GY, Kim YK, Kim MT, Lee SC. Comparison of the therapeutic effects of ultrasound-guided platelet-rich plasma injection and dry needling in rotator cuff disease: A randomized controlled trial. Clin Rehabil 2013;27:113-22. doi: 10.1177/0269215512448388.
Rossi LA, Piuzzi N, Tanoira I, Brandariz R, Huespe I, Ranalletta M. Subacromial platelet-rich plasma ınjections produce significantly worse ımprovement in functional outcomes in patients with partial supraspinatus tears than in patients with ısolated tendinopathy. Arthroscopy 2023;39:2000-8. doi: 10.1016/j.arthro.2023.03.019.
Prodromos CC, Finkle S, Prodromos A, Chen JL, Schwartz A, Wathen L. Treatment of Rotator Cuff Tears with platelet rich plasma: A prospective study with 2 year follow-up. BMC Musculoskelet Disord 2021;22:499. doi: 10.1186/s12891- 021-04288-4.
Kesikburun S, Tan AK, Yilmaz B, Yaşar E, Yazicioğlu K. Platelet-rich plasma injections in the treatment of chronic rotator cuff tendinopathy: A randomized controlled trial with 1-year follow-up. Am J Sports Med 2013;41:2609-16. doi: 10.1177/0363546513496542.
Ilhanli I, Guder N, Gul M. Platelet-rich plasma treatment with physical therapy in chronic partial supraspinatus tears. Iran Red Crescent Med J 2015;17:e23732. doi: 10.5812/ ircmj.23732.
Cai YU, Sun Z, Liao B, Song Z, Xiao T, Zhu P. Sodium hyaluronate and platelet-rich plasma for partial-thickness rotator cuff tears. Med Sci Sports Exerc 2019;51:227-33. doi: 10.1249/MSS.0000000000001781.
Centeno C, Fausel Z, Stemper I, Azuike U, Dodson E. A randomized controlled trial of the treatment of rotator cuff tears with bone marrow concentrate and platelet products compared to exercise therapy: A midterm analysis. Stem Cells Int 2020;2020:5962354. doi: 10.1155/2020/5962354.
Vaquerizo V, García-López M, Mena-Rosón A, Prado R, Padilla S, Anitua E. Plasma rich in growth factors versus corticosteroid injections for management of chronic rotator cuff tendinopathy: A prospective double-blind randomized controlled trial with 1 year of follow-up. J Shoulder Elbow Surg 2023;32:555-64. doi: 10.1016/j.jse.2022.08.017.
Ruiz-Moneo P, Molano-Muñoz J, Prieto E, Algorta J. Plasma rich in growth factors in arthroscopic rotator cuff repair: A randomized, double-blind, controlled clinical trial. Arthroscopy 2013;29:2-9. doi: 10.1016/j.arthro.2012.08.014.
Malavolta EA, Gracitelli ME, Ferreira Neto AA, Assunção JH, Bordalo-Rodrigues M, de Camargo OP. Platelet-rich plasma in rotator cuff repair: a prospective randomized study. Am J Sports Med 2014;42:2446-54. doi: 10.1177/0363546514541777.
Pandey V, Bandi A, Madi S, Agarwal L, Acharya KK, Maddukuri S, et al. Does application of moderately concentrated platelet-rich plasma improve clinical and structural outcome after arthroscopic repair of medium-sized to large rotator cuff tear? A randomized controlled trial. J Shoulder Elbow Surg 2016;25:1312-22. doi: 10.1016/j. jse.2016.01.036.
Xu W, Xue Q. application of platelet-rich plasma in arthroscopic rotator cuff repair: A systematic review and meta-analysis. Orthop J Sports Med 2021;9:23259671211016847. doi: 10.1177/23259671211016847.
Yang FA, Liao CD, Wu CW, Shih YC, Wu LC, Chen HC. Effects of applying platelet-rich plasma during arthroscopic rotator cuff repair: A systematic review and meta-analysis of randomised controlled trials. Sci Rep 2020;10:17171. doi: 10.1038/s41598-020-74341-0.
Randelli PS, Stoppani CA, Santarsiero G, Nocerino E, Menon A. Platelet-rich plasma in arthroscopic rotator cuff repair: Clinical and radiological results of a prospective randomized controlled trial study at 10-year follow-up. Arthroscopy 2022;38:51-61. doi: 10.1016/j.arthro.2021.05.017.
Kim SJ, Kim EK, Kim SJ, Song DH. Effects of bone marrow aspirate concentrate and platelet-rich plasma on patients with partial tear of the rotator cuff tendon. J Orthop Surg Res 2018;13:1. doi: 10.1186/s13018-017-0693-x.
Kwong CA, Woodmass JM, Gusnowski EM, Bois AJ, Leblanc J, More KD, et al. Platelet-rich plasma in patients with partial-thickness rotator cuff tears or tendinopathy leads to significantly ımproved short-term pain relief and function compared with corticosteroid ınjection: A double-blind randomized controlled trial. Arthroscopy 2021;37:510-7. doi: 10.1016/j.arthro.2020.10.037.
Wang A, McCann P, Colliver J, Koh E, Ackland T, Joss B, et al. Do postoperative platelet-rich plasma injections accelerate early tendon healing and functional recovery after arthroscopic supraspinatus repair? A randomized controlled trial. Am J Sports Med 2015;43:1430-7. doi: 10.1177/0363546515572602.
Flury M, Rickenbacher D, Schwyzer HK, Jung C, Schneider MM, Stahnke K, et al. Does pure platelet-rich plasma affect postoperative clinical outcomes after arthroscopic rotator cuff repair? A randomized controlled trial. Am J Sports Med 2016;44:2136-46. doi: 10.1177/0363546516645518.
Zhang J, Tan YB, Lie DTT. Outcomes of arthroscopic rotator cuff repair in stiff shoulders are comparable to nonstiff shoulders when combined with manipulation under anesthesia. Arthroscopy 2020;36:2954-61. doi: 10.1016/j. arthro.2020.06.025.
Atik OŞ. Writing for Joint Diseases and Related Surgery (JDRS): There is something new and interesting in this article! Jt Dis Relat Surg 2023;34:533. doi: 10.52312/ jdrs.2023.57916.