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