Nicola Maffulli Department of Trauma and Orthopaedic Surgery Keele University School of Medicine Tendinopathies in Sport

Human studies Animal models Cell models Tendon problems

Adequate repair (adaptation)‏ Increased demands on tendon Predisposition to further injury Inadequate repair (inadequate collagen and matrix production)‏ Further alteration in collagen and matrix production Tenocyte disruption

TRAINING CELL DAMAGE EXTRACELLULAR MATRIX FAILED HEALING RESPONSE RUPTURE Mechanical loading Poor blood supply HYPERTROPHY Increased matrix synthesis microdamage Ineffectiverepair Inability to repair damage Hyperthermia Free radicals Hypoxia Poor blood supply

Tendinopathy Do we get the right picture? Onset of symptoms Surgery Unknown factors HistologyBiochemistry Molecular biology Risk Factors Risk Factors Injury? Injury? Overuse? Overuse? Metabolic disorder? Metabolic disorder?

Tendinopathy Confusion Confusion

Modern classification of Tendinopathy  Tendinopathy of the main body of the tendon  Tendinopathy of the surrounding tissues  Pantendinopathy  Insertional tendinopathy  Ruptures Maffulli N, Khan KM, Puddu G. Overuse tendon conditions: time to change a confusing terminology. Arthroscopy 1998; 14 (8):

TENDINOPATHIES  Difficult to manage  Management – often anecdotal – rarely evidence-based – often emotional – dubiously effective

1. Genetics 2. Collagen 3. Tendon cells 4. Matrix proteins 5. Vessels 6. Nerves Something old, something new…

We do not know where the pain originates from! Therefore, we do not know why and how any therapeutic modality, including surgery, works

Normal Abnormal  Collagen degeneration = disarray  Increased ground substance Light microscopy – tendon disarray  Prominent cell nuclei & neovascularization Puddu et al AJSM 1976; Maffulli et al AJSM 2001; Khan et al., BMJ 2002 Failed healing response

No evidence of ‘classical’ inflammatory cells in human overuse tendon injuries  Light or electron microscopy  Biochemistry (common extensor origin, PGE 2 absent in Achilles, patellar tendons)‏ Alfredson 1999, 2000, 2001 – in vivo microdialysis

Hurdles to optimal management of tendinopathies DIAGNOSIS IS CLINICAL! Tennis elbow: an ultrasonographic study in tennis players. Br J Sports Med 1990; 24: Tennis elbow: an ultrasonographic study in tennis players. Br J Sports Med 1990; 24: N Maffulli, R Regine, F Carrillo, G Capasso, S Minelli

Hurdles to optimal management of tendinopathies – relative rest – physical therapy – NSAIDs – deep frictions – hyperthermia – HOT – fibrolysis – eccentric loading – ultrasound No validated conservative management protocols No validated conservative management protocols – laser treatment – ozone – injections corticoteroids corticoteroids heparin heparin aprotinin aprotininothers – ESWT – topical glyceryl trinitrate

Short-term effectiveness of hyperthermia for supraspinatus tendinopathy in athletes: a short-term randomized controlled study. Am J Sports Med 2006;34(8): A Giombini, A Di Cesare, MR Safran, R Ciatti, N Maffulli Hyperthermia induced by microwave diathermy in the management of muscle and tendon injuries. A Giombini, V Giovannini, A Di Cesare, P Pacetti, H Naito, N Maffulli Br Med Bull 2007;83:

PATIENTS Failure of three to six months of conservative management

Use the KISSO principle

K eep I t S imple for the S imple O rthopods

Surgical management of tendinopathies of elbow – needling – coblation – percutaneous (ultrasound guided) tenotomy – arthroscopic approach – (mini)open approach  No validated surgical protocols

Surgical management of tendinopathies  Aims:  promote repair  return to pre-injury activity level

Surgical management of tendinopathies  Classical orthopaedic operation:  I do not know what it does  … but I use a bigger scalpel with a heavier hammer! Surgical management of tennis elbow. J Sports Med Phys Fitness 2002; 42: D Das, N Maffulli

THE FUTURE

Effect of basic fibroblast growth factor. An in vitro study of tendon healing. Clin Orthop Rel Res 342: , 1997 B Chan, KM Chan, N Maffulli, S Webb, KKH Lee

Why do tendinopathies occur? Is there an underlying metabolic disorder?

N Maffulli, SWB Ewen, SW Waterston, JA Reaper, V Barrass Tenocytes from ruptured and tendinopathic Achilles tendon produce greater quantities of collagen type III than tenocytes from normal Achilles tendon. An in vitro model of human tendon healing. Am J Sports Med 2000; 28:

H Alfredson, H Harstad, S Haugen, L Ohberg Sclerosing polidocanol injections to treat chronic painful shoulder impingement syndrome-results of a two-centre collaborative pilot study. Knee Surg Sports Traumatol Arthrosc 2006;14:

P Jonsson, P Wahlstrom, L Ohberg, H Alfredson Eccentric training in chronic painful impingement syndrome of the shoulder: results of a pilot study. Knee Surg Sports Traumatol Arthrosc 2006;14:76-81

CS Bestwick, N Maffulli Reactive oxygen species and tendinopathy. Do they matter? Br J Sports Med 2004; 38:

ROS - RNS Training Exercise Adaptiveresponse Unusual/sudden exercise No/insufficient adaptive response Sedentary No adaptive response Genetic predisposition Poor nutrition Failed healing response No problems RUPTURE

Biomagnetic manipulation Biomagnetic particles attached to cell membrane ion channels beads internalized into cytoplasm Magnetic force applied to cells Modulates ion cells function Upregulation of cell functions P Sharma, N Maffulli Tendon injury and tendinopathy: injury and repair. J Bone Joint Surg 2005; 87A:

M Magra, N Maffulli. Molecular events in tendinopathy: a role for metalloproteases. Foot and Ankle Clinics 10: , 2005 M Magra, N Maffulli. Matrix metalloproteases: a role in overuse tendinopathies. British Journal of Sports Medicine 39: , 2005

VOCC M. Magra, S. Hughes, A. El Haj, N. Maffulli. VOCCs and TREK-1 ion channel expression in human tenocytes. American Journal of Physiology, 2006 epub TREK

IP 3 traversing gap junctions to communicate a load signal by Ca 2+ wave propagation Pipet Ca 2 + ion free Ca 2 + ion bound intercellular messenger gap junction

Normal tendon Ruptured tendon Functional tissue engineering of tendons and OCT

N Maffulli JB King F Franceschi UG Longo L Ruzzini V Denaro M Ronga

 More frequent tendon changes on the articular side of the rotator cuff

 Tendon changes not only localized at the site of rupture, but also in the macroscopic intact tendon portion  During cuff repair, not necessary to excessively freshen the torn tendon to bleeding tissue

M Ronga, E Karousou, D Vigetti, A Passi, N Maffulli Accepted for publication, CORR Department of Trauma and Orthopaedic Surgery Keele University School of Medicine Gene expression and protein analysis in ruptured human Achilles tendons Department of Trauma and Orthopaedic Surgery University of Insubria, Varese, Italy

 LHB tendons of patients undergoing arthroscopic tenotomy for a refractory biceps tendinopathy show marked histopathological changes  The same tendons from aged individuals with no known tendon abnormalities have, as a group, little histological evidence of degenerative changes

… in the end...

… still a mountain to climb...

… but progress is being made