EARLY DIAGNOSIS OF OSTEOARTHRITIS_76_05_11

EARLY DIAGNOSIS OF OSTEOARTHRITIS WHY AND HOW ?

Francis BERENBAUM Pierre et Marie Curie University Saint-Antoine Hospital, AP-HP, Paris May 27, 2011 EULAR London

THE TWO MAIN CLINICAL FEATURES OF OSTEOARTHRITIS

•PAIN •IMPAIRMENT OF FUNCTION / DISABILITY

2011

• • • •

Population-based cohort study n=1163 (southwest England) , >35 years old with knee or hip symptomatic Mean follow-up : 14 years Comparison with general population, same age and gender (SMR:standardized mortality ratios)

Excess mortality in OA patients, mainly due to CV events and dementia.

Associations between characteristics at baseline and all cause mortality up to 15 years Walking disability : independent risk factor for death

Nuesch et al. BMJ 2011

OSTEOARTHRITIS

NORMAL

OSTEOARTHRITIS Subchondral cyst Cartilage

Capsule

Synovial membrane

Subchondral osteosclerosis

Cartilage loss

Synovitis Osteophyte Cartilage erosion

Thickening of the capsule Os sous-chondral

Bijlsma, Berenbaum, Lafeber. The Lancet (in press)

« Osteoarthritis is to the joints, what are wrinkles in the skin and white hair to the scalp. » William Sydney Charles Copeman, 1933

EARLY DIAGNOSIS : WHY ?

FOR STRUCTURAL REASONS

OA is a disease ! (as complicated as RA, AS, Lupus, etc.)

Sellam & Berenbaum. Nature Reviews Rheum Nov. 2010

Potential DMOADs FOR OA (in 2010)

F. Berenbaum. Best Pract Res Clin Rheum 2010

EARLY DIAGNOSIS : WHY ?

FOR SYMPTOMS

ACUTE PAIN vs CHRONIC PAIN 2 broad categories : •Adaptive pain •Maldaptive pain Adaptive : • Nociceptive pain • Inflammatory pain Maldaptive : • Neuropathic pain • Functional pain

EARLY DIAGNOSIS : WHY ?

FOR PREVENTION

Some risk factors can be modified Risk factors for incidence and progression of OA of the knees, hips and hands

Bijlsma & Klahr. Best Pract Res Clin Rheum 2007

Lifestyle interventions in OA

EFFECT OF MASSIVE WEIGHT LOSS ON KNEE OA SYMPTOMS •140 patients involved in a gastric surgery programme.

•44 were included because painful knee OA (BMI = 50.7 ±7.2)

Richette et al. ARD 2011

Some risk factors can be modified

Risk factors for incidence and progression of OA of the knees, hips and hands

Bijlsma & Klahr. Best Pract Res Clin Rheum 2007

Meniscus damage is a risk factor for knee OA, even in non operated patients From the MOST study : Cases : 50-79 years with no baseline Rx knee OA but tibiofemoral OA at 30 months Controls : 50-79 years with no baseline Rx knee OA and no OA at 30 months

Englund et al. A&R 2009

Some risk factors can be modified Risk factors for incidence and progression of OA of the knees, hips and hands

Bijlsma & Klahr. Best Pract Res Clin Rheum 2007

Long-Term Survival of High Tibial Osteotomy for Medial Compartment OA of the Knee

KEY RECOMMENDATIONS FOR THE PREVENTION OF OA Whole population.

People should : -maintain a level of physical fitness -avoid obesity -prevent injuries due to overuse or accidents At risk population.

People should : -participate in adequate physical exercise -avoid obesity -prevent injuries due to overuse or accidents -consider preventive surgery in specific cases Adapted from Bijlsma & Klahr. Best Pract Res Clin Rheum 2007

EARLY DIAGNOSIS : HOW ?

EARLY DIAGNOSIS : HOW ?

TODAY IN PRIMARY CARE : Clinical history +/- X-rays +/- ESR, CRP +/- synovial fluid analysis

EARLY DIAGNOSIS : HOW ?

TOMORROW IN PRIMARY CARE Clinical history +/- X-rays +/- ESR, CRP +/- synovial fluid analysis +MRI ? +Biomarkers ?

HOW TO DIAGNOSE EARLY ?

Kellgreen-Lawrence score

Link T M et al. Radiology 2003;226:373-381

• Mulitcenter Osteoarthritis Study (MOST): high-risk population • No symptoms and no OA signs on X-rays at inclusion • Question at inclusion and at 15 months : ‘‘During the past 30 days, have you had pain, aching, or stiffness in your knee on most days?’’

• MRI parameters able to predict knee symptoms.

Comparison between 36 symptomatic versus 128 non-symptomatic patients.

Bone marrow lesions predictive of symptoms

OARSI MRI CONSENSUS STATEMENT 1- MRI changes of OA may occur in the absence of radiographic findings of OA 2- Certain MRI changes in isolation including cartilage loss, cartilage compositional change, cystic change, bone marrow lesions, ligamentous and tendinous damage, meniscal damage, and effusion and synovitis are not diagnostic of OA 3- No single MRI finding is diagnostic of knee OA 4- MRI findings indicative of knee OA may include abnormalities in all tissues of the joint : bone, cartilage, meniscus, synovium, ligament and capsule 5- Joint space narrowing assessed by (non weight bearing) MRI cannot be used as a diagnostic criterion

Hunter et al. Osteoarthritis Cart (in press)

OARSI MRI : Definition of Tibiofemoral OA The presence of both group A features or one group A feature and 2 or more group B features

Group A : -Definite osteophyte formation -Full thickness cartilage loss

Group B : -Subchondral BML or cyst -Menisca subluxation, maceration or degenerative (horizontal) tear -Partial thickness cartilage loss (where full thickness loss is not present) -Bone attrition Hunter et al. Osteoarthritis Cart (in press)

Cart degradation Cart synth Bone degr Bone synth

Synov degr Synov synth

uCTX-II uHELIX-II uC1 uC2C uColl 2-1 NO(2) uTIINE uPentosidine sHELIX-II sC1, 2C sC2C sColl 2-1 NO(2) sCOMP sKS sPentosidine sYKL-40

uGlc-Gal -PYR sHA

sPIIANP sPIICP sCS846

uCTX-I uPYR uD-PYR uNTX-I sNTX-I sCTX-I 2 sICTP

sBSP sOC sPICP sPINP

sPIIINP

TAKE-HOME MESSAGES -Although OA is an age-related disease, it does not mean that there is nothing to do to prevent the disease initiation and/or progression.

-By treating the symptoms earlier, a shift from an inflammatory/nociceptive pain to a neuropathic pain could be prevented.

-Although progresses are ongoing in novel approaches for diagnosis (MRI, biomarkers), it is too early to consider these tools for diagnostic purposes in practice today.