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ORIGINAL ARTICLE
Year : 2013  |  Volume : 13  |  Issue : 2  |  Page : 98-101

Injection of bone marrow concentrates for treatment of refractory tennis elbow


1 Department of Orthopaedics, Rohilkhand Medical College, Bareilly, Uttar Pradesh, India
2 Department of Physiotherapy, Jaipur College of Physiotherapy, Jaipur, Rajasthan, India

Date of Web Publication20-Dec-2013

Correspondence Address:
Ajit Singh
Department of Orthopaedics, Rohilkhand Medical College, Pilibhit Bypass Road, Bareilly - 243 006, Uttar Pradesh
India
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DOI: 10.4103/1319-6308.123392

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  Abstract 

Objective: The objective of this prospective study was the assessment of efficacy of bone marrow concentrate (BMC) (containing plasma rich in growth factors and mesenchymal stem cells) injection in treatment of refractory tennis elbow. Materials and Methods: A total of 30 adults with at least 6 months of refractory tennis elbow were administered single injection of BMC. This concentrate was made by centrifugation of iliac BM aspirate at 1800 rpm for 20-30 min and only upper layer containing platelet rich plasma and mononuclear cells was injected. Assessment was performed at baseline, 4 weeks and 12 weeks using Nirschl and visual analog scale (VAS) pain score. Results: Post-injection, significant reductions were reported in Nirschl, which decreased from a mean pre-injection score of 5.92 ± 0.85-3.19 ± 0.94 at 4 weeks (P < 0.001) and 1.65 ± 0.94 at 12 weeks (P < 0.0001). Similarly, significant reductions were found for VAS from a mean pre-injection score of 8.35 ± 0.94, to a mean VAS score of 5.23 ± 1.42 at 4 weeks (P < 0.0001) and to 1.85 ± 1.12 at 12 weeks (P < 0.0001). There were no adverse events. Conclusion: Treatment of patients with refractory tennis elbow with a single injection of BMC showed a significant improvement in short to medium term follow-up. This could be considered to be an alternative treatment for those patients who have failed non-operative treatment before surgical intervention is taken.

  Abstract in Arabic 

الهدف من هذه الدراسة الاستباقية هو تقييم فعالية حقن مركزات نخاع العظام ( تحتوي على وصل غني بعوامل النمو والخلايا الجذعية الوسيطة ) كعلاج لمرفق التنس المقاوم للعلاج . المواد والطرق : مجموعة من 30 بالغاً يعانون من مرفق تنس مقاوم للعلاج لمدة لاتقل عن 6 شهور تم حقنهم مرة واحدة بواسطة مركزات نخاع العظم تم تحضير هذه المركزات بواسطة تكثيف نقي عظم مأخوذ من الحرقعة الو ركية للمريض بواسطة 1800 دورة لمدة 20 إلى30 دقيقة واستعمل فقط البقة العلوية للمركزات التي تحتوي على مصل غني الصفيحات وخلايا وحيدة النواة . تم تقييم الحالة بعد 4 ,12 أسبوعاً باستخدام ( Nirschl ) يفرشل ومقياس النظر التناظري ( VAS) للألم ( فاز)

النتائج: تم الحصول على خفض هام بمقياس نيرشل من 5,92 ± 0,85 إلى 3,19 ± 0,94 بعد 4 أسابيع وإلى 1,65±0,94 بعد 12 أسبوعاً (P<0.0001) وأيضا خفض مماثل بـ (SAV) من 8,35 ± 0,94 إلي 5,23 ± 1,42 بعد 4 أسابيع (P<0.0001) وإلى 1,85 ± 1,12 بعد 12 أسبوع (P<0.0001) بدون وجود اختلاطات جانبية . النتيجة : إن معالجة مرضى مرفق التنس المقاوم للعلاج بواسطة حقنة واحدة من مركز نخاع العظم نتج عنه تحسناً واضحاً في الفترة القصيرة إلى المتوسطة بعد العلاج ويمكن اعتبار هذه الوسيلة العلاجية بديلاً للعلاج في المرضى الذين لم يستجيبوا للعلاج اللاجراحي وقبل أخذ قرار بالمداخلة الجراحية .


Keywords: Bone marrow plasma, lateral epicondylitis, stem cells, tendinopathy


How to cite this article:
Singh A, Gangwar D S, Singh S. Injection of bone marrow concentrates for treatment of refractory tennis elbow. Saudi J Sports Med 2013;13:98-101

How to cite this URL:
Singh A, Gangwar D S, Singh S. Injection of bone marrow concentrates for treatment of refractory tennis elbow. Saudi J Sports Med [serial online] 2013 [cited 2019 Sep 23];13:98-101. Available from: http://www.sjosm.org/text.asp?2013/13/2/98/123392


  Introduction Top


Tennis elbow is the most common cause of chronic pain on the lateral side of the elbow and wrist extensor dysfunction. Tennis players have been reported to account for 5-8% of all cases, although between 40% and 50% of all tennis players will be afflicted with the condition at some time. [1] This degenerative condition can manifest as an acute process lasting < 3 months or a chronic process often refractory to treatment. [2] The term "lateral epicondylitis" is often used indiscriminately as, historically, the primary lesion was considered to be inflammatory granulation tissue in common extensor origin. Recent studies of chronic tennis elbow have not found any significant evidence of inflammatory processes and the term epicondylosis or tendinosis has been suggested as a more appropriate term than epicondylitis. [3]

Conservative management consisting of activity restriction, splints and orthotics, non-steroidal anti-inflammatory drugs and physiotherapy are the first line of management. Local corticosteroid injection is the most common treatment given in cases where conservative management fails. Corticosteroids while providing relief of pain in the acute setting, may be detrimental to recovery in the long-term. [2] Other modalities such as prolotherapy, topical nitroglycerin, iontophoresis, phonophoresis, therapeutic ultrasound, extracorporeal shock wave therapy and low-level laser therapy have less evidence of effectiveness in treatment of tendinopathies. [4] In these patients, surgery can be performed, but it is not always successful and has much morbidity like neurovascular injury, fracture or tendon rupture and the post-operative rehabilitation is slow and time consuming. [5] To reduce the need for surgery, more effective conservative therapies are needed.

Recent studies show a beneficial role of locally delivered biological growth factors in healing of various tendinopathies. This has been tried in the form of autologous blood and platelet rich plasma (PRP) with mixed results. [4],[5],[6] While autologous blood and PRP contain only humoral growth factors, bone marrow concentrate (BMC) has the added advantage of bone marrow mononuclear stem cells (BM-MNCs). BM-MNCs are pluripotent cells and are believed to play an important role in connective tissue repair such as tendon, ligament, bone and cartilage. Recent reports have shown that these cells can accelerate tendon healing. [7] According to Pascual-Garrido et al., inoculation of BM-MNCs could be considered as a potential therapy for those patients with chronic patellar tendinopathy refractory to non-operative treatments. [8] A combination of BM-MNCs and anabolic growth factors would seem as an ideal approach for managing chronic refractory tennis elbow. The objective of this study is to evaluate the outcome of a single injection of BMC in chronic refractory tennis elbow.


  Materials and Methods Top


Participants

Adult patients, 18-65 years old, were recruited from orthopedic and physiotherapy out-patient department of a Tertiary Medical College. The study was approved by the ethical committee of the medical college and attached hospital. Thirty consecutive patients of refractory tennis having no other identifiable cause of lateral elbow pain were included in the study. A detailed clinical history and clinical examination along with standard anteroposterior and lateral radiographs of involved elbow were taken in all patients. Inclusion criteria were a diagnosis of tennis elbow and elbow pain for at least 6 months and failed each of the following conservative treatments: activity modification, physical therapy, non-steroidal anti-inflammatory drugs and corticosteroid injections. Exclusion criteria included diabetes and corticosteroid elbow injection within 6 weeks. Informed written consent was obtained from all the subjects.

Intervention

Bone marrow (BM) plasma was aspirated from anterior-superior iliac spine of pelvis in 10 mL syringe containing 1 mL of heparin. 10 mL of BM was centrifuged for approximately 15-30 min in 1800 rpm. Of the centrifuged plasma, only the clear upper layer (containing plasma) and the buffy coat layer that contained mononuclear cells was used for injection and approximately 4-5 mL was obtained from each patient. BMC was mixed with 1 mL of 2% lignocaine solution. All injections were administered taking aseptic precautions into the point of maximal tenderness at the extensor origin of the lateral epicondyle of the humerus by a single author in all cases. All subjects were advised to rest and moderate their activities to avoid aggravation of their symptoms. Tablets of tramadolol and paracetamol were given on demand for pain relief. There were no adverse events in any patient. The degree of pain was assessed by employing the visual analog scale (VAS) 0-10, with 0 no pain and 10 the worst pain they have experienced. The degree of disability was evaluated by Nirschl staging 0-7. [9]

Statistical analysis

A pre-post experimental design was used for the study. The data was analyzed using the SPSS 17 software for windows (Chicago, IL, USA) and P values of < 0.05 were considered as significant. Statistical analysis of differences between pre- and post-injection evaluation was performed using the Wilcoxon signed rank test as data from VAS and Nirschl didn't follow a normal distribution. The minimum sample size required for this study was calculated on the basis of VAS pain intensity measurements. A significance criterion of 0.05 and power of 90% was chosen. Minimum expected difference post-treatment was chosen to be 1.5 on the pain scale and standard deviation was taken to be 1.5. The minimum sample size came out to be 22.


  Results Top


A total of 30 patients of were recruited for the study. Four patients were lost in follow-up. Out of remaining 26 patients, 17 were male and 9 female. Baseline mean VAS score was 8.35 ± 0.94, which decreased to a mean VAS score of 5.23 ± 1.42 after 4 weeks of injection, which was statistically significant (P < 0.001; z = 4.50). The mean VAS score at 12 week follow-up was 1.85 ± 1.12 (P < 0.0001; z = 4.90). The mean decrease observed in VAS scores at 4 weeks and 12 weeks follow-up after BM injection was highly significant (P < 0.0001) [Figure 1].

The mean pre-injection Nirschl score was 5.92 ± 0.85. The mean Nirschl score at 4 week and 12 week follow-up was 3.19 ± 0.94 and 1.65 ± 0.94 respectively. After application of Wilcoxon signed rank test, the P value for fall in mean Nirschl score at 4 and 12 weeks came out to be less than 0.0001, which was highly significant (z = 4.52 and 4.49 respectively) [Figure 1].
Figure 1: Line diagram depicting mean visual analog scale and Nirschl scores at baseline and after 4 and 12 weeks post-injection

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  Discussion Top


Lateral epicondylosis or tennis elbow of the humerus has been recognized for over 100 years and is an enthesopathy of the common extensor origin. Recent histopathological examinations suggest that a non-inflammatory degeneration of extensor carpi radialis brevis (ECRB) is present and treatments should be aimed at normal vascularization and healing in the affected tendon. [10] The low healing capacity of the ECRB tendon leads to long and tedious treatments and hence identifying alternative strategies is a priority.

Recent studies show a beneficial role of locally delivered biological growth factors in healing of various tendinopathies. [11] A recent study by Harmon et al. has shown that biologic therapies such as autologous blood and PRP injection are effective treatment for recalcitrant tendinopathy and PRP appears to be more effective than autologous blood. [12] Mechanism of action of biological therapies is attributed to degranulation of α granule of platelets releasing growth factors responsible for tissue healing and regeneration. Platelet derived growth factor, transforming growth factor β, vascular derived endothelial growth factor, epithelial growth factor, hepatocyte growth factor and insulin like growth factor are some of the factors involved. [13] The ECRB tendon itself is relatively cell poor, with a low turnover rate. Furthermore, tendinopathy usually heal with fibrosis and scar tissue, which has suboptimal tensile strength and is prone to re-injury, resulting in life-style changes with activity restriction. So tendon regeneration along with repair seems to be an optimal treatment.

Recently, it has been proposed that adult stem cells would be good candidates for cell-based tendon regeneration. [7],[8] Mesenchymal stem cells (MSCs) are multipotent, capable of differentiating into several connective tissue types including osteocytes, chondrocytes, adipocytes, tenocytes and myoblasts. [14] MSCs can be easily obtained from BM. The exact role of implanted stem cells on tendon healing remains uncertain. One possibility is that they become differentiated into tenocytes within the healing tendon environment and participate in healing through collagen production and remodeling. [15] Alternatively, it has been suggested that BM-MNCs may contribute to healing by acting as "growth factors pumps" rather than through terminal differentiation. [16] MSCs secrete a variety of soluble autocrine and paracrine growth factors, which recruit MSCs, promote cell survival and enhance the proliferation of endogenous connective tissue cells. These growth factors stimulate mitosis in tissue progenitors, induce angiogenesis and reduce apoptosis. [16] PRP has been shown to influence the behavior of stem cells. Using tendon stem cells derived from rabbit patellar tendons, Zhang and Wang demonstrated that PRP releasate increased tendon stem cell proliferation, induced tendon stem cell differentiation into tenocytes and increased protein expression and collagen type I and type III production. [17] BMC contains MSC, which can differentiate in tenocytes and also PRP to positively influence the behavior of these MSCs. Therefore, injection of BMC seems to be most promising therapeutic approach for treating chronic tendinopathies. This is confirmed in our study, which shows positive short and medium term results from a single injection of autologous BMC in refractory tennis elbow. Our study shows a statistically highly significant improvement in terms of pain relief and down staging of the disease. We believe that BMC injection could be considered as an alternative treatment for those patients who have failed non-operative treatment before surgical intervention is considered. Further control studies will be needed to determine if injection of BMC can improve tendon healing in patients with the chronic refractory tennis elbow.

The major limitation of this study is the lack of control group, resulting in a low-level of evidence study (level 4). Other major limitation of our study is absence of long follow-up. Long-term follow-up is required to see the sustained effect of BMC injection in terms of pain relief and healing of disease. We have chosen a follow-up only up to 12 weeks as improvement in symptoms after this period may be a result of natural healing process and activity modification by patients. Studies with longer follow-up are also required to see any adverse effects like calcification in tendon or tumorogenesis. No hematological analysis was performed to determine the numbers of nucleated cells or platelets in BMC. We did not perform any pre or post-injection radiological assessment of tendon healing by magnetic resonance imaging or ultrasonography. Further studies are required to standardize the dose, number and timing of autologous BMC injection for treating refractory tennis elbow.


  Conclusion Top


Our clinical findings suggest that the use of single injection of BMC could be considered to be a potential therapy for those patients with the chronic degenerative tennis elbow refractory to non-operative treatments.

 
  References Top

1.Wadsworth TG. Tennis elbow: Conservative, surgical, and manipulative treatment. Br Med J (Clin Res Ed) 1987;294:621-4.  Back to cited text no. 1
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6.Creaney L, Wallace A, Curtis M, Connell D. Growth factor-based 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;45:966-71.  Back to cited text no. 6
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8.Pascual-Garrido C, Rolón A, Makino A. Treatment of chronic patellar tendinopathy with autologous bone marrow stem cells: A 5-year-followup. Stem Cells Int 2012;2012:953510.  Back to cited text no. 8
    
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10.Maffulli N, Longo UG, Denaro V. Novel approaches for the management of tendinopathy. J Bone Joint Surg Am 2010;92:2604-13.  Back to cited text no. 10
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11.de Vos RJ, van Veldhoven PL, Moen MH, Weir A, Tol JL, Maffulli N. Autologous growth factor injections in chronic tendinopathy: A systematic review. Br Med Bull 2010;95:63-77.  Back to cited text no. 11
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12.Harmon K, Drezner J, Rao A. Platelet rich plasma for chronic tendinopathy. Br J Sports Med 2013;47:e2.  Back to cited text no. 12
    
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14.Ouyang HW, Goh JC, Lee EH. Viability of allogeneic bone marrow stromal cells following local delivery into patella tendon in rabbit model. Cell Transplant 2004;13:649-57.  Back to cited text no. 14
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15.Connell D, Datir A, Alyas F, Curtis M. Treatment of lateral epicondylitis using skin-derived tenocyte-like cells. Br J Sports Med 2009;43:293-8.  Back to cited text no. 15
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16.Phinney DG, Prockop DJ. Concise review: Mesenchymal stem/multipotent stromal cells: The state of transdifferentiation and modes of tissue repair - Current views. Stem Cells 2007;25:2896-902.  Back to cited text no. 16
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