All about Osteoarthritis (in 20 minutes…)All about Osteoarthritis (in 20 minutes…)

Howard Amital, MD, MHAHoward Amital, MD, MHA

Daniela Amital, MD, MHADaniela Amital, MD, MHA

Department of Medicine ‘D’Department of Medicine ‘D’

Meir Medical Center, Kfar-SabaMeir Medical Center, Kfar-Saba

“Wear and tear” of the joints

DefinitionDefinition Also known as Also known as

degenerative joint degenerative joint disease or “wear and disease or “wear and tear arthritis”.tear arthritis”.

Progressive loss of Progressive loss of cartilage with cartilage with remodeling of remodeling of subchondral bone subchondral bone and progressive and progressive deformity of the joint deformity of the joint (s). (s).

Cartilage destruction Cartilage destruction may be a result of a may be a result of a variety of etiologiesvariety of etiologies

Prevalence and epidemiologyPrevalence and epidemiology Over 20 million affected in U.S. Over 20 million affected in U.S. About 60-90% of people over age 65About 60-90% of people over age 65 Under 45 yrs it is equally common in men Under 45 yrs it is equally common in men

and womenand women Over 55 yrs its more common in womenOver 55 yrs its more common in women Nodal OA involving DIP and PIP joints is Nodal OA involving DIP and PIP joints is

more common in women and their first more common in women and their first degree female relativesdegree female relatives

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Age-Related Prevalence of OA: Changes Age-Related Prevalence of OA: Changes on X-Rayon X-Ray

DIPDIP

KneeKnee

HipHip

DIPDIP

KneeKnee

HipHip

Premature OA associated with gene mutations Premature OA associated with gene mutations that encode collagen types 2, 9, 10that encode collagen types 2, 9, 10

OA of knee is more common in African American OA of knee is more common in African American womenwomen

Commonest cause of long-term disabilityCommonest cause of long-term disability Large economic impact as a result of medical Large economic impact as a result of medical

costscosts OA cost the U.S. economy nearly $125 billion OA cost the U.S. economy nearly $125 billion

per year in direct expenses and lost wages and per year in direct expenses and lost wages and production.production.

Risk factorsRisk factors Metabolic (hemachromatosis) Metabolic (hemachromatosis) Inflammatory (RA, infection)Inflammatory (RA, infection) ageage gendergender

Risk factorsRisk factors genetic factorsgenetic factors traumatrauma weightweight

ClassificationClassification PrimaryPrimary IdopathicIdopathic Localized or Localized or

generalizedgeneralized Local: knee, hip, Local: knee, hip,

spine, handsspine, hands Generalized:Generalized: large large

joints and spinejoints and spine Small peripheral joints Small peripheral joints

and spineand spine Mixed and spineMixed and spine

SecondarySecondary Post-traumataicPost-traumataic Congenital or Congenital or

developmentaldevelopmental Localized or Localized or

generalizedgeneralized Calcium deposition Calcium deposition

diseasedisease Other:Other: InflammatoryInflammatory Avascular necrosisAvascular necrosis

The process – The process – at a cellular levelat a cellular level

Cartilage matrix has increased water content and Cartilage matrix has increased water content and decreased proteoglycandecreased proteoglycan

This is different from the changes that occur with aging This is different from the changes that occur with aging cartilage dries up. cartilage dries up.

Increased activity of proteinases compared to inhibitors Increased activity of proteinases compared to inhibitors of proteinases.of proteinases.

Breakdown products of cartilage cause inflammatory Breakdown products of cartilage cause inflammatory reaction of synoviumreaction of synovium

Cytokines cause matrix degeneration. Where do they Cytokines cause matrix degeneration. Where do they come from?come from?

chondrocyteschondrocytes Cycle of destruction starts Cycle of destruction starts Compensatory bone overgrowth occurs - subchondral Compensatory bone overgrowth occurs - subchondral

bone increases in densitybone increases in density

Overview of the processOverview of the process

Articular cartilage Articular cartilage gets disruptedgets disrupted

Damage Damage progresses deeper progresses deeper to subchondral to subchondral bonebone

Fragments of Fragments of cartilage released into cartilage released into jointjoint

Matrix degeneratesMatrix degenerates Eventually there is Eventually there is

complete loss of complete loss of cartilagecartilage

Bone is exposedBone is exposed

What to look for in an x-rayWhat to look for in an x-ray Radiographic changes visible relatively Radiographic changes visible relatively

late in the diseaselate in the disease Subchondral sclerosisSubchondral sclerosis Joint space narrowing esp where there is Joint space narrowing esp where there is

stressstress Subchondral cystsSubchondral cysts OsteophytesOsteophytes Bone mineralization should be normalBone mineralization should be normal

Left: View of normal elbow cartilage through an Left: View of normal elbow cartilage through an arthroscope - white, glistening, smooth arthroscope - white, glistening, smooth

Right: severe elbow osteoarthritis - cartilage is Right: severe elbow osteoarthritis - cartilage is lost and the bone underneath is exposed lost and the bone underneath is exposed

left: Normal x-rayleft: Normal x-ray Right: worn away cartilage reflected by Right: worn away cartilage reflected by

decreased joint spacedecreased joint space

Joint space Joint space narrowing where narrowing where there is more stressthere is more stress

Subchondral bone Subchondral bone has thickenedhas thickened

bony overgrowthbony overgrowth

significant joint space narrowing as well as proliferative significant joint space narrowing as well as proliferative bone formation around the femoral neck (arrows) bone formation around the femoral neck (arrows)

painful bone on bone contact at the CMC joint and the large bone painful bone on bone contact at the CMC joint and the large bone spurs -- osteophytes. spurs -- osteophytes.

Are crystals found in osteoarthritic joints?Are crystals found in osteoarthritic joints? YesYes Calcium pyrophosphate dihydrate and Calcium pyrophosphate dihydrate and

apatite.apatite. Are of unknown significance and Are of unknown significance and

asymptomaticasymptomatic

Clinical features and diagnosisClinical features and diagnosis PainPainSourcesSources

– Joint effusion and stretching of the joint capsule Joint effusion and stretching of the joint capsule – Torn menisci Torn menisci – Inflammation of periarticular bursaeInflammation of periarticular bursae– Periarticular muscle spasm Periarticular muscle spasm – Psychological factors Psychological factors

Deep, aching localized to the jointDeep, aching localized to the joint Slow in onsetSlow in onset Worsened with activity in initial stagesWorsened with activity in initial stages Occurs at rest with advanced diseaseOccurs at rest with advanced disease

Involved jointsInvolved joints DIP, PIPDIP, PIP 11stst carpometacarpal carpometacarpal cervical/lumbar facet jointscervical/lumbar facet joints 11stst metatarsophalangeal metatarsophalangeal HipsHips KneesKnees

UncommonUncommon Wrist, elbows, shoulders, Wrist, elbows, shoulders,

anklesankles

11stst metatarso-phalangeal most commonly metatarso-phalangeal most commonly affected in OA of the foot. affected in OA of the foot.

Typical findingsTypical findings

Heberden’s nodesHeberden’s nodes

Bouchard’s nodesBouchard’s nodes

Rt: varus deformity of the kneeRt: varus deformity of the knee

TreatmentTreatment Non-pharmacokineticNon-pharmacokinetic No proven medication-based disease modifying No proven medication-based disease modifying

intervention exists. intervention exists. Analgesics (acetominophen)Analgesics (acetominophen) NSAIDSNSAIDS Help pain symptoms but controversial for long term use Help pain symptoms but controversial for long term use

in non-inflammatory OA because of risks vs benefitsin non-inflammatory OA because of risks vs benefits NarcoticsNarcotics Intra-articular steroidsIntra-articular steroids Chondroprotective agentsChondroprotective agents Anti-depressantsAnti-depressants Physical activityPhysical activity

Intra-articular corticosteroidsIntra-articular corticosteroids May be used if NSAIDS are contraindicated, May be used if NSAIDS are contraindicated,

persistent pain despite use of other medications.persistent pain despite use of other medications. (not > 4 injections per year per joint)(not > 4 injections per year per joint) 2004 meta-analysis of controlled trials (w/ 2004 meta-analysis of controlled trials (w/

placebo) showed short term improvement in placebo) showed short term improvement in knee pain, but efficacy in other joints is knee pain, but efficacy in other joints is uncertain.uncertain.

saline vs steroid injection?saline vs steroid injection? A study comparing the two in knee OA showed A study comparing the two in knee OA showed

no effect on joint space narrowing or significant no effect on joint space narrowing or significant difference in pain at the end of the study, but difference in pain at the end of the study, but over a 2 yr period saline injections has less pain over a 2 yr period saline injections has less pain relief.relief.

Intra-articular hyaluronansIntra-articular hyaluronans Evidence shows they have a small Evidence shows they have a small

advantage in terms of pain control, advantage in terms of pain control, compared to intra-articular placebos or compared to intra-articular placebos or NSAIDS.NSAIDS.

No evidence for improvement in functionNo evidence for improvement in function Two studies comparing intra-articular Two studies comparing intra-articular

steroids to hyaluronans have come to steroids to hyaluronans have come to opposite conclusions-more trials are opposite conclusions-more trials are needed.needed.

Surgical: arthroscopySurgical: arthroscopy arthroscopy is not recommended for arthroscopy is not recommended for

nonspecific "cleaning of the knee“.nonspecific "cleaning of the knee“. Used to fix specific structural damage on Used to fix specific structural damage on

imaging (repairing meniscal tears, imaging (repairing meniscal tears, removing fragments of torn menisci that removing fragments of torn menisci that are producing symptoms). are producing symptoms).

Joint replacementJoint replacement If all other rx If all other rx

ineffective, and pain ineffective, and pain is severeis severe

Loss of joint functionLoss of joint function

Joints last 8-15 years Joints last 8-15 years without complicationswithout complications

Fibromyalgia – Fibromyalgia –

Are new horizons seen ? Are new horizons seen ?

OR Fibromyalgia for the psychiatrist OR Fibromyalgia for the psychiatrist

Howard Amital, MD, MHAHoward Amital, MD, MHA

Daniela Amital, MD, MHADaniela Amital, MD, MHA

Department of Medicine ‘D’Department of Medicine ‘D’

Meir Medical Center, Kfar-SabaMeir Medical Center, Kfar-Saba

""The Three The Three GracesGraces" " by by Peter Paul Peter Paul Rubens Rubens ((1577-1577-16401640)), Prado, , Prado, Madrid, SpainMadrid, Spain. .

Fibromyalgia - criteria Fibromyalgia - criteria

• Widespread Widespread

musculoskeletal painmusculoskeletal pain

• Excess tenderness in at Excess tenderness in at

least 11 of 18 predefined least 11 of 18 predefined

anatomic anatomic

Frida KahloFrida Kahlo ( (1907-1954)1907-1954)

Frida used to describe her own paintings as "the most frank expression of myself"

The Broken Column

Chronic Pain – Defined by Chronic Pain – Defined by MechanismsMechanisms

Peripheral Peripheral (nociceptive)(nociceptive)– Primarily due to Primarily due to

inflammation or damage inflammation or damage in peripheryin periphery

– NSAID, opioid responsiveNSAID, opioid responsive– Behavioral factors minorBehavioral factors minor– ExamplesExamples

OAOA Acute pain models (e.g. Acute pain models (e.g.

third molar, post-surgery)third molar, post-surgery) RARA Cancer painCancer pain

Central (non-Central (non-nociceptivenociceptive))– Primarily due to a central Primarily due to a central

disturbance in pain disturbance in pain processingprocessing

– Tricyclic responsiveTricyclic responsive– Behavioral factors more Behavioral factors more

prominent prominent – ExamplesExamples

FibromyalgiaFibromyalgia Irritable bowel syndromeIrritable bowel syndrome Tension and migraine Tension and migraine

headacheheadache Interstitial cystitis / Interstitial cystitis /

vulvodynia, non-cardiac vulvodynia, non-cardiac chest pain / etc.chest pain / etc.

Mixed Neuropathic

Fibromyalgia - some facts Fibromyalgia - some facts

• 10 times more common in females 10 times more common in females Studies of humans and of Studies of humans and of

animals have noted that females have a lower pain threshold and tolerance and a higher animals have noted that females have a lower pain threshold and tolerance and a higher

sensitivity to various noxious stimuli. sensitivity to various noxious stimuli. Pillemer et al. Arthritis Rheum. 1997;40:1928-Pillemer et al. Arthritis Rheum. 1997;40:1928-

19391939

• Prevalence in the community increases with age Prevalence in the community increases with age

from from 2% at age 2% at age

20 to 8% at age 7020 to 8% at age 70

• Most patients present between the ages of 30 and Most patients present between the ages of 30 and

5555

• Approximately 50% of cases appear after a specific Approximately 50% of cases appear after a specific

event, event, most often (physical or emotional most often (physical or emotional

trauma)trauma)

Wolfe F et al. Arthritis Rheum 1995, 38:19-28.Wolfe F et al. Arthritis Rheum 1995, 38:19-28.

The tender point count functions The tender point count functions as a `sedimentation rate' for as a `sedimentation rate' for distressdistress

WHAT IS THE ASSOCIATION BETWEEN FM WHAT IS THE ASSOCIATION BETWEEN FM AND PSYCHIATRIC ILLNESS? - AND PSYCHIATRIC ILLNESS? - DepressionDepression

A lifetime history of depression has A lifetime history of depression has been reported in 50% to 70% been reported in 50% to 70%

Current major depression, however, Current major depression, however, was found in only 18% to 36% was found in only 18% to 36%

Goldenberg DL et al, Arthritis Rheum. 1996;39:1852-1859 Goldenberg DL et al, Arthritis Rheum. 1996;39:1852-1859

Goldenberg DL et al, Arch Intern Med, 1999;159:777-785Goldenberg DL et al, Arch Intern Med, 1999;159:777-785

WHAT IS THE ASSOCIATION BETWEEN FM WHAT IS THE ASSOCIATION BETWEEN FM AND PSYCHIATRIC ILLNESS? - AND PSYCHIATRIC ILLNESS? - DepressionDepression

Similar symptoms: fatigue, sleep Similar symptoms: fatigue, sleep disturbances, and cognitive disturbances.disturbances, and cognitive disturbances.

Similar comorbid conditions: migraines, Similar comorbid conditions: migraines, muscular headaches, CFS, IBS, and muscular headaches, CFS, IBS, and premenstrual syndrome.premenstrual syndrome.

Often improve with antidepressant Often improve with antidepressant medicationsmedicationsTriadafilopoulos G et al, Dig Dis Sci. 1991;36:59-64.

WHAT IS THE ASSOCIATION BETWEEN FM AND WHAT IS THE ASSOCIATION BETWEEN FM AND PSYCHIATRIC ILLNESS? - PSYCHIATRIC ILLNESS? - other psychiatric other psychiatric

disturbancesdisturbances

Dysthymia - 10% Current Dysthymia - 10% Current prevalence (CP)prevalence (CP)

Panic disorder - lifetime Panic disorder - lifetime prevalence (LP) -16%, CP- 7%prevalence (LP) -16%, CP- 7%

Phobia LP - 16%, CP -12%. Phobia LP - 16%, CP -12%.

Epstein SA et al. Psychosomatics 1999;40:57-63. Epstein SA et al. Psychosomatics 1999;40:57-63.

The overlapping ill defined disordersThe overlapping ill defined disorders

FIBROMYALGIA FIBROMYALGIA 2 - 4% of population; defined by widespread

pain and tenderness

EXPOSURE EXPOSURE SYNDROMESSYNDROMES e.g. Gulf War Illnesses, silicone breast implants, sick building syndrome

CHRONIC FATIGUE CHRONIC FATIGUE SYNDROMESYNDROME 1% of population; fatigue and 4/8 “minor criteria”

SOMATOFORM SOMATOFORM DISORDERSDISORDERS 4% of population; multiple unexplained symptoms - no organic findings

MULTIPLE CHEMICAL MULTIPLE CHEMICAL SENSITIVITYSENSITIVITY - symptoms in multiple organ systems in response to multiple substances

Rate of fibromyalgia Rate of fibromyalgia

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Controls(0/ 49)

PTSD (27/ 55)

Depression(1/ 20)

FM+FM-

p<0.001p<0.001

χχ22=40 (d.f – 2)=40 (d.f – 2)

Distribution of severity of FM Distribution of severity of FM

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controls PTSD Depression

0*66*10 (mild)11*14 (moderate)15*16 (severe)17*18 (extreme)

p<0.0001p<0.0001

χχ22=60.5 (d.f – 8)=60.5 (d.f – 8)

No. of No. of patientspatients

Results – average tender point Results – average tender point countcount

Controls – (n=49) 0.18 ±0.4 Controls – (n=49) 0.18 ±0.4 PTSD – (n=55) 8.9 ±5.4PTSD – (n=55) 8.9 ±5.4 Depression - (n=20) 2.85 ±3Depression - (n=20) 2.85 ±3

p<0.001, Anovap<0.001, Anova

Clinical Global Impression (CGI)

PTSD – 5.67

DEPRESSION – 5.65 p=0.62, Anovap=0.62, Anova

A SixA Six--month, Doublemonth, Double--blind, Placeboblind, Placebo--controlled, controlled, Durability of Effect Study of Pregabalin for Pain Durability of Effect Study of Pregabalin for Pain

Associated With FibromyalgiaAssociated With Fibromyalgia Crofford et al ACR 2006Crofford et al ACR 2006

By the end of the study nearly twice as By the end of the study nearly twice as many placebo patients many placebo patients ((61%61%) ) had lost had lost therapeutic response compared with therapeutic response compared with pregabalinpregabalin--treated patients treated patients ((32%32%). ).

The most common AEs considered The most common AEs considered treatment related during OL were treatment related during OL were dizziness dizziness ((36%36%) ) and somnolence and somnolence ((22%22%).).

Thank you for Thank you for your attentionyour attention