Do the data support the use of PRP as an adjunct for treatment of rotator cuff tears?
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No consensus on optimal PRP formulation
Current data do support the potential for PRP to improve the outcomes of rotator cuff repair.
Recent meta-analyses and systematic reviews demonstrate that PRP can improve the clinical outcome and reduce the rate of failed healing (“retears”) in arthroscopic rotator cuff repair. In contrast, platelet-rich fibrin has been shown to have no benefit in improving tendon healing rates or functional outcomes. A major limitation in this field is the heterogeneity between PRP formulations and the lack of information about the optimal formulation to improve tendon healing. It is imperative that we identify methods to evaluate the composition and biologic activity of different PRP formulations, and then correlate this information with the clinical and imaging outcomes. Currently, PRP preparations are characterized by platelet concentration and as leukocyte-poor vs. leukocyte-rich, and there is currently no consensus on optimal formulation for rotator cuff repair. One recent meta-analysis found leukocyte-poor PRP improved the clinical function and reduced the retear rate in arthroscopic rotator cuff repair, while leukocyte-rich PRP did not have a significant effect.
How might PRP work to improve rotator cuff tendon healing? Basic laboratory studies have demonstrated that cytokines produced by PRP can positively affect tendon cell proliferation, migration and matrix synthesis. Although this may certainly contribute to improved tendon healing, I believe it is more likely the production of numerous anti-inflammatory mediators and immunomodulatory factors plays a more important role in both improvements in pain as well as superior rotator cuff tendon healing to bone. It is well-established that signaling molecules in PRP play a role in the resolution of inflammation. Although inflammation plays a critical role in the initiation and regulation of tissue healing, pre-clinical models indicate that chronic, unresolved inflammation has a detrimental effect on tendon healing. Signaling molecules produced by PRP may modify the local tissue microenvironment, aiding in timely resolution of inflammation and inducing polarization of macrophages from an M1 proinflammatory/catabolic phenotype to an M2 proregenerative function. Further basic laboratory studies with transcriptional profiling and proteomics analysis linked with clinical outcomes studies will improve our understanding of the optimal way to use PRP to improve the results of rotator cuff repair.
- References:
- Ahmad Z, et al. Arthrosc Sports Med Rehabil. 2022;doi:10.1016/j.asmr.2021.12.012.
- Feltri P, et al. Knee Sports Surg Traumatol Arthrosc. 2022;doi:10.1007/s00167-022-07223-9.
- Galliera E, et al. J Biol Regul Homeost Agents. 2012;26:35S-42S.
- Hurley ET, et al. Am J Sports Med. 2019;doi:10.1177/0363546517751397.
- Kelly BA, et al. J Orthop Res. 2016;doi:10.1002/jor.23058.
- Peng Y, et al. Int J Sports Med. 2022;doi:10.1055/a-1790-7982.
- Peng Y, et al. Platelets. 2022;doi:10.1080/09537104.2022.2044462.
Scott A. Rodeo, MD, an Orthopedics Today Editorial Board Member, is vice chair of orthopedic research, co-director of the Orthopaedic Soft Tissue Research Program and director of the Center for Regenerative Medicine at Hospital for Special Surgery in New York.
PRP helps surgeons ‘get it right’
Among our expanding armamentarium of therapeutic biologic options, PRP remains one of my most common adjuncts for tendo-osseous healing, with or without surgical treatment. As we consider the immense burden of symptomatic rotator cuff disease, it is of paramount importance to “get it right” the first time. To avoid failure in continuity and revision rotator cuff repair, we must optimize biomechanical constructs, patient-based factors and, ultimately, the biologic milieu at the rotator cuff enthesis. Despite extensive debate on its merits alongside rotator cuff repair, we now have excellent data to present to both our patients and payers. You-zhi Cai and colleagues have shown a 50% lower risk of failure to heal with PRP augmentation. This risk reduction may be up to 65% for small to medium tears and this may be due to repetitive attritional wear, intrinsic degeneration and hypovascularity. Several other high-quality meta-analyses and systematic reviews have shown improved rates of healing with PRP use, particularly with use of solid PRP (with an activating agent) injected at the tendon-bone interface. Although patient-reported outcomes have not consistently followed structural healing rates, Eoghan T. Hurley and colleagues showed measurable improvements in Constant scores and clinically significant reductions in VAS pain scores (delta 1.4) with PRP use.
Of course, we must account for variability in growth factor concentration and leukocyte content, as these factors may modulate tenocyte proliferation, collagen synthesis and proinflammatory cytokine release leading to matrix degeneration. At present, I typically utilize leukocyte-poor PRP formulations that increase the concentration of relevant growth factors nearly five-fold. As PRP is currently only covered by a few selected insurance carriers (eg, Tricare, worker’s compensation), we preferentially offer PRP as an ala carte, cash pay option alongside arthroscopic rotator cuff repair for patients with one or more of the following: significant tendinopathy, poor tissue quality, complex tear with or without tendon delamination, and/or comorbid risk factors that predispose patients to poor tissue healing (eg, diabetes). However, biologics only serve to augment the time-honored arthroscopic techniques for rotator cuff repair. One must always perform careful soft tissue releases and footprint preparation, with or without marrow vents, prior to anatomic reduction and fixation with limited cuff tension. Tissue augmentation used in an onlay (eg, dermal allograft, autograft biceps, bioinductive xenograft) or interpositional fashion may also be selectively considered in high-risk individuals, but that’s another debate. Stay tuned!
- Reference:
- Cai YZ, et al. J Shoulder Elbow Surg. 2015;doi:10.1016/j.jse.2015.07.035.
Brian R. Waterman, MD, FAAOS, is chief and fellowship director, sports medicine; professor, department of orthopaedic surgery at Wake Forest University School of Medicine, Winston-Salem, North Carolina.
Inconsistent clinical data
PRP, a derivative of autologous blood used in transfusion medicine since the 1960s, has captured the imagination of the media and health care professionals for its promise to augment rotator cuff tendon-bone healing, improve structural healing and ultimately optimize functional performance in patients with rotator cuff tears.
Clinical data, while abundant, are inconsistent. When compared to repair only in medium to large rotator cuff tears, two quality level 1 studies have shown a significant reduction in structural healing with either augmentation with pure PRP gel (97% vs. 80%) or pure PRP (96% vs. 84%). The former study found no differences in patient-reported outcomes (PROs) 12 months after surgery, while the latter study found improvements in PROs with pure PRP. Meta-analyses, such as the one by Xiao Chen, BA, and colleagues found long-term structural healing rates improved in patients who received PRP, but this did not correlate with a minimal clinically important difference in PROs.
Contrary to these encouraging data, five randomized level 1 or 2 controlled trials reported no significant differences between treatment and control with any outcome measures. In a large 120-patient sample, Matthias Flury, MD, and colleagues noted no significant difference in the structural healing rate, PRO scores or adverse event rate 2 years after intraoperative pure PRP injection during arthroscopic rotator cuff repair. Eduardo Angeli Malavolta, MD, PhD, and colleagues reported results at 5-year follow-up after 51 arthroscopic repairs of small to medium rotator cuff tears with intraoperative injection of pure PRP to the enthesis, finding no difference over control in retear rate or PRO scores.
The absence of a clear consensus on the efficacy of PRP, despite an established base of high-quality clinical research, is multifactorial. The leading culprits that top the list are:
- Surfeit of PRP preparation techniques despite a lack of standardization among PRP preparations; and
- Intra- and inter-donor variability in PRP composition between multiple blood draws from different individuals or multiple draws from the same individual at different times despite using identical preparation systems.
A few sensible solutions can be considered by the musculoskeletal community for future efforts. Preparation methods that reduce intra- and inter-donor variation must be developed. Continued investment in clinical studies that emphasize standardization and characterization of PRP preparation for use in specific patient populations with clearly defined pathologies will be required to optimize the ideal PRP formulations for use in various indications.
- References:
- Chen X, et al. Am J Sports Med. 2020;doi:10.1177/0363546519881423.
- Flury M, et al. Am J Sports Med. 2016;doi:10.1177/0363546516645518.
- Jo CH, et al. Am J Sports Med. 2015;doi:10.1177/0363546515587081.
- Malavolta EA, et al. Am J Sports Med. 2018;doi:10.1177/0363546518795895.
- Pandey V, et al. J Shoulder Elbow Surg. 2016;doi:10.1016/j.jse.2016.01.036.
David Kovacevic, MD, FAAOS, is an attending orthopedic surgeon at Hackensack Meridian Health, Hackensack, New Jersey.
Consider the applications of PRP
Orthobiologic therapies, including PRP, and their role in management of rotator cuff tears, is an exciting, but controversial topic. When considering the use of PRP as an adjunct for treatment of rotator cuff tears, one must consider its applications in both nonoperative and operative settings.
Corticosteroid has historically been first-line injection therapy in patients with cuff tears, as supported by current AAOS treatment guidelines. With the increasing popularity of PRP, Long Pang and colleagues set out to explore the role of PRP as a viable injection alternative to corticosteroid by performing a meta-analysis of randomized control trials comparing the two options. Their data suggest that PRP results in worse improvement in several outcomes scores (American Shoulder and Elbow Surgeons, DASH, simple shoulder test) compared with corticosteroid at short-term, but then outperforms corticosteroid at midterm and long-term follow-up. Notably, no difference in any function score met the minimal clinically important difference and there were no differences in VAS pain scores at any time point. PRP did show lower rates of repeat injection or request for surgical intervention within 12 months. While these results are intriguing, the substantial heterogeneity across included trials with respect to formulation of PRP and characteristics of cuff tears makes drawing firm conclusions challenging. With growing concern for adverse effects of corticosteroid on tendon quality and outcomes of surgical repair, the role of PRP in the nonoperative setting must be considered. Ultimately, these data suggests PRP may be a viable adjunct to traditional nonoperative modalities (physical therapy, home exercise regimes, etc.); however, further data from well-designed, prospective studies remain necessary to truly elucidate the role of PRP for conservative treatment of cuff tears.
The role of PRP as an augment to rotator cuff repair is also important to consider. Numerous studies with short- and long-term follow-up have been performed evaluating clinical, functional and radiographic outcomes after augmenting surgical repair with PRP. The common theme among these studies is that PRP reduces retear rates, but there were ultimately no significant differences in clinical or functional outcomes compared with repair alone. While the available evidence suggests PRP works, it is again important to avoid sweeping recommendations supporting its use and push for quality, standardized long-term data which could justify more universal applications.
- References:
- Pang L, et al. Arthroscopy. 2023;doi:10.1016/j.arthro.2022.06.022.
- Randelli PS, et al. Arthroscopy. 2022;doi:10.1016/j.arthro.2021.05.017.
- Villarreal-Villarreal GA, et al. Arthroscopy. 2021;doi:10.1016/j.arthro.2020.12.191.
- Zhang C, et al. Arthroscopy. 2022;doi:10.1016/j.arthro.2022.02.007.
Douglas W. Bartels, MD, is a sports medicine and shoulder surgeon at Mayo Clinic Health Systems in Eau Claire, Wisconsin and an assistant professor of orthopedics at Mayo Clinic College of Medicine and Science.
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