Post on 27-Dec-2015
PRP for Lateral Epicondylitis
Matthew Bloom, OMS IV
Have you had your morning cup of coffee yet?
300mg/day
Lateral Epicondylitis
Platelet-Rich Plasma
Current research on tx of lateral epicondylitis with PRP vs CSI
Overview
Also referred to as: Elbow tendinosis Elbow tendonitis Elbow tendinopathy Epicondylalgia Tennis elbow
Lateral Epicondylitis
Lateral Epicondylitis
Lateral Epicondylitis
Epidemiology 1–3% in general population
Risk Factors Smoking Obesity Age (45–54) Repetitive movement (>2 hours daily) Forceful activity (>20 kg)
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
Lateral Epicondylitis
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?)
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
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
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
Lateral Epicondylitis
Lateral Epicondylitis
Lateral Epicondylitis
Lateral Epicondylitis
Cozen’s Test
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
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
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
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
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
JAMA Article Review
Randomization 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
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)
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
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
JAMA Article Review
Hypotheses 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”
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
JAMA Article Review
Recovery/Im-provement
Recurrence0%
20%
40%
60%
80%
100%
CSIPlacebo
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)
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
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
JAMA Article Review
JAMA Article Review
Discussion Time!
Strengths vs. Weaknesses?
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
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
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
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
Platelet-Rich Plasma
Platelet-Rich Plasma
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
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…
Platelet-Rich Plasma
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
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.
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
AJSM Article Review
Patients N = 230 Failed at least 1 conventional therapy Considerable variability in types and amounts
of treatment
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
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
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
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
AJSM Article Review
AJSM Article Review
Outcome Measures 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)
AJSM Article Review
4 Weeks 8 Weeks* 12 Weeks 24 Weeks*0
10
20
30
40
50
60
70
80
PRPControl
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
AJSM Article Review
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
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
References
Any Questions?