Download - SHAAZ SYNVISC-ONE 2.ppt
KNEE OSTEOARTHRITIS
MOHAMMED SHAAZ RAFIQUE
BRIEF ABOUT JOINTS JOINTS CLASSIFICATION:
1) Fibrous (synarthrosis)cranial bones2) Cartilaginous(amphiarthrosis) spine3) Synovial (diarhtrosis) knee
CARTILAGE TYPES:1) Hyaline cartilage2) Elastic cartilage3) Fibrous cartilage
HYALINE ARTICULAR CARTILAGE Bone ends covered by hyaline articular cartilageI. CELLULAR COMPONENTII. EXTRACELLULAR COMPONENT
I. CELLULAR COMPONENT Chondrocytes: cartilage cells producing matrix Present in: cavitites in matrix ‘cartilage lacunae’ Contains: clear protoplasm + 1-2 nuclei
II. EXTRACELLULAR COMPONENTa) Water (70-80%)b) Collagen(10-20%) compressive strength
c) Proteoglycans(10-20%) attract water(hydration)
HYALINE ARTICULAR CARTILAGE
FEATURES & ROLE: High quality thin layer 2-4mm No nerve fibres nutrition from synovial fluid Covers bone ends slide against each other Decreases friction Load distrution Exhibits stress shielding:• High water content(incompressible)• Structural organisation of collagen &
proteoglycans
HYALINE ARTICULAR CARTILAGE
ELASTIC & FIBROUS CARTILAGEELASTIC CARTILAGE (yellow cartilage)Elastin elastic bundlesTissue is elastic yet tuffEx: pinna of ear
FIBROUS CARTILAGE (white cartilage)in areas of high tensile strength & supportContains type I & II collagenEx: intervertebral discInjury: hylaline cartilage fibrous cartilage
NEWTONIAN VS NON-NEWTONIAN FLUID
NEWTONIAN FLUID NON-NEWTONIAN FLUID
Linearly viscous throughout Not linearly viscous
Obey Newton's law of viscosity
•viscosity independant of shear rate
Don’t obey Newton's law of viscosity
Example:• all gases•Liquids like water, benzene, ethyl alcohol
Example:•Complex mixtures like pastes, gels•Synovial fluid
SYNOVIAL FLUID Non newtonian fluid Exhibits thixotropic properties: viscosity(thinning) ROLE:1) Shock absorptioni. High frequency impact (shock)• Synovial fluid thick• Entangled molecular network:a) Resists deformation b) shock absorption• Energy stored as elasticity
ii. Low frequency movement• Viscosity thins out to normal lubrication• Thus decrease friction• Molecules aligned in direction of movement• Energy dissipated as viscous flow
2) Nutrient & waste transportation• Supplies oxygen & nutrients• Removes carbon dioxide & metabolic wastes
SYNOVIAL FLUID
COMPOSITION:Type A cells remove wear-tear debris Type B cells produce synovial fluid:
• HA(3mg/ml) halocytes in synovial membrane• Lubricin boundary layer lubrication• Disaccharide units:Na D-glucoronate acetyl-D-glucosamine
SYNOVIAL FLUID
B glycosic bonds
It is degenerative joint disease Most common type of osteoarthritisOne of the top 5 disabling conditions that affects
more than 1/3rd persons above 65 years
KNEE OSTEOARTHRITIS
GRADING OF KNEE OSTEOARTHRITIS
GRADE CLASSIFICATION DESCRIPTION
0 NORMAL No features of OA
1 DOUBTFUL Minute osteophyte
2 MILD Definitive osteophyte
3 MODERATE Moderate joint space reduction
4 SEVERE Joint space highly reduced
CAUSES OF OA Age:• idiopathic OA (>50years)• secondary OA (younger patients) Genetic Obesity Mechanical • joint overuse• misalignment
Decrease in HA
CAUSES OF OA
Increase in low MW HA
Change in viscosity & elasticity
Cartilage degradation & inflammation
GOALS OF TREATMENTRelieve painImprove physical conditioningImprove joint biomechanicsImprove muscle strengthSlow disease progressionPreserve functional independenceImprove quality of life
TREATMENT OPTIONS1) Non Pharmacological treatment2) Pharmacological treatment3) Surgery
NON PHARMACOLOGICAL TREATMENT
i. Exercise• Muscle strengthening • Aerobic • Aquatic/hydrotherapy• Tai Chi programii. Foot orthoses or Knee bracing (realignment)iii. Traditional Chinese Accupunctureiv. Weight lossv. Dietary supplements with glucosamine sulphate
PHARMACOLOGICAL TREATMENTI. Acetaminophen/ParacetamolII. NSAIDS/COX 2 inhibitorsIII. OpioidsIV. Topical analgesicsIV. Oral nutritional supplements:• Chondroitin Sulphate• Glucosamine SulphateV. Intra-articular injections• Corticosteroids• Viscosupplements
NSAIDS/COX-2 INHIBITORSMild to moderate pain & inflammationEx: ibuprofen, ketoprofenLimitations: GI bleeding, renal toxcity, CV risksEsomeprazole 20/40mg prevention of GI effectsCOX-2 inhibitors suggested (etoricoxib)Preference:NSAIDS/COX-2 inhibitors to paracetamol
INTRA-ARTICULAR CORTICOSTEROIDS• Acute knee pain & inflammation• Short lived effects (6weeks)• Repeated use accelerate cartilage degradation• Example: a) Prednisoloneb) Methylprednisolonec) Betamethasone
INTRA-ARTICULAR VISCOSUPPLEMENTS Approved by USFDA for treatment of OA since 1997
AVERAGE MW(million daltons)
ELASTICITY(Pa at 2.5Hz)
VISCOSITY(Pa at 2.5Hz)
HEALTHY SYNOVIAL FLUID
6 117 45
HYLAN G-F 20 6 111 25
LOW MW VISCOSUPPLEMENT
0.5-3-6 0.8-92 3-46
OSTEOARTHRITIC SYNOVIAL FLUID
1.1-2 1.9 1.1-1.9
SURGERYPreferred in advanced stage of diseaseExtensive deterioration Other options exhaustedPositive improved quality of lifeNegative costly, invasive, indicated for end stage
PREVALENCE OF MSK DISORDERS
YEARS PUNE (%) BHIGWAN (%) INDIA (%)
35-44 18.8 18.8 19.2
45-54 19.3 12.1 12.7
55-64 13.9 8.9 8.5
>65 6.6 6.6 7.4
http://bjdindia.org/PuneCPD09Jrheum.pdf
PREVALENCE OF KNEE PAIN/OA
PUNE (%) BHIGWAN (%)
KNEE PAIN 8 10/16
KNEE OSTEOARTHRITIS 6 4
YEAR MAXIMUM CASES OF KNEE OA IN AGE GROUP
1990’S >65 years
2010 45-65 years
INDIA: OA most frequent joint disease with prevalence of 22-39%
DEMOGRAPHICSFemales : most affected (63.1%)Maximum patients in age group 40-60 years(59.5%)Most patients had OA of: Back (50%) followed by
Knee and hips(14.3%)
ROLE OF HYALURONIC ACID (HA)
Surround & protect synovial tissue Protect mechanical damage of collagen cartilage Act as a lubricant Act as a shock absorber
VISCOSUPPLEMENT
VISCOSUPPLEMENT Product which replaces synovial fluid & has
similar rheological properties
Ideal features:• Tissue & blood compatible• Similar rheological properties• Permeable to metabolites & macromolecules• Improved half life for extended protection• Less injections patient compliance
Main objective:• Increase elasticity & viscosity • Decrease pain & increase joint mobility
MOA:• Analgesic : nociceptor activity & sensitivity• “Barrier Effect”• By providing elastoviscous protective barrier
around nociceptive fibres in matrix• Barrier decreases pain receptor activity• Restoration of elastoviscous properties to protect
cells
VISCOSUPPLEMENTATION
HYLAN G-F 20
Only high MW viscosupplement closest to natural synovial fluid: * MW *Elasticity *ViscosityComposed of:
HYLAN A HYLAN B
Fluid Gel
80 20
In buffered physiological NaCl solution (pH 7.2 ± 0.3)
PHARMACOKINETICS
Removed slowly from injection siteAfter reaching systemic circulation, rapidly taken up by hepatic endothelial cellsFirst order kinetics component A & BHalf life in systemic circulation : 30 minutesMore than 95% dose cleared after 4 weeksNo accumulation in blood/ major organs
HYLAN G-F 20
COMPETITORS
BRAND MANUFACTURED BY ACTIVE INGREDIENT
1 SYNJECT Gland Pharma Limited Na Hyaluronate
2 HALONIX CadilaPharmaceuticals Limited Na Hyaluronate
3 LG HYRUAN LG Life Sciences Limited Na Hyaluronate
Common approaches:o Superolateral (straight knee)o Inferolateral (flexed knee)o Anteromedial (flexed knee)o Superomedial (straight knee)o Lateral mid-patellaro Medial mid-patellar
ADMINISTRATION
TREATMENT OPTIONS1) Non Pharmacological treatment2) Pharmacological treatment3) Surgery
NON PHARMACOLOGICAL TREATMENT
i. Exercise• Muscle strengthening • Aerobic • Aquatic/hydrotherapyii. Knee bracing (realignment)iii. Accupunctureiv. Weight lossv. Dietary supplements with glucosamine sulphate
PHARMACOLOGICAL TREATMENTI. Acetaminophen/ParacetamolII. NSAIDS/COX 2 inhibitorsIII. OpioidsIV. Topical analgesicsV. Intra-articular injections• Corticosteroids• Viscosupplements
ACETAMINOPHEN/NSAIDs/OPIOIDSUsed in initial phase of OAAcetaminophen most commonly prescribedSimilar efficacy to NSAIDs ibuprofenEsomeprazole prevention of GI effectsCOX-2 inhibitors suggested (etoricoxib)Preference:NSAIDS/COX-2 inhibitors to paracetamolNarcotics not prescribed for mild-moderate painReserved: failed other means & NSAIDs
contraindicated(tramadol hydrochlroride)
INTRA-ARTICULAR CORTICOSTEROIDS• Acute knee pain & inflammation• Short lived effects (2-6weeks)• Repeated use accelerate cartilage degradation• Example: a) Methylprednisoloneb) Prednisolonec) Betamethasone
NUTRACEUTICALSGlucosamine & Chondroitin sulphateMOA: collagen synthesis production of inflammatory prostaglandinsEffective in modulation of OA except severe casesOther examples: collagen hydrosylate, diacerein
BRACINGFor young patients with active lifestyle Delay surgeryProper realignment
TOPICAL TREATMENTFor short term reliefExamples:• Diclofenac sodium• Lidocaine topical• Capsaicin• SalicylateGI complications, MI, stroke seen
ACCUPUNCTURETypes:• True accupunture• Electrical stimulation
Variable record of efficacy:• Pain relief• Improvement of function
PULSED ELECTRICAL STIMULATIONMOA: facilitate chondrocytes in synthesis of
glucosaminoglycan & type II collgen
83% treated able to defer anthroplasty for 1 year60% treated able to defer anthroplasty for4years
Poor patient compliance
PHYSICAL THERAPYBackbone of multimodal approachExcellent 1st line treatment without side effectsMOA: • restores pliability• range of motion to jointsThus improvement in joint mechanics & function
Main objective:• Increase elasticity & viscosity • Decrease pain & increase joint mobility
MOA:• Analgesic : nociceptor activity & sensitivity• “Barrier Effect”• By providing elastoviscous protective barrier
around nociceptive fibres in matrix• Barrier decreases pain receptor activity• Restoration of elastoviscous properties to protect
cells
VISCOSUPPLEMENT
Low mw viscosupplement: average half life in joint 20 hours High mw viscosupplement average half life in joint 30 days
VISCOSUPPLEMENT
KEY LEARNINGS 70% patients with mild-moderate knee OA can be treated with
Multimodal Pyramid Approach good to excellent efficacy (not only delays TKR but at time makes it unnecessary)
Injected modalities best modality:• IA steroids anti-inflammatory effect• IA viscosupplements anti-inflammatory effect
improved joint functions