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Home , Fasciitis, Tennis elbow

Nonoperative Treatment of

Health Care That Works Andrews Research & Education Foundation October 14, 2016 Brett J. Kindle, M.D.

Disclosures

• Neither I, Brett Kindle, nor any family member(s), have any relevant financial relationships to be discussed, directly or indirectly, referred to or illustrated with or without recognition within the presentation. Learning Objectives

• Review pathophysiology of tendinopathy • Discuss nonoperative treatment of tendinopathy • Understand indications & rationale of the treatments • Be aware of the current evidence supporting the interventions • Discuss a potential treatment algorithm for tendinopathy utilizing these interventions Tendon Structure

• Myotendinous Junction

• Tendon

• Enthesis Tendon Structure

Tropocollagen Triple Helix Structure Tendon Mechanics Stress: Strain curve

IV

III

II I

– I -- Toe Region, collagen fibers reduce their crimp angle – II -- Linear elongation of fibers – III -- “Microscopic failure” with triple helix slipping apart to failure of some fibers – IV -- “Macroscopic failure” with failure of additional fibers to complete failure Tendon Injury – Terms

• Tendinitis – Implying inflammatory

• Tendinosis – Implying degenerative pathology w/o inflammatory component

• Tendinopathy – Waist basket term meaning either of above terms with or without pathology

Tendinopathy

• Multiple microtrauma à degeneration of tenocytes & ECM à failure to mature into normal tendon • Angiofibroblastic hyperplasia • Generates & increases risk of re- injury Tendinopathy Cycle

Increased demand on Adequate repair tendon

Increased Inadequate vulnerability repair to injury

Further Decreased decrease in collagen & collagen & ECM ECM producon Tenocyte death Tendinosis

• Macroscopic – Disorganized tissue – Soft, yellow/brown appearance (normal is glistening white) – Thickened tendon

Achilles Tendinosis

hp://www.thefootandankleclinic.com/achilles-tendon.htm Tendinosis Normal

• Microscopic – Collagen degeneration – Fibrosis – Neovascularization – LACK of

Tendinosis

J.D. Rees et al, May 2006 Common Sites of Tendinopathy • Achilles • Common Extensor (Tennis ) • Common Flexor (Golfer’s elbow) • Distal ITB (ITBFS) • Supraspinatus (Rotator cuff) • Patella (Jumper’s knee) • Proximal Hamstring (Ischium) • Posterior Tibialis • Gluteus Medius / Minimus (Greater Trochanter) Traditional Treatments

• Relative Rest – How much is too much? – Better question… how much is too little ? • Modalities – Ice – Reduces blood flow & tendon metabolic rate which may slow healing – Heat – Probably more beneficial than ice – Increases blood supply, removal of waste & brings in fibroblasts / collagen to area • Orthotics/Bracing o Is immobilization good for tendinosis ? • – Stretching – Strengthening – ART/CFM/Graston/ ASTYM Eccentric Exercises

• Strength training, particularly eccentric-emphasis, has the best evidence supporting its use for tendinopathy of any treatment available. Eccentric Exercises

• Alfredson et al, AJSM, 1998 • Prospective • N=30 patients w/ achilles tendinosis 2-6 cm proximal to insertion • Eccentric Intervention (N=15) – Eccentric loading calf muscle w/ knee straight & bent (3 sets of 15 BID x12 weeks) using good leg to bring back to start position • Surgical Intervention (N=15) • Outcome – Both had great pain relief at 24 weeks – The exercise group had improved strength (eccentric & concentric) to match that of the good leg – The group had improvement, but still differed significantly in strength from the good leg – Exercise group came to preinjury activity levels in 3 months, surgery over 6 months Manual or Instrument Assisted Stimulation • Cross Frictional Massage • Active Release Therapy • Graston • ASTYM – Basic idea is that stimulation of degenerated tendon will help to break up adhesions, scar tissue, increase circulation/ blood supply to area. – This in turns initiate a healing cascade • Inflammation then proliferation of fibroblasts…ultimately leads to new collagen formation – Very few RCT’s on CFM, ART, & Graston ASTYM Study

• Wilson et al, Journal of Sports Rehabilitation, 2000 – 20 pts with chronic patella tendinopathy randomized to traditional PT (CFM, bicycle, stretching, exercising, ice 3x/wk for 4 wks) vs ASTYM (instead of CFM) 2x/wk for 4 wks – After 6 wks, 10/10 ASTYM group had resolution of pain, 6/10 in traditional PT group – After x- over 2/4 had resolution of pain with ASTYM tx. Traditional Treatments

• NSAIDs – Process is NOT inflammatory at clinical presentation stage – May inhibit future healing of tendon – not clinically proven – Benefit may purely be analgesia • Injections – Process is NOT inflammatory – May provide some pain relief – Can impede collagen synthesis & weaken tendon – predisposes to rupture • Surgery – Only w/ failure of conservative therapy – Involves release of adhesions, debridement of degenerative tissue, & repair of partial tears – Success rates highly variable in studies, probably 50%-80% Corticosteroid Injections

• Used since the 1950’s • Side effects: skin depigmentation, fat atrophy, tendon rupture • Krogh et al: Meta Analysis, AJSM, 2013 • No statistically significant difference in benefit compared with placebo (10 trials, 310 pts) (lateral epicondylitis) • Does show short-term pain reduction benefit Tenotoxicity of Injectates

• Yang et al, 2014 • Rat patellar tendon-derived tenocytes cultured in vitro with lidocaine & triamcinolone acetonide Tenotoxicity of Injectates Alternative Anesthetic

• Bacteriostatic Saline • Contains 0.9% benzyl alcohol • Stuns Na+ channels? • Tenotoxicity unknown Modern Treatment Options

• Glyceryl trinitrate • Platelet-rich plasma (PRP) • Extracorporeal shockwave • Autologous whole blood therapy (ESWT) • Mesenchymal stem cells • Tendon scraping • • Percutaneous needle • Sclerotherapy tenotomy • High-volume image- • Percutaneous ultrasonic guided injections tenotomy (Tenex) Glyceryl Trinitrate

• Mechanism: Modulation • Achilles tendinopathy: of local NO levels. – 1 RT: No benefit. • Stimulation of collagen – 3 RTs: Benefit. synthesis in fibroblasts. – Long-term follow-up: Benefit persisted 3 yrs. • Also improves fracture – All studies non-insertional healing in animal models. disease. • Patellar tendinopathy: – 1 RT: Did not improve outcome over eccentric strengthening alone. Extracorporeal Shockwave Therapy

• Mechanism: Disrupt • Patellar tendinopathy: abnormal collagen. – 1 RT: Benefit (but no • Stimulate tissue diff from surgery) regeneration & cell – 2 case series: Benefit. recruitment • Achilles tendinopathy: • Local analgesic effect. – 3 case series: Benefit from 2 mos to 1 yr. • Plantar fasciopathy: – 1 RT: Benefit. ESWT (Orthotripsy)

• May disrupt avascular, damaged tissues & encourage revascularization & release of growth factors as well as recruitment of stem cells • May create hyperstimulation analgesia – Gate Theory of Pain (Melzak & Wall) – Repeated stimulation of small fibers can block transmission of pain • FDA approved for plantar and lateral elbow pain – Also used in patella tendon & achilles tendon • May be best used for chronic calcific tendinopathy (achilles) – Much like breaking up kidney stones ESWT (Orthotripsy)

• Peer K. et al, Clin J Sports Med, 2003 • N=27 w/ chronic patellar tendinopathy • ESWT (N=13) – ESWT (3 sessions) after which activity was as tolerated by pain (uncertain if any therapy) • Surgical (N=14) – Resection of degenerated tendon w/ tenotomy followed by therapy • Outcome – VISA & VAS scores were not significantly different at 22 & 26 months for ESWT & surgery respectively – 8/13 in ESWT & 7/14 in surgical group achieved preinjury levels of sport – ESWT did score higher overall Percutaneous Needle Tenotomy

• Utilization of a relatively large-gauge (18-20) needle to repeatedly fenestrate the tendon, fragment calcifications, & abrade the osseous margin (as applicable). • Mechanism: Convert chronic, non-healing injury into an acute injury with increased healing potential. Percutaneous Needle Tenotomy: Case Series

• Housner 2009. • Housner 2010. • Among 14 tendons, 13 • 47 patellar tendons. were lower limb: 5 • Average follow-up time: 45 months. patellar, 4 Achilles, 1 • 81% excellent or good gluteus medius, 1 iliotibial satisfaction scores. tract, 1 proximal • 72% excellent or good results hamstring, 1 proximal with return to activity. rectus femoris. • 28/45: Unable to return to • Improved VAS at 4 & 12 desired activity level. weeks post-procedure. • 6 subsequent . • 1 rupture 6 weeks post- procedure. Percutaneous Ultrasonic Tenotomy: Tenex • Commercial release 2012 • Developed at Mayo Clinic • Mechanism: Similar to PNT, but additional benefit of removal of degenerative tissue • U/S frequency is specific to necrotic tissue Tenex

TX1 Console • User interface with circuitry for TX1 Microtip precise & targeted tissue removal •Percutaneous (18 g) pen-like function • Targeted diseased tissue is removed •Pre-assembled w/ foot pedal activation while sparing healthy tissue with •Single use – entirely disposable built-in safety features/sensors Tenex: Proprietary Technology

• Console delivers optimized ultrasonic energy to end of TX1 Microtip that precisely cuts diseased tendon tissue while sparing healthy tissue

• Cutting of tissue achieved through longitudinal movement of needle at speed of sound (ultrasonic) – cut tissue at tip only via “jack-hammer effect”

• Continuous saline irrigation cools TX1 Microtip to control unwanted heat & coupled to simultaneous removal of target tissue

Tenex

• Common extensor () • Common flexor (golfer’s elbow) • • Patellar (jumper’s knee) • ITB • Achilles • • Rotator cuff* • Proximal hamstring (ischium)* • Gluteus medius/minimus (greater trochanter)* Tenex – Patient Selection

• (>3 months) – Recalcitrant to conservative care (rest, ice, PT, bracing) • Point tenderness – Localized over site of abnormal tissue • Ultrasound abnormalities – Hypoechogenity, thickening, neo-vascularization

• No contraindications (infxn, coagulopathy, anti-coagulants, active cancer) • No other concurrent diagnoses Tenex

Ultrasound imaging used to identify diseased tissue & guide TX1 Microtip 1. Visualize during procedure damaged tendon Diseased tendon tissue (dark region) via ultrasound

2. Guide TX1 Microtip to damaged tissue TX1 MicroTip placed into with ultrasound hypoechoic region guidance

3. Foot-pedal activation of TX1 MicroTip precisely Removal of cuts & debrides hypoechoic region target damaged tissue

Tenex

• Ultrasound is key • Minimally invasive • Lower-complication rate compared to open tenotomy • 20-35 minute procedure (1-5 minute cutting time) • Usually done in ASC / procedure room* • Faster recovery times • 80+% success rate w/in 1-3 mos • Most post-procedure pain managed with OTC meds Tenex

• Koh et al • Prospective study - 20 patients, chronic lateral epicondylitis, failed nonsurgical treatment • Single treatment with TX 1 • Postprocedure care - no PT, OTC pain control, activity modification x2 weeks • Follow-up: 2 weeks, 1, 3, 6, 12, 24 & 36 months • Assessed adverse events, VAS pain score, quality of life, diagnostic ultrasound Tenex Tenex

• Barnes, Beckley, & Smith • Prospective study - 19 patients, symptomatic >6 months • 7 medial & 12 lateral epicondylosis, failed conservative treatment • Single treatment with TX 1 & no additional intervention • Total procedure time <15 minutes with mean energy time 38 seconds • No complications • Clinical outcomes at baseline, 6 weeks, 3, 6 & 12 months: VAS, Mayo elbow performance score (MEPS), DASH Tenex

VAS Q-DASH

MEPS Tenex

• Moore et al • Prospective study - randomizing Tenex vs open surgery • 45 patients, chronic lateral epicondylosis, unresponsive to conservative care: – 23 treated with TX 1 – 22 treated with open surgical repair • Outcomes measured at 1 week, 1 & 6 months

Tenex Surgery Efficacy/pain relief 91% 77% Posreatment visits 2.5 4.25 Average work weeks 1.1 8.2 missed Total cost/savings per Tenex was $11,753 less than surgery paent Tenex

• Ellattrache (Kerlan Jobe) • Prospective study involving 16 patients–symptomatic for at least 6 months (10 collegiate level athletes) • Failed conservative treatment • Single treatment with TX 1 & no additional intervention • No complications • Clinical outcomes: 15/16 (93%) had resolution of symptoms at 3 months with full activity at 6 months • All 10 athletes return to their prior level of competition Tenex

• Patel et al • Prospective study involving 12 patients–symptomatic for at least 6 months, all failed conservative treatment, PT, orthotics, extracorporal shockwave, cortisone, 4 patients failed open or endoscopic fasciotomy • Single treatment with TX 1 & no additional intervention • Twelve-month follow-up • No complications • Clinical outcomes: 11/12 (92%) pain-free at 3 months & sustained at 12 months, significant improvement in quality of life by 6 months & sustained at 12 months Tenex

• Ellis et al • Prospective study of 26 patients–symptomatic for average of 18 months • Single treatment with TX 1 no additional intervention • Mean cutting time of 4 minutes 24 seconds • Patient’s followed up in one week, one month, 12 months, in 16 months post • Clinical outcomes: 23/26 (80%) have pain relief in one month & sustain at 16 months, 24/26 (92%) would have the procedure done again Platelet-Rich Plasma (PRP)

• Type of injection therapy used for various chronic sports injuries to promote healing. History of PRP

• First human application was described in mandibular reconstruction in oromaxillary surgery in 1998 (Robert Marx, Prof. of Surgery & Chief of Oromaxillary Surgery Division at Univ. of Miami). • Since then, PRP has experienced a surge in clinical uses & research • Endorsement from athletes – Tiger Woods – Alex Rodriguez (NY Yankees) – Masahiro Tanaka (NY Yankees) – Kobe Bryant (LA Lakers) – Troy Polamalu (Pitts Steelers) – Hines Ward (Pitts Steelers, 2009)

Platelet-Rich Plasma (PRP)

• So…. What is it? – Autologous blood derived product – Plasma with concentrated platelets 2-6x above normal – Platelets contain granules which store GFs & – Alpha granules store platelet-derived growth factors which act in chondrocytes & tenocytes to: – promote cartilage matrix synthesis – increase cell growth & migration – facilitate protein transcription – PRP may inhibit growth of – Staphylococcus aureus & Escherichia coli – Not active against P. aeruginosa, K. pneumonia, or E. faecalis Normal Blood Platelet Rich Plasma

Marx & Garg. Dental & Craniofascial applications of Platelet Rich Plasma. Quintessence Publishing Co., Inc. 2005 PRP • Alpha granule contents: – Platelet-derived epidermal growth factor – Platelet-derived growth factor • Chemoattractive for mesenchymal stem cells & monocytes – Bone morphogenic protein – Transforming growth factor beta • Mitogen for fibroblasts & enhances extracellular matrix production – Insulin-like growth factor – Vascular endothelial growth factor • Stimulates angiogenesis – Endothelial cell growth factor – Basic fibroblast growth factor PRP u Delta granule contents: u Adenosine

u Cytoprotective agent prevents tissue damage, stimulate for pro-inflammatory (IL-1, IL-18) or anti-inflammatory effects (IL-10) u

u Incr capillary dilatation, attracts fibroblasts & increases their proliferation, affects function by suppression of IFN-gamma induced 1a expression u

u Vasodilator = incr inflam & immune cells greater access to marginate & enter the local area, activates macrophages u Calcium

u Involved in keratinocyte proliferation & differentiation that is essential for wound-healing

u Also: Dopamine, cathespin D & E, elastases, hydrolases Platelet-Rich Plasma (PRP) • How is it prepared? – Various systems but basics are:

Platelet-Rich Plasma (PRP)

• How is it used? – Goal is to deliver GFs directly at site of diseased tissue to stimulate the natural healing cascade & regeneration of tissue

– Tendons, , Joints, Muscle injuries, Intra-operative augmentation – Lateral Epicondylitis, Achilles tendinopathy, Patellar tendinopathy – Plantar – Platelet-Rich Plasma (PRP)

• How does it work? – PRP is injected & becomes activated via collagen w/in connective tissue or cartilage to release GFs & cytokines – Initiates & regulates all phases of healing cycle – Bioactive proteins stimulate local stem cells & enhance extracellular matrix (ECM) gene expression – Recruits reparative cells from the local circulation or bone marrow – Inhibits excess inflammation, apoptosis, & metalloproteinase activity

• Pathways help restore damaged tissue & diminish pain – Modulate microvascular environment or alter efferent or afferent neural receptors

• More is needed to understand the mechanism of action…

Platelet-Rich Plasma (PRP)

• Allan Mishra et al, AJSM, 2006 • 140 pts with lateral epicondylosis • Intervention – Treatment group – single PRP injection into CET followed by gradual increase in rehab program x4 weeks after which full activity allowed – Control group – bupivacaine injection • Outcome – 46%, 60% & 81% improvement in VAS pain scores at 1, 2 & 6 months respectively in tx group – At final F/U (12-38 months) 93% pain free (<10/100 VAS) – No complications, no one got worse Platelet-Rich Plasma (PRP)

• Plantar fasciopathy: 3 case series: Benefit at 10 mos-1 yr. • Achilles tendinopathy: 5 case series: Benefit at 6 mos-4 yrs. • Patellar tendinopathy: 3 case series: Benefit at 3 mos-1 yr. • Multiple tendon studies: – Finnoff 2011: 31/41 lower limb tendons. Case series: Benefit at 14 mos. – Mautner 2013: 116/180 lower limb tendons. Case series: Benefit at 15 mos. Platelet-Rich Plasma (PRP)

• Plantar fasciopathy: – Aksahin 2012: No benefit at 6 mos. • Patellar tendinopathy: – Vetrano 2013: Benefit of PRP over ESWT up to 1 yr. – Dragoo 2014: Benefit of PRP+PNT+eccentrics over PNT +eccentrics at 12 wks…similar outcomes at >26 wks. • Achilles tendinopathy: – de Vos 2010/de Jonge 2011: No benefit at 1 yr. – Kearney 2013: No benefit at 6 mos. • Many studies are biased Autologous Whole Blood Injections • Mechanism: Similar to PRP. • Benefits/drawbacks of RBC/WBC injection concomitantly? • RBCs: free radicals, proteolytic enzymes. • WBCs: growth factors, but free radicals, MMP-8/9. • Patellar tendinopathy: 1 prospective cohort: Benefit at 15 mos. • Achilles tendinopathy: 1 RT: Benefit at 12 wk. • 1 RT: No benefit at 12 wk. Prolotherapy

• First described in the 1930’s • Several decades of large retrospective studies on successful outcomes • Theory is that irritant solutions stimulate an acute inflammatory reaction to initiate a healing cascade for injured soft tissues. • This technique has been employed for chronic enthesopathies & ligamentous injuries/laxity. • Procedure involves injection of chemical (sodium morrhuate) or osmotic (Dextrose) proliferants over a series of shots Prolotherapy

• Mechanism: Dextrose-containing solution is hypertonic: Osmotic cell rupture. • Phenol-glycerineglucose: Local cellular irritation. • Morrhuate sodium: Chemotactic attraction of inflammatory mediators. • Proximal adductor tendinopathy: 1 case series (hypertonic dextrose): Benefit at mean of 17 mos. • Achilles tendinopathy: 1 RT (hypertonic glucose): No benefit at 12 months. Sclerotherapy

• Mechanism: Neo-vascularization may be involved in tendon pain. • Neo-vessels, & presumably adjacent “neo- nerves,” are sclerosed. – Polidocanol or sotradecol most often used. May also use lactate 2x normal levels, glutamate, & substance P • Patellar tendinopathy: 2 case series: Benefit at 1-2 yrs. • Achilles tendinopathy: 2 case series: Benefit at 6-8 mos. 1 RT: Benefit at 3 mos. Sclerotherapy

• RCT published in AJSM, 2012 by Hoksrud et al. • Prospective study 101 pt w jumper’s knee • Received 1-5 USG inj polidocanol 4-6 wk intervals • VISA-P collected before, 6, 12, 24 month after 1st injection • “Few patients cured, majority had reduced function & substantial pain after 24 months follow up” (NO)

• NO is a short lived free radical – Can induce apoptosis in inflammatory cells – Can cause angiogenesis &

• Inhibition of NO has been shown to reduce collagen synthesis by wound fibroblast in vitro • NO synthase inhibition in animal studies leads to a reduction in tendon cross sectional area & load to tendon failure • Theory is that nitric oxide may enhance collagen synthesis & remodeling as well as vasodilate & clear inflammatory mediators or other pain mediating proteins. • Be wary of side effects/ contraindications • Can be used as adjunct to other treatments Nitric Oxide

• Dr. George Murrell has done significant research into this: • Lateral epicondylosis – At 6 mo: 80% of nitrate group had no pain with ADL’s as opposed to 60% with rehab alone • Achilles Tendinosis – At 6 mo: 78% of nitrate group had no pain with ADL’s as opposed to 49% with rehab alone • Supraspinatus tendinopathy – At 6 mo: 46% of nitrate group had no pain with ADL’s as opposed to 24% with rehab alone • Think of: PRP as ”Fertilizer” Stem Cells as ”Seeds” Stem Cell Use in

• “We have had on big revelation in sports medicine over the last 50 years, and that was the arthroscope. I’ve been looking for the next wave, and stem cell therapy… will be it.” Dr. James Andrews Mesenchymal Stem Cells

• Mechanism: MSCs are multipotent stromal cells that can proliferate & differentiate into a variety of cell types, including tenocytes • Increase rate of healing by release of growth factors, cytokines & trophic immune regulators • Derived from bone marrow, adipose tissue, amniotic tissue, tendon, synovial tissue Mesenchymal Stem Cells

• First identified in bone marrow by Caplan in 1991 and, subsequently, in adipose tissues by Zuk et al at UCLA in 2001, Mesenchymal Adult Stem Cells can differentiate into: WONDER WHY? STEM CELL PROLOTHERAPY IN REGENERATIVE MEDICINE tissue,134 intervertebral disc repair,135, 136 ischemic heart tissue,137, 138 graft-vs-host disease139 and osteogenesis imperfecta.140 (See Figure 2.) Of particular interest in musculoskeletal medicine is the observation in degenerative – Ligament diseases, such as osteoarthritis, an individual’s adult stem cell frequency and potency may – Tendon be depleted, with reduced proliferative capacity and ability to differentiate.141, 142 It has been – Cartilage suggested that addition of these missing stem cell elements might help these conditions. Studies have – Muscle demonstrated such improvement with adult stem cell therapy by – Bone the successful regeneration of osteoarthritic damage and articular cartilage defects.143, 144 In 2003, – Adipose tissue Murphy et al. reported significant improvement in medial meniscus and cartilage regeneration with Figure 2. FlowCourtesy chart elucidating of Donna possible Alderman, commitment, D.O. lineage progression and autologous stem cell therapy in an maturation of adipose-derived mesenchymal stem cells. animal model. Not only was there evidence of marked regeneration of meniscal tissue, but fat graft (AFG) was transplantation of intact cellular the usual progressive destruction of articular cartilage, elements (mature adipocytes) into environments that had osteophytic remodeling and subchondral sclerosis existing adipose tissues. However it was recognized that commonly seen in osteoarthritic disease was reduced in mature adipocytes did not undergo mitosis, therefore MSC-treated joints compared with controls.145 In 2008, further understanding of how adipose tissue maintained Centeno et al. reported significant knee cartilage growth its structural integrity and volumes became an important and symptom improvement in a human case report undertaking. The past decade in cosmetic-plastic using culture expanded autologous MSC’s from bone surgery has been spent increasing understanding of the marrow.146 importance of adipose-derived stem-stromal elements to the replenishment and restoration of adipocytes in Vivo. As A U TOLOG O U S ADI POSE FAT G RAFTS adult adipocytes enter senescence stages, adherent (cell- IN COSMETI C - PLASTI C SU R G ERY to-cell) adipose progenitor cells directly differentiate into adipocytes to replace the aging cells. These progenitor Adipose tissues have long been a proven safe and efficacious cells are capable of undergoing mitosis, however do so in structural tissue amenable to successful transplantation.147 an asymmetric manner, producing another, now adipose- For more than 50 years, cosmetic-plastic surgeons have lineage committed (unipotent or terminally commited), attempted such transfers with variable success. It is clear progenitor cell and a less differentiated progenitor cell, that control of cellular fate and extracellular environment in order to maintain precursor numbers for future is critical in tissue regeneration and cell-based therapies.148 differentiation and restore stem-like progenitor availability. It was not until the advent of a patented, closed syringe Further understanding of the importance of the autocrine system was introduced in 1990 (Tulip Medical™) that and paracrine functions of such cells within their niche predictability of structural augmentation was fully has demonstrated the complex microenvironmental appreciated.149 For many years cosmetic-plastic surgeons factors involved in tissue maintenance and regeneration. believed the key to a successful structural autologous

JOURNAL of PROLOTHERAPY | VOLUME 3, ISSUE 3 | AUGUST 2011 693 How Does MSCs Help ?

• Not entirely understood. • 1) Regeneration of cartilage has been demonstrated in vitro & in animal models. (Agung et al. Knee Surg, 2006) How Does MSCs Help Arthritis? • 2) Paracrine mechanism (cell-to-cell talk) via cytokines & growth factors. (Bunnell et al. Cell Res & Therapy 2010) Many Ways to Prepare MSCs… Issue with “Expanded” MSCs

• In US, however, FDA does not allow culturing of the stem cells in clinics. (FDA does not allow these cells to be “more than minimally manipulated” or be outside of the patient for over 24 hrs.) • Clinicians have used centrifuge to concentrate MSCs from bone marrow (Bone Marrow Aspirate Concentrate) or adipose tissues (Adipose Derived Stromal Vascular Fraction) So what we do instead: Obtaining BMAC:

Bone Marrow Aspiraon & Centrifugaon. Mesenchymal Stem Cells

• FDA closely regulates based on principles of:

– Minimal manipulation – Homologous use (adipose?) – Noncombination products – Lack of systemic effect or autologous Mesenchymal Stem Cells: Obtaining “BMAC” Mesenchymal Stem Cells Mesenchymal Stem Cells

• Several animal studies show improvement of biomechanical properties, tissue architecture & functionality • Lateral epicondylitis: 1 RT with skin-derived tenocyte-like cells (vs autologous plasma injections), 11/12 w/ benefit at 6 mos. • Patellar tendinopathy: – Prospective, randomized, double blind controlled trial, skin derived tendon-like cell injections had statistically significant & faster improvement in pain & reduced functional disability at 6 months compared to PRP group (N=46) – Case series, bone marrow derived stem cells injected & followed up over the course of 5 years. 7/8 said they would have the procedure again & were completely satisfied. Statistically significant improvement for KOOS scores. Mesenchymal Stem Cells

• Future questions – Which harvest site is best – How many injections – Duration between injections – Does needle size damage the cells – Does temperature affect the cells – Inhibition or synergy with other products – Growth factor injection High-Volume Image-Guided Injections • Mechanically disrupt neovessels/neonerves through injection of a high volume of fluid, typically between a tendon & associated fat pad (Achilles tendon & Kager’s fat pad; patellar tendon & Hoffa’s fat pad). High-Volume Image-Guided Injections • Maffulli 2013: Achilles tendinopathy. • 94 patients. Injected with 10 mL of 0.5% bupivacaine, 25 mg of aprotinin, & up to 40 mL of normal saline. Follow-up to 12 months. Significant improvement in VISA-A. • Morton 2014: Patellar tendinopathy. • 20 patients. Injected with 10 mL of 0.5% bupivacaine, 25 mg hydrocortisone, & 30 mL of normal saline at the interface of patellar tendon & Hoffa’s fat pad. Eccentric loading rehabilitation protocol. Follow-up at 12 weeks. Significant improvement in VISA-P. Tendon Scraping

• Mechanically disrupt neo-vessels/neo- nerves, typically at the interface between a tendon & associated fat pad (Achilles tendon & Kager’s fat pad; patellar tendon & Hoffa’s fat pad). Tendon Scraping

• Alfredson 2011: Achilles tendinopathy. • 88 tendons: Case series of open surgical scraping. • 37 tendons: Randomized to open surgical scraping vs. percutaneous needle scraping. • Mean follow-up: 18 months. • VAS significantly improved. • In randomized arm, no significant different between open surgical scraping & percutaneous needle scraping. Treatment Decisions

• Chronicity of injury. • Patient’s desired activities. • Degree of disability. • Patient’s commitment & • Failure of eccentric compliance level. strengthening? • Co-morbid & • Failure of common sense? environmental factors. • Patient’s fitness level. • Benefits vs risks of • Patient’s competition particular treatment. level. • Age. • Patient’s expectations. • Cost. Inside vs. Outside Interventions

• “Inside” tendon interventions • “Outside” tendon may take longer to recover interventions may have a from. quicker recovery & return- • May also have better long- to-play schedule. term outcomes. • May have better short-term • May have greater risk of outcomes. tendon rupture (questionable). • May be lower risk. • Treating the disease process? • Temporizing measure? • Delayed gratification? • Treating pain more than the disease process? Proposed Treatment Approach • Tier 1: • Tier 2: • Activity modifications. • Combination HVIGI + • Training program evaluation tendon scraping (where & modification. applicable). • Technique evaluation & • Tenotomy (where modification. applicable, available, cost- • Equipment/gear evaluation & effective). modification. • Nitrates • Eccentric strengthening • ESWT program. Proposed Treatment Approach

• Tier 3: • ALL of these • Combination of interventions beyond tenotomy & PRP Tier One need more injection. $ high-quality studies. • Tier Four: • MSCs (possible combination with tenotomy). $$$$$ Summary

• There are numerous promising treatment options for tendinopathy; however, more high-quality evidence supporting their use is needed. • Characteristics of the patient & the considered treatments should help guide therapy; there is insufficient evidence for a universally agreed- upon treatment approach at this time. Take Home Points

• Tendon degeneration & neovascularization are prominent features of tendinosis • NSAIDs & steroid injections are NOT indicated, but are still widely used in treatment of tendinosis • Several novel, nonsurgical interventions for recalcitrant tendinopathy are emerging • Tenex is a minimally invasive debridement procedure that has significant data supporting its use for treating tendinosis • Regenerative medicine (PRP & SCs) for MSK application is still in its infancy with limited available evidence, but appears promising & safe, offering an exciting alternative to recalcitrant MSK conditions

References

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