- Email: [email protected]
Nonoperative Management: Who, When, and What?
Nonoperative Management: Who, When, and What? Vanessa G. Cuellar, MD, Frantz Lerebours, MD, and Eric J. Strauss, MD Disorders of the rotator cuff are among the most common shoulder pathologies encountered by orthopedic surgeons. Although both acute and chronic tears of the rotator cuff are recognized and traditionally classified based on tear size, the increasing appreciation of asymptomatic tears in population studies challenges our current treatment algorithms. Conventionally, nonoperative treatment has been reserved for patients who do not have significant pain, including those with massive tears. Recent studies demonstrating successful treatment of various cuff tear morphologies using nonoperative modalities have increased interest in conservative management. Presently, nonoperative options include exercise/physical therapy, corticosteroid injections, oral anti-inflammatory medications, and autologous biological administration. However, it is unclear at this time which patient populations benefit most among the nonoperative treatment options, as the literature to date represents heterogeneous cohorts of tear types, symptom duration, as well as varied treatment modalities. Any further comparison between operative and nonoperative outcomes necessitates prospective studies with rigorous inclusion/exclusion criteria and standardized interventions. Oper Tech Sports Med 20:207-212 © 2012 Elsevier Inc. All rights reserved. KEYWORDS conservative treatment, nonoperative management, rotator cuff, shoulder
A
lthough the incidence of shoulder pain in the United States is reported as 14.7 per 1000 patients per year, the overall prevalence during a lifetime reaches nearly 70%.1,2 Furthermore, disorders of the rotator cuff in particular are among the most common shoulder pathologies, with the incidence of symptomatic as well as asymptomatic tears increasing with age.3,4 Despite the ubiquity of rotator cuff pathology in clinical practice, the etiology remains largely unknown.5 Although both intrinsic and extrinsic mechanisms have been proposed, it is likely that rotator cuff disease is a multifactorial process. Moreover, it is unclear on a clinical as well as molecular level whether these mechanisms are primary or secondary in the pathogenesis of the disease.6 The fact that there are so many asymptomatic patients’ further obscures our understanding of the pathophysiology. Traditionally, rotator cuff tears have been classified based on size (ie, partial vs full-thickness tears). This distinction is largely because of the relationship between cuff tear size and reported success of surgical intervention.7 Notwithstanding, it appears that the presence of pain is of more relevance in
Department of Orthopaedic Surgery, New York University Hospital for Joint Diseases, New York, NY. Address reprint requests to Eric J. Strauss, MD, Department of Orthopaedic Surgery, New York University Hospital for Joint Diseases, 301 East 17th St, Suite 1402, New York, NY 10003. E-mail: [email protected]
1060-1872/12/$-see front matter © 2012 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1053/j.otsm.2012.08.001
clinical management, and conventionally, nonoperative treatment has been reserved for patients who do not have significant pain, including those with massive tears.7 However, no correlation between tears and symptoms has been shown in population studies. Therefore, although it is not difficult to diagnose a rotator cuff tear based on magnetic resonance imaging (MRI) findings, to ascertain whether this finding is causative of the patient’s pain and/or functional ability is not so clear. There is considerable interest in the field as to why some full-thickness rotator cuff tears are painful and disabling, whereas others are not. For example, it has been observed that small partial tears may disable some patients, yet other patients remain asymptomatic and functional with massive rotator cuff tears.8 Certainly, this clinical challenge remains pivotal in our development of successful treatment, operative and nonoperative alike. Thus, it is not surprising that the challenges of diagnosis have implications for treatment. Outcomes after surgical intervention are well documented in the literature, yet there is a paucity of rigorous studies concerning nonoperative management. Nonoperative investigations are often retrospective and usually complicated by their comparison with heterogeneous populations of surgical patients and varying indications. The interest in nonsurgical management of full-thickness rotator cuff tears is increasing. This may be accounted for by 207
208 a variety of reasons; however it is evident that the growing trend toward nonoperative treatment reflects better outcomes and an improved appreciation of the complexity of rotator cuff healing after surgery and the challenges of postoperative care if healing is impaired.9 Kijima et al10 recently published one of the few studies that prospectively enrolled patients with rotator cuff tears to undergo conservative treatment without selection bias. One of the strengths of this study lies in the inclusion of all patients with diagnosed rotator cuff tear for nonoperative treatment, regardless of tear size or patient age. Nonetheless, 2.8% of all patients ultimately underwent surgery, as their pain did not improve with traditional conservative intervention by 6 months. Although 103 patients were diagnosed with rotator cuff tear at the initiation of the study, at time of follow-up, 11 patients had died and 10 patients had severe dementia limiting follow-up evaluation, which resulted in analysis of 43 patients ⬎13 years. The results of the study were thus limited to follow-up of younger healthier patients. Furthermore, the investigation did not distinguish among traditional characteristics, such as acuity of symptoms, physical examination of strength, size of tear, degree of fatty infiltration, and age/ activity of the patient. At time of follow-up, 90% of patients had no or little pain and 70% reported no disturbance in activities of daily living. Of note, the authors determined that the younger patients (mean age 54 years) tended to have significant pain and disability at 10 years after diagnosis than older patients (mean age 64 years). Although limited by the heterogeneity of subjects enrolled and lack of baseline information regarding cuff pathology and physical examination findings, the prevalence of patients without significant pain and capable of completing activities of daily living at 13 years without surgical intervention is encouraging. In an exhaustive review of 86 articles pertaining to surgical indications and outcomes for rotator cuff pathology, Marx et al11 confirmed a significant heterogeneity among articles from high-quality journals. Most notably, 44% of the studies did not report duration of symptoms preoperatively, and a majority of studies did not report limitations of activities of daily living nor duration of nonoperative treatment before surgery. As these factors are clearly integral to the surgical decision-making process and subsequent outcomes, any comparison with nonoperative management casts doubt because the existing reports provide arguably unacceptable evidence. It has been documented that patients with full-thickness tears can be successfully treated both operatively and nonoperatively, thus any further comparison between operative and nonoperative outcomes demands rigorous inclusion/exclusion criteria as well as standardized pre- and postoperative regimens. Validation of both treatment options is imperative in the clinical decision-making process. Typically, given MRI and physical examination findings consistent with a diagnosis of rotator cuff tear, surgical intervention for rotator cuff tears has been relegated to those patients with refractory pain for ⬎6 months, acute full-thickness tears in young active patients, and concurrent shoulder instability. However, to date, there is no clear agreement regarding the indications for rotator cuff surgery. Needless to
V.G. Cuellar, F. Lerebours, and E.J. Strauss say, this debate has implications for the nonsurgical treatment of rotator cuff tears as well. Although there are many reports in the literature of successful outcomes after rotator cuff repair, the inclusion criteria, indications, and postoperative rehabilitation protocols and outcome measurements are so varied that there is remarkably no consensus.12
Nonoperative Management Options Nonoperative management options typically have been reserved for the elderly or for partial tears. The modalities used include exercise, electrotherapy, acupuncture, manual therapy, injection therapy, and bracing/taping. More recently, clinical outcome studies suggest that the level of degeneration within repaired tendons is the most important factor influencing tendon-to-bone healing,5 and may account for the poor response to surgical intervention in the elderly patients or chronic rotator cuff tear populations.
Exercise/Physical Therapy The approach most commonly offered to all patients with rotator cuff pathology is exercise. Although systemic reviews of the literature have been published,13-15 currently, there is no consensus as to the optimal exercise regimen. This, in part, it reflects the heterogeneity of the methods in the literature as well as distinctions in patient selection. For example, “standard” exercise regimens for rotator cuff disease may imply various degrees of stretching/strengthening maneuvers, range of motion exercises, and other modalities. Moreover, the quality of the literature dealing with exercise treatment is often retrospective studies of patients that participated in an exercise regimen, rather than several prospective studies with clear inclusion criteria. Our fundamental lack of understanding of the pathophysiology of rotator cuff tears, pain, and healing further obscures the question as to why exercise regimens should have a beneficial impact in this disease. There has been little discussion of the possibilities, but exercise may modulate pain responses, provide placebo effect, and may train other muscles to coordinate movement and restore functional ability. For example, weakness of scapular stabilizers as well as rotator cuff musculature has been proposed as an etiology of glenohumeral dysfunction and arthropathy, and its early rehabilitation has been advocated to prevent progressive disease.15,16 It has also been postulated that symptoms occur with rotator cuff pathology when glenohumeral and scapulothoracic motion is abnormal, or the muscle forces across these joints is imbalanced.17,18 Yamaguchi et al19 has published several related studies, one in particular that suggested abnormal glenohumeral motion is associated with symptomatic tears. Although there is no standard of care for exercise therapy at this time, typically rotator cuff injuries are managed in a 3-phase approach.20 The first phase focuses on range of motion and pain control, the second on strengthening scapular stabilizing muscles as well as deltoid strengthening, and the
Nonoperative management third addresses maintenance of strength, range of motion, and integration back into normal activities, including sports. Ainsworth et al13 conducted a systematic review of the literature and reported on 10 observational studies that included treatment groups receiving exercise therapy alone or as an adjunct intervention for full-thickness, massive, or inoperable rotator cuff tear. The review of the existing studies was extensive, but clearly, the variation in the types of exercise used, initiation of treatment/duration of treatment, and heterogeneous inclusion criteria makes any satisfactory conclusions impossible. The trend suggests that some sort of exercise regimen is beneficial, but further guidance regarding those patients in particular that would benefit and from which specific treatment is lacking. One possibility though is a natural resolution in certain patients, and this is supported by the few long-term follow-up studies that suggest significant improvement over time. For example, as discussed by Bartolozzi et al,21 improved outcomes after conservative treatment increased with length of follow-up evaluation. Muscle weakness has typically been an important factor in the decision to proceed with surgery and/or physical therapy for rotator cuff tears; however, the distinction between painful tears versus tears causing weakness has more recently been called into question.13 One of the few prospective studies evaluating conservative treatment, specifically musclestrengthening exercises, used a standard treatment approach with objective as well as subjective outcome measurements with respect to muscle strength.15 This study by Baydar et al enrolled 20 patients with full-thickness rotator cuff tears, which included small to massive sized tears, with a mean age of 60.9 ⫾ 7.7 years and mean symptom duration of 9.2 ⫾ 10.5 months. What is unique about this study is that all patients underwent standardized isokinetic strength testing of both shoulders at baseline and at 6 months, as well as other standardized functional outcome measurements at baseline and follow-up evaluations up to 3 years. All patients were also involved in a specific 3-week physical therapy program and 3-phase home exercise course. The authors acknowledge the limitations of the study, specifically the small sample size; however, the overall statistically significant improvement in function scores, objective muscle strength testing, and pain scores provides compelling evidence for the success of conservative treatment and a strong incentive for future larger studies.
Anti-inflammatory Medication Although conventional nonsteroidal anti-inflammatory drugs are commonly an intrinsic and intuitive component of nonoperative treatment of painful rotator cuff tears, no controlled clinical trial has been performed to date demonstrating efficacy. The American Academy of Orthopaedic Surgeons currently reports inconclusive evidence regarding the use of oral nonsteroidal anti-inflammatory drugs for rotator cuff tears.22 Subacromial corticosteroid injections are commonly used in conjunction with oral medications in patients with rotator cuff pathology, including rotator cuff tears. Inflammation of
209 the subacromial bursa has long been the proposed mechanism for pain in patients with rotator cuff pathology, both tendinopathies as well as rotator cuff tears. However, although prevalent in clinical practice for subacromial pain,23 most randomized clinical trials fail to distinguish between tendinopathies and rotator cuff tears.24 Blaine et al25 demonstrated that the expression of several cytokine, cyclooxygenase, and metalloprotease genes was increased in subacromial biopsy specimens compared with controls; however, no clinical information was provided regarding the patients with bursitis, such as age, length of symptoms, status of the rotator cuff, or indication for surgery. Similarly, in another study using immunohistochemistry, Sakai et al26 demonstrated the upregulation of tumor necrosis factor alpha, basic fibroblast growth factor, tumor growth factor beta, and interleukin (IL)-1 beta in patients with rotator cuff tears compared with anterior instability controls without evidence for rotator cuff pathology. The evidence of inflammatory mediators typically associated with nociception argues in favor of treatment with anti-inflammatories, such as steroids. Although decreasing pain and improving functional range of motion are important aspects of nonoperative management, studies demonstrating the potential deleterious effects of corticosteroid injections, such as tendon atrophy and increased inflammation, temper its ubiquitous use in the treatment of tears.27
Augmented Biological Healing Platelet-rich plasma (PRP) has gained recent popularity among orthopedic surgeons in treating pain associated with various tendinopathies, as well as augmenting tendon-tobone healing. PRP is prepared by taking a sample of whole blood and using a centrifuge to separate the cellular components of whole blood isolating a PRP solution. Several studies have found increased collagen gene expression, increased production of vascular endothelial growth factor, and hepatocyte growth factor in human tenocytes treated with PRP.28 However, as molecular components of each blood sample necessarily vary from patient to patient, and relative proportions vary from system to system, it is not surprising that there is no clear evidence for its efficacy in both operative as well as nonoperative settings. With regard to its use in rotator cuff pathology, an in vitro study by Jo et al29 applied PRP to tenocytes from human rotator cuff specimens and resulted in increased collagen and glycosaminoglycan expression at 14 days. As recent clinical studies are demonstrating little efficacy in improved healing after rotator cuff repair,30,31 and furthermore, there is evidence for increased inflammation and tendon atrophy in in vitro studies,32 it is unlikely PRP formulations at this time will play a role in the treatment of rotator cuff disease without further prospective randomized clinical trials.
Risk of Tear Progression Although there is some evidence that earlier surgical intervention, if indicated, is beneficial,33 the decision to proceed
210
Figure 1 Articular sided partial thickness supraspinatus tear and superior labral tear identified in a 22 year old male which was successfully treated with an intra-articular corticosteroid injection and physical therapy.
with surgery in a symptomatic tear is often weighed against the risk of tear progression over time. Typically, patients who respond to conservative treatment are followed clinically and often with imaging studies. In one study, 54 patients managed nonoperatively were studied retrospectively by review of MRI findings over time.34 This investigation attempted to identify risk factors associated with rotator cuff tear progression, and followed patients initially treated conservatively with a plethora of tear sizes, varying degrees of fatty infiltration, wide-ranging timings of follow-up imaging and no standardized treatment regimen. Although the authors advocate monitoring with MRI to guide patient management and identify factors, such as age ⬎60 years and fatty infiltration of the rotator cuff muscle as prognostic indicators of tear progression, the heterogeneity of subjects in this retrospective review provides no grounds for conclusive evidence. Furthermore, this study failed to incorporate functional reports or pain scores, which is pivotal in the management of rotator cuff disease. Clearly, the indication for surgery in a rotator cuff tear that has progressed over time according to MR findings must be reconciled with the clinical status of the patient, as many progressive tears over time remain asymptomatic.
V.G. Cuellar, F. Lerebours, and E.J. Strauss that a deeper understanding of the pathophysiology of the disease will improve not only patient selection but also provide new treatment options. Although, traditionally, rotator cuff tears are believed to result from one or more extrinsic and/or intrinsic factors, recently there has been more interest in the molecular and cellular aspects contributing to disease. In particular, increased or disregulated apoptosis may be an important component of tendinopathy, potentially as a result of oxidative stress (overuse). A few apoptotic mediators with regard to tendinopathy have been investigated in both in vivo models and from human patient samples based on microarray analysis, specifically caspases 3 and 8, Fas ligand, and matrix metalloproteinases (MMPs).35,36 In 2 separate investigations, Millar et al37,38 identified increased cytokine and heat-shock protein expression in supraspinatus tendinopathy. In a more recent study, the role of apoptosis was refined to a molecular analysis of hypoxia and its role in the pathogenesis of tendinopathy.39 Immunohistochemistry studies demonstrated increased expression of hypoxia-inducible factor-1-alpha, Bcell lymphoma-2 (Bcl-2), and clusterin in torn human subscapularis tendon samples, as well as an increased production of proinflammatory cytokines IL-6, IL-8, and monocyte chemoattractant protein-1. The effects of hypoxia were also investigated in an ex vivo tissue culture model, suggesting increased production of collagen type III and confirming increased production of inflammatory cytokines and mediators of apoptosis. Other cytokine biomarkers of rotator cuff tears have been investigated in the synovial fluid from glenohumeral joints, such as IL-1 and MMP-13,40 and an imbalance in the expression of MMPs and tissue inhibitors of MMPs has been implicated both in rotator tendon healing as well as tendi-
New Frontiers in Nonoperative Treatment Molecular Pathology Greater insight into the pathophysiology of rotator cuff disease and the basic biology distinguishing painful versus nonpainful tears may alter patient selection parameters for operative intervention in the future. Moreover, it is anticipated
Figure 2 Incidental partial thickness supraspinatus tear identified in a 38 year old male being worked up for symptomatic acromioclavicular degenerative disease.
Nonoperative management
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Conclusions Despite advances in surgical approaches to rotator cuff pathology, our fundamental understanding of the causative factors and natural history remains limited. There is emerging evidence that nonoperative treatment is efficacious and appropriate in a wider patient population than commonly practiced. However, the present lack of rigorous and well-controlled prospective clinical investigations of nonoperative treatment in rotator cuff tears forgoes the establishment of a treatment algorithm at this time. Future insight into the pathophysiology of rotator cuff disease may provide not only new therapeutic targets in the treatment of this disease but may also enable the physician to better distinguish which patients may benefit from specific nonoperative interventions.
References
Figure 3 Partial thickness rotator cuff tear seen in the setting of adhesive capsulitis in a 39 year old diabetic male successfully managed with physical therapy.
nopathy.41,42 Although most studies analyzing cytokine biomarkers of rotator cuff disease have focused on surgical outcomes, it is expected that future studies evaluating the molecular indicators of rotator cuff tears that do well after nonoperative management may provide new therapeutic options.
Case Examples Asymptomatic rotator cuff tears are occasionally encountered incidentally when evaluating the patient for another distinct shoulder pathology. Figure 1 demonstrates an articular-sided partial thickness supraspinatus tear in a 22-year-old righthand dominant man with a concurrent acute superior labral tear. He responded well to an intra-articular corticosteroid injection and a course of physical therapy. The patient did not require further intervention for pain control and was able to return to his previous level of activity without limitation. In another case (Fig. 2), a partial thickness supraspinatus tear was incidentally discovered in a 38-year-old right-hand dominant man being worked up for symptomatic acromioclavicular degenerative joint disease. His acromioclavicular joint was successfully treated with a corticosteroid injection and a course of physical therapy. He returned to all of his activities without limitation with no intervention required for his rotator cuff pathology. Similarly, Fig. 3 demonstrates incidental finding of a partial thickness supraspinatus tear in a 39-year-old diabetic right-hand dominant male whose symptoms resolved after a course of physical therapy for adhesive capsulitis not requiring further intervention for the rotator cuff tear.
1. van der Windt DA, Koes BW, De Jong BA, et al: Shoulder disorders in general practice: Incidence, patient characteristics, and management. Ann Rheum Dis 54:959-964, 1995 2. Luime JJ, Koes BW, Hendriksen IJ, et al: Prevalence and incidence of shoulder pain in the general population; a systematic review. Scand J Rheumatol 33:73-81, 2004 3. Milgrom C, Schaffler M, Gilbert S, et al: Rotator-cuff changes in asymptomatic adults. The effect of age, hand dominance and gender. J Bone Joint Surg Br 77:296-298, 1995 4. Sher JS, Uribe JW, Posada A, et al: Abnormal findings on magnetic resonance images of asymptomatic shoulder. J Bone Joint Surg Am 771:10-15, 1995 5. Neviaser A, Andarawis-Puri N, Flatow E: Basic mechanisms of tendon fatigue damage. J Shoulder Elbow Surg 21:158-163, 2012 6. Maffulli N, Longo UG, Berton A, et al: Biological factors in the pathogenesis of rotator cuff tears. Sports Med Arthrosc 19:194-201, 2011 7. Neri BR, Chan KW, Kwon YW: Management of massive and irreparable rotator cuff tears. J Shoulder Elbow Surg 18:808-818, 2009 8. Tempelhof S, Rupp S, Seil R: Age-related prevalence of rotator cuff tears in asymptomatic shoulders. J Shoulder Elbow Surg 8:296-299, 1999 9. Randelli P, Spennacchio P, Ragone V, et al: Complications associated with arthroscopic rotator cuff repair: A literature review. Musculoskelet Surg 96:9-16, 2012 10. Kijima H, Minagawa H, Nishi T, et al: Long-term follow-up of cases of rotator cuff tear treated conservatively. J Shoulder Elbow Surg 21:491494, 2012 11. Marx RG, Koulouvaris P, Chu SK, et al: Indications for surgery in clinical outcome studies of rotator cuff repair. Clin Orthop Relat Res 467:450-456, 2009 12. Dunn WR, Schackman BR, Walsh C, et al: Variation in orthopaedic surgeons’ perceptions about the indications for rotator cuff surgery. J Bone Joint Surg Am 87:1978-1984, 2005 13. Ainsworth R, Lewis JS: Exercise therapy for the conservative management of full thickness tears of the rotator cuff: A systematic review. Br J Sports Med 41:200-210, 2007 14. Kuhn JE: Exercise in the treatment of rotator cuff impingement: A systematic review and a synthesized evidence-based rehabilitation protocol. J Shoulder Elbow Surg 18:138-160, 2009 15. Baydar M, Akalin E, El O, et al: The efficacy of conservative treatment in patients with full-thickness rotator cuff tears. Rheumatol Int 29:623628, 2009 16. Krabak BJ, Sugar R, McFarland EG: Practical nonoperative management of rotator cuff injuries. Clin J Sport Med 13:102-105, 2003 17. Arwert HJ, de Groot J, Van Woensel WW, et al: Electromyography of shoulder muscles in relation to force direction. J Shoulder Elbow Surg 6:360-370, 1997 18. Kibler WB, McMullen J: Scapular dyskinesis and its relation to shoulder pain. J Am Acad Orthop Surg 11:142-151, 2003
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212 19. Yamaguchi K, Sher JS, Andersen WK, et al: Glenohumeral motion in patients with rotator cuff tears: A comparison of asymptomatic and symptomatic shoulders. J Shoulder Elbow Surg 9:6-11, 2000 20. Pegreffi F, Paladini P, Campi F, et al: Conservative management of rotator cuff tear. Sports Med Arthrosc 19:348-353, 2011 21. Bartolozzi A, Andreychik D, Ahmad S: Determinants of outcome in the treatment of rotator cuff disease. Clin Orthop Relat Res 308:90-97, 1994 22. Pedowitz RA, Yamaguchi K, Ahmad CS, et al: American Academy of Orthopaedic Surgeons Clinical Practice Guideline on: Optimizing the management of rotator cuff problems. J Bone Joint Surg Am 94:163167, 2012 23. Johansson K, Oberg B, Adolfsson L, et al: A combination of systematic review and clinicians’ beliefs in interventions for subacromial pain. Br J Gen Pract 52:145-152, 2002 24. Koester MC, Dunn WR, Kun JE, et al: The efficacy of subacromial corticosteroid injection in the treatment of rotator cuff disease: A systematic review. J Am Acad Orthop Surg 15:3-11, 2007 25. Blaine TA, Kim YS, Voloshin I, et al: The molecular pathophysiology of subacromial bursitis in rotator cuff disease. J Shoulder Elbow Surg 14:84S-89S, 2005 26. Sakai H, Fujita K, Sakai Y, et al: Immunolocalization of cytokines and growth factors in subacromial bursa of rotator cuff tear patients. Kobe J Med Sci 47:25-34, 2001 27. Tillander B, Franzén LE, Karlsson MH, et al: Effect of steroid injections on the rotator cuff: An experimental study in rats. J Shoulder Elbow Surg 8:271-274, 1999 28. Hall MP, Band PA, Meislin RJ, et al: Platelet-rich plasma: Current concepts and application in sports medicine. J Am Acad Orthop Surg 17:602-608, 2009 29. Jo CH, Kim JE, Yoon KS, et al: 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 40:1035-1045, 2012 30. Jo CH, Kim JE, Yoon KS, et al: Does platelet-rich plasma accelerate
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recovery after rotator cuff repair? A prospective cohort study. Am J Sports Med 39:2082-2090, 2011 de Vos RJ, van Veldhoven PL, Moen MH, et al: Autologous growth factor injections in chronic tendinopathy: A systematic review. Br Med Bull 95:63-77, 2010 Dragoo JL, Braun HJ, Durham JL, et al: Comparison of the acute inflammatory response of two commercial platelet-rich plasma systems in healthy rabbit tendons. Am J Sports Med 40:1274-1281, 2012 Lähteenmäki HE, Virolainen P, Hiltunen A, et al: Results of early operative treatment of rotator cuff tears with acute symptoms. J Shoulder Elbow Surg 15:148-153, 2006 Maman E, Harris C, White L, et al: Outcome of nonoperative treatment of symptomatic rotator cuff tears monitored by magnetic resonance imaging. J Bone Joint Surg Am 91:1898-1906, 2009 Yuan J, Murrell GA, Wei AQ, et al: Apoptosis in rotator cuff tendonopathy. J Orthop Res 20:1372-1379, 2002 Wang F, Murrell GA, Wang MX: Oxidative stress-induced c-Jun N-terminal kinase (JNK) activation in tendon cells upregulates MMP1 mRNA and protein expression. J Orthop Res 25:378-389, 2007 Millar NL, Wei AQ, Molloy TJ, et al: Cytokines and apoptosis in supraspinatus tendinopathy. J Bone Joint Surg Br 91:417-424, 2009 Millar NL, Wei AQ, Molloy TJ, et al: Heat shock protein and apoptosis in supraspinatus tendinopathy. Clin Orthop Relat Res 466:1569-1576, 2008 Millar NL, Reilly JH, Kerr SC, et al: Hypoxia: A critical regulator of early human tendinopathy. Ann Rheum Dis 71:302-310, 2012 Osawa T, Shinozaki T, Takagishi K: Multivariate analysis of biochemical markers in synovial fluid from the shoulder joint for diagnosis of rotator cuff tears. Rheumatol Int 25:436-441, 2005 Bedi A, Kovacevic D, Hettrich C, et al: The effect of matrix metalloproteinase inhibition on tendon-to-bone healing in a rotator cuff repair model. J Shoulder Elbow Surg 19:384-391, 2010 Lo IK, Marchuk LL, Hollinshead R, et al: Matrix metalloproteinase and tissue inhibitor of matrix metalloproteinase mRNA levels are specifically altered in torn rotator cuff tendons. Am J Sports Med 32:12231229, 2004
A
lthough the incidence of shoulder pain in the United States is reported as 14.7 per 1000 patients per year, the overall prevalence during a lifetime reaches nearly 70%.1,2 Furthermore, disorders of the rotator cuff in particular are among the most common shoulder pathologies, with the incidence of symptomatic as well as asymptomatic tears increasing with age.3,4 Despite the ubiquity of rotator cuff pathology in clinical practice, the etiology remains largely unknown.5 Although both intrinsic and extrinsic mechanisms have been proposed, it is likely that rotator cuff disease is a multifactorial process. Moreover, it is unclear on a clinical as well as molecular level whether these mechanisms are primary or secondary in the pathogenesis of the disease.6 The fact that there are so many asymptomatic patients’ further obscures our understanding of the pathophysiology. Traditionally, rotator cuff tears have been classified based on size (ie, partial vs full-thickness tears). This distinction is largely because of the relationship between cuff tear size and reported success of surgical intervention.7 Notwithstanding, it appears that the presence of pain is of more relevance in
Department of Orthopaedic Surgery, New York University Hospital for Joint Diseases, New York, NY. Address reprint requests to Eric J. Strauss, MD, Department of Orthopaedic Surgery, New York University Hospital for Joint Diseases, 301 East 17th St, Suite 1402, New York, NY 10003. E-mail: [email protected]
1060-1872/12/$-see front matter © 2012 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1053/j.otsm.2012.08.001
clinical management, and conventionally, nonoperative treatment has been reserved for patients who do not have significant pain, including those with massive tears.7 However, no correlation between tears and symptoms has been shown in population studies. Therefore, although it is not difficult to diagnose a rotator cuff tear based on magnetic resonance imaging (MRI) findings, to ascertain whether this finding is causative of the patient’s pain and/or functional ability is not so clear. There is considerable interest in the field as to why some full-thickness rotator cuff tears are painful and disabling, whereas others are not. For example, it has been observed that small partial tears may disable some patients, yet other patients remain asymptomatic and functional with massive rotator cuff tears.8 Certainly, this clinical challenge remains pivotal in our development of successful treatment, operative and nonoperative alike. Thus, it is not surprising that the challenges of diagnosis have implications for treatment. Outcomes after surgical intervention are well documented in the literature, yet there is a paucity of rigorous studies concerning nonoperative management. Nonoperative investigations are often retrospective and usually complicated by their comparison with heterogeneous populations of surgical patients and varying indications. The interest in nonsurgical management of full-thickness rotator cuff tears is increasing. This may be accounted for by 207
208 a variety of reasons; however it is evident that the growing trend toward nonoperative treatment reflects better outcomes and an improved appreciation of the complexity of rotator cuff healing after surgery and the challenges of postoperative care if healing is impaired.9 Kijima et al10 recently published one of the few studies that prospectively enrolled patients with rotator cuff tears to undergo conservative treatment without selection bias. One of the strengths of this study lies in the inclusion of all patients with diagnosed rotator cuff tear for nonoperative treatment, regardless of tear size or patient age. Nonetheless, 2.8% of all patients ultimately underwent surgery, as their pain did not improve with traditional conservative intervention by 6 months. Although 103 patients were diagnosed with rotator cuff tear at the initiation of the study, at time of follow-up, 11 patients had died and 10 patients had severe dementia limiting follow-up evaluation, which resulted in analysis of 43 patients ⬎13 years. The results of the study were thus limited to follow-up of younger healthier patients. Furthermore, the investigation did not distinguish among traditional characteristics, such as acuity of symptoms, physical examination of strength, size of tear, degree of fatty infiltration, and age/ activity of the patient. At time of follow-up, 90% of patients had no or little pain and 70% reported no disturbance in activities of daily living. Of note, the authors determined that the younger patients (mean age 54 years) tended to have significant pain and disability at 10 years after diagnosis than older patients (mean age 64 years). Although limited by the heterogeneity of subjects enrolled and lack of baseline information regarding cuff pathology and physical examination findings, the prevalence of patients without significant pain and capable of completing activities of daily living at 13 years without surgical intervention is encouraging. In an exhaustive review of 86 articles pertaining to surgical indications and outcomes for rotator cuff pathology, Marx et al11 confirmed a significant heterogeneity among articles from high-quality journals. Most notably, 44% of the studies did not report duration of symptoms preoperatively, and a majority of studies did not report limitations of activities of daily living nor duration of nonoperative treatment before surgery. As these factors are clearly integral to the surgical decision-making process and subsequent outcomes, any comparison with nonoperative management casts doubt because the existing reports provide arguably unacceptable evidence. It has been documented that patients with full-thickness tears can be successfully treated both operatively and nonoperatively, thus any further comparison between operative and nonoperative outcomes demands rigorous inclusion/exclusion criteria as well as standardized pre- and postoperative regimens. Validation of both treatment options is imperative in the clinical decision-making process. Typically, given MRI and physical examination findings consistent with a diagnosis of rotator cuff tear, surgical intervention for rotator cuff tears has been relegated to those patients with refractory pain for ⬎6 months, acute full-thickness tears in young active patients, and concurrent shoulder instability. However, to date, there is no clear agreement regarding the indications for rotator cuff surgery. Needless to
V.G. Cuellar, F. Lerebours, and E.J. Strauss say, this debate has implications for the nonsurgical treatment of rotator cuff tears as well. Although there are many reports in the literature of successful outcomes after rotator cuff repair, the inclusion criteria, indications, and postoperative rehabilitation protocols and outcome measurements are so varied that there is remarkably no consensus.12
Nonoperative Management Options Nonoperative management options typically have been reserved for the elderly or for partial tears. The modalities used include exercise, electrotherapy, acupuncture, manual therapy, injection therapy, and bracing/taping. More recently, clinical outcome studies suggest that the level of degeneration within repaired tendons is the most important factor influencing tendon-to-bone healing,5 and may account for the poor response to surgical intervention in the elderly patients or chronic rotator cuff tear populations.
Exercise/Physical Therapy The approach most commonly offered to all patients with rotator cuff pathology is exercise. Although systemic reviews of the literature have been published,13-15 currently, there is no consensus as to the optimal exercise regimen. This, in part, it reflects the heterogeneity of the methods in the literature as well as distinctions in patient selection. For example, “standard” exercise regimens for rotator cuff disease may imply various degrees of stretching/strengthening maneuvers, range of motion exercises, and other modalities. Moreover, the quality of the literature dealing with exercise treatment is often retrospective studies of patients that participated in an exercise regimen, rather than several prospective studies with clear inclusion criteria. Our fundamental lack of understanding of the pathophysiology of rotator cuff tears, pain, and healing further obscures the question as to why exercise regimens should have a beneficial impact in this disease. There has been little discussion of the possibilities, but exercise may modulate pain responses, provide placebo effect, and may train other muscles to coordinate movement and restore functional ability. For example, weakness of scapular stabilizers as well as rotator cuff musculature has been proposed as an etiology of glenohumeral dysfunction and arthropathy, and its early rehabilitation has been advocated to prevent progressive disease.15,16 It has also been postulated that symptoms occur with rotator cuff pathology when glenohumeral and scapulothoracic motion is abnormal, or the muscle forces across these joints is imbalanced.17,18 Yamaguchi et al19 has published several related studies, one in particular that suggested abnormal glenohumeral motion is associated with symptomatic tears. Although there is no standard of care for exercise therapy at this time, typically rotator cuff injuries are managed in a 3-phase approach.20 The first phase focuses on range of motion and pain control, the second on strengthening scapular stabilizing muscles as well as deltoid strengthening, and the
Nonoperative management third addresses maintenance of strength, range of motion, and integration back into normal activities, including sports. Ainsworth et al13 conducted a systematic review of the literature and reported on 10 observational studies that included treatment groups receiving exercise therapy alone or as an adjunct intervention for full-thickness, massive, or inoperable rotator cuff tear. The review of the existing studies was extensive, but clearly, the variation in the types of exercise used, initiation of treatment/duration of treatment, and heterogeneous inclusion criteria makes any satisfactory conclusions impossible. The trend suggests that some sort of exercise regimen is beneficial, but further guidance regarding those patients in particular that would benefit and from which specific treatment is lacking. One possibility though is a natural resolution in certain patients, and this is supported by the few long-term follow-up studies that suggest significant improvement over time. For example, as discussed by Bartolozzi et al,21 improved outcomes after conservative treatment increased with length of follow-up evaluation. Muscle weakness has typically been an important factor in the decision to proceed with surgery and/or physical therapy for rotator cuff tears; however, the distinction between painful tears versus tears causing weakness has more recently been called into question.13 One of the few prospective studies evaluating conservative treatment, specifically musclestrengthening exercises, used a standard treatment approach with objective as well as subjective outcome measurements with respect to muscle strength.15 This study by Baydar et al enrolled 20 patients with full-thickness rotator cuff tears, which included small to massive sized tears, with a mean age of 60.9 ⫾ 7.7 years and mean symptom duration of 9.2 ⫾ 10.5 months. What is unique about this study is that all patients underwent standardized isokinetic strength testing of both shoulders at baseline and at 6 months, as well as other standardized functional outcome measurements at baseline and follow-up evaluations up to 3 years. All patients were also involved in a specific 3-week physical therapy program and 3-phase home exercise course. The authors acknowledge the limitations of the study, specifically the small sample size; however, the overall statistically significant improvement in function scores, objective muscle strength testing, and pain scores provides compelling evidence for the success of conservative treatment and a strong incentive for future larger studies.
Anti-inflammatory Medication Although conventional nonsteroidal anti-inflammatory drugs are commonly an intrinsic and intuitive component of nonoperative treatment of painful rotator cuff tears, no controlled clinical trial has been performed to date demonstrating efficacy. The American Academy of Orthopaedic Surgeons currently reports inconclusive evidence regarding the use of oral nonsteroidal anti-inflammatory drugs for rotator cuff tears.22 Subacromial corticosteroid injections are commonly used in conjunction with oral medications in patients with rotator cuff pathology, including rotator cuff tears. Inflammation of
209 the subacromial bursa has long been the proposed mechanism for pain in patients with rotator cuff pathology, both tendinopathies as well as rotator cuff tears. However, although prevalent in clinical practice for subacromial pain,23 most randomized clinical trials fail to distinguish between tendinopathies and rotator cuff tears.24 Blaine et al25 demonstrated that the expression of several cytokine, cyclooxygenase, and metalloprotease genes was increased in subacromial biopsy specimens compared with controls; however, no clinical information was provided regarding the patients with bursitis, such as age, length of symptoms, status of the rotator cuff, or indication for surgery. Similarly, in another study using immunohistochemistry, Sakai et al26 demonstrated the upregulation of tumor necrosis factor alpha, basic fibroblast growth factor, tumor growth factor beta, and interleukin (IL)-1 beta in patients with rotator cuff tears compared with anterior instability controls without evidence for rotator cuff pathology. The evidence of inflammatory mediators typically associated with nociception argues in favor of treatment with anti-inflammatories, such as steroids. Although decreasing pain and improving functional range of motion are important aspects of nonoperative management, studies demonstrating the potential deleterious effects of corticosteroid injections, such as tendon atrophy and increased inflammation, temper its ubiquitous use in the treatment of tears.27
Augmented Biological Healing Platelet-rich plasma (PRP) has gained recent popularity among orthopedic surgeons in treating pain associated with various tendinopathies, as well as augmenting tendon-tobone healing. PRP is prepared by taking a sample of whole blood and using a centrifuge to separate the cellular components of whole blood isolating a PRP solution. Several studies have found increased collagen gene expression, increased production of vascular endothelial growth factor, and hepatocyte growth factor in human tenocytes treated with PRP.28 However, as molecular components of each blood sample necessarily vary from patient to patient, and relative proportions vary from system to system, it is not surprising that there is no clear evidence for its efficacy in both operative as well as nonoperative settings. With regard to its use in rotator cuff pathology, an in vitro study by Jo et al29 applied PRP to tenocytes from human rotator cuff specimens and resulted in increased collagen and glycosaminoglycan expression at 14 days. As recent clinical studies are demonstrating little efficacy in improved healing after rotator cuff repair,30,31 and furthermore, there is evidence for increased inflammation and tendon atrophy in in vitro studies,32 it is unlikely PRP formulations at this time will play a role in the treatment of rotator cuff disease without further prospective randomized clinical trials.
Risk of Tear Progression Although there is some evidence that earlier surgical intervention, if indicated, is beneficial,33 the decision to proceed
210
Figure 1 Articular sided partial thickness supraspinatus tear and superior labral tear identified in a 22 year old male which was successfully treated with an intra-articular corticosteroid injection and physical therapy.
with surgery in a symptomatic tear is often weighed against the risk of tear progression over time. Typically, patients who respond to conservative treatment are followed clinically and often with imaging studies. In one study, 54 patients managed nonoperatively were studied retrospectively by review of MRI findings over time.34 This investigation attempted to identify risk factors associated with rotator cuff tear progression, and followed patients initially treated conservatively with a plethora of tear sizes, varying degrees of fatty infiltration, wide-ranging timings of follow-up imaging and no standardized treatment regimen. Although the authors advocate monitoring with MRI to guide patient management and identify factors, such as age ⬎60 years and fatty infiltration of the rotator cuff muscle as prognostic indicators of tear progression, the heterogeneity of subjects in this retrospective review provides no grounds for conclusive evidence. Furthermore, this study failed to incorporate functional reports or pain scores, which is pivotal in the management of rotator cuff disease. Clearly, the indication for surgery in a rotator cuff tear that has progressed over time according to MR findings must be reconciled with the clinical status of the patient, as many progressive tears over time remain asymptomatic.
V.G. Cuellar, F. Lerebours, and E.J. Strauss that a deeper understanding of the pathophysiology of the disease will improve not only patient selection but also provide new treatment options. Although, traditionally, rotator cuff tears are believed to result from one or more extrinsic and/or intrinsic factors, recently there has been more interest in the molecular and cellular aspects contributing to disease. In particular, increased or disregulated apoptosis may be an important component of tendinopathy, potentially as a result of oxidative stress (overuse). A few apoptotic mediators with regard to tendinopathy have been investigated in both in vivo models and from human patient samples based on microarray analysis, specifically caspases 3 and 8, Fas ligand, and matrix metalloproteinases (MMPs).35,36 In 2 separate investigations, Millar et al37,38 identified increased cytokine and heat-shock protein expression in supraspinatus tendinopathy. In a more recent study, the role of apoptosis was refined to a molecular analysis of hypoxia and its role in the pathogenesis of tendinopathy.39 Immunohistochemistry studies demonstrated increased expression of hypoxia-inducible factor-1-alpha, Bcell lymphoma-2 (Bcl-2), and clusterin in torn human subscapularis tendon samples, as well as an increased production of proinflammatory cytokines IL-6, IL-8, and monocyte chemoattractant protein-1. The effects of hypoxia were also investigated in an ex vivo tissue culture model, suggesting increased production of collagen type III and confirming increased production of inflammatory cytokines and mediators of apoptosis. Other cytokine biomarkers of rotator cuff tears have been investigated in the synovial fluid from glenohumeral joints, such as IL-1 and MMP-13,40 and an imbalance in the expression of MMPs and tissue inhibitors of MMPs has been implicated both in rotator tendon healing as well as tendi-
New Frontiers in Nonoperative Treatment Molecular Pathology Greater insight into the pathophysiology of rotator cuff disease and the basic biology distinguishing painful versus nonpainful tears may alter patient selection parameters for operative intervention in the future. Moreover, it is anticipated
Figure 2 Incidental partial thickness supraspinatus tear identified in a 38 year old male being worked up for symptomatic acromioclavicular degenerative disease.
Nonoperative management
211
Conclusions Despite advances in surgical approaches to rotator cuff pathology, our fundamental understanding of the causative factors and natural history remains limited. There is emerging evidence that nonoperative treatment is efficacious and appropriate in a wider patient population than commonly practiced. However, the present lack of rigorous and well-controlled prospective clinical investigations of nonoperative treatment in rotator cuff tears forgoes the establishment of a treatment algorithm at this time. Future insight into the pathophysiology of rotator cuff disease may provide not only new therapeutic targets in the treatment of this disease but may also enable the physician to better distinguish which patients may benefit from specific nonoperative interventions.
References
Figure 3 Partial thickness rotator cuff tear seen in the setting of adhesive capsulitis in a 39 year old diabetic male successfully managed with physical therapy.
nopathy.41,42 Although most studies analyzing cytokine biomarkers of rotator cuff disease have focused on surgical outcomes, it is expected that future studies evaluating the molecular indicators of rotator cuff tears that do well after nonoperative management may provide new therapeutic options.
Case Examples Asymptomatic rotator cuff tears are occasionally encountered incidentally when evaluating the patient for another distinct shoulder pathology. Figure 1 demonstrates an articular-sided partial thickness supraspinatus tear in a 22-year-old righthand dominant man with a concurrent acute superior labral tear. He responded well to an intra-articular corticosteroid injection and a course of physical therapy. The patient did not require further intervention for pain control and was able to return to his previous level of activity without limitation. In another case (Fig. 2), a partial thickness supraspinatus tear was incidentally discovered in a 38-year-old right-hand dominant man being worked up for symptomatic acromioclavicular degenerative joint disease. His acromioclavicular joint was successfully treated with a corticosteroid injection and a course of physical therapy. He returned to all of his activities without limitation with no intervention required for his rotator cuff pathology. Similarly, Fig. 3 demonstrates incidental finding of a partial thickness supraspinatus tear in a 39-year-old diabetic right-hand dominant male whose symptoms resolved after a course of physical therapy for adhesive capsulitis not requiring further intervention for the rotator cuff tear.
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