1. PRP for Lateral Epicondylitis
Matthew Bloom, OMS IV

2. Have you had your morning cup of coffee yet?
300mg/day

3. Overview Lateral Epicondylitis Platelet-Rich Plasma
Current research on tx of lateral epicondylitis with PRP vs CSI

4. Lateral Epicondylitis
Also referred to as:
Elbow tendinosis
Elbow tendonitis
Elbow tendinopathy
Epicondylalgia
Tennis elbow

5. Lateral Epicondylitis

6. Lateral Epicondylitis

7. Lateral Epicondylitis
Epidemiology
1–3% in general population
Risk Factors
Smoking
Obesity
Age (45–54)
Repetitive movement (>2 hours daily)
Forceful activity (>20 kg)

8. Lateral Epicondylitis
Clinical Anatomy
Lateral humeral epicondyle serves as the bony common origin of the wrist extensor muscles
Injury to the extensor carpi radialis brevis muscle (ECRB) (felt at tip of lateral epicondyle)
Differentiate an effusion in this region, which represents intraarticular pathology or swelling posteriorly due to olecranon bursitis, from the lateral epicondylitis, which is extraarticular in nature

9. Lateral Epicondylitis

10. Lateral Epicondylitis
Pathophysiology
Chronic tendinosis rather than an acute inflammatory process
Presence of disorganized tissue and neovasculature with very few inflammatory cells
Studies using grayscale ultrasonography and color Doppler followed by anesthetic injection suggest that vasculoneural growth in the common extensor origin, most commonly the ERCB, is the likely source of pain
Targeting this degenerative tendinosis and neovascularization is the focus of emerging treatments (PRP?)

11. Lateral Epicondylitis
Mechanism of Injury
Repetitive or explosive athletic movements involving eccentric motion, in which the muscle-tendon unit is lengthened while contracting
Clinical Presentation
Lateral elbow pain with varying severity

12. Lateral Epicondylitis
Nirschl characterizes seven stages of tendinopathy:
Phase I – Mild pain after exercise activity, resolves within 24 hours
Phase II – Pain after exercise activity, exceeds 48 hours, resolves with warm-up
Phase III – Pain with exercise activity that does not alter activity
Phase IV – Pain with exercise activity that alters activity
Phase V – Pain caused by heavy activities of daily living
Phase VI – Intermittent pain at rest that does not disturb sleep; Pain caused by light activities of daily living
Phase VII – Constant rest pain (dull aching) and pain that disturbs sleep

13. Lateral Epicondylitis
Clinical Examination
Localized tenderness over the lateral epicondyle and proximal wrist extensor muscle mass
Pain with resisted wrist extension with the elbow in full extension
Pain with passive terminal wrist flexion with the elbow in full extension

14. Lateral Epicondylitis

15. Lateral Epicondylitis

16. Lateral Epicondylitis
Cozen’s Test

17. JAMA Article Review JAMA February 6, 2013 – Vol. 309, No. 5
“Effect of Corticosteroid Injection, Physiotherapy, or Both on Clinical Outcomes in Patients with Unilateral Lateral Epicondylalgia: A Randomized Controlled Trial”
Coombes BK, Bisset L, Brooks P, Khan A, Vicenzino B
Division of Physiotherapy, School of Health and Rehabilitation Sciences, University of Queensland, St Lucia, Australia

18. JAMA Article Review
Objective: To investigate the effectiveness of corticosteroid injection, multimodal physiotherapy, or both in patients with unilateral lateral epicondylalgia
Design: A 2 × 2 factorial, randomized, injection-blinded, placebo-controlled trial
Setting: Conducted at a single university research center and 16 primary care settings in Brisbane, Australia

19. JAMA Article Review Patients N = 165
Enrolled between July 2008 and May 2010
1-year follow-up in May 2011
Age 18 years or older
Eligibility was determined by telephone interview
Physical examination was conducted by one researcher and confirmed by a second

20. JAMA Article Review Inclusion Criteria
Unilateral lateral epicondylalgia > 6 weeks
Pain over the lateral epicondyle with pain severity > 30 mm on a 100-mm visual analog scale (VAS)
Pain provoked by at least 2 of the following:
Gripping
Palpation
Resisted wrist or middle finger extension
Stretching of forearm extensor muscles

21. JAMA Article Review Exclusion Criteria Receipt of injection (6 months)
Receipt of a course of physiotherapy (3 months)
Concomitant neck or other arm pain (6 months)
Symptoms suggesting radicular, neurologic, or systemic arthritic conditions
Pregnant or breastfeeding
Contraindication to injection

22. JAMA Article Review Randomization Blinding
Stratified according to pain severity greater or less than 57.5 mm on a 100-mm VAS
Blinding
Researcher who assessed outcomes was blinded to both injection and physiotherapy assignment
Patients were blinded to injection but not physiotherapy

23. JAMA Article Review Interventions Corticosteroid injection (n = 43)
10 mg/mL of triamcinolone acetonide in a 1 mL injection plus 1 mL of 1% lignocaine
Placebo injection (n = 41)
0.5 mL of 0.9% isotonic saline
Corticosteroid injection plus physiotherapy (n = 40)
Placebo injection plus physiotherapy (n = 41)

24. JAMA Article Review Interventions
Injections were applied to the site of maximum palpable tenderness at the common extensor origin
Physiotherapy consisted of 8 30-minute sessions over 8 weeks
Patients were advised to avoid any activity that caused or provoked pain and to refrain from strenuous activity for 2 weeks

25. JAMA Article Review Interventions
After 2 weeks, a gradual return to normal activity was encouraged to minimize potential for recurrence
Patients were allowed to use an analgesic or anti-inflammatory medication, heat or cold pack, or braces as needed
Patients were discouraged from seeking treatments other than those specifically assigned

26. JAMA Article Review Hypotheses Outcome Measures
At 1 year, clinical outcomes would be worse in patients receiving CSI vs. placebo
At 1 year, clinical outcomes would be better in patients receiving physiotherapy vs. no physiotherapy
Outcome Measures
Patients estimated their global rating of change at 4, 8, 12, 26, and 52 weeks on a 6-point Likert scale ranging from “complete recovery” to “much worse”

27. JAMA Article Review Primary Outcomes
CSI demonstrated lower complete recovery or much improvement at 1 year compared with placebo (83% vs. 96%)
p = .01
CSI demonstrated greater recurrence at 1 year compared with placebo (54% vs. 12%)
p < .001

28. JAMA Article Review

29. JAMA Article Review Primary Outcomes
No interaction between injection (CSI vs. placebo) and physiotherapy (yes vs. no) (p = .99)
No difference in physiotherapy vs. no physiotherapy at 1 year for complete recovery or much improvement (91% vs. 88%, p = .56)
No difference in physiotherapy vs. no physiotherapy at 1 year for recurrence (29% vs. 38%, p = .25)

30. JAMA Article Review Secondary Outcomes
At 4 weeks, significant improvement occurred across the board for CSI compared to placebo injection and physiotherapy (yes vs. no)
At 26 weeks, improvement began to decline for CSI compared to placebo and showed no difference for physiotherapy (yes vs. no)
p < .001

31. JAMA Article Review Conclusions
CSI showed improvement at 4 weeks compared to placebo, but a subsequent decline in effectiveness at 6 months, with worse outcome at 1 year
Physiotherapy showed no benefit when combined with CSI at 4 weeks and no long-term benefit overall, however, it was shown to be useful in the short-term when utilized alone
Corticosteroids are potent in suppressing inflammation, but histological evidence does not support an inflammatory response in this condition

32. JAMA Article Review

33. Discussion Time!
Strengths vs. Weaknesses?

34. Platelet-Rich Plasma Overview
PRP is a regenerative therapy useful in addressing many musculoskeletal injuries
PRP is being increasingly used for tx of chronic non-healing tendon injuries
PRP contains growth factors (GFs) that stimulate neovascularization to increase the blood supply and available nutrients for damaged tissue to regenerate
Neovascularization also brings new cells and removes debris from damaged tissue

35. Platelet-Rich Plasma Growth factors
Alpha granules are storage units within platelets that contain inactive prepackaged growth factors including:
Transforming Growth Factor Beta (TGFβ)
Vascular Endothelial Growth Factor (VEGF)
Platelet-Derived Growth Factor (PDGF)
Epithelial Growth Factor (EGF)
Fibroblast Growth Factor (FGF)
Together these factors help to stimulate cell replication, angiogenesis, epithelialization, granulation tissue formation, extracellular matrix formation, and regulation of bone cell metabolism

36. Platelet-Rich Plasma Production
PRP is a plasma suspension that contains all components of whole blood in varying amounts
Contains at least 200,000 platelets/μL, but generally 3-5× this
Centrifugation of venous whole blood containing an anticoagulant results in a plasma supernatant with a gradient of cellular concentration

37. Platelet-Rich Plasma Production
Erythrocytes are the densest and will remain at the bottom
A buffy coat of white blood cells follows
Platelets are at the highest concentration in the plasma layer just above the buffy coat and decrease in concentration toward the top

38. Platelet-Rich Plasma

39. Platelet-Rich Plasma

40. Platelet-Rich Plasma Pathophysiology
With repetitive overuse, collagen fibers in tendons form micro-tears
Injured tendons heal by scarring, which adversely effects function and increases risk of re-injury
In addition, tendons heal at a slow rate secondary to poor vascularization

41. Platelet-Rich Plasma Pathophysiology
Traditional therapies do not alter the tendon’s poor healing capabilities, but rather involve long-term palliative care
Some studies suggest CSIs have adverse side effects including atrophy and worsening structural changes to tendons
However, GFs in platelets are known to promote tissue regeneration…

42. AJSM Article Review AJSM July 3, 2013 online
“Platelet-Rich Plasma Significantly Improves Clinical Outcomes in Patients With Chronic Tennis Elbow”
Allan K. Mishra, MD, Nebojsa V. Skrepnik, MD, PhD, Scott G. Edwards, MD, Grant L. Jones, MD, Steven Sampson, DO, Doug A. Vermillion, MD, Matthew L. Ramsey, MD, David C. Karli, MD, MBA, Arthur C. Rettig, MD
Allan K. Mishra, MD, Department of Orthopedic Surgery, Menlo Medical Clinic, Stanford University Medical Center

43. AJSM Article Review Conflicts of Interest
One or more of the authors has declared the following potential conflict of interest or source of funding: This study was sponsored by Biomet Biologics. A.K.M. receives royalties for patents from Biomet and ThermoGenesis and owns stock in BioParadox and ThermoGenesis. N.V.S. has received payment for speaking and as a consultant from Auxilium and receives research support from Biomet, DePuy, Ferring Pharmaceuticals, Biomemetic, Pfizer, Smith & Nephew, Zimmer, and Wyeth. S.G.E. is a paid consultant and receives research support from Medartis, owns stock or stock options in Mylad, and receives research support from Biomet. G.L.J. is an unpaid consultant for Arthrotek and receives research support from Biomet and Genzyme. S.S. has made presentations for Sonosite. D.A.V. has made presentations for Genzyme and receives research support from Biomet. M.L.R. receives royalties from and is a paid consultant for Integra (Ascension) and Zimmer and has made presentations for Arthrex. D.C.K. is an employee of and receives royalties from Greyledge Technologies. A.C.R. receives research support from Biomet.

44. AJSM Article Review
Objective: To evaluate the clinical value of tendon needling with PRP in patients with chronic tennis elbow compared with an active control group
Design: Double-blinded, prospective, multicenter, randomized, controlled trial from 2006 – 2011

45. AJSM Article Review Patients N = 230
Failed at least 1 conventional therapy
Considerable variability in types and amounts of treatment

46. AJSM Article Review Inclusion Criteria
Pain by palpation at the lateral epicondyle
Baseline elbow pain ≥ 50 mm on a 100-mm VAS during resisted wrist extension
H/o elbow pain > 3 months
Pain unresponsive to 1 of 3 conventional tx options:
CSI
PT/OT
NSAIDs

47. AJSM Article Review Exclusion Criteria Pregnancy Age < 18 years
H/o anemia, bleeding disorder, or blood disorder
H/o CTS on the affected side within 1 year of randomization
Cervical radiculopathy
Systemic disorders such as DM, RA, or hypothyroidism

48. AJSM Article Review Exclusion Criteria
Prior surgery for elbow tendinosis
Active elbow tendinosis within 4 weeks of randomization
Low H/H
Abnormal platelet count (outside 150,000 – 400,000)
H/o arthritis or fx of affected elbow
CSI within 6 weeks, PT/OT within 4 weeks, or NSAIDs within 1 week of randomization

49. AJSM Article Review Procedure
2 – 3 mL of PRP injected into the ECRB tendon and surrounding area using a peppering technique
A single penetration into the skin and 5 penetrations of the tendon
Control group was injected with 2 – 3 mL of bupivacaine with same peppering technique
Entire 10-mL syringe was covered in black tape and patients’ arms were draped to maintain blinding

50. AJSM Article Review

51. AJSM Article Review Outcome Measures Results
Successful tx defined as > 25% reduction of the VAS pain score with resisted wrist extension as compared to baseline
4, 8, 12, and 24 week follow-ups
Results
Greater improvement in pain scores compared to control group at every follow-up
Statistically significant at 8 (p = .01) and 24 weeks (p = .027)

52. AJSM Article Review

53. AJSM Article Review Conclusions
PRP was shown to produce clinically meaningful improvements in pain scores and elbow tenderness compared with an active control group with no significant complications
“Practice-changing evidence” supporting the use of PRP for patients who have failed standard non-operative therapies

54. References
Shiri R, Viikari-Juntura E, Varonen H, Heliövaara M. Prevalence and determinants of lateral and medial epicondylitis: a population study. Am J Epidemiol 2006; 164:1065
Smidt N, Lewis M, VAN DER Windt DA, et al. Lateral epicondylitis in general practice: course and prognostic indicators of outcome. J Rheumatol 2006; 33:205
Haahr JP, Andersen JH. Prognostic factors in lateral epicondylitis: a randomized trial with one-year follow-up in 266 new cases treated with minimal occupational intervention or the usual approach in general practice. Rheumatology (Oxford) 2003; 42:1216
Nirschl RP. Elbow tendinosis/tennis elbow. Clin Sports Med 1992; 11:851
Zeisig E, Ohberg L, Alfredson H. Extensor origin vascularity related to pain in patients with Tennis elbow. Knee Surg Sports Traumatol Arthrosc 2006; 14:659

55. References
Evans WJ, Meredith CN, Cannon JG, et al. Metabolic changes following eccentric exercise in trained and untrained men. J Appl Physiol 1986; 61:1864
Newham DJ, Jones DA, Clarkson PM. Repeated high-force eccentric exercise: effects on muscle pain and damage. J Appl Physiol 1987; 63:1381
Tsuang YH, Lam SL, Wu LC, et al. Isokinetic eccentric exercise can induce skeletal muscle injury within the physiologic excursion of muscle-tendon unit: a rabbit model. J Orthop Surg Res 2007; 2:13
Croisier JL, Foidart-Dessalle M, Tinant F, et al. An isokinetic eccentric programme for the management of chronic lateral epicondylar tendinopathy. Br J Sports Med 2007; 41:269
Boswell SG, Cole BJ, Sundman EA, Karas V, Fortier LA. Platelet-rich plasma: a milieu of bioactive factors. Arthroscopy 2012 Mar; 28(3):429-39
Sampson S, Gerhardt M, Mandelbaum B. Platelet rich plasma injection grafts for musculoskeletal injuries: a review. Curr Rev Musculoskelet Med 2008 Dec; 1(3-4):165-74

56. Any Questions?