ANOTHER ONE BITES THE DUST: THE NON-SURGICAL MANAGEMENT OF OVERUSE

2017 Sports Medicine Symposium: Return to Play July 21, 2017 Stacy Majoras, DO, ATC Bronson Sports Medicine Specialists Western Michigan University Team Physician

Disclosures Objectives

• Mechanism of overuse • Pathophysiology of injury • Pathophysiology of bone injury • Non surgical management of over use injuries Outline

• Definition of • Disease pathophysiology • Common overuse injuries of tendon • Treatment overview – Eccentric exercises – Nitroglycerin – Shockwave – PRP – Others • Definition of overuse bone injury • Disease pathophysiology • Treatment overview • Return to play • Closing remarks and questions Tendinopathy

• Tendon – a flexible but inelastic cord of strong fibrous tissue attaching muscle to bone, poor blood supply • Pathology – science of the causes and effects of diseases • Tendinopathy – disease of a tendon

What Causes the Pain?

• To understand pain we should understand pathology • If pathology is not the problem why do we have pain? • Biochemical substances – Catecholamines – Acetylcholine – Glutamate – Lactate • Neurovascular infiltration (late dysrepair) • Patients in all phases with and without pain Pathogenesis

• Several opinions/theories : some proven and some based on theory • Delicate balance between cell death and proliferation • Normal tendon under stress – Increased cross-linkage and collagen deposits • Inflammatory • Overuse • Continuum • Degeneration • Under use • Chemical mediated – increased neurotransmitters sensitize pain response – lactate Degenerative Pathology

• Types described in literature – Hypoxic degeneration – Hyaline degeneration – Mucoid degeneration • Irreversible cellular changes • Disintegration of matrix • Usually associated with chronic overuse – Increased tension causes micro-tearing – Abnormal adaptation to micro-tears = tendinosis – Increasing muscle contractions lead to avascular environment for tendon – reperfusion injury • Also related to underuse – Cell and matrix changes similar to that of overuse – Mostly reversible • Decreased mechanical integrity leading to failure of the tendon • Stage 1 – Reactive tendinopathy • Stage 2 – Tendon disrepair • Stage 3 – Degenerative tendinopathy • Stage 4 – stage 2/3 + fibrosis, hard or soft calcification • Is tendon rupture end-stage degenerative tendinopathy? – Kujala et al, 2005

Stage 1

• Reactive tendinopathy – Acute overload – Initial proliferative response – Homogeneous thickening of the tendon – No neurovascular changes – Collagen remains maintained

Stage 2

• Tendon disrepair – Body’s attempt at healing – Increase in number of cells – chondrocytes – Angiofibroblastic hyperplasia – a concentration of fibroblasts – Vascular hyperplasia – Disorganized collagen

Stage 3

• Degenerative tendinopathy – Continued accumulation of pathology causes structural failure of tendon – Cell death – apoptosis – Cell exhaustion – Focal disarray amidst normal tendon

Stage 4

• Stage 2/3 + fibrosis – hard or soft calcification

Common Overuse Injury

• – Lateral epicondylitis – – Quad tendinitis – – Plantar – Biceps tendinitis – Rotator cuff tendinitis – flexor tendinitis Outline

• Definition of tendinopathy • Disease pathophysiology • Common overuse injuries of tendon • Treatment overview – Eccentric exercises – Nitroglycerin – Shockwave – PRP – Others • Definition of overuse bone injury • Disease pathophysiology • Treatment overview • Return to play • Closing remarks and questions Treatment

• Goals – Relieve pain – Increase movement – preserve movement – Increase strength – preserve strength – Increase function – preserve function – Halt and/or reverse histologic deterioration • Different treatments for different stages of pathology – ie: patient in acute phase doing overloading eccentric exercises may be more detrimental – Self-limiting: most likely will resolve with conservative measures or no interventions Treatments

• Physical therapy – • Acupuncture eccentric exercises • Prolotherapy • Iontophoresis • Tenotomy • Custom vs OTC • Tenex – percutaneous orthotics tenotomy • Bracing - HeelWhat lifts, counterforce brace, wrist • Percutaneous splints radiofrequency micro- tenotomy • NSAIDS • Laser therapy • injections • Shockwave • Platelet Rich Plasma (PRP)Works? injections • Botulinum toxin • Nitroglycerin patches • Surgery

18 NSAIDS

NSAIDS Corticosteriods • If no inflammatory • Strong anti-inflammatory mechanism why use anti- • Has been shown to decrease inflammatories? tendon size – GOOD QUESTION • Linked to tendon rupture • Retard healing Drug Failure Total Control 0 23 – Ferry et al, 2007 Ibuprofen 0 23 – Rat patellar Acetaminophen 0 24

Naproxen 3 24

Piroxicam (feldene) 4 24

Celecoxib 6 22

Valdecoxib 10 24 (Bextra) Physical Therapy

• Eccentric exercises – bent vs knee straight – Open chain vs closed chain – Use of extra weight – Stimulate cellular activity in the late disrepair phase • Iontophoresis – electrical stimulation with anti- inflammatories • Phonophoresis – use of ultrasound with anti- inflammatories • Graston – mechanical deep tissue

• 30 recreational athletes – 15 study group: eccentrics – 15 controls: no training regimen • Tried and failed – rest, nsaids, orthotics, PT, change training • Measured – Isokinetic strength – Peak torque – Total work – Pain score – VAS

Results

Nitroglycerin

• Nitroglycerin – potent vasodilator – Side effects: headache, flushing • Theory – Nitric oxide synthase stimulates collagen synthesis through wound fibroblasts – Inhibit nitric oxide synthase leads to decrease CSA and load failure of the tendon during healing – Suggests Nitric oxide is important for modulating tendon healing  Reviewed 7 articles  Split between acute/subacute vs chronic  Acute/Subacute phase  2 articles Berrazueta et al – 100% improved compared to Placebo Pons et al – 42% improvement vs 87% improvement in corticosteriods  Chronic  5 articles Paoloni et al – 81% pain excellent vs 60% in placebo; improved work Paoloni et al – 78% pain excellent vs 49% in placebo; improved work; night pain; hop test Paoloni et al – pain at rest, at night, with activity, PROM, Work Paoloni et al – Decreased pain at 8 weeks for the 0.72mg/24 hrs Kane et al - no significant decrease in pain at 6 months

Shockwave

• Basics – Use of high frequency acoustic pulses focused to area of greatest pain – Same as lithotripsy • Late tendon disrepair stage • Mechanical loading increases growth factors – Cytokines – IGF-1 – TGF-β1 – Interleukin – 6 • Increase new vessel development at the insertion site • Block gate control mechanism

Platelet Rich Plasma

• Basics – Autologous blood centrifuged to concentrate platelets in a serum • Theory – Introduce autologous growth factors to site of injury to promote a “new start” to the healing cascade – TGF – β – FGF-2 – PDGF-AB – IGF-1 – EGF – HGF – VEGF-A Platelet Rich Plasma

• Variety – 1 step vs 2 step process – Centrifuge time and speed – Leukocyte rich vs Leukocyte poor – Platelet concentration – Activation vs no activation – Buffered vs not buffered • Widely used commercial products – Arthrex – lower platelets and lower leukocytes • 1500 rpm for 5 min (10ml  3ml) – Biomet (GPSIII) – higher platelets and higher leukocytes • 3200 rpm for 15 min (27ml  3ml) – Cascade – pure platelet rich fibrin • 6 min (18ml) – Magellan – platelet leukocyte rich plasma • 17 min (26ml) – Smart PReP – platelet leukocyte rich plasma • 16 min (60ml) – Symphony II – platelet leukocyte rich plasma • 5min (54ml) – Double spin – lit based, 1500 rpm for 5 min then top layer centrifuged again 6300 rpm for 20 min

Systemic Effects of PRP Literature Review

Article Tendon PRP Control US Results

Mishra et al Flexor or Leuk rich Yes – not blinded No 0, 4, 8 wks, 6 months 2006 extensor of the Buffered VAS: PRP 80.3 - 5.7 vs Control 86 - 72 Anesthesia Mayo elbow scores: PRP 50.3 - 86.3 vs control 50-56.5 No activation

Filardo et al Patella Leuk rich Yes – no 0, 15, 30 days, 6 mo (no stat diff) 2009 Activated physiotherapy VAS: PRP 52.7-36 vs control 50.73.5 0-10 scale: PRP 6.6-3.1 vs control 6.7-3.7 Tegner: 3.7-6.6 vs 5.3-6.8

Peerbooms et Common Leuk rich Yes – cortisone No 0, 4, 8, 12, 26, 52 wks al extensor of the Buffered Double blind VAS: PRP 70.1-25.3 vs Control 65.8-50.1 2010 elbow No activation DASH: 161.3-54.7 vs 131.2-108.4 Initially steroid was better then PRP

Gaweda et al Achilles Leuk rich No Yes 6wks, 3, 6, 18 mo 2010 Non insertional AOFAS:55-96 VISA-A:24-96 Tendon thickening: 15/15 – 1/15

Gosens et al Patellar Leuk rich No No (1)14 post surg/(1)22 non surg 2012 Buffered VISA-P: (1) 41.8-56.3 No activation (2) 39.1-58.6 Ideas to Chew on

• Volume of injection • Most effective preparation • Buffering or activation • Injection technique • Single vs multiple doses • Timing of injection in relation to initial injury • Most effective post injection treatments

Acupuncture

• Theory – Needle stimulates A-delta and C fibers that then causes a release of neuropeptides as well as vasodilatation • Mechanism – Disrupted collagen fibers – Increase immature type III – Apoptosis is accelerated – Leads to imbalance of remodeling – Follows the theory of continuum • Neovascularization – Increase in glutamate seen in painful tendons • Research – Limited and most can not provide enough evidence to support or refute use of acupuncture Prospective Primary outcomes – assessed @ 1, 3, 6 months VAS Pain scale Functional assessment with quick DASH Physical exam Secondary outcomes US evaluation Ultrasound guided procedure Maximal point of tenderness

 Several tendons were  Results treated (14)  VAS score reduction at  5 patella 4 & 12 weeks  4 Achilles  Baseline – 5.8  4 wks – 2.4  12 wks –  1 Prox glut med 2.2  1 Prox IT band  No complications  1 Prox hamstring  Limitations  1 Common extensor of  No standardized elbow treatment process  1 proximal rectus  Small number of non - femoris homogenous patients  Primary outcomes  No control  VAS pain scores  Not blinded  Safety  No follow up US after procedure

Literature Review

Article Tendon PRP or Vs… group 2, US Post tx Results group 1 group 3

Vetrano et Patellar Leuk rich ESWT 3 Yes Stretch, 2, 6, 12 mo al No act sessions strength, VISA-P:55.3-76.2-86.7-91.3 vs 56.1-71.3-73.7-77.6 2013 3-5 conc q 48-72 2 wks water; VAS: 6.6-1.5 vs 6.3-3.2 Rand DB 2 inj q 2 wk 2,400 pulses 4wks up Rompe et al Achilles Eccentric ESWT 3 Yes 6, 16 wks 2007 3 sets 15 sessions q VISA-A: improved 75.6%/70.4%/55% Rand BID week 2000pul Likert: 15/25 vs 13/25 vs 6/25 were 1 or 2 7 d/w x12w Wait - NSAIDS Tendon diameter: no difference Horstmann Achilles Whole body Eccentrics 3 Yes 12 wks et al vibration sets 15, add VAS: improved 2013 Board 13- 4th Force: ROM improv with vib Rand Blind 21Hz: 4-7 m Wait – normal US: no sig changes training log Gosens et al Elbow Leuk rich Corticosteroid 4,8, 12,26, 52, 104 wks 2011 ext No act DASH: 54.3-20-17.6 vs 43.3-36.8-36.5 Rand DB VAS: 69-25.9-21.3 vs 66.2-48.8-42.4

Krogh et al Elbow Leuk rich Corticosteroid Yes Minimal use 4wks, 3,6,12 mo 2013 ext Buffered 40mg triamcin of 3-4 PRTEE: only at 1 & 3 mo due to dropout rate Rand DB Anest Saline 3ml days, stretch Outline

• Definition of tendinopathy • Disease pathophysiology • Common overuse injuries of tendon • Treatment overview – Eccentric exercises – Nitroglycerin – Shockwave – PRP – Others • Definition of overuse bone injury • Disease pathophysiology • Treatment overview • Return to play • Closing remarks and questions Definition

• Stress fracture, bone , stress reaction – Increase tensile forces across bone resulting in increased osteoclastic activity without appropriate increase in osteoblastic activity

• Pathophysiology – RANKL stimulates osteoclasts maturation – RANKL is expressed on osteoblasts – Pro-inflammatory cytokines induce RANKL causing an increase in bone resorbtion Types

• Long bones – weight bearing – Tibia, femur, fibula, metatarsals – Humerus, radius, ulna, metacarpals • Misc. bones – Sacrum, ilium, tarsal bones, – Carpal bones – Spine

Outline

• Definition of tendinopathy • Disease pathophysiology • Common overuse injuries of tendon • Treatment overview – Eccentric exercises – Nitroglycerin – Shockwave – PRP – Others • Definition of overuse bone injury • Disease pathophysiology • Treatment overview • Return to play • Closing remarks and questions Treatments

• Depends on location of fracture Tension side – Femoral – tension vs compression – Anterior tibia – Scaphoid • Lower extremity – Walk without pain if not assisted ambulation – Activity as tolerated – if activity is not painful and non traumatic this is allowed • ie: biking, elliptical, swimming but no running • Upper extremity – Similar if an UE athlete – gymnast Compression side – Limit weight bearing • Immobilization? – Cast, boot, splint, brace, crutches • Gradual return to play with intent to avoid future injury Outline

• Definition of tendinopathy • Disease pathophysiology • Common overuse injuries of tendon • Treatment overview – Eccentric exercises – Nitroglycerin – Shockwave – PRP – Others • Definition of overuse bone injury • Disease pathophysiology • Treatment overview • Return to play • Closing remarks and questions Return to Play

• Tendinitis – Continuum is a theory – Tendinitis is not linked to increased risk of rupture – Allowed to participate to tolerance • Bone – Allow proper healing times – Treatment directed by pain Outline

• Definition of tendinopathy • Disease pathophysiology • Common overuse injuries of tendon • Treatment overview – Eccentric exercises – Nitroglycerin – Shockwave – PRP – Others • Definition of overuse bone injury • Disease pathophysiology • Treatment overview • Return to play • Closing remarks and questions Treatment Controversy

• Or conundrum?? • What works ? – My personal opinions being a young up coming sports medicine physician

QUESTIONS References

• Germann CA, Fourre MW. Chapter 280. Nontraumatic Disorders of the Hand. In: Cydulka RK, Meckler GD, eds. Tintinalli's : A Comprehensive Study Guide. 7th ed. New York: McGraw-Hill; 2011. http://0- www.accessmedicine.com.library.ccf.org/content.aspx?aID=6393002. Accessed December 19, 2013. • Woods RP, Seamon J. Chapter 21. Arthritis & Back Pain. In: Humphries RL, Stone C, eds. CURRENT Diagnosis & Treatment Emergency Medicine. 7th ed. New York: McGraw-Hill; 2011. http://0- www.accessmedicine.com.library.ccf.org/content.aspx?aID=55749765. Accessed December 19, 2013. • Ahmad Z, Siddiqui N, Malik SS, Abdus-Samee M, Tytherleigh-Strong G, Rushton N. Instructional Review: and elbow: Lateral Epicondylitis: A review of pathology and management. Bone and Journal 2013; 95-B: 1158-64. • Cook JL, Purdam CR. Is tendon pathology a continuum? A pathology model to explain the clinical presentation of load-induced tendinopathy. Br J Sports Med 2009;43:409-416. • Kujala UM, Sarna S, Kaprio J. Cumulative incidence of rupture and tendinopathy in male former elite athletes. Clin J Sport Med 2005;15:133-135 • Alfredson H, Pietila T, Jonsson P, Lorentzon R. Heavy-load eccentric calf muscle training for the treatment of chronic achilles tendinosis. Am J Sport Med 1998;26:360-366. • Ferry ST, Dahners LE, Afshari HM, Weinhold PS. The effects of common anti- inflammatory drugs on the healing rat patellar tendon. Am J Sport Med 2007;35:1326- 1333. References

• Paoloni JA, Appleyard RC, Nelson J, Murrell GAC. Topical Glyceryl trinitrate for chronic achilles tendinopathy. Clin J Sport Med 2005;15:116-117 • Gambito ED, Gonzalez-suarez CB, Oquinena TI, Agbayani RB. Evidence on the effectiveness of topical nitroglycerin in the treatment of tendinopathies: a systematic review and meta-analysis. Arc Phys Med Rehabil 2010;91:1291-1305. • Paoloni JA, Appleyard RC, Nelson J, Murrell G. Topical nitric oxide application in the treatment of chronic extensor tendinosis at the elbow. Am J of Sports Med 2003;31: 915-920 • Steunebrink M, Zwerver J, Brandsema R, Groenenboom P, Akker-Scheek I, Weir A. Topical glyceryl trinitrate treatment of chronic patellar tendinopathy: a randomised, double-blind, placebo-controlled clinical trial. Br J Sport Med 2013;47:34-39 • Speed C. A systematic review of shockwave therapies in soft tissue conditions: focusing on the evidence. Br J Sports Med 2013;0:1-6 • Mazzocca AD, McCarthy B, Chowaniec D, Cote M, Romeo A, Bradley J, Arciero R, Beitzel K. Platelet-Rich plasma differs according to preparation method and human variability. J Bone Joint Surg Am. 2012;94:308-316 • Hsu W, Mishra A, Rodeo S, Fu F, Terry M, Randelli P, Canale S, Kelly F. Platelet-rich plasma in orthopaedic applications: evidence – based recommendations for treatment. J Am Acad Orthop Surg 2013;21:739-748 • Wasterlain A, Braun H, Harris A, Kim H, Dragoo J. The systemic effects of platelet-rich plasma injection. Am J Sports Med 2013;41:186-193 • Harmon K, Rao A. The use of platelet-rich plasma in the nonsurgical management of sports injuries: hype or hope? Sport Med Hematology. 2013;620-626 References

• Mishra A, Pavelko T. Treatment of chronic elbow tendinosis with buffered platelet-rich plasma. Am J Sport Med 2006;34:1774-1778 • Peerbooms J, Sluimer J, Bruijn D, Gosens T. Positive effect of an autologous platelet concentrate in lateral epicondylitis in a double – blind randomized controlled trial. Am J Sport Med 2010;38:255-262 • Gosens T, Oudsten B, Fievez E, Spijker P, Fievez A. Pain and activity levels before and after platelet – rich plasma injection treatment of patellar tendinopathy: a prospective cohort study and the influence of previous treatments. International Orthopaedics 2012;36:1941-1946 • Filardo G, Kon E, Villa S, Vincentelli F, Fornasari P, Marcacci M. Use of platelet – rich plasma for the treatment of refractory jumper’s knee. International Orthopaedics 2010;34:909-915 • Gaweda K, Tarczynska M Krzyzanowski W. Treatment of chilles tendinopathy with platlet – rich plasma. Int J Sports Med 2010;31:577-583 • Vetrano M, Castorina A, Vulpiani M, Baldini R, Pavan A, Ferretti A. Platelet-rich plasma versus focused shock waves in the treatment of jumper’s knee in athletes. Am J Sports Med 2013;41:795-803 • Rompe J, Nafe B, Furia J, Maffulli N. Eccentric loading, shock-wave treatment, or a wait-and-see policy for tendinopathy of the main body of tendo achillis. Am J Sports Med 2007;35:374-383 • Horstmann T, Jud H, Frohlich V, Mundermann A, Grau S. Whole-body vibration versus eccentric training or a wait-and-see approach for chornic achilles tendinopathy: a randomized clinical trial. J of Orthopaedic and sports physical therapy 2013;43:794-803

References

• Gosens T, Peerbooms J, Laar W, Oudsten B. Ongoing positive effect of platelet-rich plasma versus corticosteroid injection in lateral epicondylitis. Am J Sports Med 2001;39:1200-1208 • Krogh T, Fredberg U, Stengaard-Pedersen K, Christensen R, Jensen P, Ellingsen T. Treatment of lateral epicondylitis with platelet-rich plasma, glucocorticoid, or saline. Am J Sports Med 2013;41:625-635 • Rabago D, Lee K, Ryan M, Chourasia A, Sesto M, Zgierska A, Kijowski R, Grettie J, Wilson J, Miller D. Hypertonic dextrose and morrhuate sodium injections (prolotherapy) for lateral epicondylosis (). Am J phys med rehabil 2012;92:587-596 • Neal B, Longbottom J. Is there a role for acupuncture in the treatment of tendinopathy? Acupunct Med 2012;30:346-349 • Lin C, Lee J, Su W, Kuo L, Tai T, Jou I. Clinical and ultrasonographic results of ultrasonographically guided percutaneous radiofrequency lesioning in the treatment of recalcitrant lateral epicondylitis. Am J Sports Med 2011;39:2429-2435 • Housner J, Jacobson J, Misko R. Sonographically guided percutaneous needle tenotomy for the treatment of chronic tendinosis. J Ultrasound Med 2009;28:1187-1192 • Gross C, Hsu A, Chahal J, Holmes G. Injectable treatments for noninsertional achilles tendinosis: a systematic review. Foot and international. 2013;34:619-628+