Overuse Bone and Tendon Injuries -  Science and Theories of Tomorrow
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Overuse Bone and Tendon Injuries - Science and Theories of Tomorrow

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Lecture presented in the Sports Medicine presentations section of the Annual Scientific Conference of the American Podiatric Medical Association. 2012. Washington, DC.

Lecture presented in the Sports Medicine presentations section of the Annual Scientific Conference of the American Podiatric Medical Association. 2012. Washington, DC.

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Overuse Bone and Tendon Injuries -  Science and Theories of Tomorrow Overuse Bone and Tendon Injuries - Science and Theories of Tomorrow Presentation Transcript

  • Overuse Bone & Tendon Injury Theories of Tomorrow Stephen M. Pribut, D.P.M., FAAPSM, FACFAS Past President, AAPSM Clinical Assistant Professor of Surgery George Washington University Medical School drpribut.com dr.pribut@gmail.comFriday, August 17, 12
  • Friday, August 17, 12
  • Hang On TightFriday, August 17, 12
  • Thoughts • “If in the last few years you haven’t discarded a major opinion or acquired a new one, your critical thinking capacity may be broken.” • “All models are wrong, but some are useful.” (George Box)Friday, August 17, 12
  • Where We Are Going • Introduction 15% • Old Theories and New (tissue theory) 10% • Cell Mechanics and Mechanotransduction 40% • Bone 25% • Tendons 10%Friday, August 17, 12
  • And now for something completely different...Friday, August 17, 12
  • Dive Deep & Think Hard • Does it all stop with Newton & Root or McPoil & Kirby? Should we look in the frontal plane or the sagittal? Or should we look deeper? • Let’s explore general concepts to solve specific problems. • Go deeper: Cellular Biomechanics and Signaling • Cellular Concepts • Structure creates function • Mechanics or enzyme cascade or both? Dive In, Dive DeepFriday, August 17, 12
  • 4 Questions To Answer • Does eccentric stretching work? • Why didn’t PRP work better than saline for Achilles tendinopathy? • How does ultrasound stimulate bone healing? • Does mechanics play a role in healing?Friday, August 17, 12
  • More thinkers, theorists and researchers are needed!Friday, August 17, 12
  • How and from where do scientists get ideas? And where do comedians get their jokes? Ones like Lenny Bruce, George Carlin?Friday, August 17, 12
  • Dreams • Kekule - 1865 theory of resonance of Benzene. Inspired by day dream.Friday, August 17, 12
  • Literature • Quark - named from Joyce’s Finnegan’s Wake • Murray Gell-Mann chose name in 1963 • Admitted to “perusing” the book, but not reading it • Feels beauty and elegance plays role in theoryFriday, August 17, 12
  • Architecture • Donald Ingber, M.D., PhD. • Tensegrity as cellular feature inspired by Kenneth Snelson’s “Needle” and Buckminster Fuller • Cytoskeleton works through tensional regulation • Cell shape regulation (via matrix firmness) alters genetic expression and affects stem cell and cancer cell growthFriday, August 17, 12
  • Einstein • “As Newton once said, ‘If I have seen further than others, it is because I have stood on the shoulders of giants’. ” • Special relativity built on the work of Maxwell and Lorentz among others.Friday, August 17, 12
  • One View: You didn’t build that alone.Friday, August 17, 12
  • The joke was not approved by Einstein.Friday, August 17, 12
  • Break Down the Barriers • Basic Science • Chemistry, Physics, Mathematics, Engineering • Architecture, Psychology, Environmental Science • Exercise Physiology, Nutrition Science, Pharmacological SciencesFriday, August 17, 12
  • Interdisciplinary Convergence Biological Engineering Physical Sciences Science Sciences Biochemistry Molecular Biology Donald Ingber: “the boundaries between the living and non-living systems are beginning to break down.”Friday, August 17, 12
  • Podiatric Medicine • Divisions • Surgery • Biomechanics • Wound Care • Other areas • Barriers • intra-disciplinary • interdisciplinaryFriday, August 17, 12
  • Bone & Tendon Maintenance and Healing Things we know: influencing factors • Exercise • Diet • Aging • Genetics • Sleep • Psychiatric Disorders - (some evidence)Friday, August 17, 12
  • Mind & GaitFriday, August 17, 12
  • Gait Revealer of Aging & Alzheimers • Mayo Clinic: N= 1341, followed over 15 months • Lower cadence, velocity and length of stride correlated with significantly larger declines in global cognition, memory and executive function. • Basel, Switzerland: N= 1153, mean age of 78 • gait became "slower and more variable as cognition decline progressed." • Cognitively healthy, mild cognitive impairment or Alzheimers dementia. • Those with Alzheimers walked slower than those with MCI, who walked slower than those who were cognitively healthy.Friday, August 17, 12
  • Mind & BoneFriday, August 17, 12
  • Depression & Bone Risk • Affects 16% of population • Meta-analysis - lower BMD • Percentage decrease in BMD was 5.9% for the lumbar spine and 6% for the hip • 4 of 5 prospective studies on fracture risk concluded that depression was associated with an increase in fracture risk • Many patients were taking SSRI drugs • Exercise regimen not taken into accountFriday, August 17, 12
  • Possible Factors Involved in BMD and Depression • Animal data suggest a relationship between a hyperactive efferent autonomic nervous system and bone resorption. • Impairment of the immune system in depression has been documented. Proinflammatory cytokines interleukins (IL) 1 and 6 and tumor necrosis factor are high. • Cytokines are stimulants of the hypothalamic-pituitary- adrenal axis, which may account for the hyperadrenocorticism observed in depression. Eskandari et al reported a reduction in anti-inflammatory cytokine IL-13. • SSRI’s - have shown increased bone loss in post-menopausal women, increased risk of fracture, and increased rate of falling Richards JB, Papaioannou A, Adachi JD, Joseph L, Whitson HE, Prior JC, Goltzman D; Canadian Multicentre Osteoporosis Study Research Group. Effect of selective serotonin reuptake inhibitors on the risk of fracture. Arch Intern Med. 2007 January 167(2):188-94. Ziere G, Dieleman JP, van der Cammen TJ, Hofman A, Pols HA, Stricker BH. Selective serotonin reuptake inhibiting antidepressants are associated with an increased risk of nonvertebral fractures. J Clin Psychopharmacol. 2008 August 28(4):411-7.Friday, August 17, 12
  • Exercise, Mind & Bone • Reduces risk of depression • Lowers risk of osteoporosis • Seems to lessen risk of hip osteoarthropathy • Mechanics - forces, vibration, pulses of exercise and weight bearing impacts cognition and bone formationFriday, August 17, 12
  • Will we kiss tissue stress theory goodbye?Friday, August 17, 12
  • What should we look at? • The 28 types of collagen? • Cells? • Bacterial flora? • Structural mechanics and biomechanics? Where will this lead us?Friday, August 17, 12
  • Levels Of Concern: Getting Small Scanning electron micrograph: bone callus of healed complete trabecular fractures in an osteopenic vertebra probably caused by excessive local microdamage. Frost HM. The Microdamage (MDx) Connection. In: Frost HM. The Utah Paradigm of Skeletal Physiology Vol 1. Athens, Greece: ISMNI; 2004;4:208-219. Copyright © 2004, ISMNI.Friday, August 17, 12
  • Looking BackFriday, August 17, 12
  • Thinking Too Narrow • “lower extremity”specific theories • Root Biomechanics • Nigg proprioception-vibration “new paradigm” • Sagittal plane biomechanics • STJ-axis positionFriday, August 17, 12
  • Less narrow: Tissue Stress • McPoil, Hunt (1995) JOST • Did not consider their theory original • McPoil: “while the tissue stress model is by no means a novel idea” • Meant to replace STJ neutral and Root “compensation” theories for injuriesFriday, August 17, 12
  • Tenets of Tissue Stress Theory 1. Accurately identify the anatomical structure which is injured or symptomatic. 2. Determine the structural and functional characteristics of the individuals foot and lower extremity. 3. Determine the most likely type of abnormal tissue stress which is causing the pathology within the injured anatomical structure (i.e. compression, tension or shearing stress). 4. Design a treatment protocol to reduce the abnormal tissue stresses on the injured structure and reduce the local inflammatory response so that more normal gait and weightbearing function can occur.Friday, August 17, 12
  • Tissue Stress • Empirical observations • Not an explanation • Let’s look deeper!Friday, August 17, 12
  • Conceptual Limitations and Impact of Theories • Humors • Bleeding, leeches & poultices • Bleeding - is good for hemochromatosis • Leeches are good for Dr. Armstrong but nano-worms are on the way • Geocentric vs. Heliocentric • Ptolomaic • Copernican • Galileo - house arrest • Giordano Bruno - staked & burned by Cardinal Belarmine • Evolution v. 7000 year old world • Pierre Teillard de ChardinFriday, August 17, 12
  • Out of Many - One: Unified Theory • Cellular mechanics Nature doesn’t separate disciplines! • Mechanobiology • Tensegrity • Cell surface strain, activation of integrins • Physics • Newton, Hook,Young • Biomechanics • Spring theory • Pulsed forces • Biological systems theory • Enzyme cascade • Receptors (surface)Friday, August 17, 12
  • Friday, August 17, 12
  • Other possibilities (to tissue stress) • Systems biology • Genomics • Cellular Mechanobiology and Energetics (CME) (Cellular Mechanics)Friday, August 17, 12
  • Cells vs. Tissue • All tissues derive from cells, so it is at the cellular level we are likely to find our ultimate solutions. (Pribut 2009)Friday, August 17, 12
  • Let’s Not Forget Wound Care • It isn’t a magic soup you are pouring into the wound • It isn’t chef’s special sauce • There is more too it • Cellular Mechanics plays a large roleFriday, August 17, 12
  • Why look at the cell? “But which is the stone that supports the bridge?” Kublai Khan asks. “The bridge is not supported by one stone or another,” Marco answers, “but by the line of the arch they form.” “Why do you speak to me of stones? It is only the arch that matters to me.” Polo answers: “Without stones there is no arch.” - Italo Calvino (Invisible Cities, 82)Friday, August 17, 12
  • The Cell: Basic Unit of LifeFriday, August 17, 12
  • Cells > Tissues • The cell is to biology what the atom is to chemistry and physics. - after Niels Bohr • “with the cell, biology discovered its atom” - paraphrase of George Henry Lewes (1817-1878)Friday, August 17, 12
  • Cell Doctrine (1838,1839-1859) • All organisms are composed of one or more cells • The cell is the basic unit of organization • All cells come from preexisting ones Virchow and othersFriday, August 17, 12
  • Old Model of Cell Structure • Blob - like a balloon filled with fluid • Alteration in cell membrane shape via external forces have little effect across entirety of cellFriday, August 17, 12
  • Friday, August 17, 12
  • New Model of Cellular Structure • Tensegrity object • Tensional integrity (Kenneth Snelson creator/Buckminster Fuller applellation) • Microtubules (tubulin) • Microfilaments (actin) • Tension in filaments, compression in struts Bendix image: OxfordFriday, August 17, 12
  • Tensegrity • Buckminster Fuller - named it • Kenneth Snelson - made it • Donald Ingber - nailed it - brought it to a theory of the cell The NeedleFriday, August 17, 12
  • Built Like A TentFriday, August 17, 12
  • (A) A high magnification view of a Snelson sculpture with sample compression and tension elements labeled to visualize the tensegrity force balance based on local compression and continuous tension. Ingber D E J Cell Sci 2003;116:1157-1173©2003 by The Company of Biologists LtdFriday, August 17, 12
  • He la cells - CytoskeletonFriday, August 17, 12
  • HeLaFriday, August 17, 12
  • Cellular & Molecular Mechanics • Mechanobiology • Nanotechnology • Chemical Biology • Cellular biomechanicsFriday, August 17, 12
  • Course Study NSF-GEM Summer School 2012 • Introduction to Cell and Molecular Biology • Introduction to Physiology • Cell & Molecular Biomechanics: Basic Mechanics • Introduction to Continuum, Fluid and Solid Mechanics • Continuum & Statistical Mechanics • Molecular Biomechanics • Cell Biomechanics • Tissue and Muscle Biomechanics • Computational Biomechanics • Mechanosensing and Transduction • Musculoskeletal System • Immune System • Cellular/Subcellular LevelsFriday, August 17, 12
  • • Polymerizes into filaments (crosslinks) • Found in all eukaryote cells • Interact with microtubules and intermediate filaments • Polar - point in one direction • First found with myosin in musclesFriday, August 17, 12
  • Spatial Cell Biology: Location, Location, Location • Vectors of reaction • Field effect of gradients, reactions,movements, forces • Interconnectivity and connectivity • A place for everything and everything in the right place • Directionality of transmembrane proteins • Hox genes 56Friday, August 17, 12
  • Fig. 1 The genome as a GPS device. H Y Chang Science 2009;326:1206-1207Published by AAASFriday, August 17, 12
  • New Cell Theory • Not only genes - but physics and chemistry • Dynamic patterns generated by physical and biological systems can yield a “field effect” • Similarities to fields of force (electrical, magnetic, gravitational) • Cell fields sustained by concentration gradient or patterns of dynamic mechanical stress and strain • Field concept: creates discomfort among many biologists The Way of The Cell, 2002 58Friday, August 17, 12
  • Cells as Adaptive Architecture: Intelligent Building Materials • Resilient and adequately strong • Multifunctional • optic, taste, touch, otic, neuro, mechanical • Learn, adapt, self-organize • Move, grow, recover from stresses • Include self-organizing materials (protein conformation, microtubules,) After Ingber, 2011Friday, August 17, 12
  • ECM • More dynamic & versatile than previously thought • Biomechanical properties range from soft and compliant to stiff and rigid • Elasticity & biomechanical properties affect how a cell senses and detects external forces • Focal adhesion complex (FAC) (integrins and signaling proteins) act as a mechanosensor • links cytoskeleton with the ECM • Change in mechanical force alters TGF-β signaling in mouse tendon (Maeda et al., 2011) indicating other signals may also be activatedFriday, August 17, 12
  • ECM Components • Collagen & Elastic Fibers • Glycoproteins • FluidFriday, August 17, 12
  • Cells in ECM • Produce and maintain extracellular matrix • Fibroblasts: form fibers • Migratory: reactionary (immune response) • macrophages (red, orange) • mast cellsFriday, August 17, 12 • Lymphocytes
  • The extracellular matrix: A dynamic niche February 20, 2012 // JCB vol. 196 no. 4 395-406 The Rockefeller University Press, doi: 10.1083/jcb.201102147 © 2012 Lu et al.Friday, August 17, 12
  • ECM Biomechanics • Major factor in cell fate determination • Impact cell differentiation • Affect cell and tissue function • Matrix stiffening affects cell migration • Dynamic and remodels - interacting with cells and cell functionsFriday, August 17, 12
  • Stem Cell Mechanobiology: ECM and the Stem Cell • Impact of matrix stiffness – Hard - bone cell – Soft - fat cell – Medium - muscle cells • Stiffness of ECM – Youngs modulus – Impacts genetic expression 65Friday, August 17, 12
  • Integrins • Transmembrane • Cell attachment to other cells or ECM (celll-cell / cell-ECM) • Stabilize cells and tissues • Remodeling of focal adhesions affects cell shape, gene expression and tissue organisation.Friday, August 17, 12
  • Conformational changes • Alter binding affinity • Possibly force dependent • Enzymes/Proteins linked to cytoskeleton • Mechanics plays largeFriday, August 17, 12
  • • Integrins play a role in cell stiffness detection • Alteration of conformation of cytoskeletonWang et al (2009)Friday, August 17, 12
  • Summary: Integrins • Connect in 2 directions: the ECM to the cytoskeleton and cell membrane to the nucleus • Signal both outside-in and from the inside-out • Detect forces in their environment • Affects the movement of cells • Functional changes: conformation and clustering • Activate tyrosine kinasesFriday, August 17, 12
  • Cell Mechanics • Challenges the “central dogma” which is followed by disease based researchers (biologists, physicians)(DNA-RNA-Protein) • Cell/molecular mechanics is a new concept to researchers and clinicians • Young and developing field • Georgia Tech, Emory, MIT, Harvard - Leaders & LecturersFriday, August 17, 12
  • Cells and fluid shear stress Kamkin A, Kiseleva I, editors. Mechanosensitivity in Cells and Tissues. Moscow: Academia; 2005. Appendix. Available from: http:// • www.ncbi.nlm.nih.gov/books/NBK7500/ Almost all cells respond to fluid shear stress • Most endothelial cells orient in direction of fluid shear (except heart valve endothelial cells and vascular smooth muscle) • Lower cells: dinoflagellates (red tide) - produce phospholuminescence to mild fluid shear • Single cell grouping to form multicellular organisms - cell connectivity (surface receptors) response to shearFriday, August 17, 12
  • Molecular mechanisms for integration of mechanical/adhesive signals. Weber G F et al. J Cell Sci 2011;124:1183-1193©2011 by The Company of Biologists LtdFriday, August 17, 12
  • Mechanotransduction: Recent Theories (after Roger D. Kamm of MIT) • Changes in membrane fluidity and the diffusivity of transmembrane receptors --> receptor clustering (Butler, 2002, Wang, 2004) • Direct mechanical effects on the nuclear membrane, DNA, and gene expression (Ingber) • Stretch-activated ion channels (Gullinsgrud, 2003, 2004) • Force-induced changes in the conformation of load- bearing proteins (Schwartz, 2001, Jiang, 2003, Bao, 2002)Friday, August 17, 12
  • Another -ome • Ominomics - spreading widely and not happily (WSJ Aug 15, 2012) • One more: The “Mechanome” (M. Lang, MIT): • The complete state of stress existing from tissues to cells to molecules • The biological state that results from the distribution of forces • Knowledge of the mechanome requires: • the distribution of force throughout the cell/organ/body • the functional interactions between these stresses and the fundamental biological processes • “Mechanomics” is then the study of how forces are transmitted and the influence they have on biological functionFriday, August 17, 12
  • BoneFriday, August 17, 12
  • Bone • Julius Wolff (1892) • First recognized ability of tissue to adapt to mechanical stresses • Observed trabeculae matched the principal stress lines of bone • How does a force become a cascade of biological signals? • Wolff’s law - old & simplified & narrow but not wrong • Mechanotransduction - new & can be generalizedFriday, August 17, 12
  • Osteocyte: The Mechanosensor • Dynamic fluid flow with higher peak shear stress amplitudes, faster oscillating frequencies, and longer loading durations are optimal for promoting bone formation. • “Structural adaptation of the bone is mediated by loading-induced interstitial fluid flow within the bone microstructure.” • Osteocytes are the central mechanotransducer and mechanosensor • demonstrated that COX-2 mRNA levels are elevated in osteocytes subjected to higher peak shear stress and longer flow durations • RANKL/OPG mRNA levels decreased in response to higher peak shear stress amplitudes, faster oscillating frequencies, and longer flow durations.Friday, August 17, 12
  • Biomechanics • Where does what we know fit in? • Does foot strike and running mechanics play a role? • How do orthotics impact the signal to bone? • What exactly is the signal and how does the signaling work?Friday, August 17, 12
  • Gait Analysis Treadmill: Dream Machine h/p/cosmos Quasar Treadmill about $24,000Friday, August 17, 12
  • Good Vibrations • Just the right amount helps • Too much hurts • Complex signal • Alterations in running cadence, speed, shoe, terrain will alter the input into the musculoskeletal system • Standing waves - augmented wave forms • As Paul Langer mentioned: Barefoot: more variability in step rate, length. Possibly helpful for certain injuries.Friday, August 17, 12
  • Complex Functions: Body & Vibration • Shoe, Surface, Body - have an impact on vibration. In phase and out of phase qualities factor in. • Benno Nigg’s - muscle tuning + bonus • Bessel Functions - wavelike oscillatory behavior or a combination of oscillation & exponential decay or growth • Fourier Transformation - potential filter via soft tissue.Friday, August 17, 12
  • Schematic diagram of how forces applied through the ECM (A) or directly to the cell surface (B) travel to integrin- anchored focal adhesions through matrix attachments or cytoskeletal filaments, respectively F. J. Alenghat et al., Sci. STKE 2002, pe6 (2002) Published by AAASFriday, August 17, 12
  • Relationship Status: “It’s Complicated” Schematic diagram of how forces applied through the ECM or directly to the cell surface travel to integrin-anchored focal adhesions through matrix attachments or cytoskeletal filamentsFriday, August 17, 12
  • Cytokines are a part of the soup many of us are looking for.Friday, August 17, 12
  • Cytokines and Growth Factors Affecting Bone: Stimulators of ResorptionFriday, August 17, 12
  • Cytokines and Growth Factors Affecting Bone: Inhibitors of ResorptionFriday, August 17, 12
  • Cytokines and Growth Factors Affecting Bone: Stimulator of FormationFriday, August 17, 12
  • “Look for something that inhibits destruction and enhances formation” “Then you may find the MSG of cell making soup.”Friday, August 17, 12
  • • Mouse study • Stimulates osteoblast differentiation • Inhibits osteoclast activity (anti-osteoclastogenic) • Osteoprotective • Contrast with alendronate (only inhibits resorption)Friday, August 17, 12
  • SEM3a: Coupling bone synthesis and degradation. Translational medicine: Double protection for weakened bones • Mone Zaidi & Jameel Iqbal Nature 485, 47–48 (03 May 2012) doi:10.1038/485047aFriday, August 17, 12
  • Osteoporosis • Primary – Type I - Post-menopausal (estrogen-induced) • trabecular bone loss > cortical – Type II - Age related • both trabecular and cortical bone loss • Secondary –pharmaceuticals, endocrine disorder, chronic renal disease, immobilization, nutritional, connective tissue disorders 91Friday, August 17, 12
  • Cortical Bone and Aging • Trabecular bone fairs worse • With a decrease in BMD the cortex becomes thinner making for higher fracture riskFriday, August 17, 12
  • Medication: Impact On Injury • Prilosec, Protonix - increase risk of fracture and stress fracture • Fluoroquinones - increase risk of tendon and ligament injury • NSAIDs - questionable connectionFriday, August 17, 12
  • Nutrients, Aging and Bone • Decreased protein intake leads to sarcopenia • Sarcopenia leads to decreased skeletal loading and decreased IGF-1 • Decrease hormones • Vitamin deficiencies • Bone Weakens from Nutrition, Bone and AgingFriday, August 17, 12
  • Bone Healing Stimulators • Utility • Cost • EvolutionFriday, August 17, 12
  • Principles and First Attempts in Stimulating Bone Healing • Pizeoelectric crystal theory • Basset and Becker, Science 1962 • Led to implantable electrodes • Anode/Cathode - tissue destructionFriday, August 17, 12
  • Bone Stimulator: Ultrasound Based • Based on observation and thought that stress was helpful • Actions appear to be based on mechanotransduction • Cannalicular fluid flow stimulates osteocytes (shear forces) • 30 minutes per dayFriday, August 17, 12
  • Problems & Solutions in Bone Healing • Pricing - $3000 • Distribution • Company representatives • eBay • Disposable with built in obsolescence - “number of charges”Friday, August 17, 12
  • US Stimulation of Bone Healing • Yes, it works • Extremely useful delayed union • Jones and other fifth metatarsal base/shaft fracturesFriday, August 17, 12
  • TendonFriday, August 17, 12
  • Tendon: Function & Properties • Attach muscle to bone • Remember: It is a musculoskeletal system • Relatively avascular, slow metabolism 101Friday, August 17, 12
  • Tendon Loading • Transmits the force of contraction to bone • High mechanical loads – 4 times body weight (2600 N) during walking – 8 times body weight (3100–5330 N) during running and jumping • Adaptable 102Friday, August 17, 12
  • Seek Optimal LoadingFriday, August 17, 12
  • et. al. 2004 theoretical framework of strain based fiber reorientationFriday, August 17, 12
  • Does Tendon Hypertrophy With Use? http://biodidac.bio.uottawa.ca/info/regles.htmFriday, August 17, 12
  • “There was a significant difference in CSA along the length of the tendon in both runners (P<0.001) and non-runners (P<0.01) (Fig. 2” (36% greater CSA at distal aspect, but not proximal) 6 male runners ~ 80 km/ week (5 years experience) Control: 6 non runnersFriday, August 17, 12
  • Friday, August 17, 12
  • 10 male runners 10 female runners 10 female non-runners MRI/US examinations (Patellar & Achilles) Men CSA > Women Women trained = untrained Distal patellar and Achilles tendon CSAs were greater than the proximal part in all three groupsWomen seem to exhibit less adaptive response in tendonFriday, August 17, 12
  • Mechanism of Hypertrophy • Possibly increased cross linking between collagen molecules or fibrils • Slow adaptation • Men > Women • Impact of estrogen? Body builder and ROH Wrestler Mike Mondo • Methodology: US v. MRIFriday, August 17, 12
  • What makes tendons pop? • Fluroquinolone: Increase real or illusion? • Sex linked? • Overload when not properly adapted? • CSA & Genetics?Friday, August 17, 12
  • • Between 1991 - 2002 risk increased from 22.1 to 32.6/100,000 (Denmark) • Evaluated within 90 d of use • Fluoroquinolone use -Tripled the risk • Sex-standardized calculationFriday, August 17, 12
  • Friday, August 17, 12
  • • Long term exercise: improves mechanical properties • Immobilisation - weakens mechanical structure •Applied strain affects synthesis of matrix proteins • Set point: • Too low or too high = catabolism • Just right = stimulation for optimal remodelingFriday, August 17, 12
  • • 16 men • Plantar flexion isometric resistance training • Tendon stiffness increases over 2 - 3 month period • Adapts to resistance training slowly, but to detraining rapidly. • Less vigorous than Alfredson protocol • LOWER VOLUME: Less Pain = More GainFriday, August 17, 12
  • Achilles Tendinopathy • Eccentric Stretching (indiscriminately applied) • PRP • Surgery 115Friday, August 17, 12
  • Achilles Tendinopathy • Poultices and Plasters • Leeches • Bleeding 116Friday, August 17, 12
  • • Little evidence in its favor • Researchers need to determine the optimal protocol for preparation and injectionFriday, August 17, 12
  • Is PRP like “Chef’s Special Sauce” • How can we get the right stuff? • Should we throw a blender and a centrifuge at the problem?Friday, August 17, 12
  • Biologist Analysis of Circuit BoardFriday, August 17, 12
  • • all followed at 6, 12, 24 weeks • eccentric stretching + saline or PRP • no significant difference between control and study group Short & Intermediate term: No DifferenceFriday, August 17, 12
  • Am J Sports Med 2011 39: 1623 (online May 21, 2011) • 59.3% (16 patients of 54 randomized) were satisfied with treatment (insignificant difference of -2.7% in treated group) • 56.5% returned to previous sports level (difference +1.8%) • 1 Year Follow UP: No benefit of PRP over placebo Conclusion: A PRP injection in addition to eccentric exercises did not result in clinical improvement or improved structural reorganization after 1 year in chronic mid-portion Achilles tendinopathy compared with a placebo.Friday, August 17, 12
  • Plane of ProgressionFriday, August 17, 12
  • Tendinopathy • Achilles • Posterior tibial (+ deltoid ligament) • Peroneus longus or peroneus brevis • Flexor hallucis longusFriday, August 17, 12
  • FHL Tendinopathy • Causes • Dorsiflexion exercises for plantar fasciitis • Lack of flexion stability in shoe • Flip-flop or open heel shoeFriday, August 17, 12
  • FHL Tendinopathy: Treatment • Stop offending exercises • Toss bad shoes • Strengthening exercises • Use stability shoes • Orthotic to reduce load on tendonFriday, August 17, 12
  • Mechanobiology: What Else Can Be Done? • Nano-delivery of drugs • Biological nano-robotics • Nano-worms/leechesFriday, August 17, 12
  • Synthetic Platelets Model for improved handling of clot in tendon healing? Who you gonna call? Clot Busters! UC Santa Barbara, via Science Daily 2012Friday, August 17, 12
  • Liquid Plumr® for capillaries •Nanoparticles •Biodegradable •Deliver low dose tPA •New method of drug delivery •Could help in diagnosis of location by scanning •Designed to break apart at specific shear level nanoparticles release tPA - shear force trigger (Ingber, 2012) (Wyss Institute of Harvard)Friday, August 17, 12
  • Casts • Plaster • Polymer resin • Cam Walkers / Pneumatic Cast BootFriday, August 17, 12
  • Plaster • Gypsum (Calcium sulfate) • Gives off heat when mixed with water forming a dihydrate: 2CaSO4.½H2O(s) + 3H2O(l)  = 2CaSO4.2H2O(s) • Easily decorated • Not stable when wet. Not very strong • Smells, skin irritation, muscle atrophy, itchy, panic attacks Heather Tomkins, anatomical drawing on a plaster cast. via boingboingFriday, August 17, 12
  • Plastic Resin Polymers • “Fiberglass” - reinforced polymers for improved strength • Lighter, stronger, water resistant • Decorator colors • Similar problems to Plaster re: hygieneFriday, August 17, 12
  • Pneumatic Walking Cast • Previous materials • Plaster • Plastic polymer resin (fiberglass) • Solved - much of “Cast Disease” • Allows exerciseFriday, August 17, 12
  • Pneumatic Cast Boot: Problems • Occlusive • Over-inflated too often • Skin rashes - allergy to materials, fibers • Nerve damage from compression • Affects balance • Limb length related problems - back, other joints • axis alignment not correct: other painsFriday, August 17, 12
  • Fixing The Boot • Breathable material • Feedback system to prevent over-inflation • Material testing to avoid fiber shards. (Breathability improvement less moisture and leaching of materials from lining) • Limb length equalizers to be dispensed with boot • Find a better way to align with ankle axis • Production facility - stability, compliance with standardsFriday, August 17, 12
  • Answers to 4 Questions • Does eccentric • Sometimes stretching work? • Why didn’t PRP work • Eccentric better than saline for stretching Achilles tendinopathy? • Mechanics • How does ultrasound and fluid stimulate bone healing? shear • Does mechanics play a • Yes, indeed role in healing?Friday, August 17, 12
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  • After Lecture:Friday, August 17, 12
  • Ingber: View of Modern Biomechanics • “we still have no conceptual framework that embraces basic paradigms of biology together with physical principles such as conservation of mass, momentum and energy” • “we lack a comprehensive theory that permits prediction of the many shapes, material properties, motions, and fluxes that are encountered in the living world” Fredberg, Discher, Ingber et. al.. Biomechanics: cell research and applications for the next decade. Ann Biomed Eng. 2009 May, 37(5) 847-859Friday, August 17, 12
  • New Rules for Orthotics ● Problem specific planning ● Conform well or appropriately to the foot ● Be made over a 3D image or model of the foot ● Alter the application of forces as determined to be appropriate for the clinical problem. ● Be based on an examination of both the static and dynamic biomechanics, kinetics and kinematics (as much as is possible.) ● Take into account the requirements of the individual, sport, environment, and foot wear.Friday, August 17, 12
  • Cell Rules • Mechanotransduction Unit - Cell + ECM • Reset cellular activity by alteration of biomechanical forces • Impact via – Mechanics – Diet – Genetics – Hormonal considerations – Cell signaling biochemistry 142Friday, August 17, 12
  • Mechanics and Mechanotransduction Encyclopedia of Biomaterials and Biomedical Engineering, 2008, p.1783-1793, Taylor & Francis)Friday, August 17, 12