and

present

The pathophysiology of osteoarthritisThe pathophysiology of osteoarthritis

A few useful definitions and reminders

Société Française de rhumatologie website: http://www.rhumatologie.asso.fr/04-Rhumatismes/grandes-maladies/0B-dossier-arthrose/A0_definition.aspSellam J, Berenbaum F. Arthrose et Obésité. Rev Prat 2012;62:621-629.

Osteoarthritis is characterised by cartilage loss combined with synovial tissue thickening and subchondral bone osteosclerosis

Other than the spine, osteoarthritis most commonly affects the knees, hands and hips

Osteoarthritis is a common complex disorder with multiple hereditary, constitutional and environmental risk factors

Cartilage degeneration is not simply an age-related process, osteoarthritis is an individual disease entity and has both inflammatory and mechanical features.

Obesity increases the risk of osteoarthritis in the legs and fingers

2

Spine Knee Hands Hip

3

Hip-femoral osteoarthritis. Right hip arthrography, frontal image.

Cervical spine. T2 MRI.

Internal and external femorotibial osteoarthritis. Knee CT-arthrography.

MRI of the left hand, T2 weighted sequences, coronal image after saturation of the fat signal.

Cartilage and chondrocyte

Cartilage is a very specific type of dense connective tissue Non vascularised: it draws its nutrients by a process of diffusion

from the synovial fluid secreted by the synovial membrane and the subchondral bone.

Not innervated: it cannot therefore be held directly responsible for the pain experienced by osteoarthritis sufferers

Cartilage consists of a single type of cell, chondrocytes,embedded in the matrix they create

Société Française de rhumatologie website: http://www.rhumatologie.asso.fr/04-Rhumatismes/grandes-maladies/0B-dossier-arthrose/A0_definition.asp

Under normal conditions, chondrocytes have low metabolic activity whichis mainly confined to breaking down various elements in the matrix(proteoglycans and collagen) and to renewing these same matrix components

4

Healthy knee cartilage

Osteoarthritis: a separate disease entity

Osteoarthritis is not simply the result of normal ageing and excessive pressure on a joint

It is caused by a variety of factors: Local, mechanical factors General (heriditary) and systemic factors (e.g. adipokines) And in some cases, trauma

It involves changes in all joint tissues: cartilage, the subchondral bone (which could play an even more important role in this pathophysiology), the articular capsule and the synovial membrane

Sellam J, Berenbaum F. Arthrose et Obésité. Rev Prat 2012;62:621-629.5

Osteoarthritis: the disease process (1)

Excessive pressure on the cartilage: Chondrocytes are activated via pressure-sensitive

membrane receptors (mechanoreceptors) Inflammation mediators are released The cartilage matrix deteriorates

Société Française de rhumatologie website: http://www.rhumatologie.asso.fr/04-Rhumatismes/grandes-maladies/0B-dossier-arthrose/A0_definition.aspSellam J, Berenbaum F. Arthrose et Obésité. Rev Prat 2012;62:621-629.

6

The 3 features in osteoarthritis are: Degradation of the cartilage matrix

Inflammatory reaction in the synovial membrane, often accompanied by joint effusion

Reaction in the subchondral bone with proliferation of neosynthesised bone: osteophytes (hypertrophic formation)

Société Française de rhumatologie website: http://www.rhumatologie.asso.fr/04-Rhumatismes/grandes-maladies/0B-dossier-arthrose/A0_definition.aspSellam J, Berenbaum F. Arthrose et Obésité. Rev Prat 2012;62:621-629.7

Osteoarthritis: the disease process (2)

Shoulder osteoarthritis with moderate gleno-humeral joint space

narrowing and osteophyte on the lower surface of the humeral head.

Knee osteoarthritis, tibial edema and synovial inflammation. FSE T2

sagittal slices.

Mechanical osteoarthritis

Excessive weight: obesity or frequent heavy load-bearing (workplace or sport [e.g. football, weight-lifting])

Joint overload and repeated microtrauma Unevenly distributed pressure: dysplasia,

meniscectomy, malalignement (genu varum or genu valgum)

Knee instability: ligament hypermobility, cruciate ligament rupture, particularly of the anterior ligament, or a poorly managed sprain, etc.

Société Française de rhumatologie website: http://www.rhumatologie.asso.fr/04-Rhumatismes/grandes-maladies/0B-dossier-arthrose/A0_definition.asp8

Subchondral cyst under the insertion of the posterior cruciate ligament. FSE T2

sequence in sagittal plane.

Some cases of osteoarthritis are mainly mechanical in origin (caused by excessive pressure on part or all of the joint):

Secondary osteoarthritis

Diseases directly affecting the cartilage: for example: crystalline particles in the cartilage - urate crystals (gout) or calcium deposits (chondrocalcinosis); genetic hemochromatosis; ochronosis (very rare); and genetic disorders which weaken the structures in the cartilage (proteoglycans or collagen)

Disease affecting other joint tissues with an indirect impact on the cartilage, especially: disorders of the subchondral bone, such as aseptic

osteonecrosis, synovial membrane disorders, joint infections even once cured,

or synovial inflammation, for instance rheumatoid arthritis

Société Française de rhumatologie website: http://www.rhumatologie.asso.fr/04-Rhumatismes/grandes-maladies/0B-dossier-arthrose/A0_definition.asp9

Osteonecrosis of the femoral head in a patient with hip

osteoarthritis.

Osteoarthritis and Obesity

Obesity is a predisposing factor for osteoarthritis: via mechanical constraints linked to excess weight which

trigger chondrocyte activation (see following slides, 10 and 11) and no doubt also through the production of cytokines in the

fatty tissue which enter the bloodstream and have an effect on the joint tissues. This could explain the higher incidence of finger osteoarthritis in obese patients

This is best illustrated by osteoarthritis of the fingers, which is more common in overweight or obese patients

The risk of knee osteoarthritis increases by 15% for every point increase in the BMI

Sellam J, Berenbaum F. Arthrose et Obésité. Rev Prat 2012;62:621-629.10

Frontal image of advanced patellofemoral knee

osteoarthritis.

Osteoarthritis and fatty tissue

Fatty tissue, particularly abdominal fat, plays a rolein systemic inflammation by secreting specific cytokines called adipokines (adiponectin, leptin and resistin)

Adipokines have potent immunomodulating effects and are found in the synovial fluid of patients with osteoarthritis

The Hoffa fat pad, located immediately behind the patellar tendon, may also produce adipokines. These adipokines can migrate directly into the synovial fluid

11Sellam J, Berenbaum F. Arthrose et Obésité. Rev Prat 2012;62:621-629.

A new concept: "metabolic osteoarthritis"

The concept of metabolic osteoarthritis emerged afterthe following were observed: There is an epidemiological link between

osteoarthritis and type 2 diabetes andbetween osteoarthritis and metabolicsyndrome or each of its individualcomponents (abdominal obesity,hyperglycemia and dyslipidemia)

The incidence of knee osteoarthritis is higherin obese patients concomitantly presentingwith one or more features of metabolicsyndrome

Therefore, younger patients with osteoarthritis should be screened for a cardiometabolic disease (metabolic syndrome or type 2 diabetes)

12 Sellam J, Berenbaum F. Arthrose et Obésité. Rev Prat 2012;62:621-629.

The concept of metabolic osteoarthritis (according to Sellam 2012)

Knee osteoarthritis and trauma

In addition to age and excess weight, the risk factors for knee osteoarthritis which must also be taken into consideration include trauma, particularly: Meniscus injury Anterior cruciate ligament rupture, causing anterior

knee placing undue mechanical stresson the medial tibio-femoral compartment and causing premature wear

Joint fracture

Prevention: The most conservative possible treatment of meniscus

injury, given the increased risk of knee osteoarthritis after meniscectomy, therefore in this case, no meniscectomy after the age of 40

Surgical repair of the ACL will not prevent the subsequent development of osteoarthritis

13 La Revue du Praticien 2012; 62: 621-629, Situations à risque d’arthrose du genou. Charles-Henri Flouzat-Lachaniette.

Bilateral femorotibial knee osteoarthritis. Arthrography.

Osteoarthritis and physical exercise

When repeatedly exposed to extreme stress, the knee may develop osteoarthritis

Professions at higher risk of knee osteoarthritis: mainly construction workers who often work in a crouched positionor kneeling (knee hyperflexion, leading to meniscal injury and osteoarthritis)

Sport and osteoarthritis: moderate physical exercise does not increase the risk of osteoarthritis. Intense sporting activity can increase this risk through injury (joint fractures and meniscalor ligament injury) and repeated microtrauma

14 La Revue du Praticien 2012; 62: 621-629, Situations à risque d’arthrose du genou. Charles-Henri Flouzat-Lachaniette.

CONCLUSION

Osteoarthritis is not a simple age-related disease caused by wear and tear on weight-bearing joints.It is characterised by low-grade tissue inflammation

It is a disorder with a demonstrated systemic component in some forms, potentially involving the fatty tissue and the adipokines it secretes

The main risk factors are age, obesityand repeated microtrauma

15Femorotibial and patellar knee osteoarthritis. Arthrography.