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
0
20
40
60
80
20 40 60 80
MenMen
Age (years)Age (years)
Pre
vale
nce
of
OA
(%
)P
reva
len
ce o
f O
A (
%)
0
20
40
60
80
20 40 60 80
WomenWomen
Age (years)Age (years)P
reva
len
ce o
f O
A (
%)
Pre
vale
nce
of
OA
(%
)
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
0
10
20
30
40
50
60
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
0
10
20
30
40
50
60
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
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