Osteoarthritis (OA)

Osteoarthritis (OA) OrDegenerative Joint DiseaseDEFINATIONOsteo : Related to bone systemArthritis : Arthro + itis Joint Inflammation Condition in which one/ more joints are inflamed So OA is a condition in which one or more joints are inflamed involving the loss of cartilage

It is progressive disorder of joints which is caused by gradual loss of cartilage resulting in development of bony spurs and crysts at the margins of the joints.

In addition to damage and loss of articular cartilage, there is remodelling of subarticular bone, osteophyte formation, ligamentous laxity, weakening of periarticular muscles, and, in some cases, synovial inflammation

These changes may occur as a result of an imbalance in the equilibrium between the breakdown and repair of joint tissue

The most common joints involved Distal Interphalangeal joints Proximal Interphalangeal joints Carpometacarpal joints of thumb Weight Bearing joints (Hip, knee) Metatarsophalangeal joints of the foot Cervicle and lumbar vartebrae

The articular cartilage is slippery tissue that covers the end of the bones in the joints

Healthy cartilage allows bones to glid over each other & helps to absorb shock of movement

In OA the top layer of cartilage breaks down and wear awayRubbing of bones under the cartilage Due to which there isPain Swelling Loss of motion of joints Over the time joint may lose its normal shape and also there is growth of bony spurs on the edge of the joint Bits of bones/cartilage can break off and float inside the joint space Which cause more pain and damage

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So in OA there is progressive distruction of articular cartilage and also there is involvement of Diarthrodial joint Synovium Capsule Subchondral bone Surrounding ligaments Muscles

Changes in structure and function of this tissues leads to clinical Osteoarthritis Which is characterized by Joint pain Tenderness Decrease range of motion Weakness Joint instability Disability

Classification Primary OA Secondary OA (idiopathic) (Due to some other disease) A. LocalisedHandsHipKneeSpine B. GeneralisedSmall jointsLarge jointsMixed C. Erosive osteoarthritis

Congenital and developmental disorders, bone dysplasias

ii) Post-surgery / injury meniscectomy

iii) Endocrine acromegaly, iv) Metabolic hemachromatosis, ochronosis, Marfan syndrome, Ehler-Danlos syndrome, Paget disease, gout, pseudogout, Wilsons disease, Hurler disease, Gaucher disease

v) Rheumatologic rheumatoid arthritis

vi) Neurological Charcot joints.

EpidemiologyOA is one of the core reason for disabilityNearly everyone who lives long is affected by OA at any point of life, most probably after the age of 55 to 60.

Approximately 15% of population is affected by OA 50 % of those 85% of those over 65 age over 75 age

OA is most widely assessed in studies using the Kellgren and Lawrence (K&L) score.

The overall grades of severity are determined from 0 to 4 and are related to the presumed sequential appearance of osteophytes, joint space loss, sclerosis and cysts

The World Health Organization (WHO) adopted these criteria as the standard for epidemiological studies on OA

Prevalence of osteoarthritis varies with AgeGenderGeneticsEthic GroupSpecific Joint InvolvedMethod For Diagnosis

AGEWith increasing age the prevalence OA also increases

Generally for person age 25 75,prevalence is estimated 12%and for those with age over 70, it is 60 70% affectet

Hip OA AGE Hand OA Age : 30 40 Age : >70 Knee OA Age : 40 Age : 80 Pre : 1.6 % Pre : 14% Pre: 5% Pre : 65% Age : >25 Age : 55 Pre : 5% Pre : 12%

Gender Age > 50 Age >60 Men are more affacted Women are more affacted(26%) Due to higher rate of sports and Due to repeated use of Injuries weight bearing joints

Genetics Pre : 9% Pre : 4% White population Black & Asian population

Prevalence of OA is 22% to 39% in India

EtiologyThe etiology of OA is multifactorial

Many patients have more than one risk factor for developing the OA.

The most common risk factor for the development of OA includes Obesity Occupation Participation in certain sports (Often) History of joint trauma Genetic Age Sex Bone density Joint location

ObesityIncreased body weight is strongly associated with hip, knee, and hand OAObesity often precedes OA and contributes to its development,rather than occurring as a result of inactivity from joint pain In a three-decade Framingham Study, the highest quintile of body mass was associated with a higher relative risk of knee OA (relative risk of 1.5 to 1.9 for men and 2.1 to 3.2 for women).

The risk of developing OA increases by about 10% with each additional kilogram of weight, and in obese persons without OA, weight loss of even 5 kg decreases the risk of future knee OA by one-half.

Recent data suggest that OA is associated with the metabolic syndrome, suggesting a possible common pathogenic mechanism involving metabolic abnormalities and systemic Inflammation.

It is also likely that vascular disease may both initiate and hasten disease progression in OA.

This could be due to venous occlusion, stasis or microembolic disease leading to episodic reduction in blood flow through small vessels within the subchondral bone.

Subchondral ischaemia may subsequently reduce nutrient delivery and gas exchange to articular cartilage in addition to direct deleterious effects on the bone itself.

OccupationThere is increased risk of OA for those who are in occupation requiring Prolong Standing Kneeling Squatting Lifting/Moving Heavy Objects Miming Factory Work Car painteryRepetitive motion also contributes to hand OA with dominant hand usually affected

Risk OA depends on type and intensity of physical activity

SportsDamage to articular cartilage due to sports greatly increase the risk of OA

Meniscal damage (common in athlete) also increase the risk of knee OA

1.Because of loss of proper load bearing and shock absorption2.Increase focal load on cartilage and subchondral bones

TraumaAGE AT INJURY DOSE MATTER

As older individuals who damage ligaments tends to develope OA more rapidly than young people with similar injury

Trauma early in life Increased risk of OA

Genetic FactorsA number of recent studies discovered the presence of over 80 gene mutations involved in the pathogenesis of OA ,among which the most relevant one is a single nucleotide polymorphism.

This one, called rs143383 and located in the 3' untranslated region (3'UTR) of the growth and differentiation factor 5 gene (GDF5), is responsible for the development, maintenance and repair ofsynovial joints

Genes for Vitamin D receptors (VDR) and insulin-like growth factor 1(IGF-1) also seem to be involved in the patho-physiologic pathways of OA

It also includes genes related to inflaamation,bone morphogenetic protiens, protease/ its inhibitors

Pathophysiology

Normal Articular Cartilage

Articular Cartilage PossessesViscoelastic Properties Which provides 1. Lubrication With Motion 2. Shock absorbency during rapid movement 3. Load Support

In Synovial joints Articular cartilage is found between synovial cavity on one side and narrow layer of calcified tissue overlying subchondral bone on onther side

Charactristics of Articular Cartilage

1.Cartilage is easily compressed lossing up to 40% of its original hight when load is applied Compression increase area of contact Disperse force more evenly to undelying bone,tendon, ligament, muscles

2.Cartilage is frictionless

Togather with compresibility , this enables smooth movement in joint and distributes load across joint tissue to prevent damage and stabilize the joint

Structure of Cartilage

Cartilage is having1.Strength2.Low co-efficiant of friction 3.CopressiblityThese all is derived from its unique structure

So,the cartilage is composed of complex, hydrophilic , Extra- cellular matrix

It contains 75% to 85% Water 2% to 5% Chondrocytes (the only cell in cartilage) Collagen Protiens Proteoglycans Hyaluronic Acid Molecules

Two Major Structure of CartilageType II CollagenTightly woven, triple helical structure which provides TENSILE STRENGTH to cartilage AggrecansIn which there is Proteoglycan linked with hyluronic acid, having negative charge.The strong electrostatic repulsion of proteoglycan gives cartilage the ability to withstand further compression

Normal Cartilage turn overHelps repair and restore cartilageRespond to usual demand of loading and physical activity

In healthy adult cartilage chondrocyte metabolism is slow with dynamic balance between anabolic process

Metabolism is premoted byGroth factors - Bone morphogenetic protien 2 - Insulin like groth factor-1 - tranforming growth factor2. CatabolismProteolysis Stimulated by MMPs, TNF-, Interlukein-1, Other cytokines

Joint Protective Mechanisms1.Muscle Bridging The Joints2.Sensory receprtors in feedback loops to regulate muscle and tondon function3. Supporting ligaments4. Subchondral bones having shock absorbent properties

NoteArticular cartilge is avascular and aneural and chondrocytes are nourised by synovial fluid

OA CartilageOA begins with damage to articular cartilage, which is due toTrauma or other injuryExcess joint loading by obesity / other reasonInstability or injury of the joint that causes abnormal loading

Devlopement of OA is due toLocal mechanical influenceGenetic factorInflammationChondrocyte functionWhich leads to loss of articular cartilage

When there is damage to articular cartilageIncrease activity of chondrocytes to remove and repair the damage

Depending on degree of damage the balance between breakdown and resynthesis of cartilage can be lost Which leads to increase breakdown of cartilage Ultimately, loss of cartilage

Destruction of aggrecans by proteolytic enzyme is consider to play a key role

There is also involvement of collagen receptors named DDR-2 , located on chodrocyte cell surface

In healthy cartilage ,DDR-2 is inactive ,which is masked by aggrecan from contact with collegen

Damage to cartilage Triggers aggrecan destructionExposure of DDR-2 to collagenActive DDR-2 increase activity of MMP-13Which destroy collagenCollagen breakdown products further stimulate DDR-2,in whichmore collagen is destroyed

Huge research work has been done on genes involved in OA which shows thatIn OA , expression of hundreds of genes of cartilage tissue are affected which alters chondrocyte phenotype

In addition to articular cartilage there is also role of subchondral bone in OA

In OA , subchondral bone release vasoactive peptides and MMPs

Neovascularization and subsequent increase in permeability of the adjacent cartilage occurs and contributes to further cartilage loss

Substantial loss of cartilage cause joint space narrowing and leads to painful and deformed joints

The remaining catilage softens and devlopes fibrillation(Verticle cleft ) and there is splittting and further loss of cartilage and exposure of underlying bone

As cartilage is destroyed and the adgecent subchondral bone undergoes pathologic changes, cartilage is eroded completely, leaving denuded subchondral bone which becomes dence , smooth and glistening

A more brittle, stiffer bone results, with decreased weight-bearing ability and development of sclerosis and microfractures

The joint capsule and synovium also show pathologic changesin OA.

Inflammation, noted clinically as synovitis, may resultfrom release of inflammatory mediators from chondrocytes, such as prostaglandins

Inflammation is localized to the affected joint, in contrast to that seen in rheumatoid or other inflammatory arthritides.

The pain in OA is not due to distruction of cartilage but arise from the activation of nociceptive nerve ending within the joint by mechanical and chemical irritants

So,the slow progressive changes in OA consist of an increase in water content, loss of PG, and reduction of PG aggregates of cartilage.

The cartilage is subsequently unable to repair itself.

Alterations in metabolism of subchondral bone adjacent to articular cartilage appear necessary for continued cartilage destruction.

Eventually, progressive loss of articular cartilage and increasing subchondral sclerosis lead to an abnormal and painful joint.

AgeUsually elderly

GenderAge 45 more common in women

SymptomsPainDeep, aching characterPain on motionPain with motion early in diseasePain with rest late in disease

Stiffness in affected jointsResolves with motion, recurs with restUsually