Authors: Elisa Tetschke, MB Margit Rudolf, MD Christoph H. Lohmann, MD Christian Sta¨rke, MD
Therapy
Affiliations: From the Department of Orthopaedic Surgery, Otto-von-Guericke University Magdeburg, Magdeburg, Germany.
Correspondence: All correspondence and requests for reprints should be addressed to: Elisa Tetschke, MB, Department of Orthopaedic Surgery, Otto-von-Guericke University Magdeburg, Leipziger StraQe 44, 39112 Magdeburg, Germany.
ORIGINAL RESEARCH ARTICLE
Autologous Proliferative Therapies in Recalcitrant Lateral Epicondylitis ABSTRACT Tetschke E, Rudolf M, Lohmann CH, Sta¨rke C: Autologous proliferative therapies in recalcitrant lateral epicondylitis. Am J Phys Med Rehabil 2015;94:696Y706.
Disclosures: Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article.
plasma (ACP) injections and low-level laser application as therapy options for chronic lateral epicondylitis.
0894-9115/15/9409-0696 American Journal of Physical Medicine & Rehabilitation Copyright * 2014 Wolters Kluwer Health, Inc. All rights reserved.
in this study; 26 of these patients received three ACP injections and the control group, with 26 patients, received 12 laser applications, with standardized physical therapy for all patients afterward. Control examinations took place before treatment, after 2 and 6 mos, and in the 1 yr final follow-up. The control examination included the visual analog scale for pain and Disabilities of the Arm, Shoulder and Hand outcome measure scores.
DOI: 10.1097/PHM.0000000000000234
Objective: This study investigates the clinical effects of autologous conditioned
Design: A total of 52 patients with chronic lateral epicondylitis were evaluated
Results: The analysis at final follow-up after 1 yr showed that both treatment options resulted in successful therapy outcome for the patients. In total, 63.5 % were successfully treated. Successful treatment was defined as more than 30% improvement in the visual analog score and more than 10.2 points in the Disabilities of the Arm, Shoulder and Hand score. Both groups showed a significant improvement in time response.
Conclusions: This study demonstrates the beneficial effects of autologous proliferative therapies in the treatment of lateral epicondylitis. The data show that laser application and ACP therapy lead to a clinical improvement in epicondylopathia. Especially the new treatment with ACP can be highlighted as an alternative and as an easy-to-apply therapy option for clinical practice. Key Words:
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Tennis Elbow, Laser Therapy, Growth Factor, Platelet Rich Plasma
Am. J. Phys. Med. Rehabil. & Vol. 94, No. 9, September 2015 Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
L
ateral epicondylitis is the most common myotendinosis, with a prevalence of 1%Y3 % in the general population1 and an incidence of approximately 5 of 1000 patients per year in general practice.2 It affects mostly the working population in the age group of 35 to 65 yrs.1 The clinical picture is characterized by pain during specific movements, rest pain in chronic stages, tenderness on palpation in the region of the lateral epicondyle, gripping weakness of the affected hand, and exacerbated pain during specific tests.3,4 The main problem for the treatment of chronic epicondylitis is the variety of established therapeutic options.5,6 Despite numerous studies, there is no well-defined scientific treatment concept with successful long-term effects. For optimal therapy, the pathogenesis of lateral epicondylitis should be considered. The main etiology is chronic overuse of the common extensor tendon, mostly the extensor carpi radialis brevis. This leads to degeneration in the origin of the tendon with microtears, disorganized and immature collagen, and finally nonfunctional tendon tissue.3,7 Typical trigger activities are repetitive extension forces of the forearm, for instance, working with keyboard and mouse, skilled manual work, or overhead arm movement in sports. As a consequence of recurring micro trauma, the metabolism in the tendon is decreased, leading to inefficient repair of the tendon by body’s own regeneration mechanisms. Often, untreated spontaneous healing of the tendon results in unlinked and unstructured collagen fibers, which in turn lead to weak tendons and a higher risk for further injuries.8 Growth factors such as platelet-derived growth factor, transforming growth factor A, insulin-like growth factor I, and vascular endothelial growth factor play an important role in extracellular and intracellular tissue healing of the tendon. They stimulate the proliferation of fibroblasts, the collagen synthesis, the angiogenesis, and the remodeling of injured tissue.8 A relatively new, potentially promising treatment seems to be the use of autologous conditioned plasma (ACP).9,10 In vitro studies have shown that ACP (also referred to as platelet-rich plasma) induces the mechanism of healing and proliferative processes immediately at the tendon, owing to the high concentration of growth factors.11 However, it is unclear how to assess the clinical effects of ACPinjections compared with established proliferative therapies, such as laser therapy. The application of low-level laser also supports autologous healing processes. This stimulates the synthesis of growth www.ajpmr.com
factors,12 the induction of the proliferation of fibroblasts,13 and the initiation of collagen synthesis. Many studies have described the pain-relieving effect of laser application14 and its importance in the successful treatment of lateral tendinopathy.15,16 The primary goal of this study was to evaluate the clinical effects of ACP and low-level laser as treatment options for chronic lateral epicondylitis. Furthermore, the potential benefit of autologous, proliferative therapies shall be demonstrated. The hypotheses are that treatment with ACP in lateral epicondylopathia causes a clinically significant improvement and is as effective as laser treatment and that both therapies lead to successful recovery of patients.
METHODS Study Design, Sample, and Setting This is a prospective study that evaluates 52 patients with clinically diagnosed chronic lateral epicondylitis. The patients were sequentially divided into two groups, each with 26 patients. At first, a total of 61 eligible patients of the orthopedic ambulance from the University hospital, Magdeburg (Otto-von-Guericke University Magdeburg, Germany) were included, who were treated between March 2012 and July 2013. Five patients were dropouts because of wrongful inclusion and four patients were lost to follow up because of claiming exclusion therapies such as corticosteroid injections and surgical treatment before end point (Fig. 1). All patients experienced at least 3 mos of symptomatic lateral epicondylitis with previously unsuccessful physiotherapy or medical treatment. The patients who met the inclusion criteria and who gave written informed consent were included in this study. The local Medical Ethical Committee approved the study.
Inclusion Criteria Patients who fulfilled the following criteria were included in this study: Y Clinically diagnosed epicondylitis by the investigation physician (like the typical presentation in Cleland17 with pain in the epicondyle region, pain with resisted wrist extension, pain with resisted middle-finger extension). Y Minimum of 3 mos of pain with previously unsuccessful physiotherapy or medical treatment (manual therapy, ultrasonic, nonsteroidal anti-inflammatory drugs, brace, and protection). Y Home in the vicinity of the hospital. Therapies in Recalcitrant Lateral Epicondylitis
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FIGURE 1 The flow diagram shows the number of patients followed up during the study.
Exclusion Criteria Y Local injections in the last month. Y Previous laser treatment to the affected arm. Y Evidence of disordered pain perception. Y Younger than 18 yrs. Y Pregnancy, cervical radiculopathy, systemicinflammatory diseases (rheumatism, morbus bechterew), hemato-oncological diseases with low platelet numbers (myelodysplastic syndromes, leukemia, malignant lymphoma), infectious diseases (hepatitis). One group consisting of 26 patients received three intralesional ACP injections with an interval
of 7 days. The average age of the group was 51.5 yrs (Table 1). The control group, also with 26 patients, was treated with 12 laser applications with two sessions per week. This group had an average age of 53.1 yrs (Table 1). Both groups received standardized physiotherapy after treatment according to a specific therapy protocol (Fig. 2) in two different physiotherapeutic practices. The control examinations were conducted after 2 and 6 mos and at the final follow-up after 1 yr. The detected parameters at every time point were a visual analogue scale (VAS) for pain, with a range from 0 (no pain) to 10 (most severe pain), as well as
TABLE 1 Sociodemographic and clinical characteristics of the ACP and laser groups
Age, mean T SD, y Sex, female/male, n (%) Dominant hand, n (%) VAS, mean T SD DASH, mean T SD
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ACP
Laser
P
51.5 T 10.4 14 (53.8)/12 (46.2) 23 (88.5) 3.3 T 1.5 27.9 T 18.1
53.1 T 12.7 17 (65.4)/9 (34.6) 24 (92.3) 4.4 T 1.6 35.4 T 17.0
0.627 0.397 1.000 0.016 0.129
Am. J. Phys. Med. Rehabil. & Vol. 94, No. 9, September 2015 Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
the Disabilities of Arm, Shoulder and Hand (DASH) questionnaire. The DASH includes a main part with 30 questions about functional and social limitations in daily living
and also two optional item scales about limitations in occupation and spare time activities. The German translation of Germann et al.18 in revised version 2.0 from 2003 was used.19 The DASH value ranges from
FIGURE 2 Physiotherapy protocol for the after-treatment regimen for all patients. www.ajpmr.com
Therapies in Recalcitrant Lateral Epicondylitis Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
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FIGURE 2 (Continued)
0 (no disability) to 100 (most severe disability). In this study, only the main part of the DASH was used. A successful treatment was defined as at least 30% pain
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reduction on the VAS and a decrease of at least 10.2 points in the DASH score without reintervention for 1 yr. These parameters have proved to indicate a
Am. J. Phys. Med. Rehabil. & Vol. 94, No. 9, September 2015 Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
significant positive clinical effect for patients.20,21 A study by Jensen et al.20 showed that a percentage decrease of 27.9% on a rating scale of 0 to 10 points was associated with much or very much improvement for chronic pain patients. It was emphasized that a decrease in pain of 30%Y33% is a clinically significant effect.22 To define patients who benefited from treatment, in this study, a 30% decrease in VAS was considered as successful therapy. A minimal reduction of 10.2 points in the DASH score is considered as clinically significant pain improvement perceived by patients.21 For the preparation of ACP, the ACP Double Syringe System by Arthrex, Inc (Naples, FL) was used. Ten milliliters of whole blood was collected from a vein in the region of the cubital fossa with a 21-gauge butterfly needle into a double lumen syringe (Fig. 3A). After centrifugation of blood at 1500 rounds per minute for 5 mins, it resulted in 3Y5 ml of supernatant (Fig. 3B). The extracted growthfactor rich plasma (supernatant) was now transferred from the larger outer syringe into the smaller inner syringe (Fig. 3C). The ACP was injected with a 25-gauge needle at first subfascially in the region of the common head of the extensors. Then a further, intralesional dispersion followed with a two times over fan-like wheal injection (Fig. 3D). The laser application was conducted with a lowlevel laser BTL 5000 (a GaAs-infrared laser with a wavelength of 830 nm and a dose of 7 J/cm2; BTLMedizintechnik GmbH, Ulm, Germany). During this procedure, special glasses were used to protect the retina. The laser radiation was applied in circular movements to the region of the lateral epicondyle (Fig. 4). The treatment was managed by two previously instructed physiotherapy practices. Myofascial manipulation was done after the laser application for additional benefit of hyperemia and metabolism activation. After 8 wks of the first treatment, a physiotherapeutic postprocedure was initiated. It was based on 12 sessions with manual therapy techniques for trigger point elimination in the initial phase, stretching and strengthening exercises in the first 2 wks, as well as patient adapted muscle-trophic training in the advanced phase. The therapists were instructed by a treatment protocol, which was prepared in collaboration between physicians and physiotherapists (Fig. 2). In addition, the patients were assigned to do daily, self-contained stretching exercises.
measuring points. Furthermore, the averages of the scores per examination point were determined with 95% confidence intervals. Independent-samples t test (ordinal scale data) and chi-square test (nominal scale data) were used to examine the differences between sociodemographic and clinical data of the treatment groups. The same holds for the examination of the differences between the successful and unsuccessful groups. The level of significance was defined as 5%. All statistical analyses were implemented using the statistical program SPSS (IBM SPSS Statistics version 21).
RESULTS Analyses of the 52 VAS and DASH data sets with multivariate analysis of variance showed a significant improvement in time response of both therapies (P G 0.0001) (Fig. 5). The data comparison at each assessment point separately demonstrated in absolute numbers lower scores for the ACP patients than in the laser group (Table 2). An analysis of the values at each assessment point showed only significant differences of the VAS values (Table 2) between the groups before treatment was started (P = 0.008). The other assessment points showed no significant differences between the groups. In total, 33 of 52 patients (63.5%) were successfully treated (Table 3). As seen in Table 3, the ACP group was, in absolute frequencies, more often treated successfully (n = 19, 73.1%) than the laser group (n = 14, 53.8%), but without significant difference. The scores of the successful group were lower than the scores of the unsuccessful group at all assessment points as well as in average (Table 3). Sociodemographic and clinical characteristics between the ACP and laser groups are shown in Table 1. Analyses of the baseline characteristics (age, sex, dominant hand, average of VAS, average of DASH) showed no significant differences, except the VAS average. VAS pain scores were significantly higher in the laser group than in the ACP group (P = 0.016). In more than 90% of the cases, the dominant arm was affected. No complications regarding the use of ACP or the laser application could be observed.
DISCUSSION Statistical Analysis A multivariate analysis of variance was used to compare the VAS and DASH data on the itemized www.ajpmr.com
Both treatment methods implicated an accumulation of growth factors in the affected tendon tissue and promoted cellular tendon healing mechanisms. Therapies in Recalcitrant Lateral Epicondylitis
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FIGURE 3 AYD, Procedure of ACP therapy. At first, 10 ml of whole blood was collected from a cubital vein (A); second, the blood is centrifuged with 1500 rpm for 5 mins in a double lumen syringe and a supernatant of platelet-rich plasma is received (B); afterward, the plasma is transferred into the smaller, inner syringe (C); and finally, the ACP is injected intralesionally near the lateral epicondyle (D).
The process of tendon repair is composed of multiple phases after the first injury. A study done by Molloy et al.8 noted that, during the first 2 days after injury, inflammatory tissue changes with the release of growth factors, such as platelet-derived growth factor, transforming growth factor A, and insulin-like growth factor-I, as a result
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of extrinsic cell migration. After 2 days, the proliferative phase starts. During this phase, the fibroblasts’ proliferation, mitogenesis, and protein synthesis are induced by, among others, platelet-derived growth factor and insulin-like growth factor-I.23 The reparative phase is characterized by collagen deposition, revascularization, and the initiating reorganization
Am. J. Phys. Med. Rehabil. & Vol. 94, No. 9, September 2015 Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
FIGURE 4 Laser application performed in circular movements in the region of the lateral epicondyle and the following treatment with trigger point therapy and transverse friction.
FIGURE 5 A, B, VAS and DASH scores with 95% confidence interval in time response of both therapies. A, VAS pain scores at the various assessment points; B, DASH scores at the various assessment points. www.ajpmr.com
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TABLE 2 VAS and DASH scores for the ACP and laser groups at the various assessment points ACP VAS Before therapy 2 mos 6 mos 12 mos DASH Before therapy 2 mos 6 mos 12 mos
Laser
P
5.2 T 3.7 T 2.7 T 1.8 T
1.8 2.0 1.6 2.0
6.7 T 4.7 T 3.6 T 2.7 T
2.0 2.3 2.2 2.3
0.008 0.094 0.102 0.160
37.0 T 29.8 T 26.5 T 18.2 T
18.3 21.1 21.2 19.5
47.0 T 38.9 T 29.0 T 26.7 T
19.6 20.7 19.6 21.8
0.062 0.126 0.664 0.145
Data are provided as mean T SD.
of the cellular matrix.8 Finally, after 14 days, the remodeling begins with increased collagen synthesis, for instance, triggered by transforming growth factor A,23 and the new arranged collagen fibers are linked.8 Hyman and Rodeo24 demonstrated that after the healing process, the tendon tissue will approximately return to the normal original tendon. The inferiorly healed tendon tissue is weaker and has a higher risk for further injuries.8 Especially the chronicity of a disease characterizes a tissue with inferior quality because repetitive microtrauma results in disruption of the repair processes. This leads to poor tendon quality with disorganized, nonfunctional collagen fibers.7 A randomized controlled trial by Smidt et al.25 showed that there was no statistically significant difference between patients treated with physiotherapy and those treated with a wait-and-see policy. Patients who have improved without treatment are at a high risk for relapse. This is because the healing process in such
patients without relief results in only moderate resilient tissues with high risk for recidivism.8 That is inadequate for active patients with the claim to revert at their initial resilient condition. Furthermore, the natural history of any patient should have the same influence in both therapy groups because of sequential allocation. Kraushaar and Nirschl7 furthermore showed the importance of movement therapy in time for improving correct linked collagen and tendon strength. Treatment on an extrinsic as well as on an intrinsic pathway is of paramount importance for a successful healing response and optimal tendon quality. The applied therapies with ACP, respectively laser, with subsequent physiotherapeutic postprocedure both fulfill these requirements of an optimal treatment. Three ACP injections in an interval of 7 days were used to support all tissue healing phases. As recommended by Bjordal et al.,26 the laser application took place in 12 sessions with an infrared
TABLE 3 Sociodemographic and clinical characteristics and VAS and DASH scores of the successful and unsuccessful groups at the various assessment points
Treatment, ACP/Laser Age Sex, female/male Dominant hand VAS DASH VAS Before therapy 2 mos 6 mos 12 mos DASH Before therapy 2 mos 6 mos 12 mos
Successful (n = 33, 63.5%)
Unsuccessful (n = 19, 36.5%)
P
19 (73.1)/14 (53.8) 52.9 T 12.6 19 (57.6)/15 (42.4) 30 (90.9) 3.3 T 1.3 28.4 T 18.0
7 (26.9)/12 (46.2) 51.3 T 9.6 12 (63.2)/7 (36.8) 17 (89.5) 4.8 T 1.7 37.2 T 16.4
0.150 0.636 0.693 1.000 0.001 0.086
6.0 T 3.8 T 2.3 T 1.2 T
2.1 2.2 1.4 1.4
5.8 T 1.9 4.9 T 2.2 4.5 T 2.0 4.1 T 2.2
0.752 0.098 0.000 0.000
45.7 T 33.1 T 20.7 T 14.2 T
19.0 22.8 18.7 18.8
35.6 T 19.0 36.5 T 18.4 40.0 T 17.1 36.9 T 16.2
0.070 0.584 0.001 0.000
Data are provided as n (%) or mean T SD.
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Am. J. Phys. Med. Rehabil. & Vol. 94, No. 9, September 2015 Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
laser (GaAs) with a wavelength of 830 nm and a dose of 7 J/cm2. For an effective bio-stimulation, the laser application was done using continuous wavelengths. In addition, the treatment took place with a pulsed frequency of 10 Hz for an increased deep effect and a better analgesic outcome.27 This study achieved successful effects with direct autologous growth factor injection using ACP. In absolute numbers, the ACP includes 73.1% successfully treated patients, superior to the laser treatment, with 53.8% successfully treated patients (Table 3). This could have multiple causes. One possible reason could be the selection bias of the participants. The ACP group had, on average, significant inferior pain scores on the VAS than the laser group did (P = 0.016; Table 1). The DASH score, on the other hand, did not differ significantly between the treatment groups (P = 0.129). The comparison between the successful and unsuccessful groups shows significant differences in the VAS values (P = 0.001) but not in the DASH values (P = 0.086) (Table 3). In the successful group, the score data were inferior on average and at each assessment point, except the values before therapy. When the DASH score was compared at each assessment point between the two therapy groups in the unsuccessful case, the values became worse after 6 mos compared with the values after 2 mos (Table 3). A probable cause of this might be the expectations of the patients. After 6 mos, the therapies should be finished and the success should be obvious in the meantime. If this is not the case, the patients might be deeply disappointed, which could affect the values negatively. Certainly, an important limitation of the laser treatment was the expenditure of time for 12 sessions, because in comparison, the therapy with ACP demanded only three applications. No sociodemographic differences could be observed concerning age and gender between the ACP and laser groups, as well as the successful and unsuccessful groups. In total, the dominant arm was mostly affected (990%). Therefore, no relationship between success and these parameters could be established. A last limitation of the study can be seen in the selection of the 52 subjects. Even though the samples were drawn sequentially and, thus, as quasirandomization, the allocation to the therapy groups was in order of presentation in the orthopedic ambulance. In this prospective clinical trial, the clinical effects of two proliferative, metabolic activated www.ajpmr.com
therapies in chronic epicondylitis were compared. The benefit of both procedures could be supported with 64% of successfully treated patients. Both therapies proved to be easy to implement and safe (without complications).
CONCLUSION As the data show, both proliferative therapies lead to a clinical improvement of epicondylopathia. Especially the treatment with ACP can be highlighted as a successful therapy. Furthermore, the achievement of the soft laser application with also positive therapy results should accentuated. Nonetheless, when searching for an optimal treatment protocol, it should be regarded that, for the success of a laser therapy, the patient has to be very compliant and has to invest much time. Obviously, improvement of the symptoms without any intervention is possible. But for active patients, for a strong, resilient tendon and to avoid further injury, an additional treatment is probably beneficial. Further research with randomized and comparative studies between proliferative therapies with placebo or wait-and-see policy would be beneficial for determination of the optimal therapy for lateral epicondylitis. In conclusion, this study demonstrates the beneficial effects of proliferative autologous therapies, especially ACP, in the treatment of chronic epicondylitis humeri radialis. A close interaction between physicians and physiotherapists and a multimodal patient adapted concept is essential for optimum treatment. REFERENCES 1. Shiri R, Viikari-Juntura E, Varonen H, et al: Prevalence and determinants of lateral and medial epicondylitis: A population study. Am J Epidemiol 2006; 164:1065Y74. doi:10.1093/aje/kwj325 2. Verhaar JA: Tennis elbow. Anatomical, epidemiological and therapeutic aspects. Int Orthop 1994; 18:263Y7 3. Nirschl RP, Ashman ES: Elbow tendinopathy: Tennis elbow. Clin Sports Med 2003;22:813Y36 4. Taylor SA, Hannafin JA: Evaluation and management of elbow tendinopathy. Sports Health 2012;4:384Y93. doi:10.1177/1941738112454651 5. Bisset L: A systematic review and meta-analysis of clinical trials on physical interventions for lateral epicondylalgia. Br J Sports Med 2005;39:411Y22 6. Coombes BK, Bisset L, Vicenzino B: A new integrative model of lateral epicondylalgia. Br J Sports Med 2009; 43:252Y8
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7. Kraushaar BS, Nirschl RP: Tendinosis of the elbow (tennis elbow). Clinical features and findings of histological, immunohistochemical, and electron microscopy studies. J Bone Joint Surg Am 1999;81:259Y78
17. Cleland JA: Effectiveness of manual physical therapy to the cervical spine in the management of lateral epicondylalgia: A retrospective analysis. J Orthop Sports Phys Ther 2004;34:713Y24
8. Molloy T, Wang Y, Murrell G: The roles of growth factors in tendon and ligament healing. Sports Med 2003;33:381Y94
18. Germann G, Wind G, Harth A: Der DASHFragebogen-Ein neues Instrument zur Beurteilung von Behandlungsergebnissen an der oberen Extremita¨t. Handchir Mikrochir Plast Chir 1999;31:149Y52. doi:10.1055/s-1999-13902
9. Creaney L, Wallace A, Curtis M, et al: Growth factorYbased therapies provide additional benefit beyond physical therapy in resistant elbow tendinopathy: A prospective, single-blind, randomised trial of autologous blood injections versus platelet-rich plasma injections. Br J Sports Med 2011;45:966Y71 10. Peerbooms JC, Sluimer J, Bruijn DJ, et al: positive effect of an autologous platelet concentrate in lateral epicondylitis in a double-blind randomized controlled trial: Platelet-rich plasma versus corticosteroid injection with a 1-year follow-up. Am J Sports Med 2010; 38:255Y62. doi:10.1177/0363546509355445 11. Zhang J, Wang JH: Platelet-rich plasma releasate promotes differentiation of tendon stem cells into active tenocytes. Am J Sports Med 2010;38:2477Y86. doi:10.1177/0363546510376750 12. Gao X, Xing D: Molecular mechanisms of cell proliferation induced by low power laser irradiation. J Biomed Sci 2009;16:4. doi:10.1186/1423-0127-164 13. Vinck EM, Cagnie BJ, Cornelissen MJ, et al: Increased fibroblast proliferation induced by light emitting diode and low power laser irradiation. Lasers Med Sci 2003;18:95Y9. doi:10.1007/s10103-003-0262-x 14. Chow RT, Johnson MI, Lopes-Martins RAB, et al: Efficacy of low-level laser therapy in the management of neck pain: A systematic review and meta-analysis of randomised placebo or active-treatment controlled trials. Lancet 2009;374:1897Y908. doi:10.1016/S01406736(09)61522-1 15. Bjordal JM, Lopes-Martins RAB, Joensen J, et al: A systematic review with procedural assessments and meta-analysis of Low Level Laser Therapy in lateral elbow tendinopathy (tennis elbow). BMC Musculoskelet Disord 2008;9:75 16. Simunovic Z, Trobonjaca T, Trobonjaca Z: Treatment of medial and lateral epicondylitisVtennis and golfer’s elbowVwith low level laser therapy: A multicenter double blind, placebo-controlled clinical study on 324 patients. J Clin Laser Med Surg 1998;16:145Y51
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19. Germann G, Harth A, Wind G, et al: Standardisation and validation of the German version 2.0 of the Disability of Arm, Shoulder, Hand (DASH) questionnaire. Unfallchirurg 2003;106:13Y9. doi:10.1007/ s00113-002-0456-x 20. Jensen MP, Chen C, Brugger AM: Interpretation of visual analog scale ratings and change scores: A reanalysis of two clinical trials of postoperative pain. J Pain 2003;4:407Y14 21. Roy J, MacDermid JC, Woodhouse LJ: Measuring shoulder function: A systematic review of four questionnaires. Arthritis Rheum 2009;61:623Y32. doi:10.1002/ art.24396 22. Ostelo RW, Deyo RA, Stratford P, et al: Interpreting change scores for pain and functional status in low back pain: Towards international consensus regarding minimal important change. Spine 2008;33:90Y4. doi:10.1097/BRS.0b013e31815e3a10 23. Lynch SE, Colvin RB, Antoniades HN: Growth factors in wound healing. Single and synergistic effects on partial thickness porcine skin wounds. J Clin Invest 1989;84:640Y6. doi:10.1172/JCI114210 24. Hyman J, Rodeo SA: Injury and repair of tendons and ligaments. Phys Med Rehabil Clin N Am 2000;11: 267Y88 25. Smidt N, van der Windt DAWM, Assendelft WJJ, et al: Corticosteroid injections, physiotherapy, or a waitand-see policy for lateral epicondylitis: A randomised controlled trial. Lancet 2002;359:657Y62. http://dx.doi. org/10.1016/S0140-6736(02)07811-X 26. Bjordal JM, Couppe C, Ljunggren AE: Low level laser therapy for tendinopathy. Evidence of a dose-response pattern. Phys Ther Rev 2001;6:91Y9 27. Hashmi JT, Huang Y, Sharma SK, et al: Effect of pulsing in low-level light therapy. Lasers Surg Med 2010;42:450Y66. http://dx.doi.org/10.1002/lsm.20950
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Therapy
Affiliations: From the Department of Orthopaedic Surgery, Otto-von-Guericke University Magdeburg, Magdeburg, Germany.
Correspondence: All correspondence and requests for reprints should be addressed to: Elisa Tetschke, MB, Department of Orthopaedic Surgery, Otto-von-Guericke University Magdeburg, Leipziger StraQe 44, 39112 Magdeburg, Germany.
ORIGINAL RESEARCH ARTICLE
Autologous Proliferative Therapies in Recalcitrant Lateral Epicondylitis ABSTRACT Tetschke E, Rudolf M, Lohmann CH, Sta¨rke C: Autologous proliferative therapies in recalcitrant lateral epicondylitis. Am J Phys Med Rehabil 2015;94:696Y706.
Disclosures: Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article.
plasma (ACP) injections and low-level laser application as therapy options for chronic lateral epicondylitis.
0894-9115/15/9409-0696 American Journal of Physical Medicine & Rehabilitation Copyright * 2014 Wolters Kluwer Health, Inc. All rights reserved.
in this study; 26 of these patients received three ACP injections and the control group, with 26 patients, received 12 laser applications, with standardized physical therapy for all patients afterward. Control examinations took place before treatment, after 2 and 6 mos, and in the 1 yr final follow-up. The control examination included the visual analog scale for pain and Disabilities of the Arm, Shoulder and Hand outcome measure scores.
DOI: 10.1097/PHM.0000000000000234
Objective: This study investigates the clinical effects of autologous conditioned
Design: A total of 52 patients with chronic lateral epicondylitis were evaluated
Results: The analysis at final follow-up after 1 yr showed that both treatment options resulted in successful therapy outcome for the patients. In total, 63.5 % were successfully treated. Successful treatment was defined as more than 30% improvement in the visual analog score and more than 10.2 points in the Disabilities of the Arm, Shoulder and Hand score. Both groups showed a significant improvement in time response.
Conclusions: This study demonstrates the beneficial effects of autologous proliferative therapies in the treatment of lateral epicondylitis. The data show that laser application and ACP therapy lead to a clinical improvement in epicondylopathia. Especially the new treatment with ACP can be highlighted as an alternative and as an easy-to-apply therapy option for clinical practice. Key Words:
696
Tennis Elbow, Laser Therapy, Growth Factor, Platelet Rich Plasma
Am. J. Phys. Med. Rehabil. & Vol. 94, No. 9, September 2015 Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
L
ateral epicondylitis is the most common myotendinosis, with a prevalence of 1%Y3 % in the general population1 and an incidence of approximately 5 of 1000 patients per year in general practice.2 It affects mostly the working population in the age group of 35 to 65 yrs.1 The clinical picture is characterized by pain during specific movements, rest pain in chronic stages, tenderness on palpation in the region of the lateral epicondyle, gripping weakness of the affected hand, and exacerbated pain during specific tests.3,4 The main problem for the treatment of chronic epicondylitis is the variety of established therapeutic options.5,6 Despite numerous studies, there is no well-defined scientific treatment concept with successful long-term effects. For optimal therapy, the pathogenesis of lateral epicondylitis should be considered. The main etiology is chronic overuse of the common extensor tendon, mostly the extensor carpi radialis brevis. This leads to degeneration in the origin of the tendon with microtears, disorganized and immature collagen, and finally nonfunctional tendon tissue.3,7 Typical trigger activities are repetitive extension forces of the forearm, for instance, working with keyboard and mouse, skilled manual work, or overhead arm movement in sports. As a consequence of recurring micro trauma, the metabolism in the tendon is decreased, leading to inefficient repair of the tendon by body’s own regeneration mechanisms. Often, untreated spontaneous healing of the tendon results in unlinked and unstructured collagen fibers, which in turn lead to weak tendons and a higher risk for further injuries.8 Growth factors such as platelet-derived growth factor, transforming growth factor A, insulin-like growth factor I, and vascular endothelial growth factor play an important role in extracellular and intracellular tissue healing of the tendon. They stimulate the proliferation of fibroblasts, the collagen synthesis, the angiogenesis, and the remodeling of injured tissue.8 A relatively new, potentially promising treatment seems to be the use of autologous conditioned plasma (ACP).9,10 In vitro studies have shown that ACP (also referred to as platelet-rich plasma) induces the mechanism of healing and proliferative processes immediately at the tendon, owing to the high concentration of growth factors.11 However, it is unclear how to assess the clinical effects of ACPinjections compared with established proliferative therapies, such as laser therapy. The application of low-level laser also supports autologous healing processes. This stimulates the synthesis of growth www.ajpmr.com
factors,12 the induction of the proliferation of fibroblasts,13 and the initiation of collagen synthesis. Many studies have described the pain-relieving effect of laser application14 and its importance in the successful treatment of lateral tendinopathy.15,16 The primary goal of this study was to evaluate the clinical effects of ACP and low-level laser as treatment options for chronic lateral epicondylitis. Furthermore, the potential benefit of autologous, proliferative therapies shall be demonstrated. The hypotheses are that treatment with ACP in lateral epicondylopathia causes a clinically significant improvement and is as effective as laser treatment and that both therapies lead to successful recovery of patients.
METHODS Study Design, Sample, and Setting This is a prospective study that evaluates 52 patients with clinically diagnosed chronic lateral epicondylitis. The patients were sequentially divided into two groups, each with 26 patients. At first, a total of 61 eligible patients of the orthopedic ambulance from the University hospital, Magdeburg (Otto-von-Guericke University Magdeburg, Germany) were included, who were treated between March 2012 and July 2013. Five patients were dropouts because of wrongful inclusion and four patients were lost to follow up because of claiming exclusion therapies such as corticosteroid injections and surgical treatment before end point (Fig. 1). All patients experienced at least 3 mos of symptomatic lateral epicondylitis with previously unsuccessful physiotherapy or medical treatment. The patients who met the inclusion criteria and who gave written informed consent were included in this study. The local Medical Ethical Committee approved the study.
Inclusion Criteria Patients who fulfilled the following criteria were included in this study: Y Clinically diagnosed epicondylitis by the investigation physician (like the typical presentation in Cleland17 with pain in the epicondyle region, pain with resisted wrist extension, pain with resisted middle-finger extension). Y Minimum of 3 mos of pain with previously unsuccessful physiotherapy or medical treatment (manual therapy, ultrasonic, nonsteroidal anti-inflammatory drugs, brace, and protection). Y Home in the vicinity of the hospital. Therapies in Recalcitrant Lateral Epicondylitis
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FIGURE 1 The flow diagram shows the number of patients followed up during the study.
Exclusion Criteria Y Local injections in the last month. Y Previous laser treatment to the affected arm. Y Evidence of disordered pain perception. Y Younger than 18 yrs. Y Pregnancy, cervical radiculopathy, systemicinflammatory diseases (rheumatism, morbus bechterew), hemato-oncological diseases with low platelet numbers (myelodysplastic syndromes, leukemia, malignant lymphoma), infectious diseases (hepatitis). One group consisting of 26 patients received three intralesional ACP injections with an interval
of 7 days. The average age of the group was 51.5 yrs (Table 1). The control group, also with 26 patients, was treated with 12 laser applications with two sessions per week. This group had an average age of 53.1 yrs (Table 1). Both groups received standardized physiotherapy after treatment according to a specific therapy protocol (Fig. 2) in two different physiotherapeutic practices. The control examinations were conducted after 2 and 6 mos and at the final follow-up after 1 yr. The detected parameters at every time point were a visual analogue scale (VAS) for pain, with a range from 0 (no pain) to 10 (most severe pain), as well as
TABLE 1 Sociodemographic and clinical characteristics of the ACP and laser groups
Age, mean T SD, y Sex, female/male, n (%) Dominant hand, n (%) VAS, mean T SD DASH, mean T SD
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ACP
Laser
P
51.5 T 10.4 14 (53.8)/12 (46.2) 23 (88.5) 3.3 T 1.5 27.9 T 18.1
53.1 T 12.7 17 (65.4)/9 (34.6) 24 (92.3) 4.4 T 1.6 35.4 T 17.0
0.627 0.397 1.000 0.016 0.129
Am. J. Phys. Med. Rehabil. & Vol. 94, No. 9, September 2015 Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
the Disabilities of Arm, Shoulder and Hand (DASH) questionnaire. The DASH includes a main part with 30 questions about functional and social limitations in daily living
and also two optional item scales about limitations in occupation and spare time activities. The German translation of Germann et al.18 in revised version 2.0 from 2003 was used.19 The DASH value ranges from
FIGURE 2 Physiotherapy protocol for the after-treatment regimen for all patients. www.ajpmr.com
Therapies in Recalcitrant Lateral Epicondylitis Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
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FIGURE 2 (Continued)
0 (no disability) to 100 (most severe disability). In this study, only the main part of the DASH was used. A successful treatment was defined as at least 30% pain
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reduction on the VAS and a decrease of at least 10.2 points in the DASH score without reintervention for 1 yr. These parameters have proved to indicate a
Am. J. Phys. Med. Rehabil. & Vol. 94, No. 9, September 2015 Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
significant positive clinical effect for patients.20,21 A study by Jensen et al.20 showed that a percentage decrease of 27.9% on a rating scale of 0 to 10 points was associated with much or very much improvement for chronic pain patients. It was emphasized that a decrease in pain of 30%Y33% is a clinically significant effect.22 To define patients who benefited from treatment, in this study, a 30% decrease in VAS was considered as successful therapy. A minimal reduction of 10.2 points in the DASH score is considered as clinically significant pain improvement perceived by patients.21 For the preparation of ACP, the ACP Double Syringe System by Arthrex, Inc (Naples, FL) was used. Ten milliliters of whole blood was collected from a vein in the region of the cubital fossa with a 21-gauge butterfly needle into a double lumen syringe (Fig. 3A). After centrifugation of blood at 1500 rounds per minute for 5 mins, it resulted in 3Y5 ml of supernatant (Fig. 3B). The extracted growthfactor rich plasma (supernatant) was now transferred from the larger outer syringe into the smaller inner syringe (Fig. 3C). The ACP was injected with a 25-gauge needle at first subfascially in the region of the common head of the extensors. Then a further, intralesional dispersion followed with a two times over fan-like wheal injection (Fig. 3D). The laser application was conducted with a lowlevel laser BTL 5000 (a GaAs-infrared laser with a wavelength of 830 nm and a dose of 7 J/cm2; BTLMedizintechnik GmbH, Ulm, Germany). During this procedure, special glasses were used to protect the retina. The laser radiation was applied in circular movements to the region of the lateral epicondyle (Fig. 4). The treatment was managed by two previously instructed physiotherapy practices. Myofascial manipulation was done after the laser application for additional benefit of hyperemia and metabolism activation. After 8 wks of the first treatment, a physiotherapeutic postprocedure was initiated. It was based on 12 sessions with manual therapy techniques for trigger point elimination in the initial phase, stretching and strengthening exercises in the first 2 wks, as well as patient adapted muscle-trophic training in the advanced phase. The therapists were instructed by a treatment protocol, which was prepared in collaboration between physicians and physiotherapists (Fig. 2). In addition, the patients were assigned to do daily, self-contained stretching exercises.
measuring points. Furthermore, the averages of the scores per examination point were determined with 95% confidence intervals. Independent-samples t test (ordinal scale data) and chi-square test (nominal scale data) were used to examine the differences between sociodemographic and clinical data of the treatment groups. The same holds for the examination of the differences between the successful and unsuccessful groups. The level of significance was defined as 5%. All statistical analyses were implemented using the statistical program SPSS (IBM SPSS Statistics version 21).
RESULTS Analyses of the 52 VAS and DASH data sets with multivariate analysis of variance showed a significant improvement in time response of both therapies (P G 0.0001) (Fig. 5). The data comparison at each assessment point separately demonstrated in absolute numbers lower scores for the ACP patients than in the laser group (Table 2). An analysis of the values at each assessment point showed only significant differences of the VAS values (Table 2) between the groups before treatment was started (P = 0.008). The other assessment points showed no significant differences between the groups. In total, 33 of 52 patients (63.5%) were successfully treated (Table 3). As seen in Table 3, the ACP group was, in absolute frequencies, more often treated successfully (n = 19, 73.1%) than the laser group (n = 14, 53.8%), but without significant difference. The scores of the successful group were lower than the scores of the unsuccessful group at all assessment points as well as in average (Table 3). Sociodemographic and clinical characteristics between the ACP and laser groups are shown in Table 1. Analyses of the baseline characteristics (age, sex, dominant hand, average of VAS, average of DASH) showed no significant differences, except the VAS average. VAS pain scores were significantly higher in the laser group than in the ACP group (P = 0.016). In more than 90% of the cases, the dominant arm was affected. No complications regarding the use of ACP or the laser application could be observed.
DISCUSSION Statistical Analysis A multivariate analysis of variance was used to compare the VAS and DASH data on the itemized www.ajpmr.com
Both treatment methods implicated an accumulation of growth factors in the affected tendon tissue and promoted cellular tendon healing mechanisms. Therapies in Recalcitrant Lateral Epicondylitis
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FIGURE 3 AYD, Procedure of ACP therapy. At first, 10 ml of whole blood was collected from a cubital vein (A); second, the blood is centrifuged with 1500 rpm for 5 mins in a double lumen syringe and a supernatant of platelet-rich plasma is received (B); afterward, the plasma is transferred into the smaller, inner syringe (C); and finally, the ACP is injected intralesionally near the lateral epicondyle (D).
The process of tendon repair is composed of multiple phases after the first injury. A study done by Molloy et al.8 noted that, during the first 2 days after injury, inflammatory tissue changes with the release of growth factors, such as platelet-derived growth factor, transforming growth factor A, and insulin-like growth factor-I, as a result
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of extrinsic cell migration. After 2 days, the proliferative phase starts. During this phase, the fibroblasts’ proliferation, mitogenesis, and protein synthesis are induced by, among others, platelet-derived growth factor and insulin-like growth factor-I.23 The reparative phase is characterized by collagen deposition, revascularization, and the initiating reorganization
Am. J. Phys. Med. Rehabil. & Vol. 94, No. 9, September 2015 Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
FIGURE 4 Laser application performed in circular movements in the region of the lateral epicondyle and the following treatment with trigger point therapy and transverse friction.
FIGURE 5 A, B, VAS and DASH scores with 95% confidence interval in time response of both therapies. A, VAS pain scores at the various assessment points; B, DASH scores at the various assessment points. www.ajpmr.com
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TABLE 2 VAS and DASH scores for the ACP and laser groups at the various assessment points ACP VAS Before therapy 2 mos 6 mos 12 mos DASH Before therapy 2 mos 6 mos 12 mos
Laser
P
5.2 T 3.7 T 2.7 T 1.8 T
1.8 2.0 1.6 2.0
6.7 T 4.7 T 3.6 T 2.7 T
2.0 2.3 2.2 2.3
0.008 0.094 0.102 0.160
37.0 T 29.8 T 26.5 T 18.2 T
18.3 21.1 21.2 19.5
47.0 T 38.9 T 29.0 T 26.7 T
19.6 20.7 19.6 21.8
0.062 0.126 0.664 0.145
Data are provided as mean T SD.
of the cellular matrix.8 Finally, after 14 days, the remodeling begins with increased collagen synthesis, for instance, triggered by transforming growth factor A,23 and the new arranged collagen fibers are linked.8 Hyman and Rodeo24 demonstrated that after the healing process, the tendon tissue will approximately return to the normal original tendon. The inferiorly healed tendon tissue is weaker and has a higher risk for further injuries.8 Especially the chronicity of a disease characterizes a tissue with inferior quality because repetitive microtrauma results in disruption of the repair processes. This leads to poor tendon quality with disorganized, nonfunctional collagen fibers.7 A randomized controlled trial by Smidt et al.25 showed that there was no statistically significant difference between patients treated with physiotherapy and those treated with a wait-and-see policy. Patients who have improved without treatment are at a high risk for relapse. This is because the healing process in such
patients without relief results in only moderate resilient tissues with high risk for recidivism.8 That is inadequate for active patients with the claim to revert at their initial resilient condition. Furthermore, the natural history of any patient should have the same influence in both therapy groups because of sequential allocation. Kraushaar and Nirschl7 furthermore showed the importance of movement therapy in time for improving correct linked collagen and tendon strength. Treatment on an extrinsic as well as on an intrinsic pathway is of paramount importance for a successful healing response and optimal tendon quality. The applied therapies with ACP, respectively laser, with subsequent physiotherapeutic postprocedure both fulfill these requirements of an optimal treatment. Three ACP injections in an interval of 7 days were used to support all tissue healing phases. As recommended by Bjordal et al.,26 the laser application took place in 12 sessions with an infrared
TABLE 3 Sociodemographic and clinical characteristics and VAS and DASH scores of the successful and unsuccessful groups at the various assessment points
Treatment, ACP/Laser Age Sex, female/male Dominant hand VAS DASH VAS Before therapy 2 mos 6 mos 12 mos DASH Before therapy 2 mos 6 mos 12 mos
Successful (n = 33, 63.5%)
Unsuccessful (n = 19, 36.5%)
P
19 (73.1)/14 (53.8) 52.9 T 12.6 19 (57.6)/15 (42.4) 30 (90.9) 3.3 T 1.3 28.4 T 18.0
7 (26.9)/12 (46.2) 51.3 T 9.6 12 (63.2)/7 (36.8) 17 (89.5) 4.8 T 1.7 37.2 T 16.4
0.150 0.636 0.693 1.000 0.001 0.086
6.0 T 3.8 T 2.3 T 1.2 T
2.1 2.2 1.4 1.4
5.8 T 1.9 4.9 T 2.2 4.5 T 2.0 4.1 T 2.2
0.752 0.098 0.000 0.000
45.7 T 33.1 T 20.7 T 14.2 T
19.0 22.8 18.7 18.8
35.6 T 19.0 36.5 T 18.4 40.0 T 17.1 36.9 T 16.2
0.070 0.584 0.001 0.000
Data are provided as n (%) or mean T SD.
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Am. J. Phys. Med. Rehabil. & Vol. 94, No. 9, September 2015 Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
laser (GaAs) with a wavelength of 830 nm and a dose of 7 J/cm2. For an effective bio-stimulation, the laser application was done using continuous wavelengths. In addition, the treatment took place with a pulsed frequency of 10 Hz for an increased deep effect and a better analgesic outcome.27 This study achieved successful effects with direct autologous growth factor injection using ACP. In absolute numbers, the ACP includes 73.1% successfully treated patients, superior to the laser treatment, with 53.8% successfully treated patients (Table 3). This could have multiple causes. One possible reason could be the selection bias of the participants. The ACP group had, on average, significant inferior pain scores on the VAS than the laser group did (P = 0.016; Table 1). The DASH score, on the other hand, did not differ significantly between the treatment groups (P = 0.129). The comparison between the successful and unsuccessful groups shows significant differences in the VAS values (P = 0.001) but not in the DASH values (P = 0.086) (Table 3). In the successful group, the score data were inferior on average and at each assessment point, except the values before therapy. When the DASH score was compared at each assessment point between the two therapy groups in the unsuccessful case, the values became worse after 6 mos compared with the values after 2 mos (Table 3). A probable cause of this might be the expectations of the patients. After 6 mos, the therapies should be finished and the success should be obvious in the meantime. If this is not the case, the patients might be deeply disappointed, which could affect the values negatively. Certainly, an important limitation of the laser treatment was the expenditure of time for 12 sessions, because in comparison, the therapy with ACP demanded only three applications. No sociodemographic differences could be observed concerning age and gender between the ACP and laser groups, as well as the successful and unsuccessful groups. In total, the dominant arm was mostly affected (990%). Therefore, no relationship between success and these parameters could be established. A last limitation of the study can be seen in the selection of the 52 subjects. Even though the samples were drawn sequentially and, thus, as quasirandomization, the allocation to the therapy groups was in order of presentation in the orthopedic ambulance. In this prospective clinical trial, the clinical effects of two proliferative, metabolic activated www.ajpmr.com
therapies in chronic epicondylitis were compared. The benefit of both procedures could be supported with 64% of successfully treated patients. Both therapies proved to be easy to implement and safe (without complications).
CONCLUSION As the data show, both proliferative therapies lead to a clinical improvement of epicondylopathia. Especially the treatment with ACP can be highlighted as a successful therapy. Furthermore, the achievement of the soft laser application with also positive therapy results should accentuated. Nonetheless, when searching for an optimal treatment protocol, it should be regarded that, for the success of a laser therapy, the patient has to be very compliant and has to invest much time. Obviously, improvement of the symptoms without any intervention is possible. But for active patients, for a strong, resilient tendon and to avoid further injury, an additional treatment is probably beneficial. Further research with randomized and comparative studies between proliferative therapies with placebo or wait-and-see policy would be beneficial for determination of the optimal therapy for lateral epicondylitis. In conclusion, this study demonstrates the beneficial effects of proliferative autologous therapies, especially ACP, in the treatment of chronic epicondylitis humeri radialis. A close interaction between physicians and physiotherapists and a multimodal patient adapted concept is essential for optimum treatment. REFERENCES 1. Shiri R, Viikari-Juntura E, Varonen H, et al: Prevalence and determinants of lateral and medial epicondylitis: A population study. Am J Epidemiol 2006; 164:1065Y74. doi:10.1093/aje/kwj325 2. Verhaar JA: Tennis elbow. Anatomical, epidemiological and therapeutic aspects. Int Orthop 1994; 18:263Y7 3. Nirschl RP, Ashman ES: Elbow tendinopathy: Tennis elbow. Clin Sports Med 2003;22:813Y36 4. Taylor SA, Hannafin JA: Evaluation and management of elbow tendinopathy. Sports Health 2012;4:384Y93. doi:10.1177/1941738112454651 5. Bisset L: A systematic review and meta-analysis of clinical trials on physical interventions for lateral epicondylalgia. Br J Sports Med 2005;39:411Y22 6. Coombes BK, Bisset L, Vicenzino B: A new integrative model of lateral epicondylalgia. Br J Sports Med 2009; 43:252Y8
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7. Kraushaar BS, Nirschl RP: Tendinosis of the elbow (tennis elbow). Clinical features and findings of histological, immunohistochemical, and electron microscopy studies. J Bone Joint Surg Am 1999;81:259Y78
17. Cleland JA: Effectiveness of manual physical therapy to the cervical spine in the management of lateral epicondylalgia: A retrospective analysis. J Orthop Sports Phys Ther 2004;34:713Y24
8. Molloy T, Wang Y, Murrell G: The roles of growth factors in tendon and ligament healing. Sports Med 2003;33:381Y94
18. Germann G, Wind G, Harth A: Der DASHFragebogen-Ein neues Instrument zur Beurteilung von Behandlungsergebnissen an der oberen Extremita¨t. Handchir Mikrochir Plast Chir 1999;31:149Y52. doi:10.1055/s-1999-13902
9. Creaney L, Wallace A, Curtis M, et al: Growth factorYbased therapies provide additional benefit beyond physical therapy in resistant elbow tendinopathy: A prospective, single-blind, randomised trial of autologous blood injections versus platelet-rich plasma injections. Br J Sports Med 2011;45:966Y71 10. Peerbooms JC, Sluimer J, Bruijn DJ, et al: positive effect of an autologous platelet concentrate in lateral epicondylitis in a double-blind randomized controlled trial: Platelet-rich plasma versus corticosteroid injection with a 1-year follow-up. Am J Sports Med 2010; 38:255Y62. doi:10.1177/0363546509355445 11. Zhang J, Wang JH: Platelet-rich plasma releasate promotes differentiation of tendon stem cells into active tenocytes. Am J Sports Med 2010;38:2477Y86. doi:10.1177/0363546510376750 12. Gao X, Xing D: Molecular mechanisms of cell proliferation induced by low power laser irradiation. J Biomed Sci 2009;16:4. doi:10.1186/1423-0127-164 13. Vinck EM, Cagnie BJ, Cornelissen MJ, et al: Increased fibroblast proliferation induced by light emitting diode and low power laser irradiation. Lasers Med Sci 2003;18:95Y9. doi:10.1007/s10103-003-0262-x 14. Chow RT, Johnson MI, Lopes-Martins RAB, et al: Efficacy of low-level laser therapy in the management of neck pain: A systematic review and meta-analysis of randomised placebo or active-treatment controlled trials. Lancet 2009;374:1897Y908. doi:10.1016/S01406736(09)61522-1 15. Bjordal JM, Lopes-Martins RAB, Joensen J, et al: A systematic review with procedural assessments and meta-analysis of Low Level Laser Therapy in lateral elbow tendinopathy (tennis elbow). BMC Musculoskelet Disord 2008;9:75 16. Simunovic Z, Trobonjaca T, Trobonjaca Z: Treatment of medial and lateral epicondylitisVtennis and golfer’s elbowVwith low level laser therapy: A multicenter double blind, placebo-controlled clinical study on 324 patients. J Clin Laser Med Surg 1998;16:145Y51
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19. Germann G, Harth A, Wind G, et al: Standardisation and validation of the German version 2.0 of the Disability of Arm, Shoulder, Hand (DASH) questionnaire. Unfallchirurg 2003;106:13Y9. doi:10.1007/ s00113-002-0456-x 20. Jensen MP, Chen C, Brugger AM: Interpretation of visual analog scale ratings and change scores: A reanalysis of two clinical trials of postoperative pain. J Pain 2003;4:407Y14 21. Roy J, MacDermid JC, Woodhouse LJ: Measuring shoulder function: A systematic review of four questionnaires. Arthritis Rheum 2009;61:623Y32. doi:10.1002/ art.24396 22. Ostelo RW, Deyo RA, Stratford P, et al: Interpreting change scores for pain and functional status in low back pain: Towards international consensus regarding minimal important change. Spine 2008;33:90Y4. doi:10.1097/BRS.0b013e31815e3a10 23. Lynch SE, Colvin RB, Antoniades HN: Growth factors in wound healing. Single and synergistic effects on partial thickness porcine skin wounds. J Clin Invest 1989;84:640Y6. doi:10.1172/JCI114210 24. Hyman J, Rodeo SA: Injury and repair of tendons and ligaments. Phys Med Rehabil Clin N Am 2000;11: 267Y88 25. Smidt N, van der Windt DAWM, Assendelft WJJ, et al: Corticosteroid injections, physiotherapy, or a waitand-see policy for lateral epicondylitis: A randomised controlled trial. Lancet 2002;359:657Y62. http://dx.doi. org/10.1016/S0140-6736(02)07811-X 26. Bjordal JM, Couppe C, Ljunggren AE: Low level laser therapy for tendinopathy. Evidence of a dose-response pattern. Phys Ther Rev 2001;6:91Y9 27. Hashmi JT, Huang Y, Sharma SK, et al: Effect of pulsing in low-level light therapy. Lasers Surg Med 2010;42:450Y66. http://dx.doi.org/10.1002/lsm.20950
Am. J. Phys. Med. Rehabil. & Vol. 94, No. 9, September 2015 Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
